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Analyses of serum cholesterol measurements on 4,619 males and 4,730 females residing in the community of Tecumseh, Michigan, were conducted to estimate the contribution of sex, age, temporal variation, and bimodality to determining the normal variation among individuals sampled without regard to their health status. Female values had a higher mean (2.8 mg/100 ml greater) but smaller variance than males when adjusted by polynomial regression to a common age. Positive skew in the frequency distribution for both sexes was removed by natural logarithm (ln) transformation. Age variation accounted for 28.5% and 29.4% of the variance in a ln cholesterol measurement of males and females, respectively. Between 7% and 10% of the variance in a ln cholesterol value was estimated to be attributable to differences between age-adjusted replicate measurements of the same individual. The reduction in individual variability by adjustment for these contributions to variance will allow a more precise evaluation of the relative contribution of alternate genetic hypotheses as explanations for normal variation in cholesterol. Assuming bimodality, approximately one in 1,000 males and one in 1,000 females belong to a second mode of hypercholesterolemic individuals. The locus determining familial hypercholesterolemia is not a major source of normal phenotypic variation in the Tecumseh population. | US |
The high incidence of some genetic diseases in certain ethnic groups is important in planning of medical genetic programs. Simple interaction models predict that at least some lethal recessive alleles will have "hitchhiked" to increased frequencies because of linkage to genes whose alleles have been favored by selection for other reasons in certain populations. In the absence of linkage or epistasis with a gene favored by selection, heterozygote advantage for a recessive lethal may produce the same phenomenon. In the hitchhiking model (linkage), the increase in the gene frequency is temporary, but the length of time that the increased gene frequency is at least double the base frequency may be quite long. Changes in gene frequency for the unlinked epistatic model result in a new equilibrium with a possibly higher gene frequency. The most likely chromosomal regions in which hitchhiked lethal recessives would be found are in the vicinity of genes whose allelic frequencies vary substantially among human racial groups (e.g., Gm, Rh, Duffy, lactose tolerance, or HL-A). There will be a hitchhiking effect if recombination distance is less than the selective advantage. The closer the linkage of two loci, the easier hitchhiking effects will be to detect. Hitchhiking is suggested by nonrandom association of the recessive disease and one of the selected markers, as in the case of Gm and cystic fibrosis. However, there is so far insufficient evidence of linkage between them. More pedigree information is necessary than is now available. | US |
In simulated data, segregation analysis of quantitative traits was found to be powerful for resolving a major locus from polygenic and cultural inheritance. It is reasonably robust against a variety of deviations from the model if and only if a major locus, polygenic heritability, and environment common to sibs are simultaneously included in the model, and heterogeneity tests among mating types are performed. Most of the information in quantitative data about a major locus is lost when reduced to affection status. | US |
The population growth kinetics of human diploid skin fibroblasts derived from cystic fibrosis homozygotes and heterozygotes and from normal subjects were investigated. Our data suggest the following: 1. Population doubling times increase with time in culture, with no significant differences observed among the three genotypes tested, when data were compared at the same subculture times or phases of growth. 2. The fraction of dividing cells in a population decreased with the duration in which the cells were in culture. No significant differences were obtained for cells derived from the three genotypes. 3. Cell cycle times were very similar (18-20 hr) when comparing the normal and cystic fibrosis lines or when comparing cystic fibrosis lines in phases 1 and 2 of growth. 4. No significant variations in population doubling times or growth fractions could be attributed to age or sex of the biopsy donor. 5. Variability in growth fractions and doubling times was minimal through the eighth subculture period but was very great in older cultures (tenth subculture). 6. Changes in growth fractions and doubling times appear to be due to the possibility of "aging" of human diploid fibroblasts in culture rather than to the presence or absence of genes for cystic fibrosis. 7. It is strongly indicated that differences in cell kinetic parameters cannot be used as the basis for differentiation between cells derived from normal or cystic fibrosis genotypes. | US |
Chiasma frequency data on 183 males were subjected to an analysis of covariance. There appeared to be little or no linear trend in chiasma frequency with age. This conclusion was supported by a detailed analysis of chiasma frequencies for each autosome from 21 males. There were, however, significant differences among investigators in reported mean chiasma frequencies. | US |
The basal levels of adenosine 3':5'-monophosphate (cyclic AMP) in the oviductal isthmus were lower during pseudopregnancy than during estrus. No differences were observed in the ampulla. Prostaglandin E2(PGE2) significantly increased cyclic AMP levels in the isthmus during pseudopregnancy but not during estrus. In contrast, in the ampulla, PGE2 did not alter cyclic AMP levels in either hormonal condition. Theophylline increased cyclic AMP levels in the isthmus and in the ampulla during pseudopregnancy. These results show that PGE2 causes a specific increase in cyclic AMP levels in the isthmus after ovulation. | US |
The morphology of T-mycoplasmas in culture and in semen from men of infertile marriage was examined by scanning electron microscopy. In cultures obtained from semen of infected individuals, T-mycoplasmas were recognized as spherical particles, 160 to 200 nm in diameter, frequently interconnected by short, straight fibrils. Numerous T-mycoplasmas and associated fibrils with similar morphologic characteristics were also observed adhering to spermatozoa obtained from ejaculates of the infected donors. Similar granulofibrillar aggregates were never observed on control specimens. These observations indicate a physical association between the microorganisms and spermatozoa in semen of infected men. This association may contribute to the decreased motility of spermatozoa in semen from which T-mycoplasmas can be cultured. The binding of T-mycoplasmas to human spermatozoa may provide an effective mechanism for transfer of the microorganisms past the normal microbial barrier of the cervix. | US |
Spermiation and epididymal maturation of spermatozoa were studied in the bonnet monkey (Macaca radiata) by light and scanning electron microscopy. The morphology, location, and release of residual body were observed during spermiation. Along the epididymal duct, the shape of spermatozoa changed, the constriction at the anulus disappeared, the marginal thickening diminished in length, and the cytoplasmic droplet regressed and moved toward the posterior end of the middle piece. Mature spermatozoa were very similar to those of other Cercopithecidae, and they showed a forward motility and a drop in eosin stainability. | US |
A family with hirsutism in five generations in which polycystic or bilaterally enlarged ovaries were documented in three different sibships of two generations is described. Two brothers of one of the women with polycystic ovaries had a low or low-normal plasma follicle-stimulating hormone level and one of these had oligospermia due to maturation arrest of spermiogenesis. A third brother had Klinefelter's syndrome. Other abnormal features in the family included precocious adrenarche, beardless males, eunuchoidism, and prepubertal grand mal seizures. | US |
No circulating sperm-agglutinating or sperm-immobilizing antibodies were demonstrated in oligospermic or azoospermic men up to 14 days following bilateral testicular biopsies. Possible reasons for this lack of antigen-antibody response are discussed. | US |
Seven enzymes of the Embden-Myerhof pathway of glycolysis were assayed in hypotonically treated epididymal sperm from mature rabbits. These were: fructose-biphosphate aldolase, triosephosphate isomerase, glyceraldehydephosphate dehydrogenase, 3-phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase. These enzymes were firmly enough bound to the cell structure to resist removal by washing after hypotonic treatment and had maximal activities comparable to, or greater than, the rate of mitochondrial pyruvate oxidation, so that rapid oxygen uptake was observed with intermediates of the glycolytic pathway. The activity of lactate dehydrogenase in a typical preparation of hypotonically treated cells was 5.3 mumoles/minute x 10(9) cells at 25 degrees C for pyruvate reduction in the hypotonically treated cells and 4.8 mumoles/minute x 10(9) cells in the thrice-washed hypotonically treated cells. The Km for pyruvate was 1.4 mM while that for lactate was 4.4 mM. By contrast, the maximal activity of pyruvate oxidation by mitochondria was 0.10 microgram atom of oxygen/minute x 10(9) cells, corresponding to 0.020 mumole of pyruvate/minute x 10(9) cells, and the Km for pyruvate was 5 microM. These enzyme parameters favor high lactate production from glucose in aerobic glycolysis. | US |
Superovulated immature rats (24 to 25 days old) were inseminated with epididymal sperm before or after ovulation and their eggs were examined at various times. When inseminated before ovulation, the interval between insemination and sperm penetration was 7 to 9 hours; the sperm penetration began approximately 2 hours after the first appearance of eggs in the oviducts and ceased 4 to 6 hours later. When inseminated after ovulation, the interval between insemination and sperm penetration was 5 to 6 hours; sperm penetration started 5 to 9 hours after ovulation and the proportion of penetrated eggs was not increased 4 hours later. The fertilizing capacity of sperm in the immature female tract lasted for 10 to 14 hours, which is shorter than in the mature animals, and sperm penetration occurred 2 to 10 hours after ovulation. The proportion of eggs fertilized, however, was not higher than 55%. A significant greater number of eggs was penetrated by more than one sperm but the number of polyspermic eggs was not increased when insemination was delayed. Epididymal sperm were incubated for various lengths of time and similarly inseminated into the uterine horns of immature rats. The fertilizing capacity of sperm could be maintained in culture for 10 hours but the proportion of fertilized eggs decreased sharply after incubation for 8 hours. Although rat epididymal sperm in a concentrated form could not be capacitated in vitro, they could be capacitated after incubation by intrauterine insemination. | US |
A 19-month-old boy had adrenocerebroleukodystrophy and unusually severe cochlear nerve degeneration and demyelination, a condition in advance of that expected from known disease entities. We report the only known temporal bone study in adrenocerebroleukodystrophy. | US |
We describe the histopathologic features of the inner ear in a 19-year-old girl with bilateral total deafness associated with Kearns-Sayre syndrome. The inner ear shows advanced degree of cochleo-saccular degeneration, with almost complete absence of the organ of Corti in all turns. The spiral ganglion shows a reduction of about 60% to 70% of cells, with almost complete degeneration of nerve fibers in the bony spiral lamina. PAS-positive material was found accumulated in globules between the collapsed Reissner membrane and remains of marginal cells of the stria and in the degenerated sensory cell area of the saccular macula. | US |
Since arterial blood oxygen tensions are used in the evaluation of treatment of patients with meconium aspiration syndrome, it is important to recognize the occurrence of significant right-to-left shunting via a patent ductus arteriosus. The clinical findings, evidence of right-to-left ductus shunting, and outcome in eight patients with meconium aspiration syndrome are presented. Administration of tolazoline HCl and curare produced a beneficial effect on their PaO2 values. | US |
Functional human globin messenger RNA was isolated from reticulocytes of two patients with homozygous beta 0-thalassemia, three patients with sickle cell beta 0-thalassemia, and one patient doubly heterozygous for beta 0-thalassemia and hemoglobin Lepore. When incubated in the Krebs type II mouse ascites tumor-cell-free system, messenger RNA from these patients actively directed the synthesis of human beta s and/or alpha- and gamma-globin chains but failed to stimulate the synthesis of any beta A-chains, even though nonthalassemic human globin mRNA preparations consistently stimulated two to four times as much beta A- or beta S-globin chain synthesis as alpha-chain synthesis when incubated in the same system under the same conditions. These results strongly suggest that functional beta A-chain-specific globin mRNA is absent in beta 0-thalassemia. | US |
Patients with IgG multiple myeloma underwent serial studies of tumor cell kinetics including (1) estimation of the total body myeloma cell number (TBMC), (2) measurement of the myeloma cell tritiated thymidine labeling index (LI), and (3) calculation of the total number of myeloma cells undergoing DNA synthesis. Intermittent courses of chemotherapy with cycle-non-specific agents such as melphalan resulted in a marked increase in the LI of myeloma cells in patients who had a 75% reduction in TBMC. The long "plateau" phase of partial remission of myeloma in these patients was associated with a continued high LI: this suggests that the plateau resulted from a balance between the cytoreductive effects of chemotherapy and expansion of the growth fraction (GF) of the tumor. Preliminary attempts to capitalize therapeutically on this expansion of the GF in several patients included administration of the cycle-active agents vincristine and cytosine arabinoside. Vincristine appeared to induce a further reduction in tumor in several patients, although cytosine arabinoside appeared to be ineffective despite clear evidence of its inhibition of DNA synthesis in myeloma cells in vivo. Further clinical studies of the effects of cycle-active drugs on myeloma appear to be warranted; however, successful exploitation of the dynamic change in myeloma cell kinetics with chemotherapy will require the use of cycle-active agents with marked selective toxicity for myeloma cells. | US |
A patient with plasma cell myeloma producing only Bence Jones lambda protein was found to have pale intranuclear inclusions in the majority of the bone marrow plasma cells. These inclusions, previously undescribed in myeloma patients producing only Bence Jones protein, contained Bence Jones lambda protein, were non-electron dense, bound by a single membrane, and contained no cytoplasmic structures. Intracytoplasmic inclusions were not present, and the perinuclear cistern was not dilated. Thus, the inclusions may represent intranuclear protein synthesis with anomalous release in the abnormal cells. | US |
Exposure of rabbit or human erythrocytes to concentrations of puromycin as low as 7 x 10(-4)M for 2 hr causes damage to the cell membrane, as evidenced by increased susceptibility of the cells to hyposmotic lysis, increased cell rigidity, and ultrastructural changes consistent with severe membrane damage. Puromycin causes a concentration-dependent internalization of the erythrocyte membrane, resulting in vacuolization of the cells, at concentrations between 7 x 10(-4) M and 10(-2) M. Since the erythrocyte does not synthesize protein, the data indicate that puromycin has a direct toxic effect on erythroid cell membranes which is unrelated to its action in inhibiting the synthesis of protein. | US |
Deformation of the erythrocyte membrane by the micropipette technique permits analysis of intrinsic material characteristics of the membrane and provides a means to differentiate purely membrane factors from such extrinsic factors as surface area-to-volume ratio. Using small micropipettes (less than 0.5 microns radius) to deform cells, it is evident that the red cell membrane behaves like a solid for periods of time up to 5-10 min of sustained deformation; for long periods of strain, permanent deformations occur, indicative of the semi-solid structural character. In the time range in which the membrane behaves like a solid, the material is linearly elastic up to strains of 400%, implying a loose network structure in the membrane plane, and evaluation of the elastic parameter mu (mu for normal discocytes equals 7 x 10(-3) dynes/cm) suggests that the elements comprising the network may have a molecular weight of approximately that of the water-soluble membrane protein spectrin. Whether the network system is cross-linked or simply a polymer solution remains unanswered. Experimental data indicate that plastic flow of the membrane under conditions of protracted strain may lead to permanent deformation of the membrane, whereas uniform dilation of the membrane, requiring over 1000 times more energy than for plastic flow, results in membrane failure and lysis. Analyses of the data from larger micropipettes of limiting mean cylindrical diameter show their utility in evaluating extrinsic factors, e.g., surface area-to-volume relationships, which are related to the capability of the whole cell to form a new configuration with implicit resistance to total surface area change, as the cell enters narrow channels of the microcirculation. Thus, micropipettes with diameters in the 2.7-3.0-microns range can provide sensitive comparisons of cellular deformability of erythrocytes. | US |
In this investigation, we studied the importance of cellular glutathione (GSH) in the hexose monophosphate shunt (HMPS) activity of unstimulated human erythrocytes and the mechanism by which pyruvate stimulates the HMPS. The rate of HMPS activity was measured by the production of radioactive CO2 from 14C-1-glucose or 14C-1-ribose using a vibrating reed electrometer and ionization chamber. HMPS activity was not significantly impaired by N-ethylmaleimide (NEM) in concentrations which bound all red cell GSH. Red cells incubated under carbon monoxide (CO), an experimental condition which eliminates peroxide production, still had HMPS activity which was 44% of the value under air. Pyruvate stimulation of the HMPS was unaffected by doses of NEM which bound all cellular GSH or by incubation under CO. These data indicated that pyruvate stimulation of the HMPS occurs by pathways which do not involve peroxide formation, GSH, or oxygen. This study indicates that sulfhydryl blockade of GSH does not necessarily inhibit HMPS activity and that HMPS activity in red cells may respond to reactions not linked directly to glutathione reduction. | US |
Marrow regulation and iron metabolism were evaluated in 17 patients with mild or moderate anemia associated with chronic disorders. In addition, whole blood P50 and red cell 2,3-diphosphoglycerate (DPG) levels were measured. The study group consisted of seven patients with non-hematologic malignancies, nine with infection or inflammation, and one with idiopathic hypoproliferative anemia. The mean whole blood P50 and DPG levels were elevated to 28.5 +/- 1.9 mm Hg and 7.03 +/- 0.83 mumole/ml packed RBC, respectively, as compared to normal values of 26.6 +/- 0.6 mm Hg and 4.83 +/- 0.33 mumole/ml packed RBC. Erythropoietin (ESF) excretion was variable (1.1-28.7 IRP U, day), clearly elevated above normal in only three patients and, within the study group, bore no relation to hematocrit. While nine of the 17 subjects had ESF excretion rates within the 95% limits predicted by hematocrit, the remaining eight had lower than expected values. No significant differences in ferrokinetics, ESF excretion, or hematologic profile were found between patients with malignancy and those with inflammation. Marrow transit times correlated inversely with both serum and urine ESF activity (r = -0.57, p less than 0.02; and r = -0.63, p less than 0.01, respectively), indicating that the marrow reticulocyte release response to ESF stimulation was unimpaired. Erythroid iron turnovers were unrelated to serum or urinary ESF activity but were significantly correlated with serum iron levels expressed as microgram/100 ml whole blood (r = 0.56, p less than 0.02). These studies suggest that there is an intraerythrocytic response to the anemia in this group of patients, document that reduced ESF production is not a uniform finding with the anemia of chronic disorders, and provide evidence that the marrow proliferative response to anemia is limited in many patients primarily by the availability of iron. | US |
An in vitro marrow culture assay designed to measure erythropoietic capability was used to ascertain the presence of an inhibitor in the sera of patients with congenital hypoplastic anemia (CHA). Marrow cells from nine anemic CHA patients responded to the stimulatory effect of exogenous erythropoietin (EPO) by an increase in heme synthesis in the presence of normal serum. The effect on heme synthesis was less than that observed with normal marrow cells. CHA serum inhibited heme synthesis by both normal and CHA marrow cells. It is concluded that an in-inhibitor of erythropoiesis is present in serum from CHA patients. This inhibitor most likely blocks the EPO-sensitive stem cell receptor sites, causing decreased response to the hormone. | US |
Adenine nucleotide metabolism and the release reaction were studied during ristocetin-induced platelet aggregation. Decreasing platelet ATP by incubation with metabolic poisons did not decrease ristocetin-induced aggregation. ADP and ATP were released from platelets during ristocetin-induced aggregation, and ATP was converted to hypoxanthine. However, these occurred after aggregation was almost complete. Aggregation was inhibited by p-choromercuribenzoic acid. By studying platelet suspensions, we were able to determine that this effect was on platelets and not on the plasma cofactor needed for aggregation. We postulate that ristocetin and its cofactor aggregate platelets by binding platelet membranes and that the platelet plays a passive role in this reaction. | US |
A population sample of 142 men and 148 women aged 40-69 was drawn in Chittenden County, Vermont, and studied for interrelationships among several parameters of obesity, fasting serum cholesterol, triglycerides, glucose and insulin concentrations, and 2-hour post-Glucola glucose and insulin concentrations. No significant sex differences were observed with regard to mean fasting concentrations of glucose, insulin, cholesterol, or triglyceride. Post-Glucola insulin concentrations were higher in women, particularly in the older age groups. Positive correlations were observed between mean log fasting insulin concentration and all parameters of obesity except log triceps skinfold thickness in men. In addition, a positive correlation was present between mean log fasting insulin and fasting triglycerides. There was a positive correlation between fasting triglycerides and ponderal index and estimated percent body fat. Fasting triglycerides correlated with percent ideal weight in women but not in men and with log subscapular skinfold thickness in men but not in women. There was no correlation with either log triceps skinfold thickness or with combined triceps and subscapular skinfold thickness in either men or women. No positive correlations were observed with regard to serum cholesterol. The measurement of glucose and insulin concentrations 2 hours post-Glucola or the calculation of insulin-to-glucose ratios did not provide additional correlations to those observed from the fasting data alone and in some instances correlations which existed in the fasting state were largely obscured following carbohydrate administration. | US |
There are two mechanical determinants of coronary blood flow and its distribution: resistance and pressure gradient. Resistance is determined by blood viscosity and the anatomy and geometry of the coronary vascular bed. The coronary vascular pressure gradient is the difference between aortic root pressure and intramyocardial pressure. A number of factors such as coronary atherosclerosis, ventricular hypertrophy, and myocardial edema may adversely affect the determinants of coronary flow before, during, or after cardiopulmonary bypass, thereby lowering or eliminating regional or local coronary reserve and promoting the likelihood of a myocardial ischemic injury. The subendocardial layers of the left ventricle appear to be more vulnerable, perhaps in part because they depend entirely on diastolic coronary flow. | US |
Previous studies have shown that mice treated from birth with heterologous anti-mu antiserum are severely immunosuppressed with respect to numbers of splenic plaque-forming cells (PFC) to sheep red blood cells (SRBC) in all immunoglobulin classes. In this study we have investigated, using in vitro techniques, the cellular site of the deficit created by anti-mu. The primary PFC response of spleen cells originating from anti-mu-treated mice was completely suppressed in vitro. The response was restored by the addition to the cultures of B cells but not T cells. T cells were derived from normal spleens which had been depleted of B lymphocytes and adherent cells by filtration through cotton wool columns, or by educated thymus cells obtained from the spleens of lethally irradiated mice injected with syngeneic thymocytes and SRBC. Restoration of the PFC response of spleen cells from anti-mu-treated mice by normal B cells suggested that a cellular deficiency rather than an activity process by inhibitory cells was the cause of the imunosuppression. Also, co-culturing spleen cells from normal and suppressed mice did not reveal the presence of inhibitory cells. Spleen cells from x-irradiated mice, injected with bone marrow from anti-mu-suppressed mice, gave rise to PFC cells when cultured with SRBC and normal T cells, suggesting that stem cells giving rise to B cell were not affected by anti-mu treatment. Similarly, educated thymus cells derived from suppressed mice could provide helper function when reconstituted in vitro with normal B cells. Exposure of normal bone marrow and spleen cells to anti-mu serum prior to passage through syngeneic x-irradiated recipients demonstrated that spleen cells were much more sensitive than were bone marrow cells to suppression by anti-mu antibodies. It is concluded that the target of anti-mu antibody is a mu-chain bearing B cell precursor to the IgM-, IgG-, and IgA-producing cell. | US |
Thyrotropin-releasing hormone (TRH) was found to antagonize pentobarbital-induced sleeping time and hypothermia. While 3 to 100 mg/kg of TRH reduced pentobarbital sleeping time when administered prior to the barbiturate, a dose-response relationship to TRH could not be established. However, doses of 10 to 100 mg/kg of TRH enhanced the lethality of pentobarbital when these compounds were administered simultaneously. Thyrotropin or L-triiodothyronine did not imitate and hypophysectomy did not reduce the effects of TRH, indicating that the pituitary is not essential for its antagonism of pentobarbital. Studies of TRH analogs provided further support of this view. In addition, TRH reduced the sleep and hypothermia produced by thiopental, amobarbital, secobarbital and phenobarbital, and it antagonized the hypothermia and reduced motor activity produced by chloral hydrate, reserpine, chlorpromazine and diazepam. Intracisternally administered TRH also reduced pentobarbital sleeping time and hypothermia, but melanocyte-stimulating hormone release-inhibiting factor and somatostatin administered by this route did not. While reduction of pentobarbital sleeping time by TRH could not be attributed to an affect on monoamine systems or to deamidated TRH, this action was reduced by intracisternally administered atropine, suggesting that cholinergic mechanisms may contribute to the effects of TRH. Thus, the results provide evidence that TRH acts on brain independent of an effect on the pituitary. | US |
Two of twenty IgA myeloma proteins studied were found to lack J chain. Both IgA proteins contained dimers and higher polymers (trimers, tetramers, pentamers) in proportions similar to those found in most classical 'J-positive' proteins. Both the 'J-negative' proteins contained bound albumin and alpha-1 antitrypsin (alpha1AT),and reduction with mercaptoethylamine caused a release of albumin and alpha1AT concomitant with depolymerization of the higher polymers of IgA. These proteins formed complexes with secretory component (SC) in vitro, indicating that the presence of J chain is not a requirement for SC binding. | US |
The hemodynamic effects of petrinitrol, a new antianginal agent, were evaluated in 30 patients during cardiac catheterization. The administration of 5 mg and 10 mg doses, both sublingually and orally, caused significant reductions of systemic arterial pressure, cardiac index, stroke index, and pulmonary arterial pressure that were prominent 15 to 30 minutes after administration of the drug. All but the 5 mg oral dose produced an increment of heart rate. The 10 mg sublingual dose also caused a significant reduction of left ventricular work. Total systemic resistance, and the product of blood pressure and heart rate did not change significantly. It appears that petrinitrol and nitroglycerin have several similar effects upon the cardiovascular system; but in the doses administered, petrinitrol caused changes of greater magnitude and longer duration. | US |
Twenty-four members (4 generations) of a family with alpha 1 antitrypsin deficiency were studied in an attempt to determine the chromosomal location of the Pi system locus. Three alpha 1 antitrypsin alleles (PiM, PiI, and PiZ) and five phenotypes (MM, MZ, MI, IZ, and ZZ) were detected in family members. The quinacrine fluorescent banding technique was successfully utilized to reveal eight polymorphic chromosomal markers in family members. Eight red cell antigens and HL-A antigens were identified for each family member. No linkage between the Pi system and chromosomal markers, four polymorphic red cell antigens, and HL-A antigens was detected. On the basis of this family study, the Pi locus as defined by alpha 1 antitrypsin deficiency does not appear to be on chromosomes 2, 3, 13, 14, 21, or 22 within measurable distance of the markers used. | US |
Intact Fcalpha fragments from five human IgA myeloma proteins were produced by two different methods, high temperature trypsinolysis and IgA protease digestion. Three of the Fcalpha fragments activated the classical pathway as determined by the titers of the individual complement components. Two other fragments did not fix complement by either pathway. | US |
Behaviorally determined auditory thresholds of chinchillas were monitored before, during and after daily administration of kanamycin sulfate (200 mg/kg per day). Drug treatment was terminated as soon as a shift in high-frequency thresholds was observed. In surviving animals, hearing loss spread toward lower frequencies and stabilized after eight to nine days. The stable hearing loss was limited, on the average, to frequencies above 3 kHz. The magnitude of the loss was constant across frequencies and averaged about 40 dB. Virtually complete outer hair cell loss was seen in the basal portion of the cochleae of all surviving animals. | US |
A comparison of the anticonvulsant and neurotoxic effects of cannabidiol (CBD), delta 9tetrahydrocannabinol, cannabinol and antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, chlordiazepoxide, clonazepam, ethosuximide and trimethadione) was made in rats. Median effective potencies (ED 50 values) for maximal electroshock, audiogenic seizures and TD50 values for a rotor rod neurotoxicity test were calculated. Additionally, the interactive effects of CBD and the antiepileptic drugs against maximal electroshock and audiogenic seizures were studied. Each drug was given orally at peak effect time. CBD was an effective and relatively potent anticonvulsant in both maximal electroshock and audiogenic seizure tests. The anticonvulsant potency of phenytoin was significantly increased when combined with phenobarbital, CBD and phenobarbital plus CBD. Additionally, CBD reliably reduced the anticonvulsant potencies of chlordiazepoxide, clonazepam, trimethadione and ethosuximide. These data indicate that CBD is an effective anticonvulsant with a specificity more comparable to drugs clinically effective in major than minor seizures. Furthermore, it appears that CBD enhances the anticonvulsant effects of the former and reduces the effects of the latter types of antiepileptic drugs. | US |
Chronic administration of ethyl 2-methyl-2(4-chlorophenoxy)-propionate [clofibrate, CPIB], ethyl 6-cyclohexylchroman-2carboxylate, and ethyl 6-phenylchroman-2-carboxylate to normolipemic rats, in vivo, reduced serum cholesterol levels and inhibitid the activiry of hepatic 3-hydroxy-3methyl-glutaryl Coenzyme A. Only clofibrate was found to lower liver cholesterol content after pretreatment for 4 or 18 days. The cyclic analogs, ethyl 6-cholorochromone-2-carboxylate and 9-chloro-2,3-dihydro-5H-1,4-dioxepino [6,5-b] benzofuran were inaffective as cholesterol lowering agents in normolipemic rats. These findings indicate that appropriate modification of clofibrate can lead to the development of compounds which are selective and equally effective to clofibrate as potential hypocholesterolemic agents. Results obtained in these studies are also discussed in terms of the known structural requirements of biological activity for this series of cyclic analogs in the Triton WR-1339 hyperlipemic rat model and modes of action of the parent compound. | US |
Although other reports have stressed the inevitability of portal hypertension and splanchnic pooling following major liver resections, clinical observations during 30 major hepatic resections and measurements of portal pressure in three consecutive trisegmentectomies fail to support this contention. If the remaining liver is normal and careful anatomic dissection is used, major resections can be performed without inducing portal hypertension. | US |
Eighteen young (mean age = 21.50; SD = 2.23) and 18 older (mean age = 68.17; SD = 3.13) adults participated in a vocabulary task involving varying degrees of risk with a payoff structure that varied either directly or inversely with risk. In contrast to prior research using constant payoff structures, the results did not indicate that older adults are more cautious than young adults. Further, for both age groups, risk-taking is a function of payoff structure. The data clearly question the generalization that the elderly are more cautious than young adults and suggest that risk, as a concept, should not be considered independently of payoff. | US |
Tritiated thymidine incorporation, a measure of DNA synthesis, was studied in circulating leukocytes from patients with widespread psoriasis who were being treated with photochemotherapy using oral 8-methoxypsoralen (8-MOP) and high-intensity, long-wave ultraviolet light (UVA). Seven of 13 psoriasis patients treated with photochemotherapy demonstrated a significant (p less than 0.05) reduction in leukocyte incorporation of tritiated thymidine immediately after UVA in comparison to incorporation before UVA. None of 10 control subjects treated with UVA alone demonstrated such reduction in leukocyte tritiated thymidine incorporation. Photochemotherapy thus affects circulating blood cells in some patients with psoriasis in addition to its therapeutic effect on epidermal cells. Further investigations are needed to determine the reasons for the differences in susceptibility to inhibition of leukocyte DNA synthesis among patients and the possible long-term consequences of such inhibition. | US |
1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium and administered in various sequences. 2. Dose-response curves were shifted to the left in rats on a high-, compared with a low-, sodium intake. This response was maintained for 7 days on changing from high to low sodium. 3. There was no difference in the relation between the fall of cardiac output and the rise of blood pressure in any of the experimental groups. 4. Dose-response curves for peripheral resistance showed the same directional change as seen for the pressor response in rats on high- and low-sodium diets. Since depression of cardiac output was proportional to the pressure rise, the absolute change in peripheral resistance was greater than the blood pressure response. The proportional changes were similar. 5. It is concluded that alterations in the pressor response to angiotensin caused by changes in sodium loading are attributable to changes in peripheral resistance and not to changes in the cardiac output response to the acute rise in blood pressure. | US |
Rates of diffusion through the extracellular space of thin sheets of myocardium from the right ventricular outflow tract of kittens were estimated at 23 degrees C for 45Ca2+ and an inert reference tracer, [14C]sucrose. The myocardial sheets were mounted in an Ussing chamber and equilibrated with Tyrode solution with varied calcium concentrations, Cao. The tracers were added to one side and their concentrations on the other side measured at 5-15-min intervals for 6 h. The apparent tracer diffusion coefficient for sucrose was 1.11 +/- 0.06 X 10(-6) cm2s-1 (mean +/- SEM, n = 74), 22% of the free diffusion coefficient; the lag time before reaching a steady state provided estimates of the intratissue volume of distribution or diffusion space of 0.41 +/- 0.15 ml/ml tissue (n = 74), a value compatible with expectations for extracellular fluid space. Over the range of Cao from 0.02 to 9.0 mM, the intratissue apparent diffusion coefficient for Ca, DCa, averaged 1.65 +/- 0.10 X 10(-6) cm2s-1, n = 74, which is 21% of the free DoCa, and was not influenced by Cao. Because transsarcolemmal Ca permeation is slow, DCa is the diffusion coefficient in the extracellular region. The paired ratios DCa/Ds averaged 1.32 +/- 0.05 (n = 67) for all levels of Cao but at physiologic or higher Cao averaged 1.45 +/- 0.07 (n = 39), close to the ratio of free diffusion coefficients, 1.53. Equations distinguishing transient from steady state diffusion were fitted to the data, showing that the apparent distribution volume of "binding sites" external to the diffusion pathway diminished at higher Cao in a fashion suggesting that a least two different Ca2+ binding sites were present. | US |
Free diffusion appears to be the principal mechanism for movement of ions, known to concentrate in bone, across the capillaries of bone. The interstitial fluid space appears large enough to allow for determination of instantaneous fractional escape by the indicator-dilution method. The mechanism by which large molecules, such as the diphosphonate 99mTc-labeled EHDP or 99mTc-labeled pyrophosphate, pass through capillaries in bone is by passive diffusion. These molecules are larger than 85Sr and their lower extraction rate is presumably due to the effect of their sizes on passage through transcapillary clefts. A corollary of these studies might be that if transcapillary exchange is passive, then partition of anions and cations likely lies beyond the capillary and therefore is controlled by osteal cellular processes. | US |
This surgical technique has permitted re-entry into the intrahepatic and extrahepatic biliary tree for the purpose of dilatation and the manual propulsion of debris through a ductal anastomosis. The method undoubtedly has other applications in the treatment of complicated biliary duct problems. | US |
Headgroup and soft core interactions are added to a lipid monolayer-bilayer model and the surface pressure-area phase diagrams are calculated. The results show that quite small headgroup interactions can have biologically significant effects on the transition temperature and the phase diagram. In particular, the difference in transition temperatures of lecithins and phosphatidyl ethanolamines is easy to reproduce in the model. The phosphatidic acid systems seem to require weak transient hydrogen bonding which is also conjectured to play a role in most of the lipid systems. By a simple surface free energy argument it is shown that monolayers under a surface pressure of 50 dynes/cm should behave as bilayers, in agreement with experiment. Although the headgroup interactions are biologically very significant, in fundamental studies of the main phase transition in lipids they are secondary in importance to the hydrocarbon chain interactions (including the excluded volume interaction, the rotational isomerism, and the attractive van der Waals interaction). | US |
Phloretin dramatically increases cation conductances and decreases anion conductances of membranes treated with ion carriers (nonactin, valinomycin, carbonyl-cyanide-m-chlorophenylhydrazone [CCCP], and Hg(C6F5)2) or lipophilic ions (tetraphenylarsonium [tphAs+] and tetraphenylborate [TPhB-]). For example, on phosphatidylethanolamine membranes, 10(-4) M phloretin increases K+ -nonactin and TPhAs+ conductances and decreases CCCP- and TPhB- conductances 10(3)-fold; on lecithin: cholesterol membranes, it increases K+-nonactin conductance 10(5)-fold and decreases CCCP- conductance 10(3)-fold. Similar effects are obtained with p- and m-nitrophenol at 10(-2) M. These effects are produced by the un-ionized form of phloretin and the nitrophenols. We believe that phloretin, which possesses a large dipole moment, adsorbs and orients at the membrane surface to introduce a dipole potential of opposite polarity to the preexisting positive one, thus increasing the partition coefficient of cations into the membrane interior and decreasing the partition coefficient of anions. (Phloretin may also increase the fluidity of cholesterol-containing membranes; this is manifested by its two- to three-fold increase in nonelectrolyte permeability and its asymmetrical effect on cation and anion conductances in cholesterol-containing membranes.) It is possible that pholoretin's inhibition of chloride, urea, and glucose transport in biological membranes results from the effects of these intense intrafacial dipole fields on the translocator(s) of these molecules. | US |
A method is described for determining the cytotoxicity of normal and autologous lymphocytes for 51Cr-labeled isolated parenchymal liver cells in a low aggressor to target cell ratio. Results were compared from patients with chronic active liver disease (CALD), chronic persistent hepatitis (CPH), miscellaneous liver diseases, or primary biliary cirrhosis (PBC). In 53% of CALD patients, lymphocytes showed greater cytotoxicity for hepatic cells than did normal allogenic lymphocytes, but in 32% there was significantly less 51Cr release than normal; in the remainder, results were in the normal range. Lymphocyte cytotoxicity was greater in patients with disease of short duration and less in those treated with corticosteroids. In untreated CALD, decreased 51Cr release was associated with the presence of plasma factor(s) inhibiting phytohemagglutinin (PHA)-induced transformation of normal lymphocytes. Lymphocytes from approximately 50% of the patients with PBC exhibited cytotoxicity for hepatic cells but 25% showed less 51Cr release than controls and the remaining patients had results in the normal range. Lymphocyte cytotoxicity was also greater during the earlier stage of PBC. In contrast to CALD, decreased 51Cr release was not associated with the presence of plasma factor(s) inhibiting PHA-induced transformation of normal lymphocytes. Our findings support the hypothesis of in vivo lymphocyte-mediated liver cell damage in CALD and PBC, suggesting a potentially important role for lymphocyte suppression in the pathogenesis of both diseases. | US |
Patients with xeroderma pigmentosum develop severe sunlight-induced damage, including malignant neoplasms, on sun-exposed skin. Some patients also have neurological abnormalities. Xeroderma pigmentosum cells are known to have impaired ability to repair ultraviolet light- or chemical mutagen-induced damage to their DNA, and cell-fusion studies have shown five complementation groups among the DNA excision repair-deficient strains. All xeroderma pigmentosum fibroblast strains we tested had lower colony-forming abilities after ultraviolet irradiation than normal strains. Furthermore, we have found that strains from different complementation groups can have different post-ultraviolet colony-forming abilities and that strains from patients with neurological abnormalities are the most sensitive to ultraviolet light. These results suggest that extremely ineffective repair of damaged DNA in central nervous system neurons may be the cause of the neurological abnormalities. | US |
The conceptualization and operationalization of measures of health status are considered. Health indicators are conceived as a subset of social indicators, and therefore, as any social indicator, they are viewed as derivative from social issues. The interrelationships of different frames of reference for defining and measuring health that have accompained three distinct health problem patterns in the United States are viewed from a developmental perspective. Mortality and morbidity rates, the traditional health indicators, by themselves no longer serve to assess health status in developed nations. Their deficiencies as indicators serve as background for a classification schema for sociomedical health status indicators that relates health definition frames of reference, measures of health status, and health problems. The role of a group of health indicators-sociomedical heath indicators-in the current formulation of health status measures is assessed. | US |
The dose-response effects of apomorphine and ET-495 (piribedil), 2 specific dopamine (DA) receptor stimulators, and haloperidol, a DA receptor blocker, were tested on the secretion of prolactin (PRL), thyroid stimulating hormone (TSH), growth hormone (GH) and luteinizing hormone (LH) in male rats. Both apomorphine and piribedil reduced serum PRL and TSH levels, stimulated GH release at low but not at high doses and either had no effect or tended to reduce serum LH levels. The minimal effective dose of apomorphine for reducing PRL by 30 min was 0.01 mg/kg; TSH inhibition was observed with a dose of 0.1-0.3 mg/kg. The inhibitory effects of apomorphine (1.0 mg/kg) on PRL and TSH levels were maximal by 15 min and diminished by 120 min; plasma GH was highest 120 min after injection. Thyroidectomy (10 days) markedLH elevated serum TSH, had no effect on serum PRL and inhibited the ability of apomorphine (0.1 or 0.3 mg/kg) to reduce TSH but not PRL levels. These observations may indicate that separate dopaminergic control mechanisms exist for TSH and PRL secretion. Administration of haloperidol elevated serum PRL, tended to lower TSH, dramatically reduced GH and had no effect on LH levels. Haloperidol pre-treatment blocked the effects of apomorphine on PRL, TSH, and GH secretion. The overall results of this study indicate that DA agonists inhibit PRL and TSH, stimulate GH but do not stimulate LH release in male rats. | US |
A series of 102 surgical operations for arterial emboli in 85 patients during a fifteen-year period is presented. Seventeen patients were operated upon before the institution of the Fogarty balloon embolectomy catheter. 82 embolectomies using the Fogarty embolectomy catheter were carried out in 68 patients with a mortality of 32%. The amputation rate in the surviving patients was 39%. The most common cause of death was severe underlying heart disease, while the most important reason for amputation after an unsuccessful embolectomy was concomitant occlusive atherosclerosis, and to a lesser degree, a delay in the performance of the embolectomy. | US |
The effect of prolactin on adenyl cyclase, rate of fructose utilization, and glucose oxidation by human spermatozoa was studied. Prolactin stimulated all of these processes at a concentration generally available in seminal plasma. These results suggest that prolactin plays an important role in the energy metabolism of human spermatozoa. | US |
Some methodological problems encountered in age comparisons of EEG patterns are discussed in the context of an analysis of open field activity scores before and after preparation for, and recording of EEG sleep patterns. Plasma corticosterone levels 11 days after surgery for EEG electrode implantation were also measured. Activity levels were modified more for three older than for a younger group of animals following surgery/recording sessions. Corticosterone levels were appreciably elevated for the oldest group of animals. The possibility was raised that procedures designed to allow recovery from post surgical shock and adaptation to electrode connections may result in disproportionate differences across age groups. | US |
Gerontological researchers are reminded of the inappropriateness of analysis of covariance wherein the covariate is correlated with the independent variable, typically age. Two partial solutions are suggested that deal with the confounding of age effects with such uncontrolled variables as, for example, initial ability level or level of education. | US |
Four age groups of C57BL/6J mice (2.2, 6.2, 12.0, and 23.3 months) were subjected to either immobilization or handling (control) procedures. Open field behavior was observed before and after experimental treatments and plasma corticosterone levels were assessed 11 days following the immobilization or handling procedures. Eleven days following immobilization elevated corticosterone levels were observed for all but the 12.0 month group of mice. No behavioral effects were observed for the experimental groups, although both locomotor activity and exploratory behavior declined with advancing age. The age-related decrease in activity was entirely accounted for by scores on the initial open field test. Exploratory behavior was observed to be a more complex function of both age and experience. | US |
Elderly subjects when compared to young, mature subjects in a memory-scanning task were shown to have longer response times (RT). A late positive component (LPC) of the average evoked potential did not reflect this difference between groups. However, in both groups, the LPC was seen to occur with longer latency at RT increased. LPC amplitudes also declined with increasing RT. There were greater differences between left- and right-hemisphere LPC amplitude and between LPC recorded along the midline scalp in the younger group than in the older subjects. | US |
The hippocampal theta rhythm in rats exhibited an age-dependent slowing in modal frequency. However, the theta rhythm of young rats with chronic respiratory infections showed a similar slowing. Respiratory disease-free hamsters also exhibited an age-dependent slowing of modal frequencies. These findings emphasize that the health status of the animal must be examined carefully in order to establish an age-dependent slowing in hippocampal rhythm. | US |
Activity levels of COMT were measured in the frontal cortex, hippocampus, hypothalamus and amygdala of two strains of male mice, C57BL/6J and DBA/2J, at various ages between 2 and 30 months. Determinations were made in mice housed under normal conditions and in mice exposed to a form of mild stress, an open-field apparatus, for 5 minutes. There were no major significant differences between the two strains as a function of age. However, after the open-field experience, C57BL/6J mice appeared significantly more responsive to the environment, as interpreted by increases in COMT, than DBA/2J mice. Interpretation is offered that C57BL/6J mice possess a more labile norepinephrine system, in spite of aging, than DBA/2J mice. | US |
Reaction time (RT) was compared in 160 hypertensive and 43 normotensive adults. After being screened for coronary and cerebrovascular disorders, each subject completed 12 variations of a serial RT task. Subjects were blocked into normotensive, nonmedicated hypertensive, and medicated hypertensive groups, and into three age groups: 18-31; 32-45; 46-59. Response slowing was observed with increasing age. Significant slowing was also seen in the medicated but not the nonmedicated hypertensive group. Plasma renin activity (PRA) interacted with the medication factor; longest RTs were obtained for treated subjects with low and normal PRA and untreated subjects with high PRA. These results were interpreted in terms of changes in ability to autoregulate cerebral blood flow as a result of vascular damage. | US |
Mice selected genetically for high and low blood pressure (BP) were compared with regard to heart weight and heart/body ratios. Two experiments were performed with mice ranging in age from 1.3 to 9 months and 11 to 23 months respectively. In a third experiment C57BL/6J mice were compared to the high and low BP mice. Heart/body ratios and heart weights, adjusted fo body weight via covariance analysis, were significantly greater for the high BP mice, but no Age x BP Genotype interaction was observed. Results were discussed in terms of a possible relationship between heart weight and BP via genetic linkage or pleiotropy. The possibility was also raised that compensatory mechanisms for high blood pressure, e.g., cardiac hypertrophy, may operate very early in development for animals who are hypertensive by virtue of selective breeding for blood pressure extremes. | US |
After a typology is developed based on work satisfaction and attitude toward retirement, profiles are examined of respondents appearing in four typological categories. Data at three points in time (1964, 1966, 1974) from 1,922 older (50+) employed males suggest that membranes of some types will be more susceptible to negative consequences of life-cycle change (work to retirement) than others. Findings from socioeconomic status, age, social participation, health, community, housing, family, work, morale, and longevity variables indicate pre-retirement planning approaches should be developed for those having different work-retirement attitudes. | US |
Young, middle aged, and older subjects were given a Posner-type physical-name matching task, in which stimuli were presented to one or both hemispheres, and a simple discrimination reaction time (DRT) task. Reaction time differed between young and middle aged groups for both tasks with shorter RT for the DRT task. Reaction time for the older group did not differ significantly from that of the middle aged group for either task, although the reaction time for the older group was longer. Reaction time was faster for all age groups when Stimulus 1 and Stimulus 2 were presented to different hemispheres for the matching task than when both stimuli were presented to the same hemisphere. Ipsilateral finger responses (hand relative to hemisphere) were slower than contralateral responses but this was true only with regard to the visual field of presentation for stimulus 2. These data indicate that sharing of information between hemispheres under certain circumstances increases the efficiency of information processing relative to that observed with unilateral visual half-field (hemisphere) presentations and that hand or finger response relative to visual field of presentation is an important factor which must be controlled and examined relative to visual field of presentation. | US |
Information provided by Monge and Hultsch in support of the pacing variable was reinterpreted i terms of the total time principle. The re-analysis of the transformed data suggests that the total time principle provides a more parsimonious explanation of the data. | US |
This review summarizes the behavioral characteristics of C57BL/6J, DBA/2J, and B6D2F1, hybrid mice which are most likely to be of interest to gerontological scientists. Where possible, the characteristics of young and old mice are included. Where no information exists about the behavior of older mice of these genotypes, but there is reason to believe that information about mice might be useful for aging research, this information is included. The purpose of the review is to acquaint gerontologists with the availability of genetically defined animal models for aging research, to present what is known about these models, and to suggest areas of research which could profit from more attention. | US |
Angiotensin blockade was established in hypertensive patients with the competitive inhibitor saralasin and the blood pressure response was compared to prior renin determinations. Two patients with subsequently confirmed renovascular hypertension had normal peripheral renin and non-lateralizing renal vein renin ratios, yet both showed a clear-cut lowering of blood pressure after administration of the blocking agent, indicating the presence of renin-mediated hypertension. Thus, direct in vivo testing with saralasin appears to offer certain advantages over renin determinations. | US |
This study updates the experience at our hospital with cancer of the penis, which now includes 122 consecutive cases seen between 1940 and 1974 with 100 per cent followup. Historical, clinical, pathological, therapeutic and followup data were extracted for all cases in a digital code for transfer to computer storage. Life tables giving cumulative survival rates through 10 years with standard deviations and age corrections were calculated for each variable. The data were tabulated for publication to emphasize the prognostic significance of individual variables for the purpose of prospective research planning. The data were then evaluated regarding indications for prophylactic inguinal lymph node dissections, if any. | US |
Recognition that the immune system may be important in regulating the clinical evolution of tumors and that corticosteroids suppress immune responses lends relevance to determining the concentrations in which sex hormones, currently used in the treatment of urologic malignancies exert immunosuppressive effects. We have investigated the effects of the sex hormones, diethylstilbestrol, diethylstilbestrol diphosphate, testosterone and progesterone, on in vitro lymphocyte blastogenesis as determined by 3H thymidine incorporation after stimulation with phytomitogens and alloantigens, and compared their effects to the effects of cortisol. Compared to cortisol these sex hormones are relatively weak suppressors of lymphocyte blastogenesis (cortisol 10(-7) M, progesterone 5 times 10(-6) M, testosterone 5 times 10(-5) M, diethylstilbestrol 5 times 10(-5) M and diethylstilbestrol diphosphate 10(-3) M) and probably are not significantly immunosuppressive in commonly used pharmacologic dosages. Similar results were observed with the T lymphocyte mitogens, phytohemagglutinin and concanavalin A, and in the combined T and B cell mitogen pokeweed. The fact that alloantigen-stimulated lymphocyte blastogenesis also was suppressed by diethylstilbestrol indicates that sex hormones exert their effects on the lymphocytes and not on the mitogens. Furthermore, sex hormones were not found to be cytotoxic to lymphocytes. It is postulated that the sex hormones tested act by suboptimal binding to glucocorticoid receptors in the lymphocytes and that the relative immunosuppressive potency of a given hormone is related to its affinity for the glucocorticoid receptor. | US |
In the experimentally-induced hyper- or hypoglycemic state, perilymph glucose concentration paralleled the blood concentration, although a delay of about one hour was observed between the time of maximum concentration of glucose in perilymph and its concentration in blood. In hypercalcemia, perilymph calcium concentration steadily increased over a three-hour period, although blood calcium concentration fluctuated during this time. After an initial increase in the CSF calcium concentration, there were insignificant changes during the second and third hours. In animals with thyrocalcitonin-induced hypocalcemia, although blood calcium concentration steadily decreased, its concentration in perilymph and CSF remained practically constant. The present findings suggest that the chemical composition of perilymph can be altered by changing the blood concentration of glucose or calcium. The marked difference of behavior noted between glucose and calcium in these experiments would indicate the existence of different mechanisms for maintaining the homeostatic state for these two substances. | US |
The efficacy of chemoprophylaxis in the treatment of basilar skull fractures was studied in 129 patients over a 2-year period; antibiotics were found ineffective in preventing central nervous system infections, and in some cases may have proved harmful. It is suggested that a more rational approach to the treatment of basilar skull fractures includes close observation of the patient for early signs of meningitis, and if these should develop, treatment with antibiotics appropriate to the organism involved. | US |
Thirty-four beekeepers were interviewed and their blood assayed for the presence of antibodies reacting with bee venom, bee venom phospholipase A (PLA), and whole bee body extract. Following a bee sting, most beekeepers experienced only minimal local tissue reaction. Their serum contained high levels of total antibodies (primarily IgG) reacting to bee venom and phospholipase A. These antibody titres correlated with the frequency of bee stings. Bee venom and PLA specific IgE antibodies were present in serum of some beekeepers. Beekeepers who had experienced allergic reactions were characterized by low total antibody and high venom specific IgE antibody titres. Bee body IgE antibodies were found in varying degree and did not correlate with levels of venom IgE antibodies. There was no difference in the titres of bee body IgE in the sera of beekeepers with and without systemic reactions. The data suggest that allergic reactions are mediated by venom specific IgE and immunity is at least in part a function of other antibodies, probably primarily IgG. | US |
A major complication of head and neck cancer surgery following radiation and extensive resection is pharyngocutaneous fistula. A retrospective analysis of 36 fistula patients out of 376 major head and neck procedures between January 1971 and July 1973 revealed certain guidelines for improved clinical management. Since a large discrepancy existed in the incidence of fistulas between the different surgical procedures, each operative group was examined separately. The incidence, predisposing factors, and methods of treatment for this complication following composite jaw-neck resections and various laryngeal procedures are analyzed and discussed. | US |
Non-arteriosclerotic (virgin), male and female, Sprague-Dawley rats and arteriosclerotic (breeder), male and female rats were subjected to an acute myocardial infarct when injected with two subcutaneous doses of isoproterenol. Female rats, especially female breeder rats with advanced arteriosclerosis, survived their infarcts in superior fashion to male rats or those with the least severe arterial disease. Animals with severe arteriosclerosis showed the least loss of body weight and greatest increase in heart weight on Day 3 when cardiac necrosis reaches its zenith. Blood pressure and pulse pressure was most seriously reduced in animals with no or early arteriosclerosis only, being best maintained in the animals with the most severe arterial disease. Heart rate was not greatly altered in any of the various groups. Ventricular function, i.e., cardiac output, stroke volume, cardiac index, and left ventricular minute work, was severely impaired in the non-arteriosclerotic animals and in those with the least arterial disease. Total peripheral resistance was also least elevated and myocardial contractile strength (peak flow and max dF/dt) was greatest in female breeders with the most advanced arterial disease. Most intriguing, is the seemingly paradoxical but consistent finding that female breeders which develop the most severe arterial disease are able to best maintain cardiac function during the acute stress of myocardial ischemia. | US |
Randomly assigned streptokinase or heparin therapy was studied in 50 patients with deep vein thrombosis of less than 2 weeks' duration. Venography was performed prior to therapy, after 3 days, and after 10 days. Two radiologists who were unaware of the patient's therapy compiled a single average lytic score for each patient at each time interval. Lysis of venous thrombi was significantly greater with streptokinase than with heparin after 3 days, but not after 10 days of treatment. Lytic scores achieved with streptokinase were significantly better than those achieved with heparin therapy (P less than .01) in male patients who were symptomatic for 3 days or less. In females, regardless of the duration of symptoms, thrombolytic results obtained with streptokinase were not significantly different than results obtained with heparin. | US |
The variables producing lowered birthweight include prematurity, maternal genetic tendencies, low prepregnancy weight, low weight gain during pregnancy, pathologies of pregnancy, multiple births, maternal malnutrition, and intrauterine growth retardation. Reductions in intelligence related to low birthweight are distributed equally among different socioeconomic groups. However, when mental subnormality is used as the criterion of impairment, low socioeconomic status is a better predictor of poor outcome than low birthweight. Even when general intelligence is not impaired, low birthweight children show specific cognitive, perceptual and behavioral signs of organic brain damage. In the absence of frank congenital abnormality, absolute birthweight is a better predictor of impaired intelligence than intrauterine growth retardation. Maternal malnutrition during the period of pregnancy does not influence offspring intelligence. Malnutrition throughout the maternal and offspring lifespan does impair intelligence, especially when surrounding social conditions are counterproductive to its development. | US |
The care of obstetric patients in a university family medicine department was compared with that in the obstetrics-gynecology department of the same university. The obstetric service patients tended to be at higher risk due to a higher black population (24.2 percent vs 6.3 percent), greater prepregnancy weight (mean 154.0 lbs vs 113.9 lbs), and a greater number of patients referred from the community because of prenatal complications. However, the family medicine patients had a higher incidence of premature rupture of membranes (26 percent vs 11 percent), and were therefore at risk for several complications. Family medicine nulliparas had first stages of labor which lasted an average of 12.2 hours as opposed to obstetric service nulliparas whose first stages averaged only 9.2 hours. There were more family medicine than obstetric service patients who received no anesthesia (18.0 percent vs 10.2 percent). Elective low forceps were used more often by obstetric service physicians than by family physicians (28.2 percent vs 15.3 percent). Mothers on the family medicine service had more puerperal complications than those on the obstetric service (16.0 percent vs 5.6 percent). No serious discrepancies in quality of care could be found between the two services. | US |
An in-training examination for family practice residents has been developed and used in a regional network residency program over the past three years. The most striking result has been the strong preference expressed by residents for question-specific feedback in order to facilitate learning after taking the examination. A well-designed in-training examination has the potential to meet both individual resident and program goals as an additional measure of resident performance and growth, as well as of the effectiveness of teaching in the various curricular areas. In-training examinations for residents are in use by 12 other specialties in medicine, and have been well-accepted by program directors and residents. A nationally-sponsored in-training examination for family practice residents is needed which includes maximal teaching capability through comprehensive and specific feedback. | US |
Kidney samples from children with the inborn metabolic disease cystinosis contain 4 times more selenium (Se) than do kidney samples from normal individuals (p = 0.1). However, when cultured skin fibroblasts from cystinotic patients and normal control individuals are incubated in Se-D,L-methionine, Se-D,L-cystine, Se-cystamine X HCl, Se-urea, selenite or in medium without added selenium, only the cystinotic fibroblasts grown in Se-urea or selenite (SeO3=) contain more selenium than do the corresponding normal cells (p less than 0.05). In both types of cultured fibroblasts, the order of descending toxicity per ppm selenium is: Se-urea greater than Se-cystamine greater than Se-cystine greater than or equal to SeO3= much greater than Se-methionine. High (apparently toxic) concentrations of Se-urea and Se-cystamine lower the elevated intracellular free (nonprotein) cystine content of cystinotic fibroblasts to less than 60% of control values; at lower concentrations, these compounds raise the cystine content of these cells to over 140% of control values. Appropriate concentrations of SeO3=, Se-cystine and Se-methionine also elevate the free cystine content of the cystinotic cells. During a 75 minute incubation in 35S-cystine, the incorporation of 35S into the acid precipitable (protein) fraction of both cell types is significantly inhibited by Se-cystamine (approximately 55% control; p less than 0.05). The incorporation of 35S-cystine into glutathione is inhibited by Se-cystine (approximately 40% control) in both fibroblast types (p less than 0.05). In cystinotic cells, Se-cystamine significantly reduces incorporation of 35S-cystine into the cystine pool (40% control) as does SeO3= (67% control; p less than 0.05). Protein and glutathione synthesis in cystinotic fibroblasts are more strongly inhibited by Se-cystine and SeO3=, respectively, than in normal fibroblasts (p less than 0.05). These studies demonstrate that selenium compounds exhibit a different sequence of toxicity in fibroblasts than in the intact animal and that some previously unreported metabolic effects (i.e. inhibition of glutathione synthesis) may contribute to their toxicity. | US |
The respiration of Ehrlich ascites tumor cells is inhibited by 3-ethoxy-2-oxobutyraldehyde bis (thiosemicarbazanato) copper (II). State 3 oxidative phosphorylation in mitochondria from tumor cells is also inhibited, with the effect more pronounced using glutamate or pyruvate-malate as substrates than with succinate. The disruption of oxidative phosphorylation in bovine heart mitochondria is qualitatively similar. The principal site of inhibition is in coupling site one, energetically between the electron transport site chain and the locus of uncoupling by 2,4-dinitrophenol. This appears to contain thiol groups which are oxidized by the complex. For a series of bis (thiosemicarbazonato) copper complexes, the extent of inhibition of heart mitochondrial oxidative phosphorylation is correlated with the reduction potentials of the complexes and with their in vitro cytotoxic effects against Walker 256 carcinoma tumor cells. | US |
The inhibitory effect of selenium on the genesis of spontaneous mammary tumors in C3H mice is statistically significant even at toxic levels of selenium (5 and 15 ppm of Se in form of selenite added to the supply water), no evidence for stimulation of tumor growth by selenium has been obtained. Arsenite lowers the tumor incidence at higher dosage (80 ppm of As in supply water) as well, but animals developing tumors under these conditions demonstrate significantly enhanced tumor growth rates. The addition of subtoxic concentrations of zinc (200 ppm in form of ZnCl2) to supply water containing 5 ppm of Se abolishes the cancer-protecting effect of selenium. The latter result is of possible importance with respect to the human breast cancer mortality experience: The calculated dietary zinc intakes of average adults in 28 countries correlate with the female age-corrected mortalities from breast cancer directly, with P less than 0.005. The zinc concentrations in whole blood from donors in different parts of the U.S.A. are also directly correlated with the female breast cancer mortalities. | US |
125I fibrinogen test was performed in 20 selected patients who presented with symptoms suggestive of deep venous thrombosis. The incidence of a false positive study was found to be very high: 90%. An increased accumulation of fibrinogen was noted over recent, well-healed surgical incisions, diffuse or focal inflammatory sites, hematoma and also, following a venogram or arthrogram test. The large number of coincidental circumstances that result in an abnormal accumulation of 125I fibrinogen lead us to believe that venogram is the procedure of choice in patients with symptoms simulating thrombophlebitis. | US |
The interaction of metal cations with single chain globular proteins produces volume increases, the magnitude of which is determined primarily by the ion and to a lesser extent by the protein. The cations are listed in ascending order of volume change: K(I) less than Mg(II) less than Sr(II) less than Ca(II) less than Co(II) less than Ni(II) less than Cd(II) less than Zn(II) less than Cu(II) less than Pb(II). This sequence held for all cation-protein systems investigated except for Cd(II) which produced a slightly larger volume effect than Zn(II) with lysozyme. The volume changes attributed to protein-cation interaction are positive and range from 8 ml/10(5) g of protein for the reaction on 0.05 M KNO3 with bovine plasma albumin to 2320 ml/10(5) g of protein produced by the 0.20 M Pb(NO3)2-myoglobin system. A similar classification scheme was not possible for the proteins. For example, volume increases of 45, 50, 80 and 95 ml/10(5) g of protein were produced when 0.05 M Mg(II) reacted with bovine serum albumin, ovalbumin, sperm whale myoglobin and lysozyme, respectively. However, when 0.2 M Pb(II) was the reactant the values were 1930, 846, 2320, and 1120 ml/10(5) g of protein. Volume effects produced by Cr(III), Al(III) and Fe(III) were determined, but the calculated results are considered dubious because the volume changes are a complicated function of protein-cation and protein-proton interaction. | US |
As analogs for cobalt(III) complexes of bidentate azotyrosine in proteins, several cobalt(III) complexes of bidentate azophenols have been prepared and characterized. Tris(2-phenylazo-p-cresolato)cobalt(III) was shown to be a poor model complex for this purpose; while cobalt(III) complexes of either 2-phenylazo-p-cresol or 2-(4-carboxyphenylazo)-4,5-dimethylphenol with the linear tetradentate ligand ethylenediamine-N,N'-diacetic acid are very useful as model complexes. The complexes were characterized by magnetic susceptibility, visible spectra and 1H NMR. In the case of one of the mixed ligand complexes, a detailed description of the stereochemistry was possible. Comparisons of the spectral characteristics of metal complexes with bidentate and tridentate azophenols are made. These model studies are essential to a program involving the site specific modification of proteins with substitution inert metal ions. | US |
Thermodynamic equilibrium studies using model systems were carried out on the nature and extent of coordination of twelve different biogenic amines and adenosine-5'-triphosphate (ATP) with the bivalent metal ions, viz., Ca2+ and Zn2+, which occur in the subcellular fractions of the brain, at 25.0 +/- 0.1 degrees C and at an ionic strength of 1.0 (KNO3). In the combined presence of the individual monoamines and ATP the metal ions were predominantly coordinated by ATP in the pH range 3.0 to 6.5 with binding constants (log KML) of 2.84 +/- 0.06 and 3.19 +/- 0.39 for the Ca2+ and Zn2+ chelates, respectively. Each of the monoamines coordinated with the metal-ATP chelate above pH 6. The stabilities of the chelates of some of the amines with Ca2+ -ATP (1:1) system were NE, 2.33 +/- 0.33; AA, 2.24 +/- 0.19; OA, 1.94 +/- 0.29; NMeN, 1.60 +/- 0.22; DA, 2.14 +/- 0.09. Values for the Zn2+-ATP-amine systems were: NE, 8.35 +/- 0.26; OA, 4.53 +/- 0.07; DA, 10.05 +/- 0.39. Absorption spectral studies were carried out in order to examine the nature of coordination of NE, DA, TA, and AA with Cu2+, Fe2+, and Mg2+ ions in the combined presence of ATP. Results of the spectral studies taken together with the (thermodynamic) equilibrium data have indicated that in the pH range of biological interest, the catechol amines (NE and DA) and ATP are both coordinated to the "synaptosomal and vesicular" metal ions. The results further indicated that both the pyrocatechol and the ethanolamine groups of NE might be involved in the coordination of Cu2+. However, the interaction of the ethanolamine group of the NE molecule with the rest of the metal ions was not indicated. | US |
The phosphorus-containing side chains of two methylene-bridged analogs of adenosine triphosphate have been cyclized to produce the corresponding analogs of monoadenosine-5'-trimetaphosphate. (The structures are given in the journal.) The molecules, which were generated in anhydrous media through a carbodimide-mediated condensation, were characterized by 31P nuclear-magnetic resonance, and the white-noise 1H decoupled spectra were simulated. These molecules are quite reactive and readily converted to their corresponding linear forms upon hydrolysis. The second structure contains an asymmetric phosphorus atom, and both of the possible cyclic molecules have been observed and the diasteroisomeric mixture has been isolated. | US |
The preparation and crystal and molecular structure of the osmium tetraoxide bispyridine ester of 1-methylthymine are reported. The complex crystallizes in the triclinic system, space group P1, with a = 11.493(6)A, b = 16.655(7)A, c = 6.082(2)A, alpha = 92.07(3) degrees, beta = 90.58(3) degrees, gamma = 71.36(4) degrees, V = 1102.4 A3, Dm = 1.85(1) g cm-3, DC = 1.84 g cm-3. The unit cell contains 2 osmium tetraoxide bispyridine esters of 1-methylthymine, 2 waters of crystallization and 1 disordered pyridine of solvation. Intensities for 3814 independent reflections were collected by counter methods. The structure was solved by standard heavy-atom techniques and has been refined by full-matrix least squares, based on F, to a final R value of 0.065. The osmium complex binds as a cis osmate ester to the C(5)-C(6) bond of the methylated pyrimidine in a fashion which is expected to be similar to the binding of the complex to thymidine residues in nucleic acids. The conformation of the 1-methylthymine ester is that of a half chair with C(6) showing a substantial deviation, 0.55 A, from the best mean plane of the thymine moiety. The primary coordination sphere about the Os(VI) atom is completed by 2 axial Os=O bonds and the binding of the 2 pyridine ligands in cis positions in the equatorial plane containing the ester linkages. The O=Os=O group is substantially nonlinear, 164.0(5) degrees, and this nonlinearity is attributed to intracomplex electronic effects. | US |
Amoebae of Dictyostelium discoideum were attached to a surface coated with polylysine, and the upper portion of the cells was sheared off with a stream of buffer. Scanning and transmission electron microscopy showed that the cytoplasmic surface of the exposed membrane was covered with fibers consisting of actin-containing filaments. The actin was identified by its solubility properties and its ability to interact with muscle myosin. | US |
The relationship between microtubules and concanavalin A surface receptors during concanavalin A capping in primary cultures of rabbit ovarian granulosa cells was examined by electron microscopic and fluorescence labeling techniques. Cells treated with concanavalin A and hemocyanin at 4 degree or 37 degree and then incubated at 37 degree for 1 hr formed large juxtanuclear caps that were observed with shadow cast replicas of the cell surface. Thin section analysis of capped cells revealed an abundance of microtubules immediately beneath the cap which were arranged approximately perpendicular to the plane of the membrane. The capping process was unaffected by the antimicrotubule agents colchicine or vinblastine. Further, vinblastine treatment of capped calls resulted in the formation of numerous paracrystals that were confined to the cytoplasm underlying the capped region of the membrane; uncapped cells displayed paracrystals that were randomly dispersed in the cytoplasm. Exposure of fixed cells to fluorescein thiocarbamyl colchicine, which localizes colchicine binding proteins, revealed an intensely fluorescent region that corresponded to the cap; this staining pattern was absent in uncapped cells. These findings indicate that concanavalin A mediated capping modifies the cytoplasmic disposition of microtubules and colchicine binding proteins. Further, it is suggested that the capped region of the plasma membrane is a preferred site of microtubule polymerization. | US |
The lipids in bovine gingival tissue were characterized qualitatively and quantitatively. The total lipid content was 2.35% on wet weight. The total nonpolar lipids and total polar lipids were 70.69 and 29.31% of the total lipids, respectively. Cholesterol esters, free fatty acids, and triglycerides were the major nonpolar lipids. Polar lipids were predominantly phosphatidyl choline, phosphatidyl ethanolamine, and sphingomyelin. Traces of glycolipids, lysophosphatidyl choline, phosphatidyl inositol, phosphatidyl serine, and prostaglandins were present. Oleic, palmitic, and stearic acids were found to be the major fatty acids in all lipid classes. Cholesterol esters, total polar lipids, and free fatty acids were more unsaturated than glycerides. Linolenic and arachidonic acid contents were highest in cholesterol esters and total polar lipids. | US |
Venous responses to stabilized orthostasis (45 degrees head-up tilt) were studied in seven normotensive subjects and eight hypertensive patients, when on high and low dietary sodium intake. Exchangeable sodium and blood volumes were determined to permit correlation with any significant changes in venous behavior. The intent of this study was to detect and analyze any diet-induced changes in responses of forearm veins to prolonged orthostasis. The pharmacological effects of sodium depletion by medication and diet on arteries and veins of hypertensives are discussed. The results of this study indicate that dietary sodium depletion did not have adverse effects on the ability to maintain stabilized venous tone during orthostasis. These results support recommendations that moderate dietary sodium restriction be included as part of antihypertensive regimens. | US |
The general medical and laboratory findings in 60 patients having a sector hemorrhage on the optic disc were compared with the findings in 102 patients with intraocular pressure elevation but without a disc hemorrhage. Of 22 parameters studied, systemic hypertension was the only abnormality which occurred significantly more frequently in the hemorrhage group. A study of the intraocular pressures suggests that hemorrhage may not be related to the level of intraocular pressure. Examinations of 50 patients with systemic hypertension and of 50 patients with cardiac abnormalities revealed no hemorrhage on the optic disc. These factors by themselves may not be responsible for the occurrence of hemorrhages. | US |
Interrelationships of arterial sterol accumulation and blood pressures were examined in age-matched White Carneau and Show Racer pigeons. It was found that the systolic blood pressure of White Carneaux changed from 155.0 mm Hg at nine months of age to 168.8 mm Hg at 17 months of age (P less than 0.005) while that of the Show Racers did not show any age-related increases. In White Carneaux, the total sterol content in the aorta increased by 43.6% from 9 months to 17 months of age (P less than 0.001) with major changes in the steryl ester fraction while no such changes were evident in the Show Racers. This indicates interrelationships of the arterial sterol content and blood pressure in the White Carneau pigeon. | US |
The nature of Type V hyperlipoproteinemia including mode of presentation, prominent clinical and biochemical features, and genetics, was examined in 29 adults presenting with the Type V lipoprotein phenotype. Initially 23 of the 29 patients had various metabolic stimuli (diabetes out of control, estrogenic agents, pancreatitis, ethanolism) superposed on their acute hypertriglyceridemia. After metabolic stabilization, 17 of the 29 subjects were shown to have familial hypertriglyceridemia. In the 17 kindreds with familial hypertriglyceridemia, the lack of a specific, distinctive genetic marker for the Type V genotype and for the Type IV genotype restricts the conclusion that the pattern of inheritance was consistent with an autosomal dominant trait. | US |
Polyacrylamide gel electrophoresis was used to compare protein profiles of members of the family Bacteriodacceae. Cell-free extracts were prepared and the protein components separated by multistage polyacrylamide gel electrophoresis. The profiles were distinct and reproducible thus allowing identification of species, subspecies, and minor strain differences. Lyophilization of the cell-free extracts did not alter the major protein components. The results indicate that the techniques used may be useful in conjunction with conventional tests in identification at the species level. | US |
Based on our prior experience in treating children with metastatic osteogenic sarcoma, a multidrug regimen was developed. Nine children with evaluable osteogenic sarcoma were treated with vincristine 1.5 mg/m2 on day 1, highdose methotrexate 200-300 mg/kg i.v. on day 2, with p.o. citrovorum factor "rescue" 9 mg every 6 hours x 12, followed in 2 weeks by cyclophosphamide 40 mg/kg i.v., then 2 weeks later Adriamycin 1.5 mg/kg/day x 2; in 2 weeks cyclophosphamide was repeated. After a 2-week rest, the 56-day cycle was repeated for a total period of 1 year. Oropharyngeal mucositis was the most frequent severe manifestation of gastrointestinal toxicity. Hematologic depression was mild to severe. Nine patients with clinically evaluable osteogenic sarcoma and no previous chemotherapeutic treatment were treated with this regimen. One patient had only a transient shrinkage in tumor mass, and one patient had no progression of multiple pulmonary and bone metastases for 16 months while on therapy. Of the remaining seven patients, all had clinically significant responses with tumor regression demonstrated for from 5 to 20+ months. Four of these patients (three presenting with primary tumor and pulmonary metastases) demonstrated regression of their primary tumor. In an attempt to increase the cure rate in osteogenic sarcoma, chemotherapy that has proven to be effective against metastatic osteogenic sarcoma should now be employed as prophylactic therapy, after amputation, at cancer treatment centers where it can be safely and effectively administered. | US |
Peripheral blood mononuclear cells from patients with either Crohn's disease or ulcerative colitis (collectively referred to as inflammatory bowel disease) are cytotoxic in vitro for isologous or allogeneic colonic epithelial cells. Utilizing the ability of thymus-derived (T) lymphocytes to bind sheep red blood cells to their surface and the property of bone marrow-derived (B) lymphocytes to display easily detectable surface immunoglobulin determinants, the cytoxicity of these lymphocyte subpopulations was tested. The results indicate that the mononuclear cell required for the lysis of colonic epithelium was not included within the bulk of T or B lymphocytes. Indeed, enrichment for cytotoxicity correlated best with enrichment for a mononuclear cell population lacking classical T or B markers. Additionally, mononuclear cells specifically adhering to plastic petri dishes coated with heat-aggregated immunoglobulin, and thus presumably bearing a surface Fc receptor, were enriched in their cytotoxicity. Alternatively, cells not adhering to aggregated Ig-coated petri dishes were relatively depleted of cytotoxicity. The implications of these findings as they relate to possible interactions between cellular and humoral immune mechanisms as a pathogenic mechanism for the colonic inflammatory process noted in patients with inflammatory bowel disease are discussed. | US |
Three olfactory nerve branches respectively subserving either a medial, an intermediate, or a lateral region of the dorsal olfactory receptor sheet of the bullfrog Rana catesbeiana were electrically stimulated with bipolar platinum hook electrodes. Extracellular single unit responses from 93 second-order cells in different regions of the olfactory bulb were recorded with metal-filled glass micropipets. The excitatory responsiveness of each unit to the stimulation of each of the three nerve branches (response profile) was determined. Some units were sensitive to stimulation of each of the three nerve branches, thus suggesting a wide projection from the entire receptor sheet. On the other hand, other units were more selective. Of this latter group, units in the lateral bulb were excited by nerve branches subserving the more lateral regions of the receptor sheet; units in the medial bulb were excited by the nerve branches subserving the more medial regions of the receptor sheet. These data provide electrophysiological evidence for a topographical projection of the olfactory receptor sheet onto the olfactory bulb, and further suggest that the projections onto different bulbar cells vary in degree of localization. | US |
No part of the body reflects the complications of cancer chemotherapy as visibly and vividly as the mouth. The hemorrhagic, infectious, nutritional, cytotoxic, and neurologic signs of drug toxicity are registered in the mouth by changes in the color, character, and continuity of the mucosa. Although some of the complications are an inevitable part of the price of treatment, each constitutes a threat that must be kept within manageable limits. | US |
Two days after an unplanned extra-capsular cataract extraction with sector iridectomy, a patient showed typical signs of bacterial endophthalmitis. Vitreous and aqueous were aspirated for culture, and gentamicin and dexamethasone were injected. Twenty-four hours later, after isolation of Staphylococcus epidermidis, a vitrectomy to remove the central vitreous was done. Postoperatively, vision progressively improved; at the last review nine months after vitrectomy, visual acuity was 20/50. | US |
The authors studied 109 consecutive admissions to an acute psychiatric unit in a general hospital to determine the relationship of specific sensorimotor impairments to cognitive disturbance. The results indicated a strong but not exclusive correlation between neurological impairment and thought disorder as well as between neurological impairment and schizophrenia. The theoretical and etiological implications are discussed, as well as the relationship of these findings to other variables. | US |
The authors describe an effort to develop criteria for utilization review of treatment for suicide attempters. Explicit criteria proposed by a panel of experts as essential determinants for hospitalization of these patients were compared with actual clinical practice. It was found that according to the experts' criteria (which were operationalized into rating assessments), over half of the outpatient sample should have been hospitalized. After multiple regression analysis was carried out on the criteria, however, four predictors showed that only 20 percent of the outpatients should have been hospitalized. The authors discuss the issues these findings raise about the criteria of the experts, their utility for research, their validity, and their implications for utilization review. | US |
The differential synthesis rate of ribosomal protein (r-protein), alpha-r (synthesis rate of r-protein divided by synthesis rate of total protein), was measured during the cell division cycle. It was observed that alpha-r remained essentially constant and was not measurably affected by duplication of the r-protein gene cluster (i.e., str-spc region) during the process of chromosome replication. It was further observed that the rate of total protein synthesis and r-protein synthesis increased continuously and uniformly during the entire cell cycle. This gene dosage independence of the synthesis rate of r-protein was similar to that observed earlier for the synthesis of ribosomal ribonucleic acid (rRNA). These observations indicate that the synthesis rates of the protein and RNA components of the ribosome are coordinately balanced during the entire cell division cycle and are not significantly perturbed by duplication of the r-protein or rRNA genes. Furthermore, this balanced synthesis insures that neither free rRNA nor free r-protein accumulate in appreciable amounts during balanced growth. | US |
Cells of many kinds adhere firmly to glass or plastic surfaces which have been pretreated with polylysine. The attachment takes place as soon as the cells make contact with the surfaces, and the flattening of the cells against the surfaces is quite rapid. Cells which do not normally adhere to solid surfaces, such as sea urchin eggs, attach as well as cells which normally do so, such as amebas or mammalian cells in culture. The adhesion is interpreted simply as the interaction between the polyanionic cell surfaces and the polycationic layer of adsorbed polylysine. The attachment of cells to the polylysine-treated surfaces can be exploited for a variety of experimental manipulations. In the preparation of samples for scanning or transmission electron microscopy, the living material may first be attached to a polylysine-coated plate or grid, subjected to some experimental treatment (fertilization of an egg, for example), then transferred rapidly to fixative and further passed through processing for observation; each step involves only the transfer of the plate or grid from one container to the next. The cells are not detached. The adhesion of the cell may be so firm that the body of the cell may be sheared away, leaving attached a patch of cell surface, face up, for observation of its inner aspect. For example, one may observe secretory vesicles on the inner face of the surface (3) or may study the association of filaments with the inner surface (Fig. 1). Subcellular structures may attach to the polylysine-coated surfaces. So far, we have found this to be the case for nuclei isolated from sea urchin embryos and for the microtubules of flagella, which are well displayed after the membrane has been disrupted by Triton X-100 (Fig. 2). | US |