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Severe combined immunodeficient (SCID) mice were injected with peripheral blood mononuclear cells (PBMC) from normal individuals and 14 out of 18 had detectable serum human (h) IgG (maximum levels providing a mean +/- SEM 934 +/- 213 micrograms/ml) and IgM (253 +/- 93 micrograms/ml) at 3-6 weeks after transplantation. Serum human immunoglobulin levels were maximum 6-12 weeks after transplantation and declined to low levels over the subsequent 5 months. Human B cells constituted up to 10% and human T cells up to 40% of cells in the peripheral circulation and spleens of these animals 2-3 weeks after transplantation, PBMC, or intrathyroidal (IT) lymphocytes, from 6 patients with Graves' disease and high serum levels of thyroid autoantibodies were transplanted into 30 SCID mice (Graves' SCID-hu). Although serum human immunoglobulins were observed in only low amounts in the animals receiving IT lymphocytes (n = 4), increased levels of hIgG or hIgM were more easily detectable in 19 Graves' SCID-hu mice that received PBMC. The Graves' SCID-hu mice had significantly lower mean levels of hIgG and hIgM than those observed following transplantation of normal PBMC (mean maximum 328 +/- 113 and 32 +/- 21 micrograms/ml, respectively). Six of these 19 mice had detectable human autoantibody to thyroid peroxidase (TPO, as microsomal antigen) between 3 and 8 weeks after transplantation, with titers ranging from 0.05 to 0.39 (normal SCID-hu serum less than 0.02 ELISA Index). No abnormal thyroid hormone (T4 and T3) levels or thyroiditis was seen when compared to normal SCID-hu mice. Immunization of reconstituted SCID mice with recombinant immunoactive human TPO antigen failed to initiate anti-TPO in normal PBMC-treated mice nor did it increase the titer of human anti-TPO in the anti-TPO positive animals. In conclusion we successfully established human thyroid autoantibody secretion in the SCID-hu mouse and characterized the transient nature of the model. Further studies will be required to achieve successful antigen presentation in this system.

The plain film appearances of 17 patients with trauma to the major airways were reviewed and correlated with the findings at thoracotomy, bronchoscopy or post-mortem. Predictable radiographic patterns of air leak were discovered which related to the surgical anatomy of the rupture. Airway interruption was seen in two of three patients with laryngeal transection, all showing gross deep and superficial cervico-facial emphysema. Massive mediastinal and deep cervical emphysema without pneumothorax were striking features of tracheal injury. In patients with bronchial rupture all had ipsilateral pneumothorax and most had associated pneumomediastinum, the degree of each component relating to the site of rupture. Only two patients had tension pneumothoraces. These features alone, however, are non-specific and only two of seven patients with bronchial injury showed specific signs of rupture (a fallen lung). An understanding of the mechanisms of injury to the major airways and the predictable resultant patterns of air leak should ensure that such lesions are not overlooked in patients who will usually have sustained multisystem trauma.

High resolution computed tomography of the lungs was performed in three patients with the yellow nail syndrome to detect bronchiectasis. Standard CT was performed in a fourth patient. Evidence of bronchiectasis with bronchial wall thickening and bronchial dilatation was observed in all four patients. High resolution CT is a non-invasive method for detecting and assessing the extent of airway disease in the yellow nail syndrome.

Five patients with congenital broncho-oesophageal fistula confirmed by fistulectomy are presented. Clinical symptoms were chronic or recurrent pulmonary infection, and three patients experienced coughing after swallowing. Pre-operative oesophagograms demonstrated broncho-oesophageal fistulas in all five patients. The fistulous communications were from the lower oesophagus to segmental bronchi of the lower lobe and to the left main bronchus. The fistulas showed smooth marginated serpentine margins with areas of internal trabeculation, and in two patients the fistulas communicated with anomalous bronchi. One patient had anomalous bronchi and subsequently underwent lobectomy which showed microscopic findings of intralobar sequestration. The oesophagus showed localized tenting with its apex to the fistula and mild ipsilateral displacement in four patients.

One-hundred-and-thirteen mammograms of nulliparous women and 44 mammograms of women with a family history of breast cancer were graded according to Wolfe's parenchymal pattern classification. These were compared to 437 mammograms of women without these risk factors. Mammograms were read by two independent observers in order to evaluate inter- and intra-observer variation. The interobserver variation was reduced from 17% to 5% by combining high risk patterns (P2 and DY) and low risk patterns (N1 and P1). A significantly higher proportion of high risk patterns was found in nulliparous women compared to parous women (P less than 0.01). The proportion of high risk patterns decreased significantly with the number of children (P less than 0.01). Women with a family history of breast cancer had almost the same parenchymal patterns as women without a family history. In conclusion, while nulliparity and family history are recognized risk factors for developing breast cancer, only nulliparity would appear to influence the mammographic parenchymal pattern. This probably reflects the different mechanism by which the two factors affect breast tissue.

In this study 383 mammograms of women on hormone replacement therapy (HRT) for more than one year and 216 mammograms of women performed before HRT was started were examined to identify any mammographic features which are associated with a higher incidence of developing breast cancer according to Wolfe's criteria. There was no significant difference in the proportion of high and low risk parenchymal patterns as the duration of HRT increased. A significantly higher proportion of low risk patterns with ageing was observed in 216 women who had never been on HRT when compared to 194 mammograms of women who had been on HRT for more than 5 years. This difference becomes more obvious in women on HRT with less than three children compared to a similar group not taking HRT. Women who had not taken HRT appeared to undergo normal involutional changes which were reflected by an increase in the proportion of low risk patterns with increasing age. We may conclude from these findings that HRT appears to inhibit involutional processes within the breast and therefore this group have higher risk parenchymal patterns for a longer period of time and subsequently may have a higher risk of developing breast cancer.

The cardinal features of hepatic steatosis on ultrasound examination are now accepted as increased echogenicity of the liver parenchyma with increased attenuation of the ultrasound beam. Three cases are presented of patients with gross diffuse fatty infiltration of the liver, who showed a paradoxical lack of posterior attenuation on ultrasound examination. These examples serve to illustrate the role of scattering in attenuation of the ultrasound beam seen in fatty livers.

Sepsis with gas-forming organisms, e.g. Clostridium perfringens and anaerobic streptococci occurred in three of 120 liver-transplant recipients (2.5%). The diagnosis was made in all three patients by bedside ultrasound, before blood cultures revealed bacterial growth. Floating high amplitude echoes within the extra- and intrahepatic portal veins and persistent small high amplitude echoes in the non-dependent portion of the liver are indicative of portal venous gas and should prompt further laboratory investigations.

Skeletal muscle metastases most commonly originate from primary lung, breast, genito-urinary and gastro-intestinal tract malignancies. They have been seen to arise from head and neck tumours. However, the only primary tumours reported to metastasize to muscle from this region have been oesophageal and thyroid neoplasms. We present two cases with paravertebral muscle metastases from primary tongue and nasopharyngeal carcinomas.

We have studied seven patients presenting to the Royal Marsden Hospital between 1983 and 1989 with metastatic immature teratoma of the ovary. All patients underwent initial surgery followed by combination chemotherapy and a second laparotomy. Serial CT scans were performed at 2-3 monthly intervals from diagnosis until the second laparotomy, and the results of this were correlated with the CT appearances. In six of the seven patients CT scanning demonstrated 'retroconversion' of immature malignant tumour masses to benign mature disease during treatment. CT features of maturation included increased density of mass lesions, whose margins became better circumscribed in relation to adjacent tissues, and the onset of internal calcification, with fatty areas and cystic change. These changes on CT correlated exactly with normalization of an initially raised serum tumour marker, alpha feto-protein (AFP) in all six patients. The second laparotomy revealed only mature teratoma in all patients following chemotherapy. In three patients show continued growth of the mature deposits necessitated further surgery for local pressure symptoms, but overall, none has shown malignant relapse, and all are currently well between 1 and 6 years after diagnosis. This is the first report of the CT appearances of retroconversion of immature ovarian teratoma in a series of patients, which is an important radiological diagnosis to make in order to avoid confusion with advancing malignancy. A review of the literature is presented.

A case is presented of a patient requiring percutaneous stenting of a ureteroenteric stricture. A hairpin bend between the strictured ureter and the ileal conduit was easily negotiated by reforming a Sidewinder loop within the contralateral ureter and withdrawing it until the tip entered the conduit. This technique does not appear to have been described before.

A case of spontaneous duodeno-pericardial fistula is described. An elderly female presented with pericarditis. The chest radiograph demonstrated a pneumopericardium. The patient died before further investigation and a duodeno-pericardial fistula was found at necropsy. This condition has not previously been described.

Colonic carcinomas may be missed on the barium enema examination for a variety of perceptive, technical, and interpretive reasons. We report an uncommon source of error-persistent bowel spasm resulting in concealment of an underlying carcinoma. Awareness of this association is necessary in the effort to minimize diagnostic pitfalls of the barium enema examination.

Actinomycosis is an unusual intra-abdominal infection, often mistaken for other conditions. We report a case associated with bilateral ureteric obstruction in which a recto-sigmoid stricture developed in previously normal bowel, followed by its complete resolution after treatment with antibiotics, as demonstrated by serial barium enema examinations.

We report a rare case of hydatid cyst presenting as a 13 cm cyst in the wall of the lower mediastinal portion of the thoracic aorta associated with splenic and peritoneal cysts. The diagnostic problems are discussed.

The sonographic appearance of a large renal oncocytoma is described. The 'spoke-wheel' of hypoechoic radiating bands within the tumour was found to correlate closely with other imaging modalities and the histopathological appearance of the surgical specimen. This characteristic sonographic picture, which appears to be a feature of size, enabled a confident pre-operative diagnosis to be made.

Castleman disease is a rare, benign disorder characterized by proliferation of lymphoid tissue most commonly presenting as a solitary mediastinal mass. We discuss the radiological findings in a 10-year-old female child with a mesenteric Castleman tumour presenting with intermittent abdominal pain and a persistently elevated erythrocyte sedimentation rate (ESR).

We describe a case of Budd-Chiari Syndrome due to hepatic venous blockage in which there were multiple space-occupying lesions on CT simulating tumour deposits. Ultrasound directed liver biopsy and laparoscopy proved these to be areas of haemorrhagic necrosis consistent with Budd-Chiari Syndrome without any evidence of malignancy. The CT finding of multiple large focal non-enhancing areas in liver does not always indicate tumour deposits in a patient suspected to have Budd-Chiari Syndrome.

Superior vena cava syndrome, an uncommon manifestation of carcinoma of the thyroid, is usually due to retrosternal extension of the growth. Rarely, however, there may be direct tumour extension into the great veins of the neck, which may cause sudden death. Only eight such cases have been reported in the English literature. The case reported by us is the first to be documented by computed tomography. Patients with carcinoma of the thyroid with the superior vena cava syndrome should undergo computed tomography to differentiate external compression due to goitre from intraluminal tumour.

The objective of this study was to examine the physiological characteristics of gonadotropes in the bovine (b) pars tuberalis as assessed by their ability to release Luteinizing Hormone (LH) in response to LH-Releasing Hormone (LHRH) and the intracellular distribution of LH isoforms. At slaughter, the stalk median eminence and associated pars tuberalis as well as the anterior pituitary gland were collected from each of 7 castrate males. Each stalk median eminence and pituitary gland was mid-sagitally sectioned and weighed. One half of each tissue was immediately frozen and subsequently homogenized to determine the intracellular distribution of bLH isoforms. Tissue extracts were desalted by flow dialysis against water and chromatofocused on pH 10.5-7.0 gradients. The remaining half of the pituitary was sliced with a Staddie-Riggs slicer. The pituitary slices and the remaining half of the stalk median eminence were perifused (0.1 ml/min) for a total of 360 min with effluent samples (1.0 ml) collected every 10 min. At 130 min tissues were stimulated with 5 x 10(-8) M LHRH. Concentrations of LH in the effluent samples and the fractions collected from chromatofocusing were determined by radioimmunoassay. The release of LH in response to LHRH was 43.9% and 47.0% above basal secretion for the pars tuberalis and pituitary, respectively, suggesting similar degrees of responsiveness. Pars tuberalis and pituitary extracts resolved into nine LH isoforms during chromatofocusing and were coded with letters beginning with the most basic form. No differences (P greater than .05) were observed in distribution of LH isoforms between the pars tuberalis and the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian follicular dynamics of cattle were examined during the estrous cycle, early pregnancy and in response to PMSG. Number and size of follicles were monitored by ultrasonographic examinations. During the estrous cycle, distinct periods of follicular dominance (measured by the increase in difference in size between the largest and second largest follicle) occurred in both the luteal (Days 6-8) and proestrus (18-22) phases of the estrous cycle (two follicular waves). Associated with the well timed development of the first dominant follicle was a change in distribution of follicle numbers in small (less than 5 mm; increased on Days 2-4), medium (6-8 mm; increased on Days 3-5) and large (greater than or equal to 9 mm; increased on Days 6-9) follicular size classes. Follicular development was greater on the ovary bearing the CL for the period that the CL was present. The dominant follicle formed during the first follicular wave was capable of ovulating (6 of 8 heifers) following an injection of a synthetic analogue of prostaglandin F-2 alpha on Day 9 of the estrous cycle. During early pregnancy (Days 6-34), follicular development (size of largest follicle, number of follicles and total accumulated size of all follicles) on the ovary bearing the CL was suppressed between Days 24 and 34 of pregnancy. This was a local effect in that follicular development was sustained on the contralateral ovary. Therefore, the CL or conceptus may be regulating follicular development in a manner to help prevent luteolysis. Associated with the injection of PMSG was an initial increase in the number of small follicles followed by their recruitment into medium and large size classes leading to ovulation. Number of follicles greater than 5 mm on the Day of estrus was related (r = .97) to the number of subsequent embryos and oocytes collected. Ultrasonography is a valuable technique to monitor ovarian follicular dynamics in cattle, and can thereby be used to infer changes in physiological and endocrine states.

Three experiments were conducted to evaluate ovarian follicular dynamics and functional activity during pregnancy in cattle. In 11 pregnant Charolais cows of Experiment I, size of largest follicle, number of follicles and accumulated follicle size were reduced by day 27 of pregnancy on the ovary bearing the corpus luteum (CL) but not on the non-CL bearing ovary. In experiment II, local attenuation of ovarian follicular development on the CL bearing ovary of seven pregnant heifers was evident compared to the contralateral ovary without the CL. However, in four hysterectomized heifers, follicular development was sustained on both the CL- and non-CL bearing ovaries when CL maintenance was achieved without presence of the uterus or conceptus. In Experiment III, steroidogenic characteristics of the largest and second largest follicles at 17 d postestrus were evaluated for seven pregnant and six cyclic cattle. Follicle by physiological status interactions were detected for both aromatase activity of the follicle and follicular fluid concentrations of estradiol and progesterone. In cyclic cows, the largest follicle had appreciably more aromatase activity than did the second largest follicle; whereas, aromatase activity of the largest follicle from pregnant cows was less than that of cyclic cows. However, in pregnant cows the second largest follicle became the estrogen-active follicle, and this follicle occurred with a higher frequency on the ovary contralateral to the CL-bearing ovary. These changes in aromatase activity were reflected by parallel changes in estrogen concentrations of follicular fluid. The higher progesterone concentration in follicular fluid of the largest follicle in pregnant cows provided further confirmation of their atretic status. In conclusion, during early pregnancy the conceptus and/or uterus ipsilateral to the conceptus appear to secrete compounds which alter local follicular steroidogenic activity and attenuate subsequent follicular growth between 17 to 34 d of pregnancy on the CL-bearing ovary. This local mechanism acting within the ovary may contribute to the antiluteolytic effects of early pregnancy in cattle.

The effect of manual teat stimulation (milking paradigm) on release of oxytocin, epinephrine and norepinephrine was studied in (1) 15 heifers at 100, 150, 200 and 250 d of gestation and at 30 and 90 d of lactation (during machine milking) and (2) simultaneously in six heifers at less than 100 d and in six heifers at greater than 200 d of gestation. Oxytocin responses to teat stimulation, including peak heights and area under the response curves, at 150, 200 and 250 d or at greater than 200 d of gestation were similar and were significantly greater than responses at 100 d or at less than 100 d. Responses to milking were lower at 90 d compared to responses at 30 d. Catecholamines were measured only during gestation and were generally not affected by teat stimulation. Epinephrine levels were significantly higher at 200 and 250 d compared to levels at 100 and 150 d. Baseline oxytocin concentrations and responses to teat stimulation were greatest at 150 d of gestation when epinephrine levels were still low, suggesting that stimulatory mechanisms responsible for the release of oxytocin develop and/or are expressed prior to the development of inhibitory sympathetic mechanisms. For norepinephrine, linear analyses did not show significant responses to teat stimulation overall. However, elevated norepinephrine responses (greater than .2 pmol/ml) following teat stimulation were seen in 28 of 51 trials, and large oxytocin responses (greater than 75 pg/ml/min) were seen predominantly only when norepinephrine responses were low (less than = .2 pmol/ml).

An attenuated ovulatory rise in circulating concentrations of LH is characteristically associated with the first seasonal reproductive cycle of horse mares. Unlike ovulations (OV) of subsequent estrous cycles, the first OV of the breeding season (OV1) is not preceded by elevated concentrations of progesterone (PROG). Hence, the ability of pretreatment with PROG to abolish attenuation of LH-secretion associated with OV1 was investigated. Ten nonpregnant anestrous mares were randomly divided into 2 groups; control (C) and treated (T). Per individual, when diameter of the largest follicle was consistently greater than or equal to 35 mm, C mares received 3 times daily injections of cottonseed oil (IM), for 15 d or until OV, while T mares received exogenous PROG (IM) for 15 d, in a manner designed to mimic a diestrous pattern of release. Jugular blood samples were collected daily from onset of treatment through 10 d following the third OV (OV3). Repeated measures analyses of area under the ovulatory LH-rise (AUC) and the maximum concentration of LH associated with OV (MAX) revealed a significant main effect of OV (P less than .005) but no main effect of group or OV by group interaction (P greater than or equal to .5). When groups were combined, a significant increase in mean AUC and MAX from OV1 to OV3 was observed (P less than .01). To evaluate the influence of hypothalamic-hypophyseal recrudescence on ovulatory LH-release at OV1, 16 mares were bred to foal, and subsequently initiate reproductive activity, early (E; mid April; n = 8) or late (L; mid July; n = 8) in the year. A significant OV (1, 2 or 3) by group (E or L) interaction was observed for AUC (P less than .06) and MAX (P less than .04). Mean AUC and MAX increased progressively from OV1 to OV3 in E mares (P less than .05). In L mares, neither AUC or MAX changed from OV1 to OV3 (P greater than .4). Based on these data, we suggest that attenuation of the LH-rise at OV1 in the mare, is a consequence of incomplete recrudescence of the hypothalamic-pituitary axis.

Plasma concentrations of prolactin and corticosterone were determined in hourly samples collected over a 25-hr period from unrestrained turkey hens exhibiting incubation (broody) behavior. Hens were maintained in cages on a 14 hr light: 10 hr dark photoperiod. Mean plasma prolactin concentration increased significantly late in the dark period to reach maximum daily levels of 496 ng/ml at the start of the photophase. However, a well-defined daily rhythm in prolactin secretion was not evident. Plasma corticosterone concentration showed a significant daily rhythm characterized by a major secretory peak (7.14 ng/ml) in the middle of the light period and a smaller, less well-defined peak (4.11 ng/ml) during the dark period. Both prolactin and corticosterone secretion ranged widely throughout the day in individual hens in a manner suggestive of pulsatile hormone secretion. This study demonstrates that the extremely high prolactin concentrations characteristic of the incubating turkey hen reflect large, dynamic changes in plasma prolactin concentrations occurring throughout the photoperiod, rather than a constantly high level of prolactin secretion.

Basal hormone/metabolite concentrations and responses to intravenous challenges of glucose, insulin and epinephrine were examined in Friesian cows from selection lines of low or high genetic merit treated with recombinantly-derived bovine somatotropin (bST) or control formulation in a 2 x 2 factorial design. Cows from the low genetic merit (low breeding index, LBI) line had previously been shown to be more responsive to the galactopoietic effects of bST (50 mg/day) than those from the high breeding index (HBI) line. Despite this, comparisons of metabolic differences were not confounded by differences in energy balance because bST treatment had also caused an increase in voluntary intake of cut pasture. Circulating levels of somatotropin, insulin-like growth factor-I (IGF-I) and insulin were greater in bST-treated than control cows but neither bST treatment nor selection line influenced basal concentrations of glucose, non-esterified fatty acids (NEFA), beta-hydroxybutyrate, urea or creatinine. Treatment with bST produced a small increase in sensitivity of cows to the lipolytic effects of epinephrine and this effect was similar in both selection lines. HBI cows had greater circulating insulin levels following the glucose challenge than LBI cows but bST treatment did not affect the insulin response to exogenous glucose. Whereas bST treatment retarded the glycogenolytic response to epinephrine and the clearance of blood glucose in response to insulin in LBI cows, it had no effect on epinephrine-stimulated glycogenolysis, and caused enhanced glucose clearance in response to insulin, in HBI cows. Results are consistent with bST altering the homeorhetic control of metabolism but do not adequately explain the greater responsiveness of LBI cows to the galactopoietic effects of bST.

The aim of this study was to compare the ovine growth hormone (oGH) responses of 5 genetically lean and 5 genetically fat 9 month old ram lambs (selected on the basis of their ultrasonic backfat thickness) given two 0.3 micrograms kg-1 liveweight intravenous injections of synthetic human pancreatic GH releasing factor analogue Nle27 hGHRF29 -NH2 (GRF-29) 150 minutes apart. Plasma oGH response curves were analysed using an exponential 2 compartmental model and comparisons made through parallel curve analysis. Plasma oGH levels over 200 ng ml-1 were detected in response to GRF-29. Exponential model parameters indicated that lean lambs had a significantly higher rate of oGH release into the plasma after both consecutive GRF-29 injections, and a significantly lower rate of oGH clearance from the plasma after the second GRF-29 injection only. Significantly smaller peak oGH responses to the second GRF-29 injection were shown by the fat lambs. These results suggest that oGH release is impaired in genetically fat lambs and that either the synthesis of releasable oGH is reduced or the inhibitory tone is greater in the fat lambs. The lean and fat sheep may provide a useful model for the study of hormonal control of factors affecting leanness and fatness.

We describe a case of recurrent dedifferentiated retroperitoneal liposarcoma with light microscopy features of rhabdomyosarcoma, the first such reported case. The tumor contains a pleomorphic pattern consisting of plump fusiform cells, tadpole cells, malignant appearing lipoblasts, and other nondescript bizarre cells. Of particular interest is a number of tumor cells with plump, bizarre nuclei which contain cross-striations of skeletal muscle pattern. The literature on dedifferentiated liposarcoma is reviewed, and the significance of this case in terms of a current model of mesenchymal differentiation is discussed, with particular attention to the postulate of a common precursor for a variety of soft-tissue tumor histologies.

Computer simulations have been performed to calculate the transient cooling and solidification process at different locations in a flat plate-shaped freezing container filled with isotonic solution (0.9 wt% NaCl in water). The one-dimensional model accounts for the influences of the external cooling conditions, the container wall, the freezing bag, and the nonplanar solidification of an aqueous solution. The cooling rate was found to increase within the sample from the portions adjacent to the inner surface of the bag toward the center. An important result for cryobiological experiments was the fact that the geometrical center of the sample, a commonly used location for the determination of cooling rate, is not representative for the entire volume of the sample. Even worse, the calculations have shown that the center is often the least representative place. As an alternative, the most suitable location for cooling rate measurements has been determined. With the assumed surface cooling and geometry conditions an optimum location at x/(d/2) approximately 2/3 (x is the space coordinate, originating at the inner surface of the freezing bag; d is the sample thickness) has been calculated, i.e., a distance of one-third away from the center and two-thirds from the inside surface of the sample container. Admitting a 50% range of variation, the cooling rate measured at this point represents at least 80% of the entire sample volume. The survival signature, i.e., the functional dependence of cell survival from cooling rate (determined at a single location), for a fictitious cell kind is also influenced by the location of temperature determination: the "optimum" cooling rate seems to be shifted, and the shape of the signature is changed depending on the location where the cooling rate is determined.

The ability to cryopreserve human liver slices would greatly enhance the opportunities to test potentially hepatotoxic drugs and environmental contaminants as well as the metabolism of these compounds. This study focused on trying to cryopreserve pig and human liver slices. Since the acquisition of human liver tissue is unpredictable and scarce, an animal model was sought to predict problems associated with cryopreservation of human tissue. The pig liver was chosen because of its anatomical and physiological resemblance to human liver. The human liver tissues that did become available were obtained through the Arizona Organ Bank and the National Disease Research Interchange and from surgical liver resections. An in vitro culture system that employed precision-cut liver slices was used in this study. Different types and concentrations of cryoprotectants, cooling rates, and culture media were all tried in an attempt to cryopreserve pig and human liver slices. The viabilities of fresh and cryopreserved liver slices were evaluated using slice K+ retention and protein synthesis. Pig liver slices following cryopreservation retained between 80 and 85% of intracellular K+ content and protein synthesis as compared to controls using 1.4 M Me2SO, a 12 degrees C/min cooling rate, and a rapid rewarming rate of direct submersion of the slice into 37 degrees C fetal calf serum. Human liver slices following cryopreservation retained between 54 and 89% of intracellular K+ content and protein synthesis as compared to controls using the same protocol as for pigs, except that lower cooling rates were giving better results. The large variation seen in cryopreserved human liver slices was due to the length of warm and cold ischemia to which the tissue was exposed before arriving at the laboratory. This study indicated that pig and human liver slices can be cryopreserved and used for future toxicological and metabolic studies.

One of the mechanisms thought to cause injury in preserved organs is the formation of oxygen free radicals. The cell is protected from oxidative stress by many defense mechanisms. A major defense mechanism involves glutathione and glutathione-dependent enzymes. During organ preservation by simple cold storage the loss of glutathione may sensitize the organ to free radical damage after transplantation. In this study we show that glutathione is depleted from the rabbit liver, kidney, and heart cold-stored (5 degrees C) for up to 72 h in the UW solution without glutathione. In the first 24 h kidney glutathione decreased to 84 +/- 3% of control values, liver glutathione decreased to 49 +/- 3% of control values, and heart glutathione decreased to 73 +/- 3% of control values. After 48 h of storage the kidney and liver lost an additional 30 and 20%, respectively, whereas heart glutathione changed very little. By 72 h all three organs had lost more than 50% of the glutathione found in freshly obtained tissue. To determine if glutathione added to the UW solution can effectively prevent this loss of glutathione during preservation, hepatocytes were cold-stored for up to 72 h in a preservation solution with and without glutathione. We found that adding glutathione to the preservation solution slowed the rate of loss of glutathione from the cells. These data suggest that at hypothermia the cell may be permeable to GSH. Methods to suppress the loss of glutathione during preservation of organs may be an important factor in suppressing oxygen free radical injury.

It is known that cellular edema and functional impairment develop during anaerobic cold storage of organs. The extent of both is related to the storage time and the composition of the preservation solution used. We studied hypothermia-induced cell swelling and its effect on liver function after cold storage preservation with either Eurocollins (EC), a number of modified EC solutions in which glucose was replaced by various concentrations of raffinose, or UW solution. After 24 h storage, tissue swelling as determined by total tissue water (TTW) in rat liver tissue slices was most pronounced in slices incubated in Eurocollins, whereas the TTW was only moderately increased in slices stored in modified Eurocollins containing 90 to 120 mM raffinose. In contrast, slices incubated in UW solution had a TTW equal to normal rat liver tissue. Furthermore, intact rabbit livers preserved with Eurocollins had an increase in the whole organ weight, while there was no weight change after preservation with the modified solution containing 120 mM raffinose (M120). In contrast, a pronounced weight loss was observed after preservation with UW solution. After cold storage, the livers were reperfused for 2 h at 38 degrees C in an isolated perfusion circuit (IPL) with an acellular perfusate. Bile flow was significantly greater in livers preserved in M120 than in those preserved with the conventional Eurocollins. However, the bile flow in the livers stored in M120 was inferior to that in the livers preserved with UW solution, which in turn was equal to that in control livers. The release of alanine-aspartate-aminotransferase into the perfusate was higher in livers preserved with Eurocollins, with or without modification, than in the livers preserved with UW solution.(ABSTRACT TRUNCATED AT 250 WORDS)

The merit of corneal cryopreservation by vitrification as opposed to conventional freezing is the avoidance of ice damage which is believed to disrupt the integrity of the corneal endothelium resulting in loss of corneal transparency. The cornea must be equilibrated with high concentrations of cryoprotectant in order to achieve vitrification at practicable cooling rates. In an earlier study, corneas were exposed to 3.4 mol/liter propane-1,2-diol (Rich and Armitage (1990) Cryobiology 27, 42-54). The present study exposed rabbit corneas to concentrations of propane-1,2-diol between 3.4 and 5.4 mol/liter in a Hepes-buffered Ringer's solution containing glutathione, adenosine, 5 mmol/liter sodium bicarbonate, 6% (w/v) bovine serum albumin, and 2.5% (w/v) dextran sulfate. Dextran sulfate was as effective as chondroitin sulfate at improving endothelial tolerance of 3.4 mol/liter propane-1,2-diol. This beneficial effect may be linked to the polyanionic nature of these molecules. Corneas exposed to 5.4 mol/liter propane-1,2-diol were cooled in liquid nitrogen vapor at a temperature of -140 degrees C for 2 h. Warming was achieved by direct transfer to a dilution solution at -10 degrees C. Endothelial function was assessed by monitoring corneal thickness during perfusion of the endothelial surface at 34 degrees C for 6 h. Endothelial structure was observed by specular microscopy during the perfusion and by scanning electron microscopy after perfusion. Corneas tolerated exposure to 3.4 mol/liter propane-1,2-diol for 20 min at 0 degrees C and to 4.1 mol/liter for 10 min at -10 degrees C. Exposure to 4.8 and 5.4 mol/liter for 10 min at -10 degrees C caused endothelial damage, although a degree of endothelial function was retained. Function following exposure to 5.4 mol/liter was improved by reducing the temperature of exposure to -15 degrees C. Corneas cooled after exposure to 5.4 mol/liter propane-1,2-diol for 10 min at -15 degrees C apparently vitrified, but devitrified on warming. The corneas swelled to such an extent during perfusion that the endothelium could not be viewed by specular microscopy, subsequent scanning electron microscopy showed a severely disrupted endothelium.

The present study adapted the overwintering strategy employed by freeze-tolerant amphibians and reptiles to freeze-preserve the isolated rat heart. The heart was flushed with a cardioplegic solution and supercooled to -1.2 and -3 degrees C. Then freezing was induced by inoculation of ice crystal. The viability of the heart explant was assessed after reanimation by the isolated working heart perfusion. There was no recovery of function in hearts flushed with solution containing 0.28 mM CaCl2. Lowering the concentration of CaCl2 to 0.15 mM, however, rendered good functional return. Furthermore, inclusion of 50 mM glycerol in the flush solution dramatically improved functional preservation. Under the best conditions defined here, the recoveries of aortic flow, coronary flow, cardiac output, systolic pressure, and work in hearts stored at -1.2 degrees C for 3 h were 72.8 +/- 6.8, 87.2 +/- 4.2, 77.6 +/- 5.4, 83.4 +/- 2.8, and 66.6 +/- 5.9% (mean +/- SEM, n = 8) of the unstored control levels, respectively. The myocardial ice content was 18.6 +/- 5.4% (n = 5) of tissue water. Prolonging the storage time to 5 h increased the ice content to 45.3 +/- 8.1% and reduced the recovery of cardiac output to 23 +/- 11% of the control value (mean +/- SEM, n = 5). Hearts frozen at -3 degrees C for 1.5 h showed 29.4 +/- 8.7% (n = 3) of control cardiac output during reperfusion. This novel approach may provide an opportunity to advance our knowledge about freezing preservation of not only the heart but other solid organs as well.

A recent study from our laboratory indicated additional tissue injury during rewarming of a cooled rabbit leg. Oxygen-derived free radicals were believed to play a role in such "rewarming injury." Since free radicals may attack membrane phospholipids, we analyzed the phospholipid composition in the leg tissue during cooling and rewarming. Our results indicated significant breakdown of membrane phospholipids, particularly phosphatidylcholine and phosphatidylethanolamine, with a corresponding accumulation of lysophosphatidylcholine and nonesterified fatty acids. Quinacrine, a phospholipase inhibitor, was able to preserve membrane phospholipids during rewarming of the cooled leg. Rewarming of cooled tissue was also accompanied by additional tissue injury, as evidenced by the increased release of lactic acid dehydrogenase and creatine kinase, as well as enhanced lipid peroxidation, as evidenced by increased malonaldehyde formation. Quinacrine reduced the release of these intracellular enzymes and decreased lipid peroxidation, suggesting its efficacy as a therapeutic agent against hypothermic injury.

The anti-inflammatory effects of human/rat corticotropin-releasing factor (CRF), a 41-residue peptide hormone, on an experimental model of cold injury were examined. Male albino rats were anesthetized with sodium pentobarbital 60 mg/kg ip and the paws immersed for 1 or 2 min in a 22% NaCl solution maintained at -20 +/- 0.5 degrees C. Swelling in response to cold was measured by changes in paw volume using the fluid displacement method, and protein leakages from blood vessels were measured using Evans blue and Monastral blue dyes. Thirty minutes after cold exposure the paw volume increased from 1.5 +/- 0.1 to 2.4 +/- 0.1 ml/paw and the Evans blue content increased from 4 +/- 1 to 178 +/- 9 micrograms/pawskin. These responses to cold were inhibited by 40 to 60% after CRF was injected 56 micrograms/kg sc 30 min before or 28 micrograms/kg iv 10 min before or 5 min after cold exposures. Microscopic studies of the skin showed that CRF reduced leakage of Monastral blue pigment from the vascular compartment into the walls of capillaries and venules. The anti-inflammatory effects of CRF were blocked by alpha-helical CRF(9-41), a CRF receptor antagonist, injected 92 micrograms/kg iv 5 min before and 15 min before cold exposure.

The use of cocaine as a recreational drug is rapidly escalating in this country. Because of this, an increase in cocaine-related morbidity and mortality is occurring. Cocaine toxicity has been recognized for several years and was thought to be related to high doses or repeated use. Now several researchers have reported that even recreational use of cocaine may cause serious injury and even death by precipitating an acute myocardial infarction (MI). This paper explores the relationship between cocaine abuse and acute MI as well as the care of the patient with a cocaine-induced MI.

Once thought to be rare, neoplastic cardiac tamponade is beginning to be recognized more frequently, and is occasionally the presenting symptom of neoplastic disease. This article provides the critical care nurse with the knowledge necessary for care of the patient with neoplastic cardiac tamponade.

The nurse's role requires the operation of the IABP, while at the same time, the ability to deliver quality nursing care. Knowledge of physiology, coordination of the principles of timing with hemodynamic effects, and skillful problem solving assure critical care nurses that they can effectively manage the IABP challenge.

Orientation is a significant concern to all staff members in critical care units. The ideal orientation program is based on the orientee's individual needs, provides the knowledge and skills to function competently in all situations, and requires a minimal amount of time. This article presents the experiences of the staff of a cardiac surgical intensive care unit as they revised their nurse orientation program.

The high response rate of 65.1 percent to this survey suggests nurse educators across the country are interested and involved with the incorporation of critical care concepts in baccalaureate nursing education. Nurse educators are conscientiously working to provide an educational basis for graduate nurses to adequately address the complex healthcare needs of our society. Cooperative efforts between nurse educators and practicing critical care nurses can make a difference in the future delivery of healthcare.

Crisis in the myasthenic patient is a life-threatening event. The expertise of the critical care nurse is crucial to the prevention of complications and the return of the patient to a functional capacity.

The morphologic changes in ciliary processes and the associated intraocular pressure (IOP) were observed in owl and squirrel monkeys after intravitreal (IVT) and intravenous (IV) injections of water soluble marijuana-derived material (MDM). The response in monkeys differed from that reported in rabbits wherein IV injection induced severe ciliary swelling and a significant decrease in IOP. Only moderate swelling occurs in monkey processes after IV injection of relatively high dose of MDM, and this change, which includes disruption of the basal lamina of the pigment epithelium, is not associated with a change in IOP. Severe swelling occurs in the crests of monkey ciliary processes after IVT injection, which is accompanied by a fall in IOP. The difference in the response in monkey versus rabbit ciliary processes after IV injection of MDM may be due to a more compact stroma in the monkey processes.

In soluble extracts of bird lenses, crystallin subunits of apparent sizes between 30kDa and 40kDa show considerable variability in both abundance and mobility in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). This is only partly due to the taxon-specific distribution of lactate dehydrogenase-B (LDH-B)/epsilon-crystallin. Here we show that, in spite of high conservation in primary sequence, beta B1-crystallin subunits of avian lenses have a markedly slower migration in SDS PAGE than those of mammals and that the apparent subunit size of beta B1-crystallin varies among birds. This may be at least partly due to unusual post-translational modifications, since beta B1-crystallins of adult birds react strongly in a glycan detection procedure. No other crystallins in birds or mammals share this strong reaction. Modification of beta B1-crystallin could have interesting consequences for the formation of high molecular weight beta-crystallin aggregates in bird lenses.

The rate of increase of outflow facility (the wash-out rate) was measured in bovine eyes at 6 and 15 mm Hg. The time-rate-of-change of facility was less at 6 mm Hg (0.20: delta facility/hour) than at 15 mm Hg (0.44). However, when the data was analyzed as a function of volume passing through the outflow system, the volume-rate-of-change of facility was the same at 6 (0.35: delta facility/ml) and 15 mm Hg (0.34). This was consistent with the hypothesis of macromolecules "washing-out" of the aqueous outflow system, if these macromolecules were saturable in the perfusate.

Lyme disease has as its hallmark erythema migrans. However, it is only present in about one half of the patients who contract this disease. In its absence, the diagnosis of Lyme disease may be difficult. It depends upon a compatible history of exposure and clinical signs and symptoms together with positive results of serologic testing. Unfortunately, seronegativity for antibody to the pathogen may occur both during the first six weeks of infection and be chronic due to the reactive antibody being bound in immune complexes. The selective use of new diagnostic tests may be required to confirm the diagnosis. These tests include assays for antibody or antigen analysis of immune complex components, as well as polymerase chain reactions.

The skin is the most visible and easily accessible organ of the body. For an astute clinician, the skin may function as an important diagnostic window to diseases affecting internal organs. This is especially true for the renal system. Chronic renal failure, regardless of its cause, often produces xerosis, pruritus, sallow hyperpigmentation, and nail changes. Half-and-half nails occur frequently in patients with renal failure and are formed of a white proximal nail portion and a normal pink distal end. Uremic frost can occur on the skin in patients with severe renal failure of long duration. This white coating on the skin is caused by an increased concentration of urea in the sweat. However, long before failure is manifested clinically, specific dermatologic abnormalities can provide clues to the cause of renal disease. We review here the hereditary, metabolic, and vascular disorders that affect both the kidney and skin. The dermatologic manifestations are stressed as important guides to the diagnosis of renal disease.

We report a case of incomplete Reiter's syndrome in a black patient, who was first incorrectly diagnosed as having rheumatoid arthritis. We discuss the challenge involved in diagnosing incomplete forms of the syndrome and the value of a positive HLA B 27 antigen level in black patients.

Sweet's syndrome presenting with malignancy or acute neutrophilic dermatosis is an unusual cutaneous disorder associated most commonly with acute myelogenous leukemia. Although other cancers may be linked to acute neutrophilic dermatosis, a large majority of patients have associated neoplasms of hematopoietic, plasma cell, or lymphoid nature. We report a patient with aplastic anemia who showed acute neutrophilic dermatosis and, ultimately, acute leukemia. The individual lesions responded to carbon dioxide laser surgery.

Buschke-Löwenstein tumor is a rare type of anogenital squamous cell carcinoma with a distinctive clinical appearance. We present the case of a thirty-four-year-old man with this tumor, which was excised surgically. Human papillomavirus was detected in formalin-fixed, paraffin-embedded sections with a human papillomavirus 6/11 probe, but not with a human papillomavirus 16 or a human papillomavirus 18 probe.

Hypokalemia is an electrolyte imbalance that can have serious effects on the patient if not detected early. Therefore, it is important for the nurse to: (1) be aware of those patients at risk for excess potassium loss, (2) monitor those patients' ECG to observe for any changes indicative of hypokalemia, and (3) assess for physical signs and symptoms indicative of hypokalemia. Early detection of hypokalemia and early intervention will prevent potential catastrophic events.

Lyme disease, caused by infection with Borrelia burgdorferi, can affect those exposed to a vector tick. Pregnant women are no exception, and such infection places the fetus at risk. It is particularly important to recognize the disease early so that effective therapy may be instituted. Although the present patient had a favorable outcome, not all do. Clinical diagnosis is especially important since conventional laboratory tests may be inadequate or require lengthy periods of time before a positive result occurs. The dermatologic sign of Lyme disease, erythema migrans, although occurring in only 50 percent of cases, is likely to be the most important diagnostic sign.

Epidermolytic hyperkeratosis is an unusual type of ichthyosis that may be characterized in extreme cases by massive cutaneous involvement resembling a porcupine. We present such a patient who had a remarkable response to treatment with oral etretinate.

Erythema nodosum was the presenting feature of swimming pool granuloma in a twelve-year-old girl. This entity should be added to the list of disorders associated with erythema nodosum.

A twenty-eight-year-old woman seropositive for the human immunodeficiency virus and undergoing hemodialysis for end-stage renal disease sustained an infection of her arteriovenous graft. Multiple erythematous erosions appeared and a diagnosis of staphylococcal scalded skin syndrome was made when a frozen section of a fresh skin peel revealed an intraepidermal split through the granular layer and Staphylococcus aureus group II, phage type 71 was cultured from the wound and blood. Twenty-six cases of adult patients with staphylococcal scalded skin syndrome have been reported. Although this includes one patient with AIDS-related complex, this is the first case of an adult with staphylococcal scalded skin syndrome who showed seropositive results of testing for human immunodeficiency virus.

A case of periorbital and eyelid edema in an eighteen-year-old student is presented as the initial manifestation of acute infectious mononucleosis occurring one week before the typical prodrome. Although periorbital and eyelid edema have been reported in about 50 percent of patients with early infectious mononucleosis, its occurrence is much less frequent in clinical practice. Physicians, particularly those specializing in the treatment of cutaneous and ocular diseases, should now include acute infectious mononucleosis in the differential diagnosis of periorbital and eyelid edema.

Twelve patients with multiple actinic keratoses were treated with either 5-fluorouracil and pyruvic acid or pyruvic acid alone. Three patients were treated with 5 percent 5-fluorouracil cream for one to three weeks for comparison. Exposure time to alpha-hydroxy acids varied between one and ten minutes. Biopsy specimens were taken at times varying from immediately after treatment to eight weeks after treatment. The results show that the combination of 5-fluorouracil and pyruvic acid is an effective treatment for actinic keratoses. In addition, the exposure time to 5-fluorouracil is decreased and therefore this treatment is better tolerated than prolonged treatment with 5-fluorouracil alone.

A patient with a pruritic vesicular eruption closely resembling dermatitis herpetiformis is described. Histopathologic examination of a biopsy specimen showed a subepidermal blister containing abundant eosinophils and neutrophils, whereas results of direct immunofluorescence studies demonstrated linear and homogeneous deposition of IgG and C3 along the basement membrane zone. Prednisone therapy was necessary to control the clinical symptoms. Similar cases have been described as "vesicular pemphigoid."

We present a case of hypertrophic lupus erythematosus treated with topical tretinoin. To date, we believe this is the first description of such treatment of this disease.

After one to four years of participation in an intensive NIMH intervention project, 30 mothers selected because of extreme high risk for difficulties in parenting gave ratings regarding changes they had made in their lives and the services they were offered. They felt that their lives had changes markedly and ranked the caring relationship with the staff clinicians and abstract rather than concrete services as most important. Training and policy implications are discussed.

This review examines what is known about those who choose to become single adoptive parents. The demographic and personal characteristics of single parents who adopt are reviewed and the experiences of single parents with the children they adopt are summarized.

This article summarizes a two-year study of juvenile sexual offenders in Washington. Both community-based and institution-based treatment programs were evaluated. A typical profile of the juvenile sexual offender is offered, as well as recidivism data from a mean 20-month follow-up period.

Category I and II families are qualitatively different from families who can be reunited after a short period of service. This matrix attempts to further our efforts at differential diagnosis and case planning early in service delivery. Parents must not be denied the chance to succeed in reversing problems that put their children at risk. Children must not be made to suffer the effects of foster care drift, however, while their parents continually fail to meet their needs. Front-loading of services and early determination of the parents' willingness and/or ability to change protect children's right to a permanent and stable home.

The community context in which child abuse and neglect takes place may influence both reporting and outcomes of investigations into such incidents. This study examines and contrasts urban versus rural community perceptions of neglect by lay citizens and protective service workers.

A children's institution offers a creative program for single mothers and their families--a 24-hour child care facility on the campus that provides residential service for the entire family. Over several months, the staff helps with family problems such as income, housing, abuse and other family dysfunctions and prevention of separation. Though small, the program has experienced success and has operated on a small budget for the last 10 years.

Wound healing comprises an ordered sequence of events including cell migration and proliferation, synthesis of extracellular matrix, angiogenesis and remodelling. TGF-beta regulates many of these processes. Animal models are used to study healing of simple linear incision wounds and deeper dermal wounds under normal and impaired conditions. TGF-beta increases the rate of healing and the breaking strength of the repaired tissue. It also enhances angiogenesis and consequent blood flow to dermal wounds, partly by stimulating the local release of other growth factors. TGF-beta reverses the adverse affects of glucocorticoids on wound healing and thus may be useful in the treatment of chronic ulcers or wounds in patients whose normal responses have been impaired by therapy with steroids, radiation or other drugs.

The integrity of the skeleton is maintained by the continued cellular remodelling of bone that occurs throughout life and is characterized by an orderly sequence of events beginning with osteoclastic bone resorption followed by osteoblastic new bone formation to repair the localized defects made by osteoclasts. Bone resorption and formation are closely coupled by mechanisms which, until recently, have been poorly defined in both normal physiological and most pathological conditions, but are probably due to the generation during resorption of local 'coupling' factors. TGF-beta promises to be one of the key factors involved in coupling bone formation to previous bone resorption. This potent osteotropic polypeptide is abundant in the bone matrix, and is produced in response to factors that stimulate osteoclastic bone resorption. It is a very potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. TGF-beta has complex effects on bone resorption: it inhibits osteoclast formation and osteoclast activity. TGF-beta is released from bone in a biologically inert state that is due to the presence of at least two proteins which appear to regulate TGF-beta activity. Release of active TGF-beta from these latent complexes occurs during bone resorption and is mediated by osteoclasts. Knowledge of the mechanisms responsible for these activation processes may be vital to understanding the role of TGF-beta in bone remodelling.

Glomerulonephritis is an inflammation of the kidney characterized by the accumulation of extracellular matrix within the damaged glomeruli. We have shown that TGF-beta 1 is unique in regulating the production of proteoglycans and matrix glycoproteins by glomerular cells in vitro. In an experimental model of glomerulonephritis in rats we found increased proteoglycan and fibronectin synthesis by cultured nephritic glomeruli, which was greatly reduced by addition of antiserum to TGF-beta 1. Conditioned media from glomerular cultures induced elevated proteoglycan synthesis when added to normal cultured mesangial cells. This stimulation was blocked by addition of TGF-beta antiserum. Glomerular histology showed mesangial matrix expansion with a time course that roughly paralleled that of the elevated proteoglycan synthesis by the nephritic glomeruli was increased. Administration of anti-TGF-beta 1 at the time of induction of glomerulonephritis suppressed the elevated extracellular matrix production and dramatically attenuated histological manifestations of the disease. Our results provide direct evidence for a causal role of TGF-beta 1 in the pathogenesis of the experimental disease and suggest a new approach to the therapy of glomerulonephritis.

The closely related mammalian TGF-betas (TGF-beta 1, TGF-beta 2 and TGF-beta 3) are potent inhibitors of proliferation of many cell types in vitro. TGF-beta 1 has been demonstrated to be growth inhibitory in vivo for epithelial, endothelial, myeloid and lymphoid cells. Utilizing skin keratinocytes as a model system for studying the mechanism of TGF-beta 1-induced growth inhibition, it has been demonstrated that TGF-beta 1 rapidly inhibits transcription of the c-myc gene. Antisense c-myc oligonucleotides inhibit proliferation of keratinocytes as effectively as does TGF-beta 1, indicating that TGF-beta 1 suppression of c-myc expression is an important component of this growth inhibition. Studies utilizing DNA tumour virus transforming gene constructs have shown that the retinoblastoma gene product, pRb, or a related protein, is needed for TGF-beta 1 suppression of c-myc transcription. Thus, TGF-beta 1 may act through a tumour suppressor gene product, pRb, to suppress transcription of a proto-oncogene, c-myc, and subsequently inhibit cell proliferation.

TGF-beta proteins are produced as latent, high molecular weight complexes. The latent form of TGF-beta 1 (L-TGF-beta 1) in human platelets comprises three components: the mature TGF-beta 1 molecule, the N-terminal remnant of the TGF-beta 1 precursor in dimeric form and a novel component denoted TGF-beta 1-binding protein (TGF-beta 1-BP). Recombinant TGF-beta 1 expressed in CHO cells, which lacks TGF-beta 1-BP, is also produced as a latent form. Thus, the N-terminal remnant of the TGF-beta 1 precursor is sufficient for TGF-beta 1 latency, and it was denoted TGF-beta 1 latency-associated peptide (TGF-beta 1-LAP). The cDNA for TGF-beta 1-BP has been cloned. It is mainly composed of two different kinds of repeat sequences, i.e. 16 epidermal growth factor-like repeats and three copies of a cysteine-rich repeat hitherto not found in other proteins. The function of TGF-beta 1-BP remains to be elucidated. Activation of L-TGF-beta can be achieved by different chemical and enzymic treatments, or by incubation with certain cell types. Understanding of the physiological activation mechanisms and the in vivo roles of L-TGF-beta will be important for future clinical applications of TGF-beta.

TGF-beta is a potent regulator of immune functions both in vitro and in vivo. The majority of studies have examined changes in immune functions after the addition of TGF-beta that had been previously activated by acid treatment. Peripheral blood mononuclear cells (PBMC) and tumour cells can each produce latent TGF-beta. The role of endogenously produced latent TGF-beta as an autocrine or paracrine regulator of immune functions has not been extensively studied. Monoclonal antibody (mAb) 4A11 was used to detect and neutralize the activity of endogenous TGF-beta 1 produced during lymphocyte activation. We demonstrate that PBMC, after stimulation with interleukin 2 or phytohaemagglutinin-P/12-O-tetradecanoylphorbol 13-acetate, secrete significant quantities of latent TGF-beta 1. Addition of neutralizing mAbs specific for TGF-beta 1 enhances the proliferative response of the PBMC. CHO cell lines engineered to produce latent TGF-beta 1 were poor stimulators of cytotoxic T lymphocyte generation in vitro and significantly suppress natural killer cell activity in nu/nu mice. We conclude that mechanisms exist in vitro and in vivo to convert latent TGF-beta into an active form which can then regulate immune functions in an autocrine/paracrine manner. The possible role of latent TGF-beta produced by tumour cells in immune surveillance is discussed.

A lower level of BEI was demonstrated in duodenal ulcer patients in both acute and chronic cases (P less than 0.01). Treatment of patients with PI increases BEI up to values found in healthy subjects, in accordance with our previous findings (17). The basal level of BOI in ulcer patients did not differ from that in healthy subjects. A transient increase of BOI was recorded during the first phase after PI application, however, BOI decreased to basal levels at the end of the therapy (P less than 0.05). The basal PPI level was higher in both groups, primarily in acute ulcer patients (P less than 0.01). During the treatment with PI the PPI level slightly increased. Mathematical correlation between BEI and BOI, and BEI and PPI revealed a significant negative correlation (P less than 0.001). However, this correlation was found in healthy subjects only, indicating that healthy subjects with a high BEI level have lower BOI and PPI values and this relation depends on BEI. This dependence is absent in ulcer patients.

Similarly as in all war-ravaged countries of Europe, in Czechoslovakia, too, cardiosurgery did not begin being systematically developed until after 1945. Patent ductus arteriosus was first treated surgically in this country in 1947, the year 1951 saw the launching of surgical therapy for mitral stenosis (commissurotomy on the closed heart), 1955 - the introduction into clinical practice of open-heart surgery for simple heart defects (DSS, pulmonary artery stenosis and aortic stenosis) with the patient in 28 degrees C hypothermia and with the blood circulation arrested for brief periods of time. In the years 1958-1959, four Czechoslovak cardiosurgical centres began to provide surgical treatment for congenital and acquired heart defects in extracorporeal circulation. Considering the war-inflicted material and personnel shortcomings prevailing in those times, Czechoslovak cardiosurgery managed relatively soon to attain the standard of cardiosurgery of the western countries, thus testifying to the viability of the country's post-war health care services. At present, there are six cardiosurgical centres in this country systematically engaged in the surgical treatment of congenital and acquired heart defects and providing the diagnosis and surgical correction of heart defects on a professional scale equal to that in countries with advanced health care systems. While the care provided at Czechoslovak cardiosurgical centres is comparable in terms of quality, the productivity of those centres leaves much to be desired. Ways and means of coping early with this inadequacy are looked for with the help of the Ministry of Health.

In 10 patient-sibling pairs (sibling perspective bone marrow donor) the author typed HLA-A, B, DR and specific monocyte antigens MoP-1 to 6. Concurrent HLA-A, B and MoP identity was revealed in 80% of the cases, concurrent HLA-A, B, DR and MoP agreement in 60%. The author discusses the importance of this observation for the solution of the relationship between HLA and specific monocyte antigens. He recommends typing of specific monocyte antigens before transplantation of bone marrow as another way of donor selection.

Replacement therapy of hypogonadal men with testosterone isobutyrate, 100 mg by the i.m. route every two weeks, does not lead to a permanent significant change of the lipoprotein spectrum and to an increased risk of stereogenesis. The expected changes in the liver lipase activity and in the lipoprotein spectrum under the influence of the administered androgens are obviously suppressed by the antagonistic action of estrogens formed by conversion from androgens.

This work deals with preclinical stages of diabetes mellitus in 494 first-degree relatives of insulin-dependent and non-insulin-dependent diabetics: 182 parents and 66 siblings of diabetic children, 176 offspring of diabetic mothers and in 70 offspring of both non-insulin-dependent diabetic parents. In these persons the family history, oral glucose tolerance test and insulin secretion were studied, blood levels of lipids and fibrinogen were investigated, neurological examination was performed, the neurocirculatory deviations and changes on the fundus were observed and HLA antigens were typed in comparison with the control groups. Long-term follow-up proved, that offspring of both non-insulin-dependent diabetic parents are the most homogenous group. Fluctuating development of abnormalities of glucose tolerance during a long period from a relative early age of 30-40 years with primary insulin resistance, compensatory hyperinsulinism and its delayed secretion and later with relative insulin deficiency are characteristic. Such development is associated with an increase body weight and of blood pressure and often with elevated lipid and fibrinogen levels.

The submitted prognosis of need of personnel to ensure specialist diabetological care in the Czech Republic is based on an analysis of the development of the number of diabetic patients and on analysis of activities which must be provided to diabetics in order to maintain the selected standard of health care. The estimate of the future number of diabetics is assessed by the method of demographic projection for one-year age groups, separately for men and women. The analysis of activities in diabetological care was elaborated from the results of an anonymous survey among diabetologists in the South Moravian region. Reflections on different variants of the standard of provided care respect also the analysis of the hitherto recorded trend in the number of health workers in diabetology and their available time. The estimate of needs is objective and can be applied in specialized diabetological services as well as in a different organization of care of diabetics, e.g. by the general practitioner. The contemporary organization of care of diabetics cannot ensure the required standard of care. The prognosis submits several possible ways how to achieve this standard. The prognosis deals in particular with the number of working hours of doctors but does not omit other categories of health workers.

The authors report on tuberculosis situation in the Czech Republic (CR) in 1989 and compare the data with 1988. The incidence of all cases of respiratory TB was 15.5 and that of bacteriologically confirmed cases 11.1/100,000. The mortality from TB was also low (1/100,000). Two-thirds of the patients were detected because of the patients' complaints. This passive case - finding was, however, inadequate in subjects with a poor health consciousness. Active screening was restricted to subjects with a high risk of TB (in contact with tuberculosis, with different diseases, with socio-economic factors, migrating subjects, non-cooperating subjects). In 1989 for the first time in the CR stagnation of the incidence of bacteriologically confirmed TB of the respiratory organs was recorded. The number of patients (5.7/100,000) with TB with a microscopically positive bacteriological finding in sputum was also the same. A slowing down of the hitherto recorded favourable trend of TB must be foreseen. It will be important to maintain the contemporary system of TB surveillance.

The characterization of focally spared areas in a fatty liver may at times be problematic. This report illustrates the unique diagnostic role that combined xenon-133/technetium-99m sulfur colloid scintigraphy can play in such cases.

Abnormally low rates of gastric acid secretion (hypochlorhydria) are associated with bacterial overgrowth, enteric infection, and with hypergastrinemia and an increased risk of gastric neoplasms. In the present study, we evaluated the ability of fasting gastric juice pH measurements to detect true hypochlorhydria. True hypochlorhydria was defined as a peak acid output in response to a maximally effective stimulant of acid secretion that was below the lower limit of normal for 365 consecutive healthy subjects. In these healthy subjects, average basal pH was 2.16 +/- 0.09 in men and 2.79 +/- 0.18 in women. In 109 consecutive experiments in 28 subjects with true hypochlorhydria, fasting gastric pH averaged 7.44 +/- 0.11 in men and 7.65 +/- 0.33 in women. Fasting pH exceeded the upper 95% confidence limit of normal (5.09 in men and 6.81 in women) in 102 of the 109 experiments (94%). Thus, fasting pH measurement was a sensitive method for diagnosing bona fide hypochlorhydria.

The effects of N-ethylmaleimide (NEM), a sulfhydryl (SH) blocker, on ethanol-induced gastric lesions were investigated in rats by varying the route of administration. Oral administration of acidified ethanol (60% ethanol in 150 mM HCl, 1 ml) produced hemorrhagic bandlike lesions in the gastric mucosa. Pretreatment of the animals with orally administered NEM (0.1-10 mg/kg) dose-dependently inhibited these lesions (the inhibition was over 80% at 1 mg/kg or greater), and the effects were partially reversed by indomethacin (5 mg/kg, subcutaneous). However, when NEM (10 mg/kg) was given subcutaneously, this agent significantly worsened the lesions. Intragastrically applied NEM produced a dose-dependent reduction of the transmucosal potential difference (PD) and the mucosal nonprotein SH levels, an increase of the volume of gastric contents, and an inhibition of gastric motility, while these parameters remained unaltered after subcutaneous administration of the agent. The microvascular permeability in the mucosa was significantly increased by both oral and subcutaneous administration of NEM (10 mg/kg) but remained unchanged in response to lower doses of orally administered (less than 3 mg/kg). These results suggest that NEM given orally is cytoprotective to the stomach against ethanol, probably by acting as a mild irritant and due to dilution of an irritant and inhibition of gastric motility (muscle relaxation), but when given subcutaneously it aggravates the lesions by unknown mechanisms.

The purpose of this study was to examine the effect of perfusion of the colon with a fatty acid (oleic acid) on peptone-stimulated gastric acid secretion and release of gastrin in conscious dogs. Gastric acid secretion was monitored by continuous intragastric titration. Perfusion of the colon with sodium oleate (24 mmol/hr) inhibited gastric acid secretion (14.2 +/- 2.6 meq/hr) stimulated by a peptone meal (1%) significantly (P less than 0.05) when compared to perfusion of the colon with saline alone (20.1 +/- 1.6 meq/hr). The serum elevation in gastrin in response to intragastric instillation of the peptone meal was not affected by the colonic perfusion of oleic acid. Plasma concentrations of peptide YY (PYY) increased significantly in response to perfusion of the colon with saline or sodium oleate, and the integrated release of PYY in response to sodium oleate [6.9 +/- 2.8 ng (60-120) min/ml] was significantly greater than the response to saline [3.1 +/- 0.7 ng (60-120) min/ml]. The results of this study indicate that inhibition of gastric acid secretion by perfusion of the colon with fat is not due to an inhibition of gastrin release. In addition, because PYY is an inhibitor of gastric acid secretion, it is possible that PYY participates as an inhibitor of gastric acid secretion by the colon.

It remains unclear whether or not intragastric devices promote weight loss. To elucidate if an intragastric balloon reduces energy intake by a placebo effect of inducing satiety, five free-feeding dogs had balloons inserted via a gastric cannula. Meal intake was assessed with the balloons inflated to 200 and 500 ml with saline and compared with intake during a control period when the animals maintained stable weight. Average energy intake during the control period was 0.3 MJ/kg/day. Inflation to 200 ml had no significant effect on intake (0.31 MJ/kg/day), whereas inflation to 500 ml significantly reduced energy intake to 0.14 MJ/kg/day (P less than 0.0001). An intragastric balloon does create aversion to feeding, presumably by producing satiety, but the effect is volume dependent.

To test whether omeprazole would increase the susceptibility of the duodenum to damage, 200 to 250-g male Sprague-Dawley rats were given 10 mg/kg of omeprazole (Losec) by gavage every morning for 29 days. Control rats were given gavage buffer alone. After fasting overnight, half the rats received 10 mg/kg indomethacin intraperitoneally; then all rats were given 2 ml of 50% ethanol by gavage. Three hours later the rats were killed and the stomach and duodenum removed and histologic injury to the duodenal mucosal was quantitated. In omeprazole pretreated rats, gavage with ethanol resulted in a significant twofold worsening of duodenal injury. Pretreatment with indomethacin to decrease endogenous prostaglandin production resulted in more severe ethanol-induced duodenal injury in both groups; however, there were no longer statistically significant differences between the omeprazole and control groups. Measurement of duodenal mucosal synthesis of prostaglandin E2 showed no difference between the omeprazole and control groups. Thus chronic administration of omeprazole appears to increase the susceptibility of the duodenal mucosa to ethanol injury in rats. The mechanism of this effect is as yet unknown but does not appear to be prostaglandin-mediated.

The present study investigated both the healing rate (after four weeks) and the relapse rate (during six months) following treatment with the dopamine-like drugs bromocriptine (2.5 mg twice daily), amantadine (100 mg nocte), or with the H2 blockers cimetidine (800 mg nocte), and famotidine (40 mg nocte) in 124 patients with endoscopically proven duodenal ulcer (DU). The ulcer was completely healed in 27 (amantadine), 26 (bromocriptine), 23 (cimetidine), and in 24 (famotidine) patients. Relapse was noted in 34.7% (cimetidine) and 25% (famotidine) versus 11.7% (amantadine) and 7.7% (bromocriptine) DU patients. No significant difference was found in initial healing rates. However, the relapse rate in the cimetidine-treated group was significantly higher than in all the other test groups. Additional comparisons between all the treatment categories showed a significantly lower relapse rate with the dopamine-like agents. These important new results indicate that dopamine-like compounds are equally effective as H2 blockers in inducing DU healing and may offer a promising advantage over H2 blockers concerning their efficacy in preventing ulcer relapse in DU patients.

The efficacy of ranitidine 150 mg twice daily and Maalox TC three tablets four times daily were compared in patients with endoscopically confirmed duodenal ulcer. Seventy-nine patients were randomly allocated to double-blind, double-dummy treatment, stratified for smokers. Endoscopy was repeated after four weeks. Those unhealed continued treatment for a further two weeks before final endoscopy. Per protocol analysis in 53 patients showed ulcer healing rates at week 4 and at weeks 4 and 6 combined of 78 and 89% on Maalox TC, and of 81 and 91% on ranitidine, respectively. The same analysis gave overall healing rates of 81% in smokers and 100% in nonsmokers, irrespective of treatment. Both treatments provided early ulcer pain relief. Diarrhea was a commoner side effect in patients on Maalox TC. The study showed Maalox TC and ranitidine were equally effective in healing duodenal ulceration.

Gastric emptying, mouth-to-cecum transit, and whole-gut transit of a solid-liquid meal were measured in 46 chronic alcoholics and in 30 control subjects by using scintigraphic techniques, hydrogen breath test, and stool markers. In the alcoholics various parameters such as ethanol consumption, gastrointestinal symptoms, and alcoholic neuropathy were determined and related to gastrointestinal transit times. Although there was no significant overall difference of gastric emptying, abnormally delayed gastric emptying was detected in 23.9% of the alcoholics but no control subject (P less than 0.005). Mouth-to-cecum transit was significantly prolonged in the alcoholics (P less than 0.001) with 14 alcoholics (37.8%) disclosing delayed mouth-to-cecum transit. No significant differences between both groups were detected concerning whole gut transit. In the alcoholics there was a significant correlation of dyspeptic symptoms with delayed gastric emptying (P less than 0.006), and alcoholics with diarrhea had an accelerated mouth-to-cecum transit as compared to those without diarrhea (P less than 0.05). Neither the presence of autonomic or peripheral neuropathy nor the presence of liver cirrhosis or ascites was significantly related to gastrointestinal transit times. However, the daily ethanol ingestion significantly correlated with gastric emptying (P less than 0.005). It is concluded, therefore, that in chronic alcoholics the small intestine and the stomach are most likely to be affected by gastrointestinal transit disorders and that these transit abnormalities are potentially related to toxic damage of gastrointestinal smooth muscle.

Asymptomatic men (N = 114) 50 years of age or older had screening for colorectal neoplasia with flexible sigmoidoscopy followed by colonoscopy regardless of the sigmoidoscopic result. Our study objective was to determine the prevalence of patients having isolated adenomatous polyps in a proximal colonic segment in the absence of a distal index neoplasm within reach of the sigmoidoscope. Through the combined use of sigmoidoscopy and colonoscopy, adenomatous polyps were detected in 47 of 114 individuals (41%). A total of 88 adenomas was found. Seventeen patients had isolated neoplasms in proximal colonic segments in the absence of distal adenomas. These patients represented 15% of screened subjects (17 of 114) and 20% of individuals who lacked adenomas on sigmoidoscopy (17 of 84). The majority of proximal neoplasms were small (less than 1.0 cm), tubular adenomas. Flexible sigmoidoscopy may be ineffective for screening asymptomatic men for neoplasia. However, it remains to be determined if a 20% miss rate (for those with a normal sigmoidoscopic examination) is significant and whether small proximal adenomas are worth finding.

A clinicopathological analysis of endocrine tumors of the pancreas, using 800 autopsy cases (422 men, 378 women, mean age 78.7) was accomplished. The results were: (1) Endocrine tumors and similar lesions were found in 3% or 24 cases (25 lesions). Twenty lesions (20 cases) were found to be tumors and five lesions (five cases) were determined to be hyperplasia of Langerhans islets. (2) Incidence of tumor was 10% (6/60) in individuals having histological studies of all sections of the pancreas, and 1.6% (12/738) in individuals having histological studies of three random sections of the pancreas. (3) None of the cases with tumors and hyperplastic lesions showed symptoms of hormone production. (4) Immunohistochemical analysis revealed hormone production in all 20 tumor cases and multiple hormone production was found in 14 of these (70%). (5) Ductular or tubular structures were found in or adjacent to the tumors in 12 cases (60%) and hyperplasia in one case (20%). Langerhans islets, 500 microns or larger in size, were found in three lesions of the tumor (15%). Langerhans islets with the mean diameter of normal islets + 2 SD or larger also were found around five tumors (25%) and three hyperplasias (60%). The above findings suggest that endocrine tumors of the pancreas are prevalent and that they do not produce symptoms of excessive hormone production even though they do continue to produce hormones. Some of the endocrine tumors or hyperplasias develop from totipotent stem cells of the duct epithelia, and factors promoting the growth of Langerhans islets might exist.

Cell proliferation is the most central and key phenotypic property of cancer including hepatocellular carcinoma. Hepatocyte proliferation is central not only at the late steps in carcinogenesis, the cancer, but at the earliest known step, initiation. Compensatory or regenerative hepatocyte proliferation is essential to initiation with chemical carcinogens but primary hyperplasia is ineffective. During promotion, hepatocyte proliferation is the major change seen as clonal proliferation to generate nodules occurs. During progression, autonomous hepatocyte proliferation balanced by cell loss makes its appearance. This continues in a balanced fashion with only a slight excess of proliferation over loss until the earlier steps in malignancy at which time the balance is disrupted.

Rats fed a choline-devoid diet as the sole treatment develop hepatocellular carcinomas, the pathogenesis of which appears to reside exclusively in effects of the diet on the liver. Among the latter, most prominent is the induction of repeating cycles of liver cell injury, death, and regeneration. Two other models have been described recently in the literature, in which development of hepatic neoplastic lesions occurs after protracted periods of liver cell injury, death, and regeneration, without exposure of the animals to chemical carcinogens. The possibility is considered that an abnormal increase in cell turnover may result in all of the genomic alterations that are required for initiation, promotion, and neoplastic transformation of liver cells in these models of hepatocarcinogenesis. The possible involvement, in the same models, of endogenously initiated liver cells also is discussed briefly.

The interaction of [35S]methionine with hepatic tRNA in normal, carcinogen-treated, and partially hepatectomized rats was studied. tRNA was preferentially labeled following [35S]methionine (1.6 mCi, 25 mg/kg body wt) administration by intraperitoneal injection. The extent of [35S]methionine-tRNA interaction was impaired by partial hepatectomy and by conditions having a carcinogenic potential.

The basic motor function of the colon is to mix and knead its contents, propel them slowly in the caudad direction, hold them in the distal colon until defecation, and provide a strong propulsive force during defecation. Infrequently, it also produces mass movements in the proximal colon. These motor functions are achieved in most species by three different types of contractions: the individual phasic contractions that include the short- and long-duration contractions, organized groups of contractions that include the migrating and nonmigrating motor complexes, and special propulsive contractions (giant migrating contractions). The spatial and temporal patterns of all of these contractions are controlled by myogenic, neural, and chemical control mechanisms. The individual phasic contractions are highly disorganized in time and space in the colon. For this reason, they are effective in mixing and kneading and slow distal propulsion. The underlying cause of the disorganization of short duration contractions is the irregularity in the frequency and waveshape of colonic electrical control activity and its phase unlocking throughout the colon. The individual contractions in many species occur in cyclic bursts called contractile states. At least in some species, these contractile states exhibit mostly caudad and sometimes orad migration. However, there are also nonmigrating or randomly migrating contractile states in the colon. These two patterns of contractile states are called colonic migrating motor complexes and colonic nonmigrating motor complexes, respectively. The giant migrating contractions provide the strong propulsive force for defecation and mass movements. The neural control of colonic contractions is organized at three levels--enteric, autonomic, and central. The enteric nervous system contains cholinergic and peptidergic neurons and plays a major role in the control of colonic contractions. The autonomic nerves, the vagi, pelvic, lumbar colonic, hypogastric, and splanchnic nerves, seem to continuously monitor the state of the colon and provide a modulatory input when necessary. These nerves play a major role in the reflexive control of colonic motor function. The voluntary input from the central nervous system coordinates the motor activity of the colon, rectum, anal canal and sphincters for orderly evacuation of feces during defecation. The role of acetylcholine, nonadrenaline, and the yet to be completely identified nonadrenergic, noncholinergic neurotransmitter, possibly VIP, in the control of contractions is fairly well established. Besides these, there are several other peptides and chemicals that are localized in the colonic wall; their physiological roles remain unknown. Colonic motor activity has been studied in several disease states. The findings have not always been consistent.(ABSTRACT TRUNCATED AT 400 WORDS)

The automatic implantable cardioverter defibrillator (AICD) represents an exciting new technological advance in treating patients with recurrent malignant ventricular arrhythmias. The nursing care of patients undergoing this treatment modality requires early identification of nursing diagnoses so that appropriate interventions may be implemented.

Recognition of fluid volume deficit as the critical nursing diagnosis for a trauma victim with primary adrenal insufficiency maximizes the patient's chances for optimal recovery and prevents irreversible, life-threatening sequelae during adrenal crisis. The nurse is a key health care professional in the recognition, prevention, and treatment of this nursing diagnosis for patients with adrenal insufficiency. A case analysis demonstrates the defining characteristics of fluid volume deficit and the rationale for nursing interventions. The controversial use of military anti-shock trousers will also be discussed.

The philosophy of family centered care in a newborn intensive care unit encourages not only parent participation but involvement of the well sibling in the family process. This article describes how a group of staff nurses fostered the emotional well-being of the ill neonates's sibling by changing the status of sibling visitation in their unit.

The popularity of self-learning is on the rise. Despite its overwhelming appeal, this instructional method also has its shortcomings. The author presents the pros and cons of self-learning and their implications in critical care education.

The term "quality of life" is being used to evaluate ethical cases in health care literature and practice, yet rarely is a precise definition of the term given. It remains an abstract and ambiguous phrase. This author clarifies the concept quality of life through concept analysis methods using critical care scenarios.

The documentation of critical care nurses' competence is essential so that required standards are met. The authors set criteria against which a competency documentation system can be evaluated.

The concentration of procholecystokinin (pro-CCK) in the fetal hypothalamus was 126 +/- 41 pmol/g (mean +/- SEM; n = 20), 22 +/- 9 pmol/g at day 7 postpartum and 3 +/- 2 pmol/g in the adult. In contrast, the concentration of bioactive carboxyamidated CCK rose from 6 +/- 2 pmol/g in the fetal hypothalamus to 52 +/- 10 pmol/g in the adult. The concentration of glycine-extended processing intermediates first decreased from 21 +/- 5 pmol/g in the fetus to 5 +/- 1 pmol/g at day 21 postpartum. Subsequently, the concentration rose to 21 +/- 4 pmol/g in the adult. The results show that the CCK gene is well expressed in the fetal hypothalamus. However, only a small fraction of pro-CCK reaches maturation before weaning. We conclude that expression of the CCK gene in the hypothalamus as bioactive peptide to a large degree is regulated at the posttranslational level.