bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programming of defective rat pancreatic β-cell function in offspring from mothers fed a low-protein diet during gestation and the suckling periods
Authors: HEYWOOD Wendy E. , MIAN Nasi , MILLA Peter J. , LINDLEY Keith J. 
Published: June 2004

Poor fetal and infant nutrition has been linked to impaired glucose tolerance in later life. We studied the effect of protein deficiency during gestation and the suckling period in a rat model and found that poor nutrition ‘programmes’ pancreatic β-cell GK (glucokinase; known as the glucose sensor) and glucose-stimulated insulin secretion response in newborn, suckling and adult rat offspring. Pregnant female rats were divided into three groups: a control group was kept on a normal protein (20%) diet, another group was fed a low-protein (LP) (6%) diet during gestation and suckling periods (LP-G + S group) and another was fed a LP diet during gestation then a normal protein diet during the suckling period (LP-G group). The pulsatile glucose-stimulated insulin secretion response was acutely disrupted and the peak insulin secretion was markedly decreased in newborn and 3-week-old offspring of the LP-G + S group compared with the control group. Also, there was an altered pulsatile secretory response in adults of the LP-G + S and 3-week-old and adult offspring of the LP-G groups compared with the control group. GK protein levels, detected by Western blotting, were decreased in newborn and 3-week-old offspring of both LP-G + S and LP-G groups compared with the control groups. The Km and Vmax of GK were altered. The prenatal and postnatal LP diet appeared to have a permanent effect in increasing the affinity of GK for glucose (indicated by decreased Km values) and decreasing the Vmax. This showed that the critical period of programming of the function of GK was after birth and during the postnatal weaning period, since the adult offspring of the LP-G + S group when fed a normal protein diet showed no reversal in the Km values of the enzyme. Similar experiments in adult offspring of the LP-G group showed normalization of the Km values of GK at 3 weeks of age. In conclusion, fetal and infantile nutrition ‘programmes’ pancreatic β-cell function; poor nutrition during this period caused irreversible effects on glucose homoeostatic mechanisms in the offspring, which may predispose the offspring to diabetes in later life.
Fetal alcohol syndrome at the cellular level
Authors: Olney John 
Published: June 2004

AbstractA single exposure of infant rats or mice to ethanol during synaptogenesis (mid to late pregnancy for humans) can cause developing neurons to commit suicide (die by apoptosis) on a massive scale. The neuronal loss demonstrated in recent studies is more severe and much more widely distributed (many brain regions, plus spinal cord and retina) than has been documented in prior animal ethanol studies. By suppressing neuronal activity via NMDA glutamate and GABAA receptors, ethanol disrupts synaptogenesis, thereby activating in developing neurons a programmed signal to commit suicide. These recent findings help clarify important aspects of the fetal alcohol syndrome, and demonstrate the usefulness of an in vivo infant rodent model for studying the neurotoxic effects of ethanol on the developing central nervous system.
Fetal alcohol syndrome in the United States corrections system
Authors: Burd Larry , Selfridge Rachael , Klug Marilyn , Bakko Stacy 
Published: June 2004

AbstractPrenatal alcohol exposure can result in fetal alcohol syndrome (FAS), which may increase the risk of confinement in the corrections system. In the United States each state and four major cities' corrections systems were asked to complete a questionnaire on the prevalence of FAS and alcohol‐related neurodevelopmental disorder (ARND) in the offender population, the availability of screening and diagnostic services to identify offenders with FAS and staff training needs related to FAS. The total population in the 54 entities was 3 080 904 inmates. Completed questionnaires were obtained from 42 entities (78%). The mean rate of reported substance abuse in offenders was 60.1%. Specialized programs for persons with mental retardation were reported for 44.4% of corrections facilities and 25.9% of community corrections facilities. Programs for pregnant women were reported for 46.3% of corrections facilities and 29.6% of community facilities. One program (1.9%) reported having a screening program for FAS in the corrections system. Only four programs (7.4%) reported having access to diagnostic services for FAS in the corrections facilities. Of the 3 080 904 offenders, only one offender was reported to have a diagnosis of FAS. Reported staff training needs were very large. In conclusion, corrections systems have high unmet needs to screen, identify, and treat offenders with FAS and ARND. Staff training needs are substantial.
Increased sibling mortality in children with fetal alcohol syndrome
Authors: Burd Larry , Klug Marilyn , Martsolf John 
Published: June 2004

AbstractWe compared the rate of all‐cause mortality in siblings of children diagnosed with fetal alcohol syndrome (FAS) with the siblings of matched controls. The siblings of children with FAS had increased mortality (11.4%) compared with matched controls (2.0%), a 530% increase in mortality. The age of death in case siblings deaths occurred later (between 1 day and 7 years) compared with the controls (1 day to 4 years) [odds ratio (OR) = 2.4 (0.4 ‐ 15.6)]. Siblings of children with FAS had increased risk of death due to infectious illness [OR = 13.7 (1.2 ‐ 361)] and sudden infant death syndrome compared with controls [OR = 10.2 (1.2 ‐ 75.1)]. A diagnosis of FAS is an important risk marker for mortality in the siblings of the proband even if they do not have FAS. Maternal alcoholism appears to be a useful risk marker for increased mortality risk in diagnosed cases and their siblings. This has important implications in the management of family members of children with FAS.
THE ISOLATION AND SELECTED PROPERTIES OF BLOOD MONOCYTES
Authors: Bennett William E. , Cohn Zanvil A. 
Published: June 2004

A technique is described for the quantitative recovery of monocytes from horse blood by means of flotation on dense albumin solutions. Monocytes are concentrated in a surface pellicle along with a few lymphocytes which are then removed when the monocytes adhere to a glass surface.
The in vitro cultivation of homogeneous populations of monocytes results in an increase in (a) cell size, (b) number of mitochondria, and (c) phase-dense granules of the centrosphere. The phase-dense granules are osmiophilic and acid phosphatase positive.
Quantitative biochemical analysis during cultivation have revealed increased levels of cytochrome oxidase, acid phosphatase, arylsulfatase, and BPN hydrolase. In addition, glucose utilization and lactic acid production are stimulated under the same conditions.
The uptake of both bacteria and colloidal gold is stimulated during in vitro cultivation. The phagocytic activity of cultured monocytes may be enhanced by a purified bacterial lipopolysaccharide.
These data are consistant with the in vitro maturation of monocytes to macrophages, a cell with greater metabolic and functional potentional.
THE ROLE OF METHIONINE DEFICIENCY IN POLIOVIRUS REPLICATION IN TISSUE CULTURES
Authors: Mohajer Soussan , Gabliks Janis 
Published: June 2004

The role of methionine in poliovirus infection in HeLa and monkey kidney cells was investigated by using the methionine analogue l-ethionine. In the presence of 2.0 x 10–3 and 4.0 x 10–3 moles ethionine, the growth of HeLa and monkey kidney cells was significantly inhibited. Under the same experimental conditions, ethionine had no significant effect on the biosynthesis of two strains of poliovirus (Mahoney and Lansing) in HeLa cells, whereas in primary monkey kidney cells, it markedly inhibited the biosynthesis of the Lansing strain of poliovirus. HeLa cells partly depleted of their intracellular amino acids did not change the rate of viral biosynthesis.
The inhibitory effect of ethionine on cell growth and viral biosynthesis was reversed by addition of an excess of l-methionine.
THYMUS-DEPENDENT AREAS IN THE LYMPHOID ORGANS OF NEONATALLY THYMECTOMIZED MICE
Authors: Parrott Delphine M. V. , de Sousa Maria A. B. , East June 
Published: June 2004

Specific areas of lymphocyte depletion, termed thymus-dependent areas, have been delineated in neonatally thymectomized C3H/Bi and F1 (C57BL x C3H/Bi) mice. They occur within the lymphoid follicles of the spleen immediately surrounding the central arterioles, and constitute the mid and deep cortical zones of the lymph nodes. These depleted areas appear in healthy thymectomized mice as early as 3 wk after operation but, in mice which survive for more than 6 to 7 wk, the thymus-dependent areas are repopulated by rapidly dividing pyroninophilic cells, the majority of which are immature plasma cells.
Syngeneic thymus cells, labeled in vitro with tritiated adenosine localize preferentially in the thymus-dependent areas after intravenous injection. Similarly labeled spleen cells also accumulate in these areas but, in addition, are distributed at the periphery of splenic follicles and in the outer cortical zone of the lymph nodes. Many more spleen than thymus cells enter the lymphoid tissues and the spleen appears to be the primary target.
The apparent paradox that syngeneic thymus cells are less efficient than spleen cells in restoring neonatally thymectomized mice to normality is discussed in the light of these results and possible routes by which the migrating cells could enter the lymphoid tissues are considered. The origin of the plasma cells which repopulate the lymphocyte depleted areas is also discussed.
It is concluded that the normal thymus produces cells which contribute directly to the migratory or circulatory lymphocyte population but that there also exists another source of supply for the plasma cell series. These two systems may function synergistically so that the thymus may control, directly or indirectly, the balance of cell populations within the body.
THE REACTION MECHANISM OF ß1C-GLOBULIN (C'3) IN IMMUNE HEMOLYSIS
Authors: Müller-Eberhard Hans J. , Dalmasso Agustin P. , Calcott Mary Ann 
Published: June 2004

During immune hemolysis by human complement, C'3 (ß1C-globulin) becomes physically attached to the erythrocyte membrane. Binding of C'3 was found to be mediated by cell-bound, activated C'2 and to have the characteristics of an enzymatic reaction. A single C'4,2a site on the cell surface effected the binding of several hundred molecules of C'3 if the latter was provided in excess. The accumulation of hemolytically inactive, physicochemically altered C'3 in the fluid phase was found to be an inherent feature of the process of C'3 binding. It is postulated that C'4,2a activates C'3 for its subsequent reaction with cell membrane receptors. Antierythrocyte antibody did not play an essential role in C'3 uptake; C'3 could be bound to erythrocyte-C'4,2a complexes which were entirely devoid of antibody.
Cell-bound C'3 proved hemolytically active, the degree of hemolysis being proportional to the number of C'3 molecules per cell. Binding of a large number of C'3 molecules per cell was found to be a prerequisite for the production of the immune adherence phenomenon and for immune hemolysis.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: Smart K. Marilyn , Kilbourne Edwin D. 
Published: June 2004

The initial observations that cortisone may act as an inhibitor of viral interference (11, 4) are now explicable as an inhibitory effect on interferon synthesis. The suggestion that the action of interferon is also inhibited by cortisone or its analogues (6) has not been confirmed in a plaque reduction type of interferon assay system in which autointerference by the challenge inoculum is a lesser problem. In this respect, the present results are in accord with those obtained by DeMaeyer and DeMaeyer (8) with hydrocortisone in a system in which a low multiplicity (0.1) Sindbis virus infection in monolayer culture was employed with cytopathic effect (CPE) as an end-point. It has been shown that hydrocortisone is restrictive to the synthesis of interferon induced by inoculation of either infective or inactivated virus into the chick embryo, and that this inhibitory effect is temporary. However, in another study in the chick embryo, three spaced injections of hydrocortisone (0.25 mg/dose) prevented the appearance of detectable interferon during the entire 64 hr observation period following inoculation of 103.3 EID50 of Lee virus (12).
The importance of explicit definition of experimental conditions in assessing hormonal effects on infection is illustrated by the capacity of hydrocortisone either to inhibit or increase interferon synthesis in vitro, depending on the proportion of inactivated and infective virus in the inoculum employed, and the time at which interferon is measured. As suggested previously, it is not unlikely that similar shifts in hormone-virus-interferon balance may operate in vivo to influence the outcome of infection.
STUDIES ON DELAYED CUTANEOUS INFLAMMATORY REACTIONS ELICITED BY INOCULATION OF HOMOLOGOUS CELLS INTO HAMSTERS' SKINS
Authors: Ramseier Hansruedy , Billingham R. E. 
Published: June 2004

The intracutaneous inoculation of lymph node cell suspensions from normal hamsters into normal, homologous hosts causes the development of delayed inflammatory reactions, normal lymphocyte transfer (NLT) reactions, the intensities of which reflect the antigenic disparity between donor and recipient. The immunogenetic situations in which they occur indicate that these reactions are due to sensitization in situ on the part of inoculated immunologically competent cells against alien antigens of the host. They are graft versus host reactions. If hamsters are sensitized by cellular or solid tissue homografts and then challenged intracutaneously with lymphoid or epidermal cells from the donor strain, direct reactions are provoked. A positive correlation exists between the development of transplantation immunity and the capacity to give direct reactions. The sensitivity responsible for direct reactions can be suppressed by irradiation or administration of cortisone, and it is transferable by means of viable lymphoid tissues or cells but not by means of serum.
Intracutaneous inoculation of viable node or splenic cells from specifically sensitized hamsters into hosts of the donor strain incites transfer reactions, the intensities of which depend upon the number of cells transferred and the level of sensitivity in the animal that provided them. These reactions are not incitable by thymocytes, by killed lymphoid cells, or by serum. Transfer reactions differ from NLT reactions only on a quantitative and chronologic basis. However, a sharp experimental distinction can be drawn between them. For example, if normal MHA node cells and node cells from MHA hamsters sensitized against CB antigens are injected into the skins of MHA's tolerant of CB tissue, only the sensitized cells incite reactions.
Both direct and transfer reactions are highly specific immunologically. The inability of node cells to incite NLT or transfer reactions in heavily irradiated hosts and other findings sustain the thesis that it is host cells of hematologic origin, rather than indigenous skin cells, that contribute the antigenic stimulus required for these reactions.
All the findings presented are consistent with the hypothesis that the various delayed inflammatory reactions described are manifestations of immunological responses on the part of immunologically competent cells against alien transplantation antigens.
STUDIES ON THE EFFECT OF THE CARRIER MOLECULE ON ANTIHAPTEN ANTIBODY SYNTHESIS
Authors: Paul William E. , Siskind Gregory W. , Benacerraf Baruj 
Published: June 2004

Equilibrium measurements of interactions of anti-DNP antibodies, prepared using DNP-PLL and several DNP-proteins for immunization, with DNP0.6-PLL240 and with the univalent hapten, ϵ-DNP-L-lysine, were made utilizing the technique of fluorescence quenching. Carrier specificity of anti-DNP-PLL antibodies was demonstrated by a higher average intrinsic association constant (K0) of anti-DNP-PLL antibodies with DNP0.6-PLL240 than with ϵ-DNP-L-lysine. The free energy contribution of the PLL carrier to the interaction of intact anti-DNP-PLL antibodies with DNP0.6-PLL240 was from –0.8 to –2.1 kcal/mole. On the other hand, intact anti-DNP-protein antibodies displayed a lower energy of interaction with DNP0.6-PLL240 than with ϵ-DNP-L-lysine of up to +2.4 kcal/mole.
Fab' fragments of both anti-DNP-PLL and anti-DNP-BGG antibodies have K0's with ϵ-DNP-L-lysine identical to the K0's of the intact anti-DNP antibodies from which they were prepared. However, K0 of interaction of Fab' fragments with DNP0.6-PLL240 (a large proportion of the conjugated PLL molecules in this preparation bear more than one DNP group) is considerably lower than that of the intact antibody. Thus a cooperative effect in the binding of bivalent antibody and bivalent (or greater) antigen exists and is of the order of –1.2 to –2.0 kcal/mole of IgG antibody.
Although the direct contribution of the carrier to the interaction of Fab' fragment of anti-DNP-PLL and DNP0.6-PLL240 is –0.4 kcal/mole, the energy of carrier specificity, based upon consideration of cooperative effects and of repulsion of anti-DNP-protein antibodies for portions of the DNP-PLL determinants, is of the order of –3 kcal/mole (approximately 30% of total binding energy).
INTERACTION OF DIPHTHERIA TOXIN WITH CELL CULTURES FROM SUSCEPTIBLE AND RESISTANT ANIMALS
Authors: Gabliks Janis , Falconer Marcia 
Published: June 2004

The cytotoxicity (TD) level of diphtheria toxin for human Chang liver strain was 0.1 guinea pig MLD per ml; for mouse liver NCTC 1469 strain, the TD was 500 MLD per ml. The results of cell culture toxicity correlated well with relative susceptibility of both man and mouse. The initial effects of toxin on the susceptible Chang liver cells were studied at one half the TD level (0.05 MLD per ml). At this low concentration of toxin, the number of cells per culture was reduced slightly below the "0" hr values, whereas the amounts of cell protein, RNA, and DNA were increased. Analysis of the toxin-treated cells indicated an enlargement of the cells. The individual cells contained significantly more protein, RNA, and DNA than the control cells and the cell volume was increased 1.9 times.
When purified diphtheria toxin was incubated with the susceptible Chang liver cells and then tested for its biological activity, the results showed an increased diffusion rate in parabiotic culture chambers and definite cytotoxicity to the normally resistant mouse liver cells. The cytotoxicity was neutralizable with antitoxin. The results suggest that the toxin-susceptible cells transform the toxin molecule to a more active derivative which affects the highly resistant mouse liver cell.
EFFECT OF SPLENECTOMY ON THE SUSCEPTIBILITY OF MICE INOCULATED WITH DIPLOCOCCUS PNEUMONIAE
Authors: Shinefield Henry R. , Steinberg Charles R. , Kaye Donald 
Published: June 2004

An experimental model is described which demonstrated increased susceptibility of mice to infection with D. pneumoniae following splenectomy. It was necessary to use small numbers of a particular strain of pneumococcus (D. pneumoniae type 6), intravenous infection and a particular strain of mouse (pathogen-free NCS strain). The increase in susceptibility persisted for at least 4 months after splenectomy.
With modifications in experimental design such as use of large numbers of organisms, a different strain of pneumococcus, the intraperitoneal route of infection or a different mouse strain no increase or a much less impressive increase in susceptibility was demonstrated.
Following intravenous injection of small numbers of D. pneumoniae Type 6 bacteremia tended to persist in all NCS mice. Multiplication of pneumococci subsequently occurred in a higher proportion of mice with splenectomy and at a more rapid rate than in control animals. Mice with splenectomy usually had more D. pneumoniae per ml of blood than per gram of any tissue. This suggested that in these mice multiplication of microorganisms occurs primarily in blood. In control mice higher concentrations of bacteria were present in spleen than in blood, and higher concentrations were found in blood than in other tissues. These results suggested that in normal mice infected intravenously with small numbers of D. pneumoniae Type 6, the spleen protects by removing and killing small but critical numbers of D. pneumoniae which are circulating in the blood.
No evidence was found to suggest that the altered susceptibility is mediated by an effect of splenectomy on numbers of circulating leukocytes or on the antibacterial activity of mouse blood.
THE FUNCTIONAL CAPACITY OF HYPERTROPHIED NEPHRONS
Authors: Morrison Ashton B. , Howard Ruth M. 
Published: June 2004

A method is described for the measurement of inulin and PAH clearances in rats without killing the animal. Inulin clearance measurements of partially nephrectomized rats and sham-control rats were made before operation and at intervals following the operation; inulin clearances were determined on normal rats at intervals during their growth. In another series of partially nephrectomized rats and their sham-operated controls, inulin and PAH clearances were determined in all the animals before and at intervals following the operation. Glomerular counts were made in some rats.
After partial nephrectomy the inulin clearance is reduced but not as much as would be expected considering the amount of renal tissue removed. The mean inulin clearance per nephron is greatly increased in the partially nephrectomized rat when compared to the value determined for the control rat. The inulin clearance of the partially nephrectomized rat shows a progressive decline which is first clearly evident about 6 months after operation. The sham-operated rats showed an inulin clearance slightly less than that of nonoperated controls about 24 to 30 wk after the operation. In the normal rats the inulin clearance relative to body weight is much greater in rats with a mean weight of 197 ± 3 g than in normals which are older and heavier.
The PAH dearance of the partially nephrectomized rat is reduced following operation but undergoes no further change in the ensuing 24 wk.