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Biomedical subjects

S Shaw

Publications and source records attributed to S Shaw.

At least 433 records · Page 24Linked to original sources
PubMed1981

Effects of chronic alcohol feeding on thiamin status: biochemical and neurological correlates.

The effects of chronic alcohol feeding on thiamin status are controversial; both adverse and beneficial effects have been reported. In order to study these effects, rats and baboons were pair-fed liquid diets containing thiamin in excess of dietary requirements and either ethanol (rats 36%, baboons 50% of total calories) or the identical diet with ethanol substituted isocalorically by carbohydrate. In the rat, chronic alcohol feeding for up to 6 months had no effects on tissue thiamin measured by transketolase assay, thiamin pyrophosphate effect, or bioassay with Ochromonas danica. Shuttle box avoidance learning in rats was impaired in animals rendered thiamin deficient but not in animals fed control or alcohol-containing liquid diets. In baboons, chronic alcohol feeding for up to 3 yr had no effects on blood levels of thiamin or on urinary excretion of thiamin. Thus, chronic alcohol feeding along with nutritionally supplemented diets does not appear to significantly affect thiamin status.

Animals↗
PubMed1981

The role of histocompatibility antigens (HLA) in infection.

We have tried to describe and evaluate in epidemiologic terms what has been done in less than a decade to define the influence of a unique genetic system on susceptibility and response to infection. The extent of its influence on disease susceptibility has only begun to be measured, and our understanding of the mechanistic and functional aspects of HLA and disease association is in its infancy. We hope it is clear from the foregoing review that the immunogeneticist, the epidemiologist, and the biostatistician all have much to offer each other as the work progresses.

Communicable Diseases↗
PubMed1981

Influenza virus-specific cytotoxic T cells are restricted by multiple HLA-A3-related self antigens: evidence for recognition of distinct self structures in conjunction with different foreign antigens.

In the experiments described in this report we examined the similarities and differences in target cell recognition by influenza-immune CTL that share HLA-A3 but no other defined HLA-A, -B, or -C specificity with each of a panel of virus-infected target cells. Virus-immune CTL populations obtained from selected HLA-A3-positive donors can distinguish between the virus-infected target cells of unrelated donors, as assessed by direct cytotoxicity and cold target inhibition. The CTL restriction antigens that are associated with HLA-A3 in the population are encoded by gene(s) that segregate with HLA-A3 in an HLA-A/C recombinant family. These results suggest that HLA-A3-positive cells from unrelated individuals may differ with respect to 1 or more individual CTL restriction antigens associated with their HLA-A3 molecules, and that each of these distinct restriction antigens is recognized by a different subpopulation of virus-immune CTL. Analysis of the self specificity of T cells from individual donors sensitized against 2 noncross-reacting viruses, type A and type B influenza, indicated that CTL can recognize different foreign antigens in conjunction with different HLA-A3-related self antigens. These results are consistent with a model that proposes that each HLA-A and -B molecule possesses multiple CTL restriction antigens, each of which may function as self recognition structures for CTL that respond to different foreign antigens.

Binding, Competitive↗
PubMed1981

Ethanol-induced lipid peroxidation: potentiation by long-term alcohol feeding and attenuation by methionine.

Lipid peroxidation has been incriminated in some types of drug-induced liver injury, but it is unclear whether it contributes to or is present in alcoholic liver injury. In order to study this question, hepatic lipid peroxidation (measured as formation of diene conjugates) and hepatic GSH were assessed in baboons and rats after short- and long-term ethanol administration. Compared to controls, baboons fed alcohol for 1 to 4 years (chronic administration) had increased hepatic diene conjugates (16.9 +/- 4.8 OD/gm of liver) and depressed GSH (3.8 +/- 0.6 VS. 6.3 +/- 0.8 mumol/gm of liver; p less than 0.01) after an overnight withdrawal from ethanol. Administration of 1.6 gm/kg ethanol over 6 hr (acute administration) increased diene conjugates (17.6 +/- 4.3) and decreased GSH (3.2 +/- 0.5; p less than 0.01) in control animals and had an even greater effect in animals chronically fed alcohol (diene conjugates 48.5 +/- 9.2; GSH 1.8 +/- 0.3; p less than 0.001). In six rats fed alcohol for 5 to 6 weeks (chronic administration), an increase in diene conjugates was detected in microsomes (0.343 +/- 0.210 OD/mg of lipid) and mitochondria (0.143 +/- 0.061), accompanied by decrease in arachidonic acid and C22 polyenes, after acute ethanol administration (3 gm/kg p.o.) but no significant change in GSH. Simultaneous administration of methionine attenuated diene conjugate formation (0.107 +/- 0.058 and 0.035 +/- 0.020 OD/mg of lipid, respectively) and fatty acid changes. Thus chronic alcohol feeding potentiates lipid peroxidation produced by an acute dose of ethanol; these changes are not dependent on GSH depression but may be potentiated by it.

Animals↗
PubMed1980

Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region and that stimulate secondary allogenic proliferative and cytotoxic responses.

Five new histocompatibility antigens, designated secondary B cell or (SB) antigens, have been identified by secondary allogeneic proliferative and cytotoxic responses. The reagents used to define the SB antigents are lymphocytes primed between donors matched for all known HLA antigens. The SB antigens stimulate weak primary allogeneic proliferative responses (a mean relative response of 8%) but strong secondary proliferative responses. Strong secondary cell-mediated cytotoxicity is generated against target antigens that are distinguishable from the SB antigens defined by proliferation. Studies by direct lysis and by cold-target inhibition indicate that these target antigens are preferentially expressed on B cells relative to T cells. The SB antigens segregate with HLA, and the gene(s) encoding the SB1, 3, and 4 antigens maps centromeric to HLA-B. The SB antigens are major histocompatibility antigens not only because they are encoded by major histocompatibility complex (MHC) genes, but also by the functional criteria that the proliferative and cytotoxic responses to SB antigens are not restricted by HLA-DR or HLA-A,-B. Parallel studies of the SB antigens and the DR antigens with respect to: (a) their preferential expression on B cells, (b) their function in secondary allogeneic proliferative and cytotoxic respones, and (c) the location of their structural gene within the MHC. However, the SB antigens and the DR antigens are clearly distinct antigens, because population studies indicate that they can occur independently, and family studies indicate that specific SB antigens segregate with HLA haplotypes having different D and DR specificities. Our data are consistent with the hypotheses that the SB antigens are a new segregant series of B cell alloantigens, and that the SB gene and the DR gene derive from a duplicated ancestral gene.

Antigens, Surface↗
PubMed1980

Human cytotoxic T cell responses to trinitrophenyl hapten and influenza virus. Diversity of restriction antigens and specificity of HLA-linked genetic regulation.

This report compares both the HLA restriction patterns and Ir gene regulation of human in vitro T cell-mediated cytotoxic responses to the trinitrophenyl (TNP) hapten and the type A and B influenza viruses. Comparison of the restriction patterns of these cytotoxic responses indicates that A/HK and B/HK are recognized in conjunction with polymorphic HLA-A and -B self determinants, whereas TNP is recognized in association with a more complex spectrum of self determinants. These self determinants include polymorphic HLA-A and -B determinants, polymorphic non-HLA-A and -B determinants that probably include DR antigens, and non-polymorphic determinants that appear to be species specific. Analysis of the self determinants recognized by human T cells in conjunction with influenza virus demonstrates that (a) the antigens recognized by virus-immune T cells can be distinguished from the serologically defined HLA-A and -B antigenic determinants, and (b) there may be multiple self determinants on individual HLA-A molecules that T cells can recognize in conjunction with virus. The results of family studies indicate that donors' T cells often preferentially respond to virus (and to a lesser extent TNP) in conjunction with products of one parental HLA haplotype (haplotype preference). In the family study, three HLA-identical siblings preferentially recognize paternal HLA antigens in conjunction with A/HK, and maternal HLA antigens in conjunction with B/HK and TNP, which indicates antigen-specific HLA-lined genetic control. Population studies demonstrate virus-specific differences in the ability of donors to respond to selected self HLA-A and -B antigens in conjunction with virus. These differences may be controlled by Ir genes that are distinct from HLA-A and -B, because differences are observed in the response patterns of HLA-A- and -B-matched individuals.

Antigens, Viral↗
PubMed1980

Human cytotoxic T-cell responses to type A and type B influenza viruses can be restricted by different HLA antigens. Implications for HLA polymorphism and genetic regulation.

The present study compares human cytotoxic T-cell responses to two closely related viruses (type A and type B influenza) to understand the antigen-specific elements involved in HLA-linked genetic control of cytotoxic T-cell responses. The HLA antigens function as self antigens that are recognized by cytotoxic T cells sensitized against either virus. However, studies in an informative family indicate that in this family, the HLA antigens preferentially recognized in conjunction with type A influenza (A/HK) differ from the HLA antigens preferentially recognized in conjunction with type B influenza (B/HK). Similarly, population studies demonstrate that some (but not all) donors whose T cells recognized A/HK in conjunction with HLA-A2 failed to recognize B/HK in conjunction with HLA-A2. Thus, HLA-linked regulation must operate by a mechanism(s) that is specific both for the self HLA antigen and the viral antigen. Furthermore, these findings indicate that different HLA antigens may facilitate T-cell responses to different pathogens, which would result in an evolutionary advantage for HLA heterozygosity.

Cytotoxicity, Immunologic↗
PubMed1980

Virus-immune cytotoxic T cells recognize structural differences between serologically indistinguishable HLA-A2 molecules.

The self-specificity of human influenza virus-immune cytotoxic T cells has been analyzed in order to identify the relationship between the self-determinants which they recognize and the serologically defined HLA-A and -B antigenic determinants. Virus-immune T cells were generated in vitro by culture of normal adult peripheral blood lymphocytes with A/HK influenza virus. Virus-immune effectors from HLA-A2 positive donors were tested on panels of virus-infected target cells from donors who were either HLA-mismatched or matched only for the HLA-A2 specificity. Virus-immune T cells from 11/11 A2-positive donors lysed all A2-matched virus-infected target cells (and no HLA-mismatched targets), except that each of these effector cell populations consistently failed to lyse the virus-infected target cells from one A2-positive donor (designated M7). Although the A2 antigen of donor M7 could also be distinguished from the A2 antigen of other donors by alloimmune cytotoxic T cells, no differences in the A2 antigen of donor M7 could be defined by extensive serological analyses. Results of isoelectric focusing of A2 molecules from three individuals plus M7 demonstrated that the M7 A2 heavy-polypeptide chain is structurally distinct. These results indicate that: 1) there is a strong but incomplete association between a self antigen recognized by virus-immune T cells and the serologically defined HLA-A2 specificity; and 2) there may be at least two structurally and functionally distinct epitopes on the same A2 molecule: one is the serologically defined HLA-A2 antigenic determinant; the other is the self determinant recognized by T cells on HLA-A2 molecules.

Cell Line↗
PubMed1980

HLA-linked B cell alloantigens of a new segregant series: population and family studies of the SB antigens.

In order to define the new human histocompatibility antigens, we have generalized primed lymphocytes using responder and stimulator cells matched for all recognized HLA-linked histocompatibility antigens (A,B,C,D,DR,MB). Many such primed lymphocytes give highly discriminatory proliferative responses specific for antigens which differ between HLA-A,B,C,D,DR, and MB matched restimulating cells. Five distinct antigens have been defined which appear to be part of a single segregant series (designated "SB"). Studies in a DR/GLO recombinant family indicate that the antigens are coded by an HLA-linked gene telomeric to GLO. Family studies of 57 HLA haplotypes provide an estimate of genotype frequency which is 12% or less for four of the SB alleles but approximately 50% for the most common (SB4, which may be a "public: determinant); approximately 25% of haplotypes are blank. Population studies of one of the SB antigens (SB1) suggest that it is in linkage disequilibrium with the SB antigens are part of a highly polymorphic new segregant series of B cell alloantigens encoded by a gene that maps between HLA-B and GLO.

B-Lymphocytes↗
PubMed1980

Phenotypic and genetic variation in the susceptibility of Haemophilus influenzae type b to antibodies to somatic antigens.

Haemophilus influenzae type b (H.i.b) has been investigated with respect to phenotypic and genetic variations resulting in differential susceptibility to bactericidal antibody. Previous studies had shown that after growth in infected rats or in dialysate of rat serum, H.i.b strain Eag became more resistant to the bactericidal activity of antisomatic antibody. We now report that a similar phenotypic shift occurs when strain Eag is incubated with dialysate of human serum, that the increased resistance is to antibodies against determinants in the lipopolysaccharide not for the somatic antigens generally, and that most strains of H.i.b undergo the shift. To assess genetic differences in exposed antigens, a panel of 13 H.i.b isolates from cerebrospinal fluid were analyzed with cross-adsorbed antisera. Seven different patterns were found that could be accounted for through the variable expression of six antigens. These ranged from infrequent (found on 1:13 strains) to common (10:13 strains). At least four were somatic rather than capsular determinants; the most common (antigen 1) was contained in lipopolysaccharide. The epidemiologic relevance of the genetic variations was explored using pairs of isolates from two children who had had two documented infections with H.i.b. In both cases the isolates varied in somatic antigen expression. The strains from one patient differed in the expression of antigen 1. The isolates from the other were indistinguishable in sub-typing for the six classified antigens, but differed in the expression of an additional antigen identified by use of the patient's serum.

Antibodies, Bacterial↗
PubMed1980

The self determinants recognized by human virus-immune T cells can be distinguished from the serologically defined HLA antigens.

The self specificity of human influenza virus-immune cytotoxic T cells has been analyzed in order to clarify the relationship between the self antigens that they recognize and the serologically defined HLA-A and -B antigens. Virus-immune effectors from HLA-A2-positive donors were tested on panels of virus-infected target cells from donors who were either HLA-mismatched or matched only for HLA-A2. Virus-immune T cells from 11 out of 11 A2-positive donors lysed all A2-matched virus-infected target cells (and no HLA-mismatched targets), except that each of these effector cells consistently failed to lyse virus-infected target cells from one A2-positive donor (designated M7). Although the A2 specificity of donor M7 could also be distinguished from the A2 antigen of other donors by alloimmune cytotoxic T cells, no differences in the A2 antigen of donor M7 could be defined by extensive serologic analyses. These results indicate that there is a strong but incomplete association between a self antigen recognized by virus-immune T cells and the serologically defined HLA-A2 specificity.

Absorption↗
PubMed1980

Increased hepatic production of alpha-amino-n-butyric acid after chronic alcohol consumption in rats and baboons.

Chronic alcohol consumption produces an increase in plasma alpha-amino-n-butyric acid (AANB) in humans. The mechanism of this increase was investigated in experimental animals. In the rat, administration of ethanol as 36% of total calories for 4--6 wk produced a threefold rise in plasma AANB associated with a sixfold increase in hepatic AANB. The increased gradient from liver to plasma suggested enhanced hepatic production. This was verified in liver slices from these animals: They showed a twofold increase in hepatic production of AANB. In the baboon, hepatic vein catheterization studies revealed a marked stimulation in splanchnic release of AANB after chronic but not acute alcohol consumption. Liver slices from these animals showed a two- to threefold increase in AANB production. Thus, increased hepatic production of AANB may explain the increased plasma levels seen in experimental animals and humans after chronic alcohol consumption.

Alcoholism↗
PubMed1979

HLA-linked genetic control of the specicity of human cytotoxic T-cell responses to influenza virus.

We have investigated elements of the genetic control of human in vitro cytotoxic T-cell responses to influenza virus-infected autologous cells by studies of a large family. The pattern of virus-immune cytotoxicity among siblings demonstrated T-cell recognition of influenza virus predominantly (greater than 90%) in association with determinants which are coded by genes linked to HLA (P less than 0.0002). Many family members consistently generated cytotoxic activity against influenza predominantly in association with antigens coded by genes of only one of their HLA haplotypes. Such haplotype preferences were consistent among HLA-identical siblings, indicating that the specificity of the T-cell response to influenza virus in association with HLA-A and -B antigens is controlled by genes linked to HLA.

Cytotoxicity, Immunologic↗
PubMed1979

Sequelae of prolonged ventilatory support for pediatric surgical patients.

The evolution of intensive prolonged respiratory support has been a major development in improving survival in the critically-ill child. That intensive respiratory support can be maintained for prolonged periods of time even in the home with survival of good babies is the subject of this report. In a 3-yr period, 2112 surgical patients were admitted to intensive care facilities with an over-all survival of 95%. Ventilatory support was required in 368 (17.4%) of these children, and survival in this group was 75.3%. Prolonged mechanical ventilation was necessary in 13 of the 368 children (3.5%) for a mean support time of 359 days (range 101 to 1095). Of these 13 children, 4 died while hospitalized (30.8%), and 3 died subsequently after being discharged (23.1%) for a total mortality of 53.8%. However, 6 children (46.2%) survive, 3 free of ventilatory support and 3 being weaned from their machine at home. The greatest cost in this expensive program was delivered to the survivors and psycho-social and developmental data confirm that these children are good babies with favorable long-term prognoses.

Child↗
PubMed1979

Detection of alcoholism relapse: comparative diagnostic value of MCV, GGTP, and AANB.

Mean red blood cell volume (MCV), plasma gamma glutamyl transpeptidase (GGTP), and plasma alpha amino-n-butyric acid (AANB) were measured in 245 patients undergoing treatment for alcoholism at the V.A. Medical Center, Bronx, N.Y. and Raleigh Hills Hospitals, Denver, Colo. AANB and GGTP, but not MCV, decreased following withdrawal from alcohol and during a period of abstinence. Among patients who relapsed, AANB and GGTP, but not MCV, increased in a majority of subjects. The combined use of AANB and GGTP identified 28/33 heavy drinkers, while 4/33 patients in remission had positive tests. In conclusion, measurement of AANB and GGTP are useful in documenting the success of treatment for alcoholism and in identifying patients who relapse following treatment for alcoholism.

Alcoholism↗