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L A Sherman

Publications and source records attributed to L A Sherman.

At least 55 records · Page 3Linked to original sources
PubMed1997

CELSS-3D: a broad computer model simulating a controlled ecological life support system.

CELSS-3D is a dynamic, deterministic, and discrete computer simulation of a controlled ecological life support system (CELSS) focusing on biological issues. A series of linear difference equations within a graphic-based modeling environment, the IThink program, was used to describe a modular CELSS system. The overall model included submodels for crop growth chambers, food storage reservoirs, the human crew, a cyanobacterial growth chamber, a waste processor, fixed nitrogen reservoirs, and the atmospheric gases, CO, O2, and N2. The primary process variable was carbon, although oxygen and nitrogen flows were also modeled. Most of the input data used in CELSS-3D were from published sources. A separate linear optimization program, What'sBest!, was used to compare options for the crew's vegetarian diet. CELSS-3D simulations were run for the equivalent of 3 years with a 1-h time interval. Output from simulations run under nominal conditions was used to illustrate dynamic changes in the concentrations of atmospheric gases. The modular design of CELSS-3D will allow other configurations and various failure scenarios to be tested and compared.

Atmosphere↗
PubMed1996

The mouse mammary tumor virus env gene is the source of a CD8+ T-cell-stimulating peptide presented by a major histocompatibility complex class I molecule in a murine thymoma.

CD8+ cytotoxic T cells recognize their targets by the presence of unique peptide bound to a major histocompatibility complex (MHC) class I molecules on the cell surface. The MHC molecules normally display thousands of distinct peptides, making it difficult to identify individual antigenic peptides, their protein precursors, and their relative importance in the T-cell response. Here we used the EL-4 tumor-specific lacZ-inducible KZ30.6 T cell as a probe for detecting the peptide/MHC ligand that was generated in cells transfected with an EL-4 cDNA library. These expression screens allowed identification of a mouse mammary tumor virus (MMTV) transcript as the source of the antigenic peptide presented by the Kb MHC molecule. The antigenic activity was encoded within the MMTV env gene and was defined by the octapeptide ANYDFICV (AFV8). Synthetic AFV8 stimulated KZ30.6 T cells at picomolar concentrations and coeluted with one of two active peptides in HPLC-fractionated extracts of EL-4 cells. The AFV8/Kb complex was also recognized by two other EL-4-specific T cells. The results illustrate a novel strategy for identifying T-cell-stimulating antigens and suggest that the MMTV env gene and its naturally processed AFV8 peptide product can serve as a model for study of antigen processing and tumor immunotherapy.

Amino Acid Sequence↗
PubMed1996

CD8(+) T cell-mediated spontaneous diabetes in neonatal mice.

Transgenic mice that express the influenza virus hemagglutinin (HA) on pancreatic islet beta cells (ins-HA) demonstrate tolerance of HA even after immunization with influenza virus. Surprisingly, when Ins-HA mice were mated with a transgenic mouse expressing a TCR specific for an epitope of HA that is restricted by MHC class I H-2Kd (Clone-4 TCR), the resulting double transgenic (Ins-HA x Clone-4 TCR)F1 neonates developed spontaneous autoimmune diabetes immediately after birth and died within 10 days. This represents a unique situation in which all safeguards within the immune system that normally maintain tolerance of self-antigens in the neonate are insufficient.

Animals↗
PubMed1996

Evaluation of Cyanothece sp. ATCC 51142 as a candidate for inclusion in a CELSS.

Controlled ecological life support systems (CELSS) have been proposed to make long-duration manned space flights more cost-effective. Higher plants will presumably provide food and a breathable atmosphere for the crew. It has been suggested that imbalances between the CO2/O2 gas exchange ratios of the heterotrophic and autotrophic components of the system will inevitably lead to an unstable system, and the loss of O2 from the atmosphere. Ratio imbalances may be corrected by including a second autotroph with an appropriate CO2/O2 gas exchange ratio. Cyanothece sp. ATCC 51142 is a large unicellular N2-fixing cyanobacterium, exhibiting high growth rates under diverse physiological conditions. A rat-feeding study showed the biomass to be edible. Furthermore, it may have a CO2/O2 gas exchange ratio that theoretically can compensate for ratio imbalances. It is suggested that Cyanothece spp. could fulfill several roles in a CELSS: supplementing atmosphere recycling, generating fixed N from the air, providing a balanced protein supplement, and protecting a CELSS in case of catastrophic crop failure.

Air Conditioning↗
PubMed1996

Differential effects of insulin and exercise on Rab4 distribution in rat skeletal muscle.

Insulin and exercise cause the translocation of GLUT4 from an intracellular location to the plasma membrane in skeletal muscle. The purpose of this study was to determine if Rab4, a small GTP binding protein that has been implicated in the insulin-stimulated translocation of GLUT4 in adipose cells, is involved in the regulation of transporter translocation in skeletal muscle. Male rats were injected with insulin (20 U i.p.) or exercised on a treadmill(1 h, 20 m/min, 10% grade). Rats were killed 30 min after insulin injection or immediately after exercise, and the hind limb muscles dissected. Plasma membrane and intracellular microsomal membrane fractions were prepared, and the distribution of GLUT4 and Rab4 was determined by immunoblotting. Both insulin and exercise caused GLUT4 translocation as demonstrated by a decrease in microsomal membrane GLUT4 and an increase in plasma membrane GLUT4. In contrast, only insulin caused a decrease in Rab4 in the microsomal membrane. Rab4 was associated with GLUT4-containing vesicles isolated by immunoprecipitation. Rab4 was not detected in plasma membrane under any condition. These data demonstrate that insulin modulates the subcellular distribution of both GLUT4 and Rab4 in rats skeletal muscle, suggesting that Rab4 may play a role in the insulin-stimulated movement of GLUT4-containing vesicles. Although both insulin and exercise increase skeletal muscle glucose uptake by the translocation of GLUT4, the regulation of translocation may occur by different mechanisms.

Animals↗
PubMed1996

Potential contribution of the diazotrophic cyanobacterium, Cyanothece sp. strain 51142, to a bioregenerative life support system.

Long-duration manned space missions will likely require the development of bioregenerative means of life support. Such a Controlled Ecological Life Support System (CELSS) would use higher plants to provide food and a breathable atmosphere for the crew and employ a waste processing system to recover elements for recycling. The current study identifies ways in which a cyanobacterial component may enhance the sustainability of a space-deployed CELSS, including balancing CO2/O2 gas exchange, production of bioavailable N, dietary supplementation, and contingency against catastrophic failure of the higher plant crops. Relevant quantitative data have been collected about the cyanobacterium, Cyanothece sp. strain ATCC 51142, a large, aerobic, unicellular diazotroph. This organism grew rapidly (466 g dry wt. m-3 d-1) and under diverse environmental conditions, was amenable to large-scale culture, could be grown with relative energy efficiency (3.8% conversion), could actively fix atmospheric N2 (35.0 g m-3 d-1), could survive extreme environmental insults, and exhibited gas exchange properties (assimilatory quotient of 0.49) that may be useful for correcting the gas exchange ratio imbalances observed between humans and higher plants. It is suggested that a diazotrophic cyanobacterium, like Cyanothece sp. strain ATCC 51142, may be a safe, effective, and renewable complement or alternative to physicochemical backup systems in a CELSS.

Air Conditioning↗
PubMed1996

A role for the diazotrophic cyanobacterium, Cyanothece sp. strain ATCC 51142, in nitrogen cycling for CELSS applications.

Simple calculations show that fixed nitrogen regeneration in a CELSS may not be as efficient as stowage and resupply of fixed nitrogen compounds. However, fixed nitrogen regeneration may be important for the sustainability and safety of a deployed CELSS. Cyanothece sp. strain ATCC 51142, a unicellular, aerobic, diazotrophic cyanobacterium, with high growth rates and a robust metabolism, is a reasonable candidate organism for a biological, fixed nitrogen regeneration system. In addition, Cyanothece sp. cultures may be used to balance gas exchange ratio imparities between plants and humans. The regeneration of fixed nitrogen compounds by cyanobacterial cultures was examined in the context of a broad computer model/simulation (called CELSS-3D). When cyanothece sp. cultures were used to balance gas exchange imparities, the biomass harvested could supply as much as half of the total fixed nitrogen needed for plant biomass production.

Biomass↗
PubMed1996

Legal issues in blood banking. Elements of informed consent.

In the past, informed consent in pathology was confined chiefly to autopsies. Changes in both consent law and pathology practice led to consent being important in a broader sense in the laboratory. Areas discussed in this article include blood transfusion, tissue specimens, fine needle aspiration, and phlebotomy.

Autopsy↗
PubMed1995

Targeting p53 as a general tumor antigen.

A major barrier to the design of immunotherapeutics and vaccines for cancer is the idiosyncratic nature of many tumor antigens and the possibility that T cells may be tolerant of broadly distributed antigens. We have devised an experimental strategy that exploits species differences in protein sequences to circumvent tolerance of high-affinity T cells. HLA transgenic mice were used to obtain cytotoxic T lymphocytes specific for peptides from the human p53 tumor-suppressor molecule presented in association with HLA-A2.1. Although such p53-specific cytotoxic T cells did not recognize nontransformed human cells, they were able to lyse a wide variety of human tumor cells lines, thus confirming the existence of broadly distributed determinants that may serve as targets for immunotherapy.

Amino Acid Sequence↗
PubMed1995

Human CD8 transgene regulation of HLA recognition by murine T cells.

A series of human CD8 transgenic (hCD8 Tg) mice with differential expression in the thymus and periphery were produced to investigate CD8 coreceptor regulation of repertoire selection and T cell responses. Expression of hCD8 markedly enhanced responses to both HLA class I molecules and hybrid A2/Kb molecules providing functional evidence for a second interaction site, outside of the alpha 3 domain, which is essential for optimal coreceptor function. Peripheral T cell expression of hCD8 was sufficient to augment responsiveness to HLA class I, as hCD8 Tg mice which lacked thymic expression responded as well as mice expressing hCD8 in the thymus and periphery. Both murine CD8+ and CD4+ T cells expressing hCD8 transgenes exhibited markedly enhanced responses to foreign HLA class I, revealing the ability of T cell receptor repertoires selected on either murine class I or class II to recognize human class I major histocompatibility complex (MHC). In contrast to recognition of foreign class I, thymic expression of hCD8 transgenes was absolutely required to enhance recognition of antigenic peptide restricted by self-HLA class I. Thus, our studies revealed disparate requirements for CD8 coreceptor expression in the thymus for selection of a T cell repertoire responsive to foreign MHC and to antigenic peptides bound to self-MHC, providing a novel demonstration of positive selection that is dependent on human CD8.

Amino Acid Sequence↗
PubMed1995

Compositional and toxicological evaluation of the diazotrophic cyanobacterium, Cyanothece sp. strain ATCC 51142.

Compositional analyses of Cyanothece sp. strain ATCC 51142 showed high protein (50-60%) and low fat (0.4-1%) content, and the ability to synthesize vitamin B12. The amino acid profile indicated that Cyanothece sp. was a balanced protein source. Fatty acids of the 18:3n-3 type were also present. Mineral analyses indicated that the cellular biomass may be a good source of Fe, Zn and Na. Caloric content was 4.5 to 5.1 kcal g dry weight-1 and the carbon content was approximately 40% on a dry weight basis. Nitrogen content was 8 to 9% on a dry weight basis and total nucleic acids were 1.3% on a dry weight basis. Short-term feeding studies in rats followed by histopathology found no toxicity or dietary incompatibility problems. The level of uric acid and allantoin in urine and tissues was low, suggesting no excess of nucleic acids, as sometimes reported in the past for a cyanobacteria-containing diet. The current work discusses the potential implications of these results for human nutrition applications.

Amino Acids↗
PubMed1995

Clinical significance of anti-At(a).

Ata is a high-frequency red blood cell (RBC) antigen. Anti-At(a) has been reported in rare At(a-) black subjects. We report two cases of anti-At(a). A clinically significant anti-At(a) was found in a 26-year-old black woman with systemic lupus erythematosus. The patient had a transfusion reaction with chills and nausea during a RBC survival study, and 95% of the radiolabeled At(a+) RBCs were destroyed within 3 h. A concurrently performed monocyte monolayer assay was strongly reactive. Anti-At(a) thus can cause rapid hemolysis of transfused RBCs, but At(a-) donor units are extremely scarce in rare donor registries. A second patient at our hospital had anti-At(a) which did not affect her newborn. She also had autoimmune disease, insulin-dependent diabetes mellitus.

Adult↗
PubMed1995

Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects.

To determine whether the impaired insulin-stimulated glucose uptake in obese individuals is associated with altered insulin receptor signaling, we measured both glucose uptake and early steps in the insulin action pathway in intact strips of human skeletal muscle. Biopsies of rectus abdominus muscle were taken from eight obese and eight control subjects undergoing elective surgery (body mass index 52.9 +/- 3.6 vs 25.7 +/- 0.9). Insulin-stimulated 2-deoxyglucose uptake was 53% lower in muscle strips from obese subjects. Additional muscle strips were incubated in the basal state or with 10(-7) M insulin for 2, 15, or 30 min. In the lean subjects, tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), measured by immunoblotting with anti-phosphotyrosine antibodies, was significantly increased by insulin at all time points. In the skeletal muscle from the obese subjects, insulin was less effective in stimulating tyrosine phosphorylation (maximum receptor and IRS-1 phosphorylation decreased by 35 and 38%, respectively). Insulin stimulation of IRS-1 immunoprecipitable phosphatidylinositol 3-kinase (PI 3-kinase) activity also was markedly lower in obese subjects compared with controls (10- vs 35-fold above basal, respectively). In addition, the obese subjects had a lower abundance of the insulin receptor, IRS-1, and the p85 subunit of PI 3-kinase (55, 54, and 64% of nonobese, respectively). We conclude that impaired insulin-stimulated glucose uptake in skeletal muscle from severely obese subjects is accompanied by a deficiency in insulin receptor signaling, which may contribute to decreased insulin action.

Adult↗
PubMed1994

Role of disulfide linkage and putative intermolecular binding residues in the stability and binding of the extrinsic manganese-stabilizing protein to the photosystem II reaction center.

Site-directed mutations were produced at three highly conserved amino acid positions of MSP of the photosystem II (PSII) reaction center in the transformable cyanobacterium Synechocystis sp. PCC6803. The highly conserved aspartate at position 9 of the mature MSP was changed to a lysine (strain MSP-D9K) to assess its role in the proposed N-terminal binding region (Eaton-Rye & Murata, 1989; Odom & Bricker, 1992). This strain accumulates normal levels of MSP, and the properties of the H2O-splitting enzyme are only slightly altered relative to the wild-type. In contrast, replacement of cysteine 20 with a serine, which is proposed to disrupt the intramolecular disulfide bridge (Tanaka et al., 1989), produces a phenotype with no detectable accumulation of MSP, despite normal levels of mRNA transcripts. Like the psbO deletion strain, the MSP-C20S mutant exhibits impaired O2 evolution activity and a greater stability of the S2 state as measured by thermoluminescence. Mutation of strictly conserved aspartate 159 to asparagine (MSP-D159N) does not affect the accumulation of MSP, but causes a reduction in the H2O-oxidation activity and thermoluminescence properties intermediate between the wild-type and the psbO deletion strain. In addition, we report upon improved methods for obtaining oxygen-evolving membranes from mutant cells.

Aspartic Acid↗
PubMed1994

Conformational differences in major histocompatibility complex-peptide complexes can result in alloreactivity.

Mutations within the class I major histocompatibility complex (MHC) molecule that affect a peptide binding can result in strong allogeneic responses. It is believed this reflects, in part, binding of a different set of endogenous peptides by each MHC molecule. We have examined the representation of allopeptides recognized by Kb-specific cytotoxic T lymphocytes (CTL) clones among targets that express either the Kb or the Kbm8 mutant. These class I molecules mutationally differ by several residues at the base of the peptide binding groove resulting in lack of recognition of bm8 targets by most Kb-specific CTL, and in strong mutual alloreactivity. Since these differences involve pockets in the base of the peptide binding groove that are presumed to contribute to the affinity of peptide binding, and there is evidence for differences in peptide binding by the mutant and wild type molecule, it was considered most likely that alloreactivity was due to binding of different sets of peptides by each of these molecules. Surprisingly, the allopeptides recognized by Kb-specific clones from a variety of responders, including bm8, are often found associated with both the wild type and mutant class I molecules. Although for some allopeptides the amount of peptide normally found associated with bm8 is less than that associated with Kb, reactivity could not be restored by increasing the amount of the relevant peptide. Thus, the basis for much of the alloreactivity observed in this particular mutant and wild type combination is not the presence or absence of the relevant allopeptide but rather the different conformation adapted by the peptide-MHC complex. These results allow us to conclude that strong alloreactive responses can result from T cell recognition of conformational differences between the stimulation and responder MHC molecules.

Amino Acid Sequence↗
PubMed1994

Effect on cardiovascular function and iron metabolism of the acute removal of 2 units of red cells.

BACKGROUND: The collection from a donor of 2 red cell units at one time would decrease recipient exposure to viruses and alloantigens. If the donor is a large person, the blood volume lost and the postdonation hemoglobin and/or hematocrit should be within acceptable limits. If the donor is a large person, the blood volume lost and the postdonation hemoglobin and/or hematocrit should be within acceptable limits. The effect on cardiovascular function and iron metabolism requires description. STUDY DESIGN AND METHODS: Manual 2-unit erythropheresis was performed on eight donors, with the plasma returned. Donors had treadmill testing of maximum aerobic power (VO2max) before donation, 24 hours after, and 8 to 11 weeks after. Serial samples were drawn for iron metabolism studies. RESULTS: Donors weighed 61.2 to 74.8 kg, and 9.6 to 11.4 percent of their blood volume was removed. Mean VO2max decreased from 84 percent of that predicted before donation to 74 percent 24 hours afterward. By 8 to 11 weeks, hemoglobin returned to acceptable donor levels and mean VO2max was 92 percent of that predicted. Mean hemoglobin fell from 14.4 to 11.7 g per dL (144 to 117 g/L) and rose to 13.9 g per dL (139 g/L) at 16 weeks. At 16 weeks, serum iron (120 +/- 47 vs. 83 +/- 33 micrograms/dL [21 +/- 8 vs. 15 +/- 6 mumol/L]), ferritin (40 +/- 24 vs. 18 +/- 10 ng/mL [40 +/- 20 vs. 20 +/- 10 micrograms/L]), and free erythroprotoporphyrin (19 +/- 5 vs. 28 +/- 5 micrograms/dL [0.34 +/- 0.09 vs. 0.50 +/- 0.09 mumol/L]) differed significantly from baseline levels. No major donor symptoms occurred. CONCLUSION: Two-unit erythropheresis was done with blood volume loss and postdonation hemoglobin no worse than those that would occur in a 50-kg donor donating 450 mL. Cardiovascular effects and donor symptoms were mild. Two-unit red cell donations would be clinically advantageous, and they warrant further studies of both utility and donor safety.

Adult↗
PubMed1994

An evaluation of intravenous immunoglobulin in the treatment of human immunodeficiency virus-associated thrombocytopenia.

BACKGROUND: Anecdotal evidence suggests that high-dose intravenous immunoglobulin (IVIG) is useful in the management of human immunodeficiency virus (HIV)-associated thrombocytopenia. STUDY DESIGN AND METHODS: To rigorously evaluate this therapy, a crossover study was designed to compare IVIG, given at 1 g per kg per day for 2 consecutive days each week for 4 weeks, with intravenous saline placebo administered according to the same schedule. Subjects were randomly assigned to receive either IVIG or saline during the first 4 weeks; if IVIG was given, there was a 4-week period of no therapy before beginning placebo administration. Criteria for eligibility were platelet count of less than 50,000 per microL (50 x 10(9)/L), elevated platelet-associated IgG levels, increased megakaryocytes in the bone marrow, and positive HIV antibody test. Twelve patients (11 men, 1 woman) were studied. Seven patients completed the full protocol. Four dropped out: after 2, 5 (2 patients), and 8 weeks that included at least 2 weeks of IVIG. RESULTS: All patients sustained an increase in platelet count in response to IVIG, with increments ranging from 15,000 to 358,000 per microL (15 to 350 x 10(9)/L) (mean, 180,000/microL [180 x 10(9)/L]; median, 174,000/microL [174 x 10(9)/L]). No patient had an increase after placebo infusions. There were no adverse effects of treatment, and weekly chemical analyses showed no new abnormalities except for mild elevations in the serum protein. The duration of responses ranged from 2 to 10 weeks. No patient demonstrated refractoriness to IVIG. CONCLUSION: IVIG consistently raises platelet counts in patients with HIV-associated thrombocytopenia.

Adult↗