Search PubMed⌕ Search

Biomedical subjects

R Shapiro

Publications and source records attributed to R Shapiro.

At least 91 records · Page 5Linked to original sources
PubMed1999

Salmonella Thompson associated with improper handling of roast beef at a restaurant in Sioux Falls, South Dakota.

In October 1996, we investigated an outbreak of Salmonella serotype Thompson infections associated with Restaurant A in Sioux Falls, South Dakota, and conducted two cohort studies among persons who ate at luncheons catered by Restaurant A. Fifty-two Salmonella Thompson infections were identified between 29 September and 14 October 1996. Infections occurred among employees and patrons at Restaurant A and among attendees at three luncheons catered by the restaurant on 7 October. Roast beef cooked at Restaurant A was the only food item significantly associated with illness. Cooking times and storage temperatures for roast beef were inadequate to prevent multiplication of Salmonella, and the chefs were unaware of proper cooking and storage temperatures. We conclude that improper handling of roast beef probably caused this outbreak of Salmonella Thompson infections. Better knowledge of food safety practices by the cooking staff at Restaurant A, through required food safety education, might have prevented the outbreak.

Adolescent↗
PubMed1999

Outcome of kidney transplantation under tacrolimus-based immunosuppression in elderly patients.

Kidney transplantation has become a reasonable treatment option for selected patients aged 60 years or older, and a number of different immunosuppressive drug protocols have been described. This article concerns 230 recipients who were aged 60 years or older and who were undergoing kidney-only transplantation at the University of Pittsburgh between January 1990 and April 1997. All recipients were treated with a tacrolimus-based immunosuppression regimen. The median follow-up was 31.5 months (range, 1-86). The 1-, 3-, and 5-year actuarial patient survival rates were 90%, 83%, and 76%, respectively. There were 42 (19%) deaths, cardiovascular disease (50%) and infection (38%) being the main causes. Death with a functioning kidney occurred in 28 (67%) patients. The 1-, 3-, and 5-year actuarial graft survival rates were 84%, 74%, and 64%, respectively. The delayed graft function rate was 33%. Rejection was seen in 57 (25%) elderly patients. The mean serum creatinine was 2.6 +/- 2.7 mg/dL and the serum urea nitrogen was 35 +/- 22 mg/dL. The mean tacrolimus level was 8.5 +/- 3.8 ng/mL. These results suggest that renal transplantation in older recipients under tacrolimus-based immunosuppression is associated with reasonable outcomes, and can be offered to appropriately selected patients.

Actuarial Analysis↗
PubMed1999

Simultaneous pancreas-kidney transplantation at the University of Pittsburgh.

Analysis of the SPK program at the University of Pittsburgh has led to a number of observations: 1. Under tacrolimus-based immunosuppression, without antibody induction, it has been possible to achieve (a) One- and 3-year actuarial patient survival rates of 98% and 95% (b) One- and 3-year actuarial kidney survival rates of 95% and 87% (c) One- and 3-year actuarial pancreas survival rates of 86% and 80% 2. Steroid withdrawal has been achieved in over half of the successfully transplanted recipients, with excellent outcomes and a low rate (4.7%) of subsequent rejection. 3. Bone marrow augmentation has been associated with (a) less rejection (b) less pancreatic graft loss to rejection (c) an increased ability to withdraw steroids 4. Rejection has been associated with a rising serum lipase. 5. Renal allograft rejection in SPK patients with elevated serum lipase levels has been seen in the setting of normal renal function. 6. Enteric drainage has been associated with a reasonably low complication rate. 7. SPK transplantation is a successful therapeutic option in selected type I diabetics with end-stage renal disease.

Adult↗
PubMed1998

Repression of interleukin-2 mRNA translation in primary human breast carcinoma tumor-infiltrating lymphocytes.

Human breast carcinoma tumor-infiltrating lymphocytes (TIL) express activation antigens in situ indicative of ongoing immune response-CD28, CD45RO, CD69, CD71, and DR. However, interleukin 2 (IL-2) receptor was poorly expressed: CD25 was detected in only 1/24 samples and CD122 in only 2/24 samples. Furthermore, isolated breast cancer TIL were defective in proliferative response but recover when treated with recombinant IL-2. Nineteen of 24 tumor samples expressed B7-1, B7-2, and CD28 protein, showing that absence of costimulator proteins or counter ligand was not the basis for TIL proliferative deficit. Expression of IL-2 activity was not detected; however, mRNA encoding IL-2 was produced and translatable in vitro. These findings show that human breast cancer tumor-induced repression of IL-2 RNA translation is the basis of failure of TIL to express the IL-2 receptor and subsequent T cell hyporesponsiveness.

Breast Neoplasms↗
PubMed1998

Zinc-binding of endostatin is essential for its antiangiogenic activity.

Endostatin is a potent angiogenesis inhibitor in vitro and in vivo. We used the yeast Pichia pastoris to express and purify soluble endostatin. It was discovered that metal chelating agents can induce N-terminal degradation of endostatin. We theorized that a metal was removed from endostatin which changed the conformation and allowed a contaminating protease to degrade the N-terminus. Atomic absorption and amino acid analysis of endostatin purified from Pichia pastoris and mammalian cells showed a 1:1 molar ratio of Zn2+ to protein. Ding et al. have shown that histidines 1, 3, 11, and aspartic acid 76 coordinate the Zn2+ atom (1). An H1/3A double, an H11A, and a D76A single mutant of endostatin were not able to regress Lewis lung carcinoma. We conclude that the ability of endostatin to bind Zn2+ is essential for its antiangiogenic activity.

Amino Acid Sequence↗
PubMed1998

Mutations of the adenomatous polyposis coli and p53 genes in a child with Turcot's syndrome.

Turcot's syndrome is a rare heritable complex that is characterized by an association between a primary neuroepithelial tumor of the central nervous system and multiple colonic polyps. The aim of this study was to analyze genetic alterations in a case of Turcot's syndrome in a 10.5-year-old boy in whom a colorectal tumor developed 3.5 years following astrocytoma. An APC germline non-sense mutation at codon 1284 leading to a truncated protein was identified, as was a somatic p53 mutation in the colorectal carcinoma in exon 7, codon 244. The latter was not identified in the primary astrocytoma. However, immunohistochemistry revealed high p53 protein expression in both tumors, suggesting an additional p53 mutation in the primary astrocytic tumor. The diverse p53 mutations observed in this unique syndrome in two different sites and stages of the disease may shed light on the multistep progression of the malignant events.

Adenomatous Polyposis Coli↗
PubMed1998

Zinc-dependent dimers observed in crystals of human endostatin.

The crystal structure of human endostatin reveals a zinc-binding site. Atomic absorption spectroscopy indicates that zinc is a constituent of both human and murine endostatin in solution. The human endostatin zinc site is formed by three histidines at the N terminus, residues 1, 3, and, 11, and an aspartic acid at residue 76. The N-terminal loop ordered around the zinc makes a dimeric contact in human endostatin crystals. The location of the zinc site at the amino terminus, immediately adjacent to the precursor cleavage site, suggests the possibility that the zinc may be involved in activation of the antiangiogenic activity following cleavage from the inactive collagen XVIII precursor or in the cleavage process itself.

Base Sequence↗
PubMed1998

Structural features that determine the enzymatic potency and specificity of human angiogenin: threonine-80 and residues 58-70 and 116-123.

Human angiogenin (Ang), a homologue of bovine pancreatic ribonuclease A (RNase A), is a potent inducer of blood vessel formation. It exerts a ribonucleolytic activity that is 10(5)-10(6)-fold lower than that of RNase A but nonetheless essential for biological action. Previous studies revealed some of the structural features of Ang that underlie its catalytic inefficiency: Gln-117 blocks the space corresponding to the pyrimidine binding site of RNase A and Ang lacks the disulfide loop 65-72 that forms most of the purine binding site of RNase A. Additional features have now been identified by mutagenesis and kinetics. Thr-80, which hydrogen-bonds to the pyrimidine-binding residue Thr-44, plays an important part in attenuating activity and in determining pyrimidine specificity: mutation to Ala increases activity toward cytidylyl substrates by 11-15-fold but has only a minimal effect on cleavage of uridylyl substrates. The properties of T44A/T80A and Q117A/T80A double mutants demonstrate that these changes are mediated by Thr-44 and are largely independent of the blockage by Gln-117. The side chain of Ser-118 also suppresses enzymatic activity: S118A is 5-7-fold more effective than Ang. This increase appears to reflect the loss of a hydrogen bond with Asp-116 that helps to orient Gln-117. The effects of deleting residues 119-123 suggest that main-chain atoms of the C-terminal 3(10) helix make a small further contribution. Finally, the significance of the absence of the RNase A loop 65-72 from Ang has been investigated by reexamining the earlier derivative ARH-I (in which Ang residues 58-70 have been replaced by residues 59-73 of RNase) and generating new derivatives of this hybrid protein. The results suggest that the RNase A segment of ARH-I not only provides more effective purine recognition but also counteracts the deleterious effects of Gln-117 and Thr-80 on the pyrimidine site.

Amino Acid Sequence↗
PubMed1998

Identification of melanoma antigens that are immunogenic in humans and expressed in vivo.

BACKGROUND: In the development of an antimelanoma vaccine, a critical factor is the identification of antigens that induce a strong immune response in humans and that are expressed by melanoma cells in vivo. The aim of this study was to identify candidate antigens for such vaccine. METHODS: Sixty-nine patients with surgically resected melanomas (American Joint Commission on Cancer [AJCC] stage III) were immunized with a polyvalent vaccine containing multiple melanoma antigens. Antimelanoma antibodies generated in the patients' sera were used as probes to identify the melanoma antigens that are immunogenic in humans and that are expressed on the tumor tissue in vivo. Such responses were determined by an immunoblotting assay that employed an antigen source prepared from membrane fractions of freshly excised melanoma tissue. RESULTS AND CONCLUSIONS: Vaccine treatment stimulated antibody responses in 35 (51%; 95% confidence interval [CI] = 39%-63%) of 69 sequentially enrolled patients. The antibodies were directed to one or more antigens with molecular masses of 45, 59, 68, 79, 89, 95, and/or 110 kd. The most immunogenic antigens were p110 and p68, which induced responses in 33% (95% CI = 22%-44%) and 25% (95% CI = 15%-35%) of patients, respectively. Both antigens were commonly expressed on different melanomas, but they were absent on autologous normal tissue and on an unrelated allogeneic tumor. All the above antigens are attractive candidates for vaccine construction.

Adult↗
PubMed1998

Risk-taking patterns of female adolescents: what they do and why.

A total of 58 college-age adolescent females were asked to provide information about their risk-taking behaviors. Participants completed a risk-taking questionnaire and were asked to keep a diary of their risk-taking behaviors for 1 week. Participants were also asked to provide reasons for engaging in each behavior they listed. Results indicated that participants engaged in a variety of risky behaviors ranging from traditional adolescent risk-taking behaviors, e.g. drinking and sex, to other behaviors not typically included in studies of risk-taking, e.g. interpersonal and financial risky behaviors. An analysis of the justifications given for engaging in the various behaviors were largely goal-oriented (e.g. engaging in a behavior as a means to an end) or reflected a preoccupation with personal needs (e.g. engaging in a behavior to relieve loneliness or stress). These results are contrary to the widely held belief that adolescents' risk-taking is "mindless," "aimless," or mere "sensation seeking."

Adolescent↗
PubMed1998

Tacrolimus without antilymphocyte induction therapy prevents pancreas loss from rejection in 123 consecutive patients.

In this series, antilymphoid induction therapy did not appear to be necessary to prevent early graft loss from rejection. In addition, we have followed cytomegalovirus (CMV) antigenemia (pp65) for CMV infection. Although some patients developed a positive antigenemia in the seropositive to negative donor-recipient combinations, only one patient had a prolonged febrile course for 1 week.

Diabetes Mellitus↗