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Biomedical subjects

P Heeger

Publications and source records attributed to P Heeger.

8 recordsLinked to original sources

Immune responses to hepatitis C and non-hepatitis C antigens in hepatitis C virus infected and HIV-1 coinfected patients.

OBJECTIVE: To characterize immune phenotype and function in hepatitis C virus (HCV) infection in the presence and absence of HIV-1 infection. DESIGN: Cross-sectional comparison among controls (group A), patients with HCV infection (group B), HCV-HIV-1 coinfected patients (group C), coinfected patients receiving treatment for HIV-1 (group D), and untreated HIV-1 infected patients (group E). METHODS: Flow cytometric analysis for lymphocyte phenotypes, lymphocyte proliferation and cytokine production by ELISPOT. RESULTS: HCV infected patients tended to have an increased percentage of activated (CD38, HLA-DR) CD8 cells (group A, 2+/-1.4%; group B, 6+/-3.9%; P=0.08). Proliferative responses to non-HCV antigens were comparable in group A and group B subjects. A greater proportion of group B patients had stimulation indices (SI) > 3 to the HCV protein NS3 compared to group C and D patients (67%, 0%, and 11% respectively; P < 0.003), but only two patients in group B had SI > or = 5. The SI to NS3 was significantly higher in group B patients [median, 4; interquartile range (IQR), 3-9) than in group C (median, 2; IQR, 1-3; P < 0.04) or group D (median, 1; IQR, 1-4; P < 0.009) patients. Plasma HCV RNA levels correlated directly with alanine aminotransferase levels (p, 0.52; P < 0.05) and inversely with the number of CD4 lymphocytes (rho, -0.55; P < 0.009) and proliferation to NS3 (p, -0.55; P < 0.009). CONCLUSIONS: Lymphocytes of HCV infected patients show weak proliferative responses to HCV antigens while responses to other antigens are preserved. Infection with HIV-1 potentiates this deficiency. Poor CD4 T cell responses to HCV are associated with and may determine the failure to control HCV propagation.

Adult↗

Isolation and characterization of cDNA from renal tubular epithelium encoding murine Rantes.

We have been interested in identifying proinflammatory molecules which might play a role in attracting monocytes and T cells to the kidney. Some of the new intercrines are potential candidates. In this report we have isolated cDNA encoding murine Rantes (MuRantes) from renal tubular epithelium (MCT cells). MuRantes is a 91 amino acid member of the -C-C- or intercrine beta subgroup of the Scy superfamily. The amino acid sequence for mature MuRantes was deduced from its coding cDNA and was found to be 90% homologous to its mature human counterpart (HuRantes). MCT epithelium expresses a single mRNA transcript for MuRantes of approximately 1100 bp. The MuRantes protein could be detected in cell lysates of MCT epithelium by western blotting and in the cytoplasm of MCT cells by immunofluorescence using a polyclonal antibody generated against HuRantes fusion protein. A search protocol using MuRantes-specific primers and cDNA amplification revealed that mRNAs for MuRantes are expressed additionally in syngeneic mesangial cells (MMC cells), whole kidney, liver, and spleen, as well as in nephritogenic antigen-specific CD4+ helper and CD8+ effector T cells. cDNA amplification studies also demonstrated a significant elevation in mRNA transcripts encoding MuRantes in response to the stimulation of MCT epithelium with TNF alpha and IL-1 alpha in culture, but not with TGF beta, gamma IFN, or IL-6. Our findings indicate that proximal tubular epithelium is an authentic source of MuRantes, and that transcripts encoding MuRantes are responsive to the modulating influence of paracrine factors having a known role in the development of parenchymal injury.

Amino Acid Sequence↗

Comparison between acetate and bicarbonate dialysis for the treatment of lithium intoxication.

Lithium is used to treat manic-depressive disorders, but toxic side effects commonly occur. The preferred treatment of severe lithium intoxication is hemodialysis. No data, however, exist comparing the effectiveness of acetate to bicarbonate dialysis for the removal of lithium. We present a case of lithium intoxication treated with both. During acetate dialysis, lithium removal occurred exclusively from the extracellular fluid space, while during bicarbonate dialysis, lithium removal occurred equally from both the extracellular and intracellular fluid spaces. We hypothesize that acetate but not bicarbonate activates the sodium-hydrogen antiporter on cell membranes, and that lithium, substituting for sodium, is driven into cells. This may explain the rebound in lithium levels commonly noted after conventional dialysis. We recommend bicarbonate hemodialysis as the therapy of choice for severe lithium intoxication.

Acetates↗

Protein-induced glomerular hyperfiltration: role of hormonal factors.

High protein diets acutely elevate the glomerular filtration rate. To characterize this response we administered 1 g of protein/kg body weight as a beef steak meal to nine, healthy male subjects and measured glomerular filtration rate (inulin clearance), renal plasma flow (p-amino hippurate clearance), plasma renin activity, aldosterone and plasma and urinary catecholamines. The subjects ingested the meal on three separate days and were pretreated with either placebo, 50 mg indomethacin (to inhibit renal prostaglandin synthesis), or 10 mg enalapril (to inhibit angiotensin II synthesis). Following placebo treatment protein feeding significantly increased the glomerular filtration rate, from a pre-meal level of 101 +/- 7 ml/min/1.73 m2 to a post-meal level of 130 +/- 6 ml/min/1.73 m2, P less than 0.005. A parallel rise in renal plasma flow and a fall in renal vascular resistance were noted. Indomethacin pretreatment attenuated the increase in glomerular filtration rate following the protein meal, 105 +/- 6 ml/min/1.73 m2 pre-meal level to 118 +/- 4 ml/min/1.73 m2 post-meal, P greater than 0.1. Enalapril pretreatment had no significant effect on protein-induced glomerular hyperfiltration. Protein feeding following placebo increased plasma aldosterone concentration while the concentrations were unchanged in the studies where enalapril or indomethacin was administered. Protein feeding following placebo or indomethacin did not alter plasma renin activity while plasma renin activity rose following enalapril administration. Urinary norepinephrine excretion rose while plasma norepinephrine concentration was unchanged in all three study groups. A decrease in urinary dopamine excretion was also noted four hours after the protein meal was ingested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Magnetic resonance imaging diagnosis of Budd-Chiari syndrome.

Noninvasive imaging modalities may suggest the diagnosis of Budd-Chiari syndrome but they are rarely diagnostic. Inferior vena cavography, hepatic venography, and liver biopsy, alone or in combination, are usually necessary for definitive diagnosis. Because of its excellent depiction of blood vessels as regions of absent signal, magnetic resonance imaging has the potential to make a noninvasive diagnosis of hepatic vein thrombosis. A case illustrating the usefulness of magnetic resonance imaging in the diagnosis of Budd-Chiari syndrome is presented.

Adult↗

Hemophilus influenzae cellulitis.

To define the clinical features of cellulitis due to Hemophilus influenzae type B, we reviewed the records of 78 children admitted to the hospital with cellulitis during a one-year period. Fifty-two children were afebrile (T less than 38 degrees C) and none had infections due to H. influenzae. Twenty-six children were febrile, 19 with facial and seven with extremity lesions. H. influenzae type B was recovered from seven of the febrile children with facial cellulitis, and one with extremity involvement. The mean WBC count of children with disease due to this organism was 17,500/mm3. Both fever and a leukocytosis (WBC count greater than 15,000/mm3) occurred more often in children with H. influenzae type B cellulitis than among those with infections due to other organisms.

Adolescent↗

Biosynthesis of tropoelastin by elastic cartilage.

Elastic ear cartilage and aortae from nine-day-old hamsters were incubated in Krebs-Ringer medium containing ascorbate, beta-aminopropionitrile and either [14C]proline or [3H]valine. The [14C]proline-labeled proteins were separated by chromatography on Agarose A-5 m in sodium dodecyl sulfate and their [14C]-hydroxyproline content measured. A fraction having an approximate molecular weight of 70,000 measured by polyacrylamide gel electrophoresis had a [14C]hydroxyproline content of 9.1% in the cartilage and 11.8% in the aorta. This fraction was also relatively heavily labeled with [3H]valine. The 70,000 dalton, [3H]valine-labeled protein of both the aorta and ear cartilage was precipitated by elastin-specific antibody prepared against hamster insoluble aorta elastin, but no higher molecular weight protein was immunoprecipitated. Based on these results we identify the 70,000 dalton protein from the elastic cartilage as tropoelastin.

Animals↗