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Biomedical subjects

P Lowry

Publications and source records attributed to P Lowry.

28 records · Page 2Linked to original sources

Assessment of corticotropin-releasing factor, vasopressin and somatostatin secretion by fetal hypothalamic neurons in culture.

The concomitant release of corticotropin-releasing factor (CRF), vasopressin (AVP) and somatostatin (SRIF) has been followed from primary cultures of rat hypothalamic neurons. 18-day-old fetal rat hypothalami were dissociated enzymatically and mechanically, then plated and maintained in a serum-containing medium at a density of 2.5 x 10(6) cells per dish (equivalent to 3 hypothalami). Cultured neurons remained viable for up to 6 weeks, and peptide release was followed by immuno-assay between days 14 and 39 in culture. The incubation media were concentrated on C4 and C8 silica columns to facilitate detection of CRF and AVP. Peptide release was measured at various times up to 4 h, at which point it was still increasing. To optimise measurements, taking into account peptide degradation, a 1-hour incubation period was chosen for further studies. Release of CRF, AVP and SRIF by 56 mM K+ or 10 microM veratridine was statistically significantly greater than basal (p less than 0.01) and was Ca2-dependent. For CRF and AVP, stimulated release increased considerably with the age of culture, whereas SRIF release was steadier. Basal release for all 3 peptides did not fluctuate greatly over this period. Basal and stimulated release of the peptides continued over at least 5 successive 1-hour periods. At day 35 of culture, the peptide content was still increasing in a pattern which paralleled the increasing content in hypothalami freshly removed from age-matched rats. In conclusion, we have demonstrated a development of CRF, AVP and SRIF production by neurons over extended periods in culture as assessed by their peptide content and increasing responses to depolarizing stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Human lymphocyte antigens in hypertrophic cardiomyopathy.

An increasing number of genetic studies in hypertrophic cardiomyopathy challenge conventional views on inheritance and suggest genetic heterogeneity or non-genetic disease. We have found changes in relative risk for some antigens with significantly increased frequency of HLA antigen DR4 in this condition. These findings are consistent with there being a genetic component in susceptibility to hypertrophic cardiomyopathy. No evidence was found for HLA linkage using either sib pair analysis or lod scores. This suggests that hypertrophic cardiomyopathy does not have a disease susceptibility gene related to the HLA region on the short arm of chromosome number six. Population HLA associations with hypertrophic cardiomyopathy must thus be explained by other influences of the genetic background on disease susceptibility.

Adult↗

Cyclosporin-A nephrotoxicity and acute cellular rejection in renal transplant recipients: correlation between radionuclide and histologic findings.

Serial radionuclide studies using both Tc-99m DTPA (perfusion) and I-131 hippuran (tubular function) were correlated with histologic findings in 25 patients with renal transplants. These cases included 15 cases of cyclosporin-A nephrotoxicity (CsA-NT) and ten cases of acute cellular rejection that were retrospectively selected on the basis of biopsy findings and favorable clinical response to therapy specific for each of these conditions. The serial radionuclide studies enabled the correct diagnosis in 12 of 15 cases of CsA-NT and eight of ten cases of acute rejection. Posttherapy radionuclide studies, furthermore, demonstrated improvement consistent with clinical response. In all cases, the radionuclide results were available at least 24 hours before biopsy findings. These results indicate that serial radionuclide studies evaluating interval changes in both perfusion and tubular function are of significant value in the diagnosis and follow-up of CsA-NT and acute cellular rejection in transplant recipients. This initial experience suggests a sensitivity of 80%.

Acute Disease↗

Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis.

Cholescintigraphy is a sensitive procedure for diagnosing or excluding acute cholecystitis. However, when rapid diagnosis is critical, the requirement for delayed images (4 hr or more after injection) to minimize the false-positive rate diminishes its utility. We prospectively evaluated 40 cholescintigraphic examinations that did not visualize the gallbladder 1 hr after injection of 99mTc diisopropyliminodiacetic acid. These examinations were then augmented by administration of IV morphine, followed by an additional 30 min of imaging. After the morphine, 18 of these examinations demonstrated visualization of the gallbladder; none subsequently required surgical exploration. Of the remaining 22, who demonstrated persistent nonvisualization of the gallbladder post-morphine, 11 were explored surgically and found to be abnormal. The 11 others were treated medically. Low-dose morphine administered when the gallbladder fails to visualize after 1 hr is a useful adjunct to conventional cholescintigraphy because it reduces the time required to obtain a diagnostic result and decreases the number of false-positive results.

Acute Disease↗

Plasmapheresis in thyroxine overdose: a case report.

Thyrotoxicosis from an overdose of medicinal thyroid is a condition which may be associated with a significant delay in onset of toxicity. We report a case treated with plasmapheresis, and conclude that the amount of thyroid hormone removed was insignificant compared to the total ingestion. We also note that the plasma half-life of thyroxine is apparently reduced in an acute massive ingestion.

Adult↗

Histamine and sympathetic blockade in septic shock.

The relative roles of endogenously released histamine and the sympathetic nervous system in septic shock were indirectly studied by blocking each one separately. Antihistamines in doses of 3-10 mg/kg prevented severe blood pressure drops and improved urinary output in groups treated before and after shock. Release of histamine seems to be important at least in the pathogenesis of early septic shock, although analysis of blood pressure pattern and survival implicates additional factors in late shock. Epidural block in combination with E. coli injection was detrimental, producing severe hypotension and even immediate death. Neural sympathetic tone is essential to survival in shock.

Anesthesia, Epidural↗

Characterization of highly purified, inactivated HIV-1 particles isolated by anion exchange chromatography.

This report characterizes inactivated, gp120 depleted, HIV-1 particles purified by an anion exchange chromatography production process. This antigen formulated with incomplete Freund's adjuvant constitutes Remune, which is being evaluated in a phase III clinical endpoint trial to determine the effect of this immune-based therapy on clinical progression of HIV-1 seropositive patients. Multiple production lots of the inactivated HIV-1 antigen strain HZ321, isolated by anion exchange chromatography, exhibit purity of > 95% by gel filtration. These findings are corroborated by thin section electron microscopy showing a homogenous field of intact particles. Analyses of the purified virus particles for protein, lipid, carbohydrate and RNA show structural retention of the envelope proteins, lipid bilayer and core components after large scale processing. The qualitative identification of at least 85% of total HIV-1 protein is determined by ELISA, Western blot, HPLC and amino acid sequencing analyses. Quantitative values are assigned to 50% of these proteins. The data confirm the presence of virally encoded proteins p6, p7, pI15, p17, p24, p32, pI39Gag, gp41, pp55Gag, p66/51, Vpr, Vif and Nef. Excellent consistency between production lots and equivalency to HIV-1 preparations purified by sucrose density gradient sedimentation has been established for protein and lipid composition, and overall purity. These findings further establish that non-viral encoded proteins and lipids are integral structural components of the intact virion and are not contaminants unique to a particular isolation method. The data confirm the presence of multicomponent antigens in the viral particles for stimulating a broad HIV-1 specific immune response. Finally, the work demonstrates that the two inactivation procedures (beta-propiolactone and gamma irradiation), which achieve efficient viral inactivation meeting US FDA guidelines, do not damage the protein antigens of the viral particles.

Carbohydrates↗

The development of a genetic profile of placental gene expression during the first trimester of pregnancy: a potential tool for identifying novel secreted markers.

OBJECTIVES: Many of the maternal serum markers used in prenatal screening have been developed or evolved based on serendipity. This study determines the feasibility of developing a genetic profile of placental gene expression during early pregnancy; such a gene repertoire may serve as a tool for identifying novel secreted markers. METHODS: RNA fingerprinting was used to produce a differential expression map in normal aborted placentae of weeks 9 and 13. RESULTS: Out of 212 gene expression differences, 115 were up-regulated at week 9 and the remaining 97 up-regulated at week 13. Ninety-four were found to be previously characterised genes and 118 were expressed sequence tags or novel genes. Seven of the known genes were found to be secreted proteins and included well-characterised pregnancy markers. mRNA levels of these secreted proteins were found to correlate with levels found in maternal serum. CONCLUSION: This approach enabled the identification of known secreted markers leaving open the possibility of finding new markers. With the human genome project nearing completion, it will be vital to use a systematic approach to understand the actual pattern of gene expression during pregnancy. This will also allow a more ordered and precise identification of novel prenatal diagnostic markers.

Amino Acid Sequence↗