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Biomedical subjects

R Green

Publications and source records attributed to R Green.

At least 379 records · Page 21Linked to original sources
PubMed1984

Somatostatin discriminates between the intracellular pathways of secretory and membrane proteins.

Somatostatin is a14-amino acid peptide hormone that inhibits the secretion of a variety of other polypeptide hormones, including growth hormone. Here we describe an experimental system used to determine whether somatostatin can discriminate in its inhibition between secretory and plasma membrane proteins. Growth hormone-secreting cells (GH3) were infected with vesicular stomatitis virus and pulse-chased with [35S]methionine to follow the simultaneous intracellular transit of growth hormone and the viral membrane glycoprotein, G protein. Secretion of growth hormone was monitored by immunoprecipitation of chase media, while appearance of G protein on the plasma membrane was detected by cell surface labeling and virus purification. In the presence of somatostatin (10 micrograms/ml), the secretion of growth hormone was inhibited by 80%. In contrast, G protein appeared on the plasma membrane with slightly enhanced kinetics. When cells were treated with the ionophore monensin (0.2 microM), there was a dramatic inhibition of both the secretion of growth hormone and the incorporation of G protein into plasma membranes. Our results on the differential effect of somatostatin provide evidence for sorting of secretory and membrane proteins into distinct compartments in the secretory pathway. The data further suggest that this sorting event occurs late in the Golgi complex or after proteins exit from that organelle.

Animals↗
PubMed1984

Luminal hypotonicity: a driving force for fluid absorption from the proximal tubule.

The ability of rat proximal tubules to generate a hypotonic luminal fluid was investigated. Simultaneous perfusion of tubules and peritubular capillaries was performed with simple solutions. When tubules were perfused at 10 nl X min-1 and NaCl was the perfusate for tubules and capillaries, solute and fluid (0.41 nl X min-1 X mm-1) were transported and the luminal fluid became hypotonic (delta osmol = -1.7 mosmol X kg-1). When the same solutions were used but the tubule was perfused at 45 nl X min-1, more fluid (0.89 nl X min-1 X mm-1) was reabsorbed and the fluid became more hypotonic (delta osmol = -3.9 mosmol X kg-1). Bicarbonate in the peritubular capillaries increased the fluid reabsorption (1.21 nl X min-1 X mm-1) but did not generate cryoscopically hypotonic fluid. Cyanide abolished all net movement of fluid and solute. It is concluded that the tubule can generate a hypotonic fluid, that the hydraulic conductivity for proximal tubular epithelium is 3,200-3,400 microns X s-1, and that the reflection coefficient for NaHCO3 is slightly higher than for NaCl.

Absorption↗
PubMed1984

Sodium butyrate stimulates somatostatin production by cultured cells.

Expression of the neuropeptide SRIF can be enhanced by sodium butyrate, a known modulator of gene transcription. Two different cell lines, RIN cells (derived from a rat pancreatic islet tumor) as well as HeLa cells, showed basal secretion of SRIF immunoreactive material that was induced between 5- and 15-fold by sodium butyrate. The induction was dose and time dependent, fully reversible, and specific for sodium butyrate. Analysis of the induced mRNAs by Northern blot hybridization using a SRIF specific cDNA probe revealed a 12-fold increase in the level of SRIF mRNA caused by butyrate treatment. These results suggest that sodium butyrate may be a useful tool for studying the regulation of SRIF gene expression.

Adenoma, Islet Cell↗
PubMed1983

Transitory hematologic effects of moderate exercise are not influenced by iron supplementation.

A young women's exercise/fitness class tested the idea that administration of supplemental iron would prevent "sports anemia" that may develop during exercise and training and improve iron status of exercising females of menstrual age. Fifteen women (aged 18-37) were selected for each of three treatment groups: (1) no supplemental iron; (2) 9 mg X d-1 of Fe; and (3) 18 mg X d-1 of Fe (1 US Recommended Daily Allowance). Women exercised at approximately 85% of maximal heartrate for progressively increasing lengths of time in a jogging program and worked up to 45 min of exercise 4 d X week-1 for 8 weeks. Hematologic analysis was performed in weeks 1, 5, and 8. A significant decline in hemoglobin (Hb) concentration and hematocrit (Hct) was observed at week 5 when all data were examined without regard for iron intake; these red cell indices returned to pre-exercise levels by week 8. Reduction of mean cell hemoglobin concentration (MCHC) indicated that the midpoint decline was not caused by simple hemodilution during exercise. Serum ferritin (SF) concentration changed in parallel with Hb and Hct. Although the midpoint decline in SF was not statistically significant, it ruled out the possibility that turnover of red cell iron was directed to storage. Lowered MCHC and SF suggested lower availability of iron during the synthesis of a new generation of red cells. Few iron treatment effects of magnitude were observed. Iron did not prevent the midpoint decline in Hb concentration. Iron intake did not affect SF, serum iron, transferrin saturation, or final Hb, and Hct.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Purification of biologically active simian virus 40 small tumor antigen.

The simian virus 40 small tumor antigen (t antigen) gene has been cloned downstream from a hybrid Escherichia coli trp-lac promoter and a suitable ribosome binding site. A bacterial clone (865i) transformed by such a plasmid (pTR865) expresses this gene and, under optimal conditions, can produce greater than or equal to 5% of its total protein as t antigen. Soluble extracts of such a clone were relatively depleted in t antigen, which was found in the initial pellet fraction. The protein was recovered from this fraction in a significantly purified form by extraction with urea-containing buffer. After gel filtration of such t antigen-enriched solutions, highly purified protein was obtained. When either this fraction (freed of urea) or NaDodSO4 gel-purified 865i t antigen (rendered free of detergent) was injected into untransformed rat cells, dissolution of intracellular actin cable networks was observed.

Animals↗
PubMed1983

Cancer chemotherapy via ambulatory infusion pump.

One hundred twenty-four patients with metastatic malignancy were treated with four different single agent infusion programs by constant intravenous infusion for 30 or more days. Drug was administered via a tunneled subclavian line by a battery-driven peristaltic pump (Cormed model ML6) on an ambulatory basis. This schedule allowed for increased cumulative drug dose for 5-Fu, decreased tolerated dose for vinblastine, and comparable doses for adriamycin and mitomycin-C relative to that delivered with the standard intermittent bolus schedule. Therapeutic effects were observed for three of four drugs studied: 5-Fu 13/31 colorectal cancer; adriamycin 7/29; and vinblastine 4/12, including 2/4 melanoma. Adverse effects were significantly reduced, particularly with regard to gastrointestinal toxicity, but also in adriamycin-associated cardiac effects and hair loss. Phase III comparative trials of intermittent bolus therapy with protracted infusion therapy are in progress for 5-Fu in advanced colorectal cancer and for adriamycin in specific tumors. Ambulatory pump infusion (API) chemotherapy is technically feasible and has improved patient tolerance to chemotherapy while demonstrating similar, if not comparable, antitumor effects.

Ambulatory Care↗
PubMed1983

Renal function during lactation in the rat.

1. Glomerular filtration rate (g.f.r.), renal plasma flow (r.p.f.), salt and water reabsorption and plasma concentrations of progresterone and prolactin were measured in virgins, 19 day pregnant and lactating rats. 2. G.f.r. was raised by about 40% in animals at 6-7 days of lactation when compared with virgins but towards the end of lactation returned to virgin levels. Salt and water reabsorption followed a similar pattern. 3. At the time of maximum change of g.f.r. during lactation r.p.f. was raised by about 30% and so filtration fraction rose by about 10% when compared with virgins. 4. Plasma prolactin and progesterone concentrations rose early in lactation but remained elevated when the renal changes had returned to normal. 5. Factors other than changes in prolactin and progesterone concentrations must be implicated in the changes in renal function that occur during lactation.

Animals↗
PubMed1983

Glucose handling by distal portions of the nephron during pregnancy in the rat.

Reabsorption of glucose, salt and water was measured in 7-8 day pregnant and virgin rats by micropuncturing distal nephrons during saline and glucose infusions. Unidirectional fluxes of glucose were measured in loops of Henle and collecting ducts. There were no significant differences in single nephron glomerular filtration rate (S.N.G.F.R.) between virgin and pregnant animals during saline infusion. During glucose infusion S.N.G.F.R. was higher in pregnant animals than in virgins. There is no evidence of a failure of reabsorption of glucose by the proximal tubule in pregnant animals. More glucose is reabsorbed from the loop of Henle in virgin animals than in pregnant animals during saline infusion but during glucose infusion the converse is true. During both saline and glucose infusion there is less reabsorption of glucose from the collecting duct in pregnant animals than in virgin animals. It is concluded that the increased excretion of glucose during pregnancy can be attributed to alteration of glucose handling by distal segments of the nephron.

Absorption↗
PubMed1983

Acute and chronic effects of progesterone and prolactin on renal function in the rat.

The renal effects of acute and chronic progesterone and prolactin administration were investigated in rats. Acute progesterone treatment caused a reduced urinary potassium excretion compared to controls (0.80 +/- 0.03 vs. 1.30 +/- 0.04 mumole min-1; P less than 0.01). No other renal changes were apparent. Acute prolactin administration produced no significant changes in renal function. Chronic progesterone treatment reduced urinary potassium output by increasing tubular reabsorption. Absolute reabsorption (mumole min-1) for controls was 4.70 +/- 0.42 and for progesterone treatment, 6.40 +/- 0.57 (P less than 0.05 comparing the two). No other renal changes were apparent. Animals made pseudopregnant by chronic prolactin administration showed a significant (16%) elevation in glomerular filtration rate, similarly enhanced fluid and solute reabsorption, and a significant (16%) increase in proximal tubule length. This would imply a role for prolactin in early rat pregnancy and pseudopregnancy when similar renal changes are evident and circulating hormone levels high.

Absorption↗
PubMed1983

Constant infusion schedule for adriamycin: a phase I-II clinical trial of a 30-day schedule by ambulatory pump delivery system.

Eighteen patients received a continuous intravenous infusion of adriamycin for 14-60 days in a phase I study in which the dose rates were escalated from 2 mg/sq m/day to 5 mg/sq m/day to establish the optimal dose to be delivered over a 30-day period. The drug was delivered via a tunneled subclavian catheter by a portable infusion pump (Cormed model ML-6) primed to provide a volume of diluted drug of 10 cc/day. Leukopenia and stomatitis were observed at 4 mg/sq m/day doses or greater in 50% of courses. At doses less than 4 mg/sq m/day, only 3/17 courses (18%) were associated with stomatitis. Partial alopecia developed in all patients, but less than 50% of scalp hair was affected. The cumulative dose of continuous infusion adriamycin at 30 days is comparable to the dose delivered by standard bolus intermittent schedules (60-90 mg/sq m g 21 days), but the adverse drug effects are eliminated or substantially reduced. Cardiac toxicity was assessed in selected patients treated to 450 mg/sq m or greater by cardiac biopsy and/or gated pool studies. No histopathologic lesions were noted in 3 patients receiving 450 mg/sq m or greater. The recommended daily dose rate of adriamycin in this protracted infusion regimen is 3 mg/sq m/day. The phase II study of this schedule and dose rate in 38 additional patients (a total of 52 evaluable patients) demonstrated objective responses in 1/9 soft tissue sarcoma, 1/3 mesothelioma, 1/3 hepatoma, and 2/13 breast cancer. Phase III studies of the protracted continuous infusion schedule for adriamycin are indicated in that clinical activity is demonstrated at a substantial reduction in toxicity. Pharmacologic studies expanding the existing data base are also necessary.

Adult↗