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Biomedical subjects

J B Smith

Publications and source records attributed to J B Smith.

At least 271 records · Page 15Linked to original sources

Evidence for environmental familiality of kallikrein excretion in Utah kindreds.

In investigating the role of urinary kallikrein in the pathophysiology of hypertension, we measured 12-hour kallikrein excretion in 1,100 persons in 68 Utah kindreds. The kallikrein excretion was statistically adjusted to account for variations in body size and urine output. Adjusted kallikrein excretion was greater in youths than in adults and correlated with potassium excretion and sodium excretion in persons with normal blood pressure. It was decreased in normotensive subjects with strong family histories of stroke and hypertension, but was not significantly different in adults with hypertension. Adjusted kallikrein excretion was correlated between pairs of siblings, parent-offspring pairs and spouses. Our results indicate that kallikrein excretion is a familial variable, with the familiality due more to shared environmental than genetic factors.

Adolescent↗

In vitro prostacyclin production in the hemolytic-uremic syndrome.

Reports from Europe suggest that the hemolytic-uremic syndrome is associated with an impaired ability to produce prostacyclin (prostaglandin [PG] I(2)), a potent inhibitor of platelet aggregation and thrombus formation. In comparing the production of PGI(2) by cultured endothelial cells using serum obtained from 22 children with the hemolytic-uremic syndrome with values obtained using serum from 22 normal children, we found that cultured endothelial cells produced less PGF(1alpha) (the stable metabolite of PGI(2)) when incubated with affected serum. The relationship of this observation to the pathogenesis of the hemolytic-uremic syndrome is unclear.

6-Ketoprostaglandin F1 alpha↗

Temperature and nucleotide dependence of calcium release by myo-inositol 1,4,5-trisphosphate in cultured vascular smooth muscle cells.

Inositol 1,4,5-trisphosphate (IP3) rapidly increased 45Ca2+ efflux from a nonmitochondrial organelle in cultured vascular smooth muscle cells that were permeabilized with saponin. A nucleotide, preferably ATP, was essential for IP3-evoked 45Ca2+ release. Two nonhydrolyzable ATP analogues satisfied the nucleotide requirement for IP3-evoked 45Ca2+ release. IP3 strongly stimulated 45Ca2+ efflux at low temperatures (1 to 15 degrees C). Decreasing the temperature from 37 to 4 degrees C inhibited the rate of IP3-stimulated efflux by only about 33%. The failure of such low temperatures to strongly inhibit IP3-induced 45Ca2+ efflux suggests that IP3 activated a Ca2+ channel, rather than a carrier, by a ligand-binding, rather than a metabolic, reaction.

Adenine Nucleotides↗

Bryostatins: potent, new mitogens that mimic phorbol ester tumor promoters.

Bryostatins (2 ng/ml), when combined with insulin in serum-free culture medium, are strongly mitogenic for Swiss 3T3 cells that have been arrested in the G1/G0 phase of the cell cycle. The mitogenic effect of the bryostatins is similar to that of 12-O-decanoylphorbol-13-acetate (TPA). A prior treatment of the cultures with TPA eliminated the mitogenic response to bryostatin and to a second addition of TPA. Conversely, a prior treatment of the cultures with bryostatin eliminated the mitogenic response to TPA. Bryostatin potently inhibited the binding of [3H]phorbol dibutyrate to a high affinity receptor in the cells. The findings suggest that the bryostatins and TPA act via the same receptor, possibly protein kinase C.

Animals↗

Turnover of arachidonic acid in the major diacyl and ether phospholipids of human platelets.

In this work, the uptake and release of [3H]arachidonic acid by the diacyl and ether species of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in human platelets were studied. Uptake of [3H]arachidonic acid into 1,2-diacyl-PC and 1,2-diacyl-PE was much greater than into the ether phospholipids of the same class. In [3H]arachidonoyl-labeled platelets stimulated by thrombin, there was a decrease in total [3H] arachidonoyl-PC. This was accounted for mostly by a decrease in 1-acyl-2-[3H]arachidonoyl-PC while the level of 1-O-alkyl-2-[3H]arachidonoyl-PC (a precursor for platelet-activating factor) increased slightly. However, in ionophore A23187-stimulated platelets, the reduction of total [3H]arachidonoyl-PC was due to a decrease in both 1-acyl-2-[3H]arachidonoyl-PC and 1-O-alkyl-2-[3H] arachidonoyl-PC, suggesting that ionophore should yield more platelet-activating factor than thrombin. In both thrombin- and ionophore-stimulated platelets, there was a net increase in total [3H]arachidonoyl-PE. This consisted of a decrease in 1,2-diacyl-PE, which was essentially complete by 1 min, followed by an increase in 1-O-alk-1'-enyl-2-[3H]arachidonoyl-PE, which was slower and not apparent until 3-5 min after thrombin. During reincubation of labeled platelets with saline, the 1-O-alkyl-2-[3H]arachidonoyl-PC increased by a factor of 2, between 0 and 4 h, with no significant change in the radioactivity of any other phospholipid. Thus, upon stimulation of human platelets, arachidonic is released from both 1,2-diacyl-PC and 1,2-diacyl-PE for metabolism by platelet cyclooxygenase and lipoxygenase, while certain ether pools of PC and PE also collect arachidonic acid.

Arachidonic Acid↗

Urinary kallikrein: assay validation and physiological variability.

Decreased urinary kallikrein (UK) output has been suggested as a preclinical indicator of essential hypertension. In preparation for UK studies in hypertension prone Utah kindreds, we assessed selected UK assay parameters and physiological variability. Precision for the colorimetric kallikrein assay was quite acceptable, coefficient of variation (CV) less than 5% within run and 14% day-to-day at a concentration of 9.5 TU/l. The mean recovery was 105% and assay results were correlated with results from the 3H-TAME esterase method, r = 0.990. Urine specimens were stable at room temperature for up to 4 days, frozen at -20 degrees C for 6 weeks, or frozen at -80 degrees C after Sephadex treatment for a year. UK output varied significantly throughout the day with excretion highest in the morning. Urine collections at 10.00, 12.00 and 14.00 had significantly (p less than 0.05) more UK than the overnight collection. Intra- and inter-individual variations were of the same magnitude, mean 20%. In children UK output increased with age until the adult levels were reached at age 15. Male and female values were similar. Smoking; consumption of alcohol, coffee, tea, cola of chocolate; and female hormone medications did not significantly influence the 12-hour UK output in the 1110 caucasian subjects.

Adolescent↗

The effects of cyclophosphamide, ketoconazole, aclacinomycin-A, methotrexate, and scheduled methotrexate-5-fluorouracil combination chemotherapy on the transplantable R-3327 prostatic adenocarcinoma in the F1 hybrid male rat.

Male F1 hybrid rats bearing the R-3327 transplantable prostatic adenocarcinoma demonstrating similar growth patterns within the original sample of animals were carefully separated into control and treatment groups. This assured treatment of tumors with similar cell kinetics within each group. In the first study, two separate drug protocols were investigated by intraperitoneal injection, namely cyclophosphamide (100 mg/kg) once every 4 weeks for 8 weeks and scheduled methotrexate (7.5 mg/kg) followed in 90 minutes by 5-fluorouracil (50 mg/kg) once each week for 8 weeks. Excellent suppression of tumor growth was obtained with each treatment protocol. Both were significant at the 0.01 level. In the second study, methotrexate (100 mg/kg) intraperitoneally once each week for 6 weeks, aclacinomycin-A intraperitoneally once each week for 4 weeks, and ketoconazole (60 mg/kg) via gavage 5 times a week for 6 weeks were administered to the animals in each respective group. Aclacinomycin-A and ketoconazole showed significant suppression of tumor growth at the 0.01 and 0.05 levels, respectively. Methotrexate suppressed tumor growth, but did not reach levels of significance over the duration of the study (0.2 less than P less than 0.3).

Aclarubicin↗

Measurement of arachidonic acid liberation in thrombin-stimulated human platelets. Use of agents that inhibit both the cyclooxygenase and lipoxygenase enzymes.

The formation of radiolabelled oxygenated products of arachidonic acid in thrombin-stimulated, [3H]arachidonic acid-prelabelled human platelets is inhibited in a concentration-dependent manner by BW 755C (3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline) or propyl gallate, both of which are combined inhibitors of lipoxygenase and cyclooxygenase. These compounds do not inhibit the thrombin-induced decrease in the radioactivity of platelet phospholipids but, instead, allow the accumulation of free radiolabelled arachidonic acid. Thrombin causes an increase in the levels of free, endogenous palmitic, stearic, oleic, linoleic and arachidonic acids of up to 10 nmol/10(9) platelets. In the presence of BW 755C or propyl gallate, further increases in the level of free arachidonic acid, of 20-50 nmol/10(9) platelets, occur. The enzyme inhibitors do not affect the accumulation of the other free fatty acids. The increase in arachidonic acid is optimal at 1 U/ml thrombin and 60% complete by 1 min at 37 degrees C. In the platelets from eight donors, the average increases in free fatty acids (in nmol/10(9) platelets) induced by 5 U/ml thrombin in 5 min at 37 degrees C in the presence of 100 microM BW 755C were 1 for linoleic acid, 3.6 for oleic acid, 4.5 for palmitic acid, 7.6 for stearic acid and 32.0 for arachidonic acid.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Progressive-addition lenses in the treatment of accommodative esotropia.

Thirty-two children ranging in age from 18 months to 16 years were treated for accommodative esotropia with variable-focus lenses instead of executive bifocals. The major advantages were the improved appearance of the glasses and the more natural progression of accommodative treatment from distance to near which provided more relaxation of convergence in the intermediate zone. The chief disadvantage was the difficulty fitting small children with lenses that were originally designed for the use of presbyopic adults. The maximum power for the effective control of the deviation for reading is at the bottom of the lens. Keeping this portion of the lens high enough proved to be difficult in small children. None of the patients were willing to return to executive bifocals after having worn progressive-addition lenses.

Adolescent↗

Sulfate transport in human lung fibroblasts (IMR-90).

Sulfate transport in a fibroblast cell line derived from human lung (IMR-90) occurred mainly via high- and low-affinity, SITS-sensitive pathways and to a lesser extent by an SITS-insensitive mechanism. In low-ionic-strength media (sucrose substituted for salts) the apparent Km of the carrier-mediated sulfate influx was 1 mM. At 0.3 mM, the sulfate concentration normally found in human serum, the contribution of the SITS-insensitive pathway was negligible. In physiological salts solution, an SITS-sensitive, high-affinity (Km 34 +/- 14 microM) sulfate influx system was observed at extracellular sulfate concentrations less than 100 microM. Between 100 and 500 microM sulfate, the range normally found in human serum, sulfate influx occurred via an SITS-sensitive, low-affinity pathway and to a small extent by an SITS-insensitive mechanism. Extracellular chloride inhibited the influx and stimulated the efflux of sulfate. Bicarbonate and thiosulfate inhibited sulfate influx but had no effect on sulfate efflux. Phosphate, arsenate, or Na+ did not affect sulfate uptake. These results indicate that in human lung fibroblast IMR-90 cells sulfate is transported mainly via an SO4(2-)/Cl- exchange system independent of the phosphate or Na+ transport. Since sulfate concentration as high as 50 mM only slightly increased sulfate efflux, SO4(2-)/SO4(2-) exchange is probably a minor component of sulfate uptake.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Effects of single and repeated daily injections of morphine, clonidine, and l-nantradol on avoidance responding of rats.

Interruption of a photobeam by rats was maintained under a continuous shock avoidance schedule, and moderate response rates were maintained at low shock frequencies. Responding decreased, and shock frequency increased, in a dose-dependent manner after acute injections of the narcotic morphine, the antihypertensive l-nantradol clonidine, and the cannabinoid l-nantradol. Clonidine and l-nantradol were about 100 times more potent than morphine for decreasing overall responding, and l-nantradol was about 3 times more potent than clonidine for decreasing escape responding. When drugs were given repeatedly prior to daily experimental sessions, tolerance developed to response rate decreases of morphine and l-nantradol within seven to ten sessions, but tolerance did not develop to rate decreases of clonidine for up to 30 sessions. Continued decreased responding by clonidine was antagonized by yohimbine, but not by prazosin or naltrexone. These results extend observations for the acute effects of l-nantradol and clonidine to operant responding under a schedule of continuous shock avoidance. Different potencies for drugs in the present and previous experiments suggest important effects of response topography on dose effects.

Animals↗

Suppression of a polyclonal B-cell response by supernatants from the murine autologous mixed lymphocyte reaction.

Previously, we have demonstrated that supernatants from autologous mixed lymphocyte (AMLR) cultures contain helper factors which can mediate the development of a cytotoxic T-cell response to hapten modified self. In the current study, the effect of AMLR supernatants on the humoral response was explored. BALB/C splenic non-T cells produced a large polyclonal antibody response to lipopolysaccharide (LPS), as measured in a Protein A SRBC plaque assay. Surprisingly, syngeneic AMLR supernatants suppressed the LPS-induced generation of plaque-forming cells. The presence of T cells in the stimulated cultures did not affect suppressor activity. The decreased response was not the result of a shift in kinetics, as maximal activity was observed on Day 4, whether or not AMLR supernatants were added. The AMLR culture supernatants were most effective in suppressing the plaque-forming cell response when added at the initiation of culture. AMLR supernatants added after 24 hr of culture resulted in only about 50% of maximum suppression. Supernatants added at 48 or 72 hr had no effect. Interferon-gamma (IFN-gamma) has been detected in AMLR culture supernatant and has been reported to suppress the development of plaque-forming cells in response to LPS. However, it is unlikely the suppressive activity observed in these studies is due to IFN-gamma. Dialysis of the AMLR culture supernatant against a pH 2 buffer for 24 hr or incubation at 70, 80, or 90 degrees C for 10 min, treatments that inactivate IFN-gamma, enhanced suppression. These results suggest that in addition to cytotoxic-T-cell helper factors, the cellular interactions in the AMLR induces the production of a stable mediator(s) which is able to directly suppress B cells at an early stage of their development into plasma cells.

Animals↗

Helper factors for hapten-self cytotoxic T cells occur in NZB culture supernatants despite deficient AMLR.

The ability of helper T cells from NZB mice to produce non-interleukin 2 (IL-2) lymphokines in the autologous mixed lymphocyte reaction (AMLR) was examined. Factors present in normal AMLR culture have been previously reported to mediate the development of a cytotoxic T-cell response to trinitrophenyl (TNP)-modified syngeneic thymocytes. Young NZB mice, like the normal strains, were able to produce the helper factors in the AMLR and to utilize these mediators in the cytotoxic induction system. Old autoimmune NZB mice demonstrated a poor proliferative response in the AMLR and were unable to activate hapten-specific cytotoxic cells in the presence of AMLR culture supernatant from either young or old mice. This was not due to a lack of cytotoxic precursors, nor was it a normal consequence of aging, but may be related to decreased IL-2 production by helper T cells. Interestingly, supernatant from AMLR proliferation deficient old NZB mice contained normal amounts of the AMLR helper factor. These data suggest that AMLR helper factor production is not directly related to the proliferative response and that two different helper-T-cell subpopulations may be responsible for these activities. The production of these mediators in mice which cannot utilize them raise questions about their role in autoimmunity.

Aging↗

Modulation of leukotriene synthesis and actions by synthetic derivatives of arachidonic acid.

Seven analogs of arachidonic acid were tested for their coronary vasoactivity and their ability to inhibit LTC4 and LTD4 synthesis by lung tissue and to antagonize LTD4 induced coronary constriction. None of the seven arachidonic acid analogs significantly altered peptide leukotriene production by minced cat lung. Two of the analogs (i.e., 7, 13-diethanoarachidonic acid and 7, 10, 13-triethanoarachidonic acid) exerted modest but significant coronary vasodilation in isolated cat coronary arteries, and significantly antagonized the coronary vasoconstrictor response to LTD4. These analogs may be of interest in modulating leukotriene actions.

Animals↗

Sterilization in the northeast of Brazil.

Results of household surveys carried out in four states in the Northeast of Brazil showed that female sterilization is the most prevalent method among women who want no more children. Many women who indicated an interest in tubal ligation, however, had not been sterilized. Access to sterilization depends on the type of hospital in which the child was delivered and the type of delivery the woman had. Over 60% of the sterilized women reported that they had a tubal ligation at the time they were hospitalized for a cesarean delivery. Compared with unsterilized women, the sterilized women are characterized by relatively higher education levels and a greater likelihood of urban residence and were far more likely to have had cesarean deliveries and, therefore, to have qualified for postpartum sterilization on medical grounds.

Adolescent↗

"Retrospectoscopic" arthroscopy.

Examination of the posterior compartments through posterior portals was recommended in 1974, and since then surgical techniques with arthroscopes and instruments in posterior portals have been described. Use of the 120 degrees arthroscope for the last 9 years has proven the merit of those recommendations. We consider arthroscopy to be incomplete without examination of the posterior compartments. The examination is possible with standard scopes in posterior portals, but it is easier, quicker, safer, and more complete using the technique described with the 120 degrees scope in an anterior portal. The 120 degrees arthroscope is helpful in diagnostic and operative arthroscopy. It permits comprehensive arthroscopy without additional punctures, and allows the use of surgical instruments without the arthroscope itself getting in the way. Although it is difficult to learn the technique, we believe the benefit is worth the effort, and recommend its routine use.

Arthroscopy↗