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Biomedical subjects

H L Brown

Publications and source records attributed to H L Brown.

At least 55 records · Page 3Linked to original sources

A cross-sectional study of in utero growth of the above average sized fetus.

In a cross-sectional study of 210 pregnancies resulting in above-average-sized term infants, biparietal diameter, femur length, and abdominal circumference were found to differ among three birth weight percentile groups (greater than 90, 76 to 90, and 51 to 75). Growth rates, however, were similar. Estimated fetal weights, derived from four formulas, showed the same pattern. Differences between large for gestational age infants and other above average sized infants exist; changes in growth are likely to have occurred before the thirty-third week of gestation.

Birth Weight↗

Leprosy in a mangabey monkey--naturally acquired infection.

Naturally acquired leprosy was detected in an otherwise normal "sooty" mangabey monkey (Cercocebus atys). This animal was imported from West Africa in 1975 and developed clinical symptoms of leprosy in 1979. Histopathologic findings were those of subpolar-lepromatous to borderline-lepromatous leprosy in the Ridley-Jopling classification. The disease was progressive, with crippling neuropathic deformities of the hands and feet. The disease regressed under specific therapy. The etiologic agent was identified as Mycobacterium leprae by the following criteria: invasion of nerves of host, staining properties, electron microscopic findings, noncultivable on mycobacteriologic media, DOPA-oxidase positive, lepromin reactivity, infection patterns in mice and armadillos, sensitivity to sulfone, and DNA homology. We believe the animal acquired the disease from a patient with active leprosy. The mangabey monkey offers promise as a primate model for leprosy, and adds a third reported species to animals with naturally acquired leprosy.

Animals↗

Adverse drug reactions.

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Drug-Related Side Effects and Adverse Reactions↗

Evidence for polymorphonuclear-leucocyte-derived proteinases in arthritic cartilage.

1. An enzyme that degrades proteoglycan at neutral pH was extracted with 4 M-guanidine hydrochloride from the articular cartilage of rabbits with antigen-induced arthritis. 2. The enzyme had an apparent molecular weight on Ultrogel AcA 54 of about 8000 and was optimally active at pH 7.5 in Tris/HCl buffer containing 0.2 M-NaCl. The partially purified preparation was totally inhibited by 0.01 mM-N-acetyldialanylprolylvalylchloromethane, severely inhibited by 2 mM-phenylmethanesulphonyl fluoride and soya-bean trypsin inhibitor (200 microgram/ml) and slightly inhibited by 10 mM-EDTA. Marked inhibition was also obtained with a cytosolic fraction prepared from rabbit polymorphonuclear leucocytes. 3. All properties of the enzyme were virtually identical with those of an 'elastase-like' proteinase that was isolated from rabbit polymorphonuclear-leucocyte granules. 4. The results are consistent with the idea that cartilage proteoglycan degradation in acute joint inflammation is due at least partly to the diffusion into the cartilage of proteinases derived from synovial-fluid polymorphonuclear leucocytes.

Animals↗

Control of proteoglycan synthesis. Studies on the activation of synthesis observed during culture of articular cartilages.

When slices of adult rabbit articular cartilage were incubated in culture medium, the rate of incorporation of [35S]sulphate or [3H]acetate into glycosaminoglycans increased 4-8 fold during the first 5 days of incubation. Similar changes in biosynthetic activity were observed during culture of adult bovine cartilage. The activation of synthesis was not serum-dependent, but appeared to be a result of the depletion of tissue proteoglycan that occurs under these incubation conditions [Sandy, Brown & Lowther (1978) Biochim. Biophys. Acta 543, 536--544]. Thus, although complete activation was observed in serum-free medium, it was not observed if the cartilage was cultured inside dialysis tubing or in medium containing added proteoglycan subunit. The average molecular size of the proteoglycans synthesized by activated tissue was slightly larger than normal, as determined by chromatography on Sepharose CL-2B, and the average molecular size of the glycosaminoglycans synthesized by activated tissue was markedly increased over the normal. The increase in chain size was accompanied by an increase in the proportion of the chains degraded by chondroitinase ABC; these results are consistent with the preferential synthesis by activated chondrocytes of chondroitin sulphate-rich proteoglycans. The increase in glycosaminoglycan chain size was observed whether the chains were formed on endogenous core protein or on exogenous benzyl-beta-D-zyloside. An approximate 4-fold activation in culture of glycosaminoglycan synthesis on protein core was accompanied by a 1.54-fold increase in the rate of incorporation of [3H]serine into the chondroitin sulphate-linkage region of the proteoglycans. A 2.8-fold activation in culture of glycosaminoglycan synthesis on benzyl-beta-D-zyloside was accompanied by a 1.7-fold increase in the rate of incorporation of [3H]benzyl-beta-D-zyloside into glycosaminoglycans. The activation of glycosaminoglycan synthesis was, however, accompanied by no detectable change in the activity of xylosyltransferase (EC 2.4.2.26) in cell-free extracts. These results are discussed in relation to current ideas on the control of proteoglycan synthesis in cartilage.

Animals↗

Antigen-induced arthritis. Studies on the inhibition of proteoglycan synthesis observed in articular cartilage during short-term joint inflammation.

During the acute phase of antigen-induced arthritis, cartilage was obtained from five different sites within the joint, and chondrocyte activity was assessed by autoradiography of sections labeled with 35S-sulfate. There was a marked inhibition of chondrocyte proteoglycan synthesis in all weight-bearing areas; in addition, the complete superficial layer of cells and many mid-zone cells in these areas were completely inactive. Electron microscopy showed that the inactive surface cells had degenerated completely, and that many mid-zone cells contained an accumulation of intracytoplasmic filaments and were depleted in biosynthetic organelles. A biochemical study of the inhibition showed that: 1) the incorporation of 35S-sulfate and 3H-acetate into glycosaminoglycans was inhibited to a similar extent; 2) the inhibition of glycosaminoglycan synthesis could not be reversed either by the addition of benzyl-beta-D-xyloside to incubations or by maintenance of the cartilage in organ culture for 6 days; 3) the inhibited chondrocytes exhibited a decreased ability to secrete proteoglycans into the extracellular fraction of the cartilage.

Animals↗

Degradation of proteoglycan in articular cartilage.

Adult rabbit articular cartilage was labelled in vivo over 48 h with [35S]sulphate and was then incubated in organ culture at pH 7.2. Approx. 65% of the tissue content of [35S]proteoglycan was released into the culture medium during the first 48 h of incubation. The average molecular size of the released proteoglycans, as assessed by fractionation on Sepharose 2B/CL and 4B/Cl, was only slightly smaller than that of the proteoglycans extracted from non-cultured cartilage with 4 M guanidine HCl. The percentage of released proteoglycans and extracted proteoglycans which formed aggregates with hyaluronic acid was approx. 25% and 75%, respectively. The results indicate that proteoglycan degradation in adult articular cartilage is initiated by a limited proteolysis of subunit core protein, with the production of non-aggregating species which diffuse readily from the tissue.

Animals↗

Onchocercal dermatitis: ultrastructural studies of microfilariae and host tissues, before and after treatment with diethylcarbamazine (Hetrazan).

Specimens of skin from four Cameroon patients with severe onchocercal dermatitis, before and after treatment with diethylcarbamazine (DEC), were studied by light and electron microscopy. Microfilariae of Onchocerca volvulus have ultrastructural features resembling those of microfilariae of other genera. Between the surface layer of the cuticle and the trilaminate membrane, there is an electrolucent zone which is much wider in degenerating microfilariae than in intact microfilariae. Widening of the zone may result from DEC-induced release of component(s) of the cuticle, possibly collagen or mucopolysaccharide. Between the cuticle and dermal collagen there are granular deposits which might be immune complexes involving the collagenous component of cuticle. Others have shown that DEC does not kill microfilariae in vitro. Treatment with DEC presumably "unmasks" microfilariae in the skin so that they are recognized as foreign bodies and are destroyed by the host's defenses. Histiocytes and eosinophils are seen in close proximity to degenerating microfilariae. Enzymes from histiocytes and eosinophils might readily penetrate the cuticle altered by DEC treatment, and digest various components within the microfilariae. Alternatively, the widening of the electrolucent zone might result directly from the action of leucocytic or histiocytic enzymes, after the microfilaria has been killed by other mechanisms.

Adult↗

Hepatitis B antigen in saliva, urine, and stool.

A survey of hepatitis B patients, asymptomatic hepatitis B antigen (HBsAg) carriers, and control subjects was conducted to determine the relationship between antigenemia and antigen excretion in saliva, urine, and stool. Radioimmunoassay was used to detect HBsAg. Specificity-confirmed HBsAg was detected in the saliva of 6 (30%) of 20 antigenemic patients, 1 (5%) of 20 nonantigenemic patients, 14 (34%) of 41 carriers, and 0 of 112 controls. HBsAg was detected in urine only after 100-fold concentration of first-morning specimens. Specificity-confirmed HBsAg was present in the urine of 7 (16%) of 43 carriers; unconfirmed HBsAg was found in the urine of 5 (13%) of 38 patients and 5 (5%) of 112 controls. Unconfirmed HBsAg was detected in concentrated stool specimens from 5 (46%) of 11 patients and 3 of 8 carriers and controls. Longitudinally collected specimens from antigenemic subjects showed no consistent patterns of antigen excretion.

Carrier State↗

Cervical ripening: randomized comparison of intravaginal prostaglandin E2 gel with prostaglandin E2 gel plus laminaria tents.

The purpose of this study was to evaluate the efficacy of adding laminaria tents to sequential intravaginal prostaglandin E2 (PGE2) gel for cervical ripening. A prospective, randomized study was conducted from October 1994 to May 1995. Pregnant women with maternal or fetal indications for induction of labor at > or = 37 weeks gestation and a Bishop score of < or = 4 were eligible. Nineteen patients received laminaria tents in addition to 4 mg PGE2 gel, while 25 patients received PGE2 gel alone. After 4 hr, the laminaria tents were removed and the gel was continued in both groups at 4-hr intervals. Induction with oxytocin was initiated after a Bishop score of > or = 5 was achieved. The groups were comparable with respect to maternal age, parity, gestational age, reason for induction, and initial Bishop score. The addition of laminaria tents to sequential PGE2 gel did not statistically improve the time to a favorable cervix (control group 12.7 +/- 8.5 hr (95% CI, 9.1-16.3) and study group 10.9 +/- 7.1 hr (95% CI, 7.5-14.3) (P = 0.59). The 6-hr difference from the time of the initial PGE2 gel placement to delivery was not detected (control group 22.4 +/- 11.2 hr, 95% CI 17-27 and study group 23.4 +/- 13.1 hr, 95% CI 17-29.6 (P = 0.79). The combination approach of laminaria tents and PGE2 gel did not have a significant impact on the vaginal delivery rate, with 28.0% of patients in the control group and 26.3% of patients in the study group undergoing cesarean section (P = 0.90). Maternal and neonatal complications were rare in both groups. We had insufficient evidence to show that the addition of laminaria tents to PGE2 gel improved cervical ripening, the induction to delivery interval, or the cesarean section rate in patients at term undergoing induction of labor.

Administration, Intravaginal↗

Outcome of patients undergoing transabdominal cerclage: a descriptive study.

OBJECTIVE: Transabdominal cerclage is now evolving as an alternative to transvaginal cerclage in patients with cervical incompetence. The purpose of our study was to evaluate and describe our experience in patients selected to undergo transabdominal cerclage placement. METHODS: Outcome data for all patients who underwent transabdominal cerclage from January, 1990, through December, 1994, was collected. Indications for transabdominal cerclage included patients with prior failed vaginal cerclage, extremely shortened cervix, or anatomical defects judged unsuitable for transvaginal cerclage. RESULTS: Eleven patients underwent 12 transabdominal cerclage procedures. The mean gestational age at the time of cerclage placement was 12.5 weeks (range 10-14 weeks). The mean gestational age at delivery was 34 weeks. There were two neonatal deaths, which were related to extreme prematurity. The mean birthweight was 2,622 g. The fetal salvage rate was 83%. CONCLUSIONS: These findings suggest that in a highly select group of patients, the transabdominal cerclage can be a safe and effective procedure.

Abdomen↗

Antigen-induced arthritis. Decreased proteoglycan content and inhibition of proteoglycan synthesis in articular cartilage.

An arthritis was induced in rabbits immunized with human serum albumin by injection of antigen into the hind knee joint. Histological changes in the synovial membrane and an increase in polymorphonuclear granulocytes in the synovial fluid indicated an inflammatory response similar to that described with fibrin as antigen (1). The arthritis was accompanied by no significant change in the collagen content, but a marked decrease in the proteoglycan content of the cartilage was noted. Cartilage from inflamed joints generally exhibited a decreased ability to synthesize proteoglycan in vitro.

Animals↗

Effect of cocaine on intracellular calcium regulation in myometrium from pregnant women.

OBJECTIVE: To evaluate the effect of cocaine on intracellular free calcium ([Ca2+]i) regulation in human myometrial cells by determining the sources of Ca2+ it might mobilize, as well as assess the role cocaine might play in the catecholamine's effect on the cell's [Ca2+]i. METHODS: Primary culture of myometrial cells from pregnant women was used as an experimental model. [Ca2+]i relative changes in response to cocaine and norepinephrine were measured with fura-2 fluorometry and analyzed by means of one-way analysis of variance. RESULTS: Cocaine alone (10(-8) to 10(-3) mol/L) increased [Ca2+]i by up to 43 +/- 18% over basal level in a dose-dependent manner. Norepinephrine also elevated [Ca2+]i in a concentration-dependent manner (202 +/- 24% over basal level at 10(-4) mol/L). The norepinephrine-evoked increase was inhibited in Ca(2+)-free media by 48%, whereas the cocaine response was not affected. The Ca(2+)-channel antagonist nifedipine caused decrease in the [Ca2+]i response to 10(-5) mol/L of norepinephrine by 84%, whereas the [Ca2+]i rise to 10(-5) mol/L cocaine was not significantly changed. Inhibitor of the sarcoplasmic reticulum Ca2+ pump, thapsigargin, completely blocked cocaine-evoked increases in [Ca2+]i, whereas norepinephrine responses were greatly reduced. At the same time, cocaine (10(-8) to 10(-3) mol/L) did not potentiate norepinephrine-evoked Ca2+]i increases in the cells. CONCLUSION: These results indicate that cocaine increases [Ca2+]i in pregnant human myometrial cells, primarily by stimulating release of Ca2+ from intracellular stores rather than by direct stimulation of Ca2+ influx.

Adrenergic alpha-Agonists↗