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Biomedical subjects

J Robinson

Publications and source records attributed to J Robinson.

At least 361 records · Page 20Linked to original sources
PubMed1990

Probabilistic secretion of quanta from nerve terminals at synaptic sites on muscle cells: non-uniformity, autoinhibition and the binomial hypothesis.

A model of the secretion of a quantum at a release site is proposed in which, following the influx of calcium ions, synaptic vesicles are made available for release by the activation of kappa phosphorylation steps with rate alpha. At any time during this process the vesicles may become unavailable for secretion at rate gamma. On completion of the kappa phosphorylation steps the vesicles participate in the formation of a fusion pore with the terminal membrane to give exocytosis at rate delta. Changes in alpha, delta and kappa are shown to produce characteristic changes in the number and timecourse of quantal secretions following a nerve impulse, which are similar to those observed following drug treatments that are thought to act selectively on each of these processes. The number of quanta secreted from nerve terminals that consist of many release sites does not fluctuate much during a low frequency train of impulses: the variance is small compared with the mean level, so secretion follows binomial rather than Poisson statistics. A theory is derived that shows that variations in the probability of secretion amongst these release sites of any particular kind fails to reduce the variance of the total secretion from the terminal; Poisson rather than binomial statistics then still apply. The theory shows that an interaction between release sites is required to reduce this variance and such an effect is provided if secretion at a site inhibits secretion at nearby sites. Simulations show that incorporating this process of autoinhibition into the model reproduces the experimental observations on the effects of calcium ions on the binomial parameters p and n as well as on the relative constancy of p during facilitation and depression of quantal secretion. Methods for estimating the timecourse of changes in the probability of secretion at release sites following an impulse, by using either the time of occurrence of first, second, third or later quantal latencies, are given. These procedures show that current methods for estimating the time-dependent probability changes are inadequate for detecting interaction between release sites, such as autoinhibition, unless this is relatively large. Therefore, estimates from third quantal latencies are used.

Animals↗
PubMed1990

Protection of spermatogenesis in rats from the cytotoxic procarbazine by the depot formulation of Zoladex, a gonadotropin-releasing hormone agonist.

The hypothesis that adjuvant treatment designed to produce testicular atrophy would preserve fertility in males receiving cancer chemotherapy was examined in the rat. Testicular atrophy was induced by a depot formulation of Zoladex [D-Ser(Bu(t))6-Aza-Gly10-GnRH], a gonadotropin-releasing hormone (GnRH) analogue. The experiments were conducted in albino Wistar as well as in the piebald variegated rat. Rats received the depot Zoladex formulation 2 weeks before and immediately prior to being treated with four weekly doses of procarbazine (200 mg/kg). Testicular function was evaluated 50 and 90 days after the last procarbazine dose. Procarbazine induced testicular atrophy concomitant with marked germinal cell aplasia in both strains of rat. In the Wistar rat adjuvant treatment with Zoladex caused slight but not significant alleviation of the testicular toxicity of procarbazine. The testicular toxicity of procarbazine was more extensive in the piebald variegated rat, and 50 days after the last procarbazine treatment the testes were small, sperm were absent, and the stem cell index was close to zero. Serum luteinizing hormone (LH) concentrations were raised and testicular LH receptor binding was low in the presence of normal serum and testicular testosterone concentrations, indicating compensated Leydig cell failure. Testicular weight and sperm content, as well as LH receptor binding, were still decreased in rats which received both Zoladex and procarbazine, suggesting that the analogue offered no protection. However, the stem cell index of the seminiferous tubules in the procarbazine-Zoladex-treated rats was not significantly different from vehicle-treated rats, which suggested that recovery from the effects of procarbazine was in progress. Ninety days after the end of procarbazine treatment alone the testes of rats were still atrophied and there was little evidence of active spermatogenesis. Leydig cell failure appeared to have progressed as, in addition to the low testicular LH receptor content and raised serum LH concentration, the prostate and seminal vehicle weights were decreased. The combination of Zoladex treatment with procarbazine was successful in preserving testicular function in the piebald variegated rats as virtually all the functional and morphological parameters of both the seminiferous tubule and the Leydig cell were not significantly different from those of vehicle-treated rats. This study demonstrates for the first time that effective gonadal protection from the toxic effects of procarbazine chemotherapy can be achieved by administration of the depot formulation of the gonadotropin-releasing hormone analogue Zoladex. The results show clearly that complete suppression of spermatogenesis is not a prerequisite for the successful outcome of treatments designed to protect the gonad from cytotoxic chemotherapy.

Animals↗
PubMed1990

Ectopic pregnancy after luteal phase initiation of gonadotropin-releasing hormone analog before in vitro fertilization.

Three patients had an undetected pregnancy when they commenced a GnRH-a on the 21st day of their cycle before ovulation stimulation for IVF. Two of the three pregnancies were later diagnosed as ectopic gestations. Based on this and previous case reports in the literature, it is suggested that luteal phase administration of GnRH-a may predispose to EPs, particularly in patients with damaged tubes, by reducing tubal motility secondary to a transient increase in circulating P concentrations.

Adult↗
PubMed1990

Severe preeclampsia: is vasodilation therapy with hydralazine dangerous for the preterm fetus?

Increasing experimental and clinical evidence points to a subset of severe preeclamptic women who are hypovalemic with a low cardiac index and a high systemic vascular resistance, and in whom vasodilatory therapy may cause precipitate falls in maternal perfusion pressure, unless anticipated by prior correction of the hypovolemia. Since there is a paucity of adequately controlled clinical trials with appropriate definitions of hypotension or perinatal outcome, the consequences of such episodes for the preterm fetus are unknown. Epidemiologic evidence, using a logistic regression analysis model, is reviewed, which points to an association between a hypotensive episode following a commonly used drug, hydralazine, and a worse perinatal outcome in a study of severely hypertensive women delivered less than 32 weeks. An estimate of this risk, using the odds ratio, is 5.97 (95% confidence interval 1.84 to 19.35).

Female↗
PubMed1990

Intracellular vacuolization caused by the urease of Helicobacter pylori.

Tissue culture cells were exposed to supernatants of Helicobacter pylori for 24 h at 37 degrees C in the presence of various quantities of urea. In the normal human stomach the concentration of urea is less than or equal to 4 mmol/l, and in the presence of this low concentration up to 10% of Vero cells showed intracellular vacuolization. In the presence of 7.5 mmol/l urea, 25% of the cells showed vacuolization. With 30 mmol/l urea, the final pH was 7.6, indicating that vacuolization was not due to change of pH. The first report of vacuolization of tissue culture cells by H. pylori was in a system without added urea but with concentrated bacterial supernatant; 30% of H. pylori strains demonstrated a cytotoxic effect. In those experiments fetal calf serum was used; it contains 6 mmol/l urea but was used at a concentration of 10%. A urease inhibitor, acetohydroxamic acid, caused a 75% drop in the number of cells showing vacuolization, and ammonia caused vacuolization. Thus the urea of H. pylori probably causes this vacuolization.

Animals↗
PubMed1990

Soluble and cell-associated haemagglutinins of Helicobacter (Campylobacter) pylori.

Some plate-grown strains of Helicobacter (Campylobacter) pylori that were harvested into phosphate-buffered saline and left for 1 h released soluble haemagglutinins. These caused high-titre agglutination of human and guinea-pig erythrocytes, whereas chicken, sheep and bovine erythrocytes were agglutinated at various titres. Six of 10 strains which had been subcultured repeatedly did not possess soluble haemagglutinins. Slide agglutination of bacterial suspensions demarcated the strains into two groups; Group 1 gave strong agglutination with most types of erythrocyte, Group 2 did not. By microtitration assay, all Group-1 strains but only two Group-2 strains produced a soluble haemagglutinin. Cell-associated haemagglutinins were found by microtitration assay in all strains of H. pylori, but higher titres were found within Group-1 strains. The supernates of broth-grown, shaken cultures also showed the presence of soluble haemagglutinins, with higher titres for recently isolated strains. Pre-treatment of human erythrocytes with neuraminidase from Arthrobacter ureafaciens and Clostridium perfringens abolished haemagglutination by the soluble, but not by the cell-associated haemagglutinin. The soluble haemagglutinin was inhibited by sialoproteins containing predominantly the N-acetylneuraminyl (2-3) galactopyranosyl [NeuAc(2-3)Gal] structure, fetuin, glycophorin and bovine N-acetylneuraminyl-lactose (NeuAc-Lac). Transferrin and human NeuAc-Lac, which contain predominantly the N-acetylneuraminyl (2-6) galactopyranosyl [NeuAc(2-6)Gal] structure were not inhibitory. However, bovine submaxillary mucin (BSM) was strongly inhibitory; it contains several structures with sialic acid linked 2-6 to oligosaccharides. These results suggest that the soluble haemagglutinin recognises a NeuAc(2-3)Gal structure, but has high affinity for another, as yet undetermined, sialic acid-containing structure.

Animals↗
PubMed1990

Pupillary diameter and reaction to light in preterm neonates.

The pupil controls the amount of light entering the eye. We have examined both the time course for the development of the light reflex and pupil diameter before and after this event in 50 neonates. The pupillary light reflex was absent in all neonates of less than 30 weeks' gestational age, it gradually developed from this age and by 35 weeks it was present in all. Several possible mechanisms that may explain the onset of this reflex are considered. Before the onset of the pupil reflex mean horizontal pupillary diameter was 3.46 mm compared with 3.02 mm after the reflex development. We have estimated the amount of light reaching the retina (retinal irradiance) for preterm neonates and although it is less than that known to cause retinal damage in animals, further research is necessary to determine whether early light exposure has an adverse or beneficial effect on the immature visual system.

Female↗
PubMed1990

Illuminance of neonatal units.

We have measured the illuminance (brightness) of seven neonatal units during both the day and the night. When the units were lit solely by fluorescent tubes the mean illuminance was 348 lux (range 192-690). During the day the mean illuminance was 470 lux (range 236-905). The high dependency regions in four of the seven units were significantly brighter than the corresponding low dependency nurseries at all times. In two of these units there is a policy of reducing the amount of artificial light in the low dependency areas at night, and in these the normal mean illuminance was 50 lux. We have measured the general levels of illumination to which a neonate might be exposed; the ocular exposure to light of a neonate depends, however, on both physical and biological factors and more research is required before an accurate estimate can be made.

Humans↗
PubMed1990

Serotype and serum sensitivity of Pseudomonas aeruginosa from children with cystic fibrosis: longitudinal studies and typing with monoclonal antibodies.

Pseudomonas aeruginosa isolated from the respiratory tract of children with cystic fibrosis from Perth, Sydney or Brisbane, were serotyped with polyclonal antisera using the International Antigenic Serotyping System. Predominant strains were untypable among isolates from Brisbane (86% of 50 strains) and Sydney (60% of 50 strains) but 64% of the 408 isolates from Perth were polyagglutinating. The frequency distributions of typable strains showed differences from those reported in clinics in the northern hemisphere, but it appears that these local differences do not affect the emergence of strains with defective lipopolysaccharide antigens. Isolates from patients studied longitudinally showed correlation between duration of colonization, appearance of untypable or polyagglutinating strains and sensitivity to normal serum. Mucoid colonies were found more commonly from patients colonized for at least 12 months but, overall, there was no significant association between serotype and mucoid colonial morphology. Commercial monoclonal antibodies did not react with polyagglutinating or untypable strains and gave identical results to the polyvalent typing system with strains classified as typable.

Antibodies, Monoclonal↗
PubMed1990

Nephrotic syndrome associated with nonsteroidal anti-inflammatory drug use in two children.

Two children with nephrotic syndrome in association with nonsteroidal anti-inflammatory drug (NSAID) use are described, and the literature concerning this association is reviewed. NSAIDs are drugs with the potential for causing significant renal toxicity including the nephrotic syndrome, interstitial nephritis, and renal failure even in children without obvious preceding renal disease. Children prescribed such drugs should be regularly monitored with urinalyses and plasma creatinine estimations. The possibility of toxicity to over-the-counter use of NSAIDs should be remembered.

Adolescent↗
PubMed1990

Home-like architectural features of residential environments.

Adults who had no experience in the area of mental retardation viewed slides of residential settings, five providing housing for people with mental retardation, and rated their "home-likeness" (1 = home-like, 5 = institutional). Of 55 two-way comparisons, the mean home-likeness ratings of 48 such pairs differed significantly from one another. A .98 log-linear correlation was found between number of residents in a given facility and institutional ratings. Of 26 features of living rooms studied in detail, furniture position, lighting type, and lighting flexibility were highly correlated with home-likeness, whereas building code-specific features and seating type were minimally related to home-likeness.

Adult↗
PubMed1989

Growth and elimination of nerve terminals at synaptic sites during polyneuronal innervation of muscle cells: a trophic hypothesis.

This paper examines the possibility that the elimination of synapses from cells arises from a competition between the nerve terminals for trophic molecules made available by the cells. This idea is applied to the elimination of synapses that occurs during the polyneuronal innervation of muscle cells which accompanies both the development and reinnervation of muscles. In the proposed model, each motorneuron makes the same amount of receptor in its soma for a trophic molecule provided in limited quantities by each muscle cell; this receptor is then distributed to the collateral terminals of the motorneuron in concentrations proportional to the amount of receptor made in the soma by the motorneuron; the more collateral terminals initially possessed by a motorneuron the less will be their concentration of receptor. The receptors in the several collateral terminals on a muscle cell then compete for the trophic molecule provided by the muscle, and terminal growth is proportional to the number of receptor-trophic-molecule bonds formed. An autocatalytic effect has been introduced whereby the increase in size of a terminal accelerates the rate by which the trophic molecule is made available to that terminal for bonding with its receptors. In addition, the affinity between nerve terminal receptors and muscle molecules can be varied in the model. Finally, motorneuron cell death has been analysed as the elimination of neurons that have insufficient terminal area to take up a growth factor in amounts that will allow for the survival of the neuron.

Animals↗