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Biomedical subjects

R Mason

Publications and source records attributed to R Mason.

At least 127 records · Page 7Linked to original sources

Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against gram-negative organisms.

The macrolide antibiotic azithromycin (CP-62,993; 9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A; also designated XZ-450 [Pliva Pharmaceuticals, Zagreb, Yugoslavia]) showed a significant improvement in potency against gram-negative organisms compared with erythromycin while retaining the classic erythromycin spectrum. It was up to four times more potent than erythromycin against Haemophilus influenzae and Neisseria gonorrhoeae and twofold more potent against Branhamella catarrhalis, Campylobacter species, and Legionella species. It had activity similar to that of erythromycin against Chlamydia spp. Azithromycin was significantly more potent versus many genera of the family Enterobacteriaceae; its MIC for 90% of strains of Escherichia, Salmonella, Shigella, and Yersinia was less than or equal to 4 micrograms/ml, compared with 16 to 128 micrograms/ml for erythromycin. Azithromycin inhibited the majority of gram-positive organisms at less than or equal to 1 micrograms/ml. It displayed cross-resistance to erythromycin-resistant Staphylococcus and Streptococcus isolates. It had moderate activity against Bacteroides fragilis and was comparable to erythromycin against other anaerobic species. Azithromycin also demonstrated improved bactericidal activity in comparison with erythromycin. The mechanism of action of azithromycin was similar to that of erythromycin since azithromycin competed effectively for [14C]erythromycin ribosomebinding sites.

Anti-Bacterial Agents↗

Circadian variation in sensitivity of suprachiasmatic and lateral geniculate neurones to 5-hydroxytryptamine in the rat.

Extracellular single-unit recordings were obtained from neurones in the suprachiasmatic nuclei (s.c.n.) of the rat (a putative circadian pace-maker), the ventral lateral geniculate nucleus (v.l.g.n.) and the hippocampus. These areas receive a 5-hydroxytryptamine (5-HT) innervation from the raphe nuclei. Recording of neuronal activity in the s.c.n., v.l.g.n. and the hippocampus revealed a diurnal variation in the response to the ionophoresis of 5-HT. This variation was manifest as a 2-3-fold increase in post-synaptic sensitivity to 5-HT during the subjective dark (active) phase of the circadian cycle. In contrast there was no apparent circadian variation in the sensitivity of s.c.n., v.l.g.n. or hippocampal neurones to ionophoresed gamma-aminobutyric acid (GABA). Neuronal activity recorded in the s.c.n., v.l.g.n. and hippocampus also exhibited a circadian variation in the recovery from 5-HT-induced suppression of firing. This may reflect reuptake processes as recovery can be prolonged by ionophoresis of uptake blockers (imipramine or fluoxetine). Rats (n = 15) expressing circadian arrhythmicity in their rest-activity behaviour induced by long-term continuous illumination (150-200 lx) showed no apparent circadian variation in 5-HT sensitivity. This loss was accompanied by either the development of a 5-6-fold subsensitivity to ionophoresed 5-HT (eleven out of fifteen rats) or a 2-3-fold supersensitivity to ionophoresed 5-HT (four out of fifteen rats). A similar loss of circadian variation and the development of a subsensitivity to ionophoresed 5-HT was also found in three rats sustaining complete electrolytic lesions of the s.c.n. These changes were not found in rats (n = 4) with partial s.c.n. lesions. These results implicate the s.c.n., or fibres passing through it, in the circadian modulation of 5-HT sensitivity in neurones both intrinsic to the s.c.n. circadian pace-maker itself and in the hippocampus and lateral geniculate nucleus (regions remote from the s.c.n.).

Action Potentials↗

Time course of the binding of platinum to subfractions of the kidney cytosol in the cisplatin-treated rat.

In male rats treated with cis-dichlorodiammine platinum II (cisplatin, 5 mg/kg, s.c.), the accumulation of Pt in the kidneys occurred in two phases. Total renal Pt content peaked after 15 min and decreased rapidly, then increased to a second peak after 48 hr and thereafter decreased slowly during the next 6 days. Sephadex G-50 chromatography showed that in the kidney cytosol Pt was located in three subfractions; a high molecular weight (HMW) fraction (relative elution volume, Vr = 0.9-1.2), a heterogeneous low molecular weight (LMW) Pt-binding fraction (Vr = 1.2-2.2) and a LMW complex fraction (Vr = 2.2-2.7). Initially, most of the Pt was located in the HMW- and LMW complex fractions and the initial loss of Pt from the cytosol occurred from the latter fraction. In contrast, during the second phase much of the additional Pt accumulated in the LMW Pt-binding fraction, the Pt content of which paralleled that in the whole kidney. It is suggested that the LMW Pt-binding fraction may play a significant role in the accumulation and retention of Pt and may provide a site of detoxification during the second phase of influx of Pt into the kidneys.

Animals↗

Erythrocyte morphology in women with severe preeclampsia and eclampsia. Preliminary observations with scanning electron microscopy.

Scanning electron microscopy was used to study the morphologic characteristics of erythrocytes in women with preeclampsia and eclampsia. In nine nulliparous women with eclampsia, the proportion of abnormal red cells (schistocytes, echinocytes, and spherocytes) was significantly greater than in 12 normally pregnant control women (p less than 0.001). Likewise, the proportion of these abnormal erythrocyte forms was significantly greater in 12 nulliparous women with preeclampsia than in 25 normally pregnant control women (p = 0.009). Six women with mild pregnancy-induced hypertension without proteinuria were studied before and after magnesium sulfate therapy had been given, and no differences in the proportion of abnormal erythrocyte forms were found. Evidence for microangiopathic hemolysis, manifest by reticulocytosis and thrombocytopenia, was apparent with eclampsia, although only reticulocytosis was identified in women with preeclampsia. There was evidence for hepatic dysfunction in more than half of the women with eclampsia, and in nearly one third of those with preeclampsia. We speculate that compositional changes in the membrane, induced by plasma/erythrocyte lipid interchanges, which are predisposed by normal pregnancy and amplified by severe preeclampsia, especially in the presence of liver dysfunction, may have participated in the genesis of the red cell abnormalities observed. Furthermore, these abnormalities in the cell membrane may increase erythrocyte susceptibility to microangiopathic hemolysis.

Eclampsia↗

Small male body size in garter snake depends on testes.

In the red-sided garter snake (Thamnophis sirtalis parietalis) adult females are larger than adult males; this difference is apparent within 3 wk of birth, a time coinciding with high circulating levels of androgens. To study the ontogeny and regulation of this sexual dimorphism, male neonates were either castrated, castrated and given Silastic capsules containing testosterone or estradiol, or given a sham operation at 8, 9, or 10 wk of age. Female neonates were either given a Silastic capsule containing testosterone or dihydrotestosterone or given a sham operation at 8, 9, 10, or 14 wk of age. The sex difference in body size and growth rate in neonates was abolished by castration; the pattern of growth of castrated males was similar to sham-operated females. Androgens in the amounts administered failed to reverse the effects of castration, because castrated male and female neonates receiving exogenous androgens grew at the same rate as did sham-operated females. Males castrated as adults grow larger than adult males given a sham operation, indicating the inhibitory role of the testes on body size exists after sexual maturity. Treatment of adult males with testosterone, however, prevented the increase in body size after castration, suggesting that the mechanism regulating weight gain in the garter snake depends on gonadal androgen.

Androgens↗

Development of gallstone pancreatitis. The role of the common channel.

Whether bile reflux through a common channel into the pancreatic duct is a causative factor in the development of gallstone pancreatitis is controversial. To address this issue, we have reviewed a consecutive series of cholecystectomies performed with intraoperative cholangiograms. The cholangiograms and the patients' charts were reviewed independently to determine the incidence of a common channel in patients both with and without pancreatitis and to analyze their clinical courses. The group of patients who had pancreatitis showed a common channel in 19 (90%) of 20 cases, while those patients who did not have pancreatitis showed a common channel in 23 (35%) of 66 cases. The patients who had pancreatitis were less likely to have choledocholithiasis than were those patients who did not have pancreatitis, and these patients were less likely to require exploration of the common bile duct.

Ampulla of Vater↗

Interaction of platinum with metallothionein-like ligands in the rat kidney after administration of cis-dichlorodiammine platinum II.

After the administration of the anticancer drug cis-dichlorodiammine platinum II (cisplatin) to male rats, the Pt in the soluble fraction of the kidney is isolated, by gel filtration, in association with a high molecular weight component and a low molecular weight fraction. At 24 h, Pt is also recovered in a metallothionein-like fraction which elutes from Sephadex G-50 with a lower apparent molecular weight than endogenous (Cu, Zn)-thionein or Cd-thionein isolated from the kidneys of Cd2+-treated rats. None of these low molecular weight metal-binding fractions binds to Octyl Sepharose CL-4B. On DE-52 ion exchange chromatography, Cd-thionein is resolved into two isometallothioneins whereas the low molecular weight Pt-binding fraction is only partially purified and contains at least six components which elute at higher gradient concentrations than metallothionein. Pretreatment with Cd2+ which stimulates the synthesis of renal and hepatic metallothionein has no effect on the uptake and subcellular distribution of Pt in the liver and kidneys. Cisplatin treatment reduces the concentration of Cu and Zn in the renal metallothionein and other soluble protein fractions in the kidney. When administered to Cd2+-pretreated rats, cisplatin promotes the loss of Zn from the soluble protein fractions but causes the redistribution of Cd from the metallothionein to the high molecular weight fraction and fails to inhibit the Cd2+-induced accumulation of Cu in the kidneys and the binding of Cu to the soluble protein fractions. It is suggested that metallothionein probably does not have a significant role in the renal metabolism of Pt following the administration of cisplatin to rats.

Animals↗

Hormonal independence of courtship behavior in the male garter snake.

Garter snakes exhibit a dissociated reproductive tactic in which gonadal activity is minimal at the time of mating, increasing only after the breeding season has ended. Experiments are presented demonstrating that neither short-term nor longterm castration affects courtship behavior in adult male red-sided garter snakes (Thamnophis sirtalis parietalis). So long as males have passed through a low-temperature dormancy period (hibernation), castration either shortly after emergence in the spring, or before entering winter dormancy in the fall, does not prevent the display of intense courtship behavior on emergence. Similarly, males castrated during mating activity the previous spring prior to the annual testicular growth phase actively courted females on emergence from hibernation. Males adrenalectomized and castrated during low-temperature dormancy also courted females on emergence. Hypophysectomy during or before low-temperature dormancy did not prevent males from displaying high-intensity courtship behavior on emergence from hibernation. Treatment with sex steroid hormones, as well as hypothalamic and pituitary hormones, and a variety of neural and metabolic affectors also fails to elicit courtship behavior in noncourting males during the summer. It was concluded that causal mechanisms controlling courtship behavior in the red-sided garter snake are fundamentally different, at least at the physiological level, from those mechanisms described for many laboratory and domesticated species.

Adrenal Glands↗

Profound hypocalcaemia associated with oestrogen treatment of carcinoma of the prostate.

A case of profound hypocalcaemia which occurred in a patient with osteoblastic metastatic carcinoma of the prostate after treatment with oestrogens is reported. Although there may have been other contributory factors, it was felt that the administration of oestrogens was the most important causative element. Treatment with high doses of oestrogens in patients with osteoblastic metastatic carcinoma of the prostate should be accompanied by frequent measurements of plasma calcium levels.

Adenocarcinoma↗

Electrical and pharmacological properties of the suprachiasmatic nuclei.

The suprachiasmatic nuclei (SCN) of the mammalian hypothalamus are in important circadian pacemaker. The electrical activity of these nuclei exhibits an intrinsic circadian rhythm. The rhythmicity of the SCN is also reflected in cyclic glucose consumption and serotonin metabolism. These rhythms are entrained to the light-dark cycle via the retinohypothalamic projection. This pathway, possibly together with a visual projection via the ventral lateral geniculate nuclei, innervates light-responsive SCN cells, which exhibit the functional properties of luminance detectors. The SCN contain various peptides, acetylcholine, and serotonin either intrinsically or in terminals of afferent projections. For acetylcholine it has been demonstrated that the SCN mediate the process of photic entrainment and light suppression of pineal synthetic activity. In the case of serotonin and vasopressin it seems certain that the SCN do not depend on their presence for generating circadian rhythms or for entrainment. Both substances may modulate the intrinsic pacemaker frequency through mechanisms that remain to be established.

Action Potentials↗

Pregnancy and sickle cell hemoglobinopathies: results with and without prophylactic transfusions.

Maternal morbidity and perinatal outcome in 108 pregnancies complicated by sickle cell anemia (hemoglobin SS disease), sickle cell-hemoglobin C disease (hemoglobin SC disease), or sickle cell-beta-thalassemia disease were analyzed. Women given prophylactic red cell transfusions (1973-1982) during pregnancy were matched with historic controls whose care was almost identical except that blood was not given unless indicated (1955 to 1972). In women with hemoglobin SS disease who received prophylactic red cell transfusions, there was a sevenfold reduction in perinatal mortality and negligible maternal morbidity. In pregnancies complicated by hemoglobin SC disease during which transfusions were given, there were no perinatal losses, whereas there were in 18% of women not given transfusions. Maternal morbidity in women given transfusions was negligible; however, half of those not transfused experienced morbidity and, importantly, pulmonary complications were common. Transfusion-related complications included hepatitis and alloimmunization. From these experiences the authors conclude that prophylactic red cell transfusions reduce maternal morbidity and perinatal mortality appreciably, although perinatal morbidity is not eliminated. Transfusion therapy is justifiably started early in pregnancy for women with hemoglobin SS disease; however, transfusions may be withheld until the end of the second trimester for women with hemoglobin SC or sickle cell-beta-thalassemia disease.

Anemia, Sickle Cell↗

Metabolism of cadmium in the neonate: effect of hepatic zinc, copper and metallothionein concentrations on the uptake of cadmium in the rat liver.

The accumulation and subcellular distribution of Cd2+ (1 mg/kg body wt, i.p.) in the liver of the neonatal rat is age-dependent. At 4 hr after treatment the liver Cd2+ contents in the 12-day-old, 20-day-old and adult rat are similar and greater than in the 2-day-old animal. The differences in hepatic Cd2+ concentration in the older age groups are consistent with the nonlinear weight gain of the liver in the developing animal. In the hepatic cytosol Cd2+ is incorporated into a high molecular weight and metallothionein fractions and transferred from the former to the latter. This process occurs less rapidly with increasing age. The uptake of Cd2+ by the whole liver and th hepatic metallothionein is not related to the total liver concentration of Zn2+ or copper and is not significantly influenced by the concentration of pre-existing metallothionein or the concentration of thionein-bound Zn2+ or copper. The results are discussed in relation to the possible effects of Cd2+ on the liver metabolism and tissue distribution of Zn2+ and copper in the developing animal.

Animals↗

SV-40 virus-induced neoplastic transformation of hamster brain cells in vitro. Studies with scanning and transmission electron microscopy.

Neoplastic transformation of one-day-old hamster brain cells was produced by infection with SV-40 virus and verified by phase contrast microscopy, growth in semisolid media, and intracranial tumor production after inoculation of the cells into other one-day-old hamsters. Transformed cells were studied by transmission and scanning electron microscopy. The numerous alterations in cell surface structure and in nuclear and cytoplasmic organization suggest a marked increase in cell metabolism and in the rate of mitosis and cell division. Cilia with a nine-to-zero pattern of microtubule doublets were present in cells with intermediate size filaments which stained for glial fibrillary acidic protein. The findings indicate that infection of one-day-old hamster brain cells in culture by SV-40 virus results in their transformation to a neoplastic state and the transformed cells are differentiating neoplastic astrocytes.

Animals↗

Norepinephrine sensitivity and desensitization of cultured single vascular muscle cells.

Isolated single vascular muscle cells were used for studies of the inherent norepinephrine sensitivity and the conditions important for detecting highest norepinephrine sensitivity. Rat vascular muscle cell contractions were quantitated from spontaneous contractions during pulse applications of the drugs, with a time course designed to simulate norepinephrine release in situ. Isolated vascular muscle cells showed a sensitivity to norepinephrine two orders of magnitude greater than those found from isolated intact blood vessels. Associated with the high sensitivity, there was a marked reduction in the response to a second application of norepinephrine or phenylephrine. The reduced second response appears to result from desensitization that is more pronounced in cells that have been exposed to only trace concentrations of catecholamines. These data appear to suggest that there might be continuous suppression of transmitter sensitivity that occurs as a result of transmitter exposure, and possibly cell-to-cell associations. Desensitization would at first severely limit the response to norepinephrine by reducing or eliminating the response to prolonged exposure or a second dose. Thereafter, a lessening of the desensitization process on continuous exposure to catecholamines would be the result, in part, of lowered sensitivity and, in part, of a smaller desensitization response. This process would continuously modulate norepinephrine sensitivity, based on the frequency and extent of stimulation, and we have called it the theory of physiological desensitization.

Animals↗