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Biomedical subjects

R George

Publications and source records attributed to R George.

At least 199 records · Page 11Linked to original sources

Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in Morris hepatoma 7800 after intravenous injection of mevalonic acid.

The effect of i.v. injection of mevalonate on the activity of microsomal 3-hydroxy-3-methylglutaryl Coenzyme A reductase was studied in livers from non-tumor-bearing rats and in host liver and hepatomas from rats bearing transplantable Morris hepatoma 7800. We confirmed that a single bolus injection of 100 mg of mevalonate in non-tumor-bearing male rats caused a 90% inhibition of hepatic 3-hydroxy-3-methylglutaryl Coenzyme A reductase activity within 2 hr. In two experiments mevalonate injection caused a 50 to 60% reduction in enzyme activity of hepatomas but no significant decline in the enzyme activity in host livers. Thirty in after injection of [14C]mevalonate in a similarly sized bolus, the ratio of specific activities of cholesterol in liver:hepatoma:kidney:blood was 13:5.6:0.5:1. Thus, both the liver and hepatoma efficiently utilized mevalonate for the synthesis of cholesterol. The precise cause of the inhibition of enzyme activity in the liver of non-tumor-bearing rats and in the transplantable hepatomas is not clear from this study. However, on the basis of other published reports, we suggest that it resulted from the accumulation of endogenous cholesterol in microsomal membrane. The activity of cholesterol 7 alpha-hydroxylase, the rate-controlling enzyme for bile acid synthesis, was also studied in the hepatoma, but, in general, it did not differ from that in the host liver or control liver.

Animals↗

Behavioral changes produced in the cat by acute and chronic morphine injection and naloxone precipitated withdrawal.

To address the issue of feline manic responses to morphine, studies were designed to examine the effects of low doses of intravenous morphine on cat behavior with emphasis placed on motor activity changes. An adaptation of an existing scoring system was used in an effort to quantify and describe behavioral patterns or shifts in activity patterns occurring during a cycle of addiction. The acute administration of 1, 2 or 4 mg/kg of morphine induces a response pattern characterized by sitting with fixed staring. An increase in motor activity with dose was also observed. When naloxone was administered prior to morphine injection all behavioral changes normally elicited by morphine were blocked completely. After 7 days of daily morphine injections certain changes in activity profiles occurred, indicating that some degree of tolerance although not complete, was beginning to occur by this time. Naloxone administered to cats maintained for 12 days on1, 2 or 4 mg/kg/day consistently produced a number of withdrawal signs including wet-dog shakes and a catatonic-like posturing. This is the first report describing behavioral responses of the cat during a complete cycle of addiction to low doses of morphine. We not only found that morphine will elicit definite quantifiable changes in behavior in the absence of any feline mania but that cats become readily dependent on these low doses of morphine as evidenced by a characteristic naloxone precipitated withdrawal syndrome.

Animals↗

Heterogeneity of hemoglobin gamma chains in normal newborns and in cases of alpha and beta thalassemia.

The ratio of Ggamma to Agamma was studied in 13 normal healthy newborns and in eight neonates with hydrops fetalis due to homozygous alpha-thalassemia. The findings in the normal healthy newborns agreed with those of earlier reports. In homozygous alpha-thalassemia the Ggamma and Agamma ratio appeared generally lower than in healthy control newborns, but one of the hydrops fetalis cases had a very high Ggamma value. In all 13 normal healthy newborns, in 8 patients with homozygous alpha-thalassemia, and in 4 patients with homozygous beta-thalassemia, Tgamma chains with threonine at position 75 were detected in addition Igamma chains with isoleucine at position 75. In homozygous alpha-thalassemia, the Tgamma-to-Igamma ratio seemed lower and in homozygous beta-thalassemia higher than in normal newborns.

Alanine↗

Radiation and microwave therapy in the treatment of advanced cancer.

Seventy-two patients with advanced cancer were treated with combinations of heat and radiation in two groups: (a) heat + radiation, and (b) radiation + heat. Of those treated with heat prior to radiation therapy, 32/60 (53%) experienced complete remission of symptoms. In the group exposed to heat after radiotherapy, 11/12 patients (92%) achieved complete remission. The authors present two cases and a review of the literature.

Aged↗

Long-term analysis of cerebrospinal fluid shunt infections. A 25-year experience.

The authors have retrospectively analyzed 840 cerebrospinal fluid shunting procedures over a 25-year period to determine the relationships between infection rates and several possible influences on infection. Two-thirds of all shunt infections occurred within 1 month of surgery. The very young and very old had higher infection rates. Infections became less prevalent over the period of the study, and mortality from infection decreased from 35% to 6%. Successive shunts (revisions) were found to have progressively higher infection rates. Ventriculoatrial and ventriculoperitoneal silicone plastic shunts had similar infection rates (11.4% and 12.0%). The uncontrolled use of prophylactic antibiotics had no effect on shunt infections. Staphylococcus epidermidis became gradually more prevalent over the period of the study, and eventually caused one-half of all infections. Where infection occurred in the presence of prophylaxis, the infectious organism was usually sensitive to the antibiotic being used. The surgeon was found to be the largest single factor in the incidence of shunt infections. A 25-fold variance in infection rates among surgeons could be related to individual experience and technique.

Adolescent↗

Potentiation of morphine hyperthermia in cats by pimozide and fluoxetine hydrochloride.

Administration of morphine sulfate (1--4 mg/kg i.v.) to cats produces changes in body temperature, with hyperthermia appearing with larger doses. Since the central neurotransmitters dopamine and serotonin have been implicated in thermoregulation, studies were done to determine whether morphine's action could be mediated via these transmitters. Temperature responses were measured in freely moving cats by means of rectal thermometer probes. Either pimozide, 0.5 mg/kg i.p., a specific DA receptor blocker, or fluoxetine HCl, 10 mg/kg i.p., a specific inhibitor of 5-HT uptake, was administered 2--3 h prior to morphine injection. Temperatures were monitored for 3.5 h after morphine administration. Both agents were found to enhance the hyperthermic response to morphine with the maximum morphine effect occurring in most cases by 2 h. The results indicate that a balance in the ratio of 5-HT : DA may be involved in cat thermoregulation and that the hyperthermic response in the cat to morphine may be effected by shifting this 5-HT : DA ratio.

Animals↗

Beta-endorphin is behaviorally active in rats after chronic intravenous administration.

Male Sprague-Dawley rats received 14 daily intravenous injections of saline or human beta-endorphin (2.5 mg/kg). Animals were given one-way active avoidance training on the eleventh day, and analgesia testing on the twelfth (tail-flick) and thirteenth (hot-plate) days. Beta-endorphin had no effect on the number of trials needed to reach the avoidance criterion, but significantly lengthened response latencies. Beta-endorphin had no analgesic effect in either test procedure.

Animals↗

Nature of the stimulation of biogenesis of cholesterol in the liver by noradrenaline.

1. Administration of noradrenaline increased the incorporation of [1-14C]acetate into hepatic sterols and the activity of liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase. 2. The stimulation was observed at short time-intervals with a maximum at 4h and was progressive with increasing concentrations of noradrenaline. 3. Protein synthesis de novo was a necessary factor for the effect. 4. The stimulatory effect was not mediated through the adrenergic receptors, but appears to involve a direct action of the hormone within the hepatocyte.

Animals↗