Adaptations in skeletal muscle capillarity following changes in oxygen supply and changes in oxygen demands

Summary The effects of changes in oxygen supply and oxygen demands on fiber cross-sectional areas, capillary dersities and capillary to fiber ratios were determined in three skeletal muscles of rat. The muscles examined were the vastus lateralis, soleus, and diaphragm. Reduced oxygen supply was produced by subjecting rats to ambient hypoxia, and increased oxygen demands were produced by subjecting rats to low ambient temperatures or treatment with thyroxin. Capillaries were visualized by injecting fluorescent dyes into the circulation. Muscles were quick frozen at resting lengths to preserve normal fiber geometry and were subsequently sectioned on a cryostat. All of the muscles sampled from animals in the experimental groups had elevated capillary densities. However, capillary to fiber ratios were not increased significantly in any muscle, for any experimental condition. Thus, all of the observed differences in capillarity were due to changes in the intrinsic rate of muscle fiber growth. Further, the relations of capillary density and capillary to fiber ratio to fiber area were the same as those obtained during normal maturation, suggesting that capillary growth is closely linked to the intrinsic rate of fiber growth.     

Morphine-induced metabolic changes in human brain. Studies with positron emission tomography and [fluorine 18]fluorodeoxyglucose

Morphine sulfate effects (30 mg, intramuscularly) on cerebral glucose utilization and subjective self-reports were examined in 12 polydrug abusers by positron emission tomography and [fluorine 18]fluorodeoxyglucose in a double-blind placebo-controlled crossover study. During testing, subjects sat with eyes covered, listening to white noise and "beep" prompts. Morphine significantly reduced glucose utilization by 10% in whole brain and by about 5% to 15% in telencephalic areas and the cerebellar cortex, assuming no contribution of hypercapnia. When the contribution of PaCO2 (45 minutes after morphine was administered) was partialled out, significant morphine-induced reductions persisted in whole brain and six cortical areas. Irrespective of morphine, left-greater-than-right asymmetry occurred in the temporal cortex, and an interaction between hemisphere and drug was noted in the postcentral gyrus. In most cases, effects on glucose utilization were not significantly related to measures of euphoria.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

A factor analysis of the Klein sexual orientation Grid in two disparate samples

Many researchers interested in sexual orientation can be separated into two camps: The lumpers, who try to reduce sexual classifications to as small a number of categories as possible, and the splitters, who try to show differences among groups and individuals that make classification schemes increasingly difficult and/or intricate. We report factor analyses of the Klein Grid (a questionnaire with 21 sexual orientation items) to see how many factors emerge in two samples of strikingly different origins. In both samples, the first factor to emerge loaded substantially on all of the Klein Grid's 21 items. This factor accounted for a majority of the variance. In both samples, a second, correlated factor emerged which indexed a separation between most of the items and those having to do with social and/or emotional preferences. In both samples, a third correlated factor also emerged, but this factor differed between the two populations: one refined the social/emotional distinction and the other distinguished ideal behavior from past and current behavior. We conclude on the basis of our analysis that both the lumpers and the splitters are correct.Supported by NIMH grants IP50 MH 45294 and R01 MH 43298.     

Prion infections in Creutzfeldt-Jakob disease and its variants

Prions (PrP(Sc)) are proteinaceous infectious particles that occur as sporadic (85 percent), infectious (iatrogenic) (5 percent) or hereditary (10 percent) diseases in humans and animals. These unique infectious agents produce a spongiform change in the central nervous system without any inflammation, inclusion bodies or apparent antibody response. A helper (X) protein and genetic predisposition appear to be required to establish the infection, which seems associated with a post-translational change of a normal protein (PrP(C)) encoded by a gene on human chromosome 20. Sporadic human prion disease (Creutzfeldt-Jakob disease) is the most common form of human transmissible spongiform encephalopathy. Nevertheless, it is undoubtedly under-recognized as a result of both low autopsy rates and confusion with other dementing diseases like Alzheimer's disease. Although no therapy is currently available for this infectious dementia, which has a prolonged incubation period, these unfortunate victims should be offered supportive care and postmortem examinations. Universal precautions will protect laboratorians from this infectious, but not contagious, disease.     

Caring for adults with mental retardation: survey of family practice residency program directors

In their core curriculum guidelines, the Society of Teachers of Family Medicine has recognized the importance of training family physicians in caring for persons with mental retardation. We mailed surveys to all family practice residency directors in the United States, questioning them about experiences and methods used to teach residents about health care needs of adults with mental retardation and the importance of this education. We found that 84% of programs provide residents with one or more experiences, and 60% instruct residents in this area. Most directors ranked this education as very important or important. There was no relationship between type or age of residency program and likelihood that residents were educated about mental retardation. The importance of this education is discussed.     

Differential cellular expression of isoforms of inositol 1,4,5-triphosphate receptors in neurons and glia in brain

Inositol 1,4,5-trisphosphate receptors (IP3R) are mediators of second messenger-induced intracellular calcium release. Three isoforms are known to be expressed in brain, but their regional distributions and cellular localizations are little known. In order to better understand the roles of IP3 receptor isoforms in brain function, a first step is to define their distributions. We have used affinity-purified antibodies directed against peptides unique to each isoform to determine their sites of expression in rat brain. Type 1 IP3R (IP3R1) is dramatically enriched in Purkinje neurons in cerebellum and neurons in other regions, consistent with previous studies. By contrast, IP3R2 is only detected in glia, whereas IP3R3 is predominantly neuronal, with little detected in glia. IP3R3 is enriched in neuropil, especially in neuronal terminals (which often contain large dense core vesicles) in limbic and basal forebrain regions including olfactory tubercle, central nucleus of the amygdala, and bed nucleus of the stria terminalis. In addition, IP3R1 and IP3R3 have clearly distinct time courses of expression in developing brains. These data suggest separate roles for inositol 1,4,5-trisphosphate receptor isoforms in development, and for glial and neuronal function. The IP3R3 may be involved in regulation of neurotransmitter or neuropeptide release in terminals within specific nuclei of the basal forebrain and limbic system.     

Cardiovascular effects of acute and chronic cocaine administration in pregnant and nonpregnant rabbits.

The effects of cocaine administration on cardiovascular parameters were studied in anesthetized nonpregnant and pregnant rabbits with no prior exposure to cocaine and in pregnant rabbits repeatedly administered cocaine (4 mg/kg, bid, iv) for 15-20 days prior to the experiment. Rabbits were instrumented to determine the effects of cocaine on blood pressure, heart rate, and organ blood flows. Administration of the 1 and 2 mg/kg doses of cocaine increased blood pressure and decreased heart rate in both pregnant and nonpregnant rabbits. In contrast, the 4 mg/kg dose of cocaine caused reductions in both blood pressure and heart rate. Cocaine (1, 2, and 4 mg/kg, iv) also caused dose-dependent reductions in organ blood flows. Interestingly, cocaine did not affect uterine blood flow in the nonpregnant rabbits, whereas uterine and placental flows were markedly reduced in both groups of pregnant rabbits. Chronic treatment with cocaine caused a significant increase in the basal blood flow to the placenta and spleen, and a more precipitous decrease in blood flow in both organs in response to an acute injection of cocaine. The chronically treated rabbits also had a greater incidence of cardiac arrhythmias in response to an acute injection of cocaine (4 mg/kg, iv). Rabbits that received repeated administrations of cocaine experienced more prolonged reductions in blood flow than rabbits with no prior exposure to cocaine. These studies show that cocaine has marked effects on organ blood flows and that pregnancy and repeated prior administrations of cocaine can enhance these effects.