The role of control activity levels in the reported strain differences to the behavioral effects of drugs in mice

The effect of d-amphetamine (3-100 mumoles/kg), scopolamine (0.3-100 mumoles/kg) and morphine (3-1000 mumoles/kg) were studied on the spontaneous motor activity (SMA) of four strains of mice: CF-1, DBA/2, C57BL/6 and CD-1. All three drugs increased the SMA of the CF-1, C57BL/6, and CD-1 strains at low to moderate doses and decreased SMA at higher doses. In the DBA/2 strain, d-amphetamine and scopolamine increased SMA at low doses and decreased SMA at high doses; only decreases in SMA were observed with morphine. When the drug effect was expressed relative to control levels of SMA, large apparent strain differences were shown to exist for all three drugs. In general, these strain differences were shown to exist for all three drugs. However, the majority of these strain differences could be attributed to the large differences which existed in the control level of SMA among the four strains. One important exception to this statement was shown to exist. The DBA strain responded differently (only decreases in SMA were observed) to morphine than did the other three strains. This decrease was not related to the control SMA level and could not be antagonized by naloxone (3 mumoles/kg, IP).     

Clinical guidelines for cardiovascular disease prevention: Should they differ by gender?

The effects of cardiovascular disease are substantial in women, yet cardiovascular preventive therapies for women are underused. The prevalence and impact of many coronary risk factors differ by gender. Coronary risk interventions (eg, using aspirin) have diverse outcomes in women and men. Results from studies of preventive interventions specific to women (eg, menopausal hormone therapy) have changed preventive recommendations and clinical practice.     

T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

Cellular Distribution of G Protein Goa in Pituitary Lactotrophs: Effects of Dopamine

Membrane-bound GTP-binding (G) proteins mediate signal transduction in a variety of cell systems. The exact mechanisms of G proteins action are still under investigation but they appear to involve effectors located in the plasma membrane as well as in other parts of the cell. With this study, we investigated the cellular and ultrastructural localization of G protein subunits, and particularly of Goa, in normal rat anterior pituitaries and in estrone-induced rat adenomatous lactotrophs. We also evaluated the effects of Goα cellular redistribution in rat adenomatous lactotrophs following short-term exposure to dopamine (DA). Using the Protein A-gold (PAG) methodology, Goα was found to be present in the cysternae of the endoplasmic reticulum of normal pituitary cells and of adenomatous lactotrophs. In the latter, Goα could be co-localized with prolactin (PRL). By immunoblots, using specific antisera, significant amounts of Goα and Gs42α, together with smaller amounts of Giα, Gs47α and Gβ were found to be present in the uncontaminated supernatant fraction of adenomatous lactotrophs. Unexpectedly, exposure of the cells to DA induced a rapid and short-lived decrease in the cytosolic fraction of Goα and Gβ associated with a decrease of PRL release. Since cytosolic Goα can be ADP-ribosylated by pertussis toxin (PT) and is therefore in a heterotrimeric form, our data suggest that the soluble Go protein may play a role during lactotrophs' exposure to an inhibitor of PRL release, perhaps through its relocalization after being internalized with the D₂ receptor or by being used for interaction with intracellular and/or membrane-bound effectors.     

Dopamine D2 receptor imaging with SPECT: studies in different neuropsychiatric disorders.

The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(-)-Iodobenzamide [S-(-)-IBZM] has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(-)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 +/- 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 +/- 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 +/- 0.14), but a reduction in L-Dopa-treated cases (1.59 +/- 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75-80%. S-(-)-IBZM binding was reduced with increasing age (p less than 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Support networks and dementia

Based on data from a sample of 4500+ people aged 65+ living in the community (ie not in residential care) in Liverpool, this article presents data on the availability of kin and levels of contact with family, friends neighbours and community groups, and compares the distribution of support network types of those identified as cases of dementia with non-cases. It is shown that dementia sufferers are more likely to live with others and to have more contact with family members and less contact with friends, neighbours and community groups than non-sufferers. It is also shown that the distribution of network type is distinctively different for cases and non-cases and it is suggested that this reflects the greater ability of some types of network to support continued community residence in the face of the onset of dementia.     

Physician performance of laboratory tests in self-service facilities. Residents' perceptions and performance

Primary care physicians perform simple laboratory tests in clinical practice, frequently with little formal training. To determine the frequency of tests that are performed and evaluate house officer laboratory skills, we surveyed house officer attitudes and tested their ability to perform four common laboratory tests. We received 193 responses from 254 house officers at one university teaching hospital. While most perceived the need to use ward laboratories (ie, self-service laboratories located on patient care wards), 67% used them infrequently. Barriers included poor laboratory condition, inadequate time, accuracy, and infectious exposure concerns. Twenty-four percent felt they did not know or were unsure if they knew how to perform simple tests. Forty-seven house officers completed the practical examination. Most accurately reported a spun hematocrit and correctly identified white blood cell findings on a blood smear. Only 50% counted 100 cells. Urinary dipstick interpretation was generally acceptable but the microscopic examination was less accurate. Twenty-three percent failed to identify gram-negative rods on a slide with both gram-positive cocci and gram-negative rods. If physicians are to perform selected laboratory tests, these data suggest, at least in one institution, more formal training, practice, and evaluation are necessary to ensure their performance with adequate proficiency.     

Cardiovascular disease in the elderly.

The current worldwide explosive increase in the numbers of older persons is unprecedented in history. In the 1990s and beyond, the preponderance of patients with cardiovascular illness will be elderly, with a substantial subset among the frail elderly, 85 years old and older. Cardiovascular disease remains the leading cause of death and disability in this population, and cardiovascular risk increases steadily with age. Pascal defined old age as "just a time that is farther from the beginning and nearer to the end." Elderly persons, with and without cardiovascular disease, vary widely in their physical, behavioral, cognitive, and emotional functioning; severity of illness; and expectations from medical care. The challenge to the clinical and research communities alike is to delineate the appropriate components of preventive, diagnostic, and therapeutic care for elderly cardiac patients in our society, interventions that are likely to relieve suffering, restore function so as to limit disability and dependency, and maintain a dignified and meaningful life-style for the end years of life. Major societal strides have been made in redefining both the onset of old age and its limitations. The eighteenth century poet, Robert Burns, wrote of his fears that he would be 45 years old at a time when life expectancy was 40 years; he saw himself as being weary, wrinkled, creeping, and joyless. For, ance that five-and-forty's speel'd, See crasy, weary, joyless Eild, Wi' wrinkled face, Comes hostin', hirplin', owre the field, Wi' creepin' pace. Burns died at the age of 37 years. A more attractive option is offered by Abraham Joshua Heschel, 1907-1972. According to all the standards we employ ... the aged person is condemned as inferior. ... Conditioned to operating as a machine for making and spending money, with all other relationships dependent upon its efficiency, the moment the machine is out of order and beyond repair, one begins to feel like a ghost without a sense of reality. ... Regarding himself as a person who has outlived his usefulness, he feels as if he has to apologize for being alive. May I suggest that ... old age be regarded not as the age of stagnation but as the age of opportunities for inner growth. ... The years of old age ... are indeed formative years, rich in possibilities to unlearn the follies of a lifetime, to see through inbred deceptions, to deepen understanding and compassion, to widen the horizon of honesty, to refine the sense of fairness.     

The controversy about a sexual dimorphism of the human corpus callosum

A sexual dimorphism of the splenium corporis callosi in man was reported in 1982. The authors described the posterior part of the female corpus callosum to be larger and more bulbous than its male counterpart. From the lateralization research, it has previously been stated that the female brain is less well lateralized for visuospatial functions than the male. The authors postulated that a larger splenium implies a larger number of fibers and that the number of interhemispheric fibers correlates inversely with lateralization of function. However, their sample was very small and not adequately matched for sex. Therefore, we reinvestigated this question. A standardized computer assisted program will be presented. With this program the "classical" parameters have been evaluated and the "rotatory diameter measurement" was performed. No differences between the sexes were seen either for the splenium corporis callosi or for the other parts of the corpus callosum.