Medical abortion.
Explore the source record for details and available documents.
Abnormalities, Drug-Induced↗
Biomedical subjects
B Grant
Publications and source records attributed to B Grant.
Protein CVermont: symptomatic type II protein C deficiency associated with two GLA domain mutations.
This study investigates type II protein C deficiency in a family with manifestations of both arterial and venous thrombosis. Of 64 members of the kindred, 14 have been tested and 7 have PC deficiency. Among affected individuals (n = 7), mean protein C levels by different assays were as follows: enzyme-linked immunosorbent assay (ELISA), 3.8 micrograms/mL (2.1 to 4.3 micrograms/mL); amidolytic with venom activator, 115% (60% to 140%); clotting with venom activator, 42% (23% to 59%). The mean ratio of clotting to amidolytic assays for the affected individuals was 0.37 compared with a normal range of 0.8 to 1.2. Thus, the affected individuals have normal total protein C and their activated protein C has a normal active site assessed by chromogenic substrate; however, they have markedly diminished clotting activity. Immunoassay and chromatography data suggested an abnormality of carboxylation in the gamma carboxyglutamic acid (Gla) domain. Polymerase chain reaction amplification and direct DNA sequencing of exon 2 from genomic DNA of affected individuals showed two nucleotide substitutions. One of the mutations (A----C) results in Glu20----Ala, thereby eliminating a site for vitamin K-dependent gamma-carboxylation. The other substitution (G----A) results in a Val34----Met mutation. DNA sequencing of the other exons from affected individuals has shown no further difference from that of the wild-type gene. The former mutation also removes a Bgl II restriction endonuclease site, which has allowed us to confirm the mutation in affected individuals by direct digestion and Southern hybridization of genomic DNA from family members. This is the first reported family with documented Gla domain mutations in the protein C gene.
Adolescent↗
Developmental expression of regionally specific cell surface antigens in the Xenopus gastrula.
Molecular markers for specific cell lineages would be useful in studies of cellular differentiation. To isolate such markers monoclonal antibodies (MoABs) were raised against plasma membranes isolated from gastrulating Xenopus embryos. Those antibodies that recognized subsets of cells within the embryo were selected by indirect immunofluorescence. The analysis of eight such MoAbs is presented. Western blot analysis showed that all but one MoAb recognized a complex pattern of glycoconjugates associated with glycoproteins. All the antigens recognized by the MoAbs were maternal in origin and displayed similar spatial patterns of pregastrular expression. This pattern of immunoreactivity at the apical surface was inherited passively during cleavage by the resulting superficial blastomeres suggesting that ectodermal specific markers of maternal origin are pre-localized to the cortical ooplasm in mature oocytes. We suggest that these maternal components may be specific glycosyl transferases. Three different patterns of expression were observed during gastrulation as exemplified by MoAbs 1F10C1, 3A4D1, and 6F10B6. MoAb 6F10B6 was specific for both neural and non-neural epithelium. MoAb 3A4D1 was specific for non-neural epidermis. MoAb 1F10C1 appeared to recognize a protein epitope on an extracellular component expressed by the superficial and involuting epithelial cells. The pattern of expression for the 1F10C1 antigen suggests that it may play a role in facilitating the movement of the involuting cells during gastrulation.
Animals↗
The natural history of alcohol abuse: implications for definitions of alcohol use disorders.
Is the DSM-III-R category of alcohol abuse validly differentiated from the DSM-III-R category of alcohol dependence, or is abuse primarily a mild, prodromal condition that typically deteriorates into dependence? A 4-year longitudinal epidemiologic study of male drinkers provided data to answer this question. The study used identical questions at baseline and follow-up. At follow-up, 70% of the subjects who were initially classified as alcohol abusers were still abusers or were classified as remitted. This contrasted significantly with outcome in the subjects who initially reported alcohol dependence. Although additional research is needed, these results indicate that alcohol abuse often has a course distinct from that of alcohol dependence.
Adult↗
Male and female differences in liver cirrhosis mortality in the United States, 1961-1985.
Changes in the social roles of American women have led to questions about convergence in drinking practices and alcohol-related problems between men and women. To address this issue, we utilized mortality data for liver cirrhosis derived from United States death certificates for the years 1961 to 1985. Using age-adjusted rates, we found no evidence of a major shift toward convergence in cirrhosis mortality over this time period for the total population. When age-specific rates were examined, we found evidence for increasing divergence in liver cirrhosis mortality rates for those under the age of 55, whereas the general trend among the older age groups was toward convergence. Straightforward interpretation of the results is hampered by the lack of research in related areas, but the findings do suggest that greater public and professional education may serve a preventive purpose for older U.S. females.
Adult↗
Multiple alcohol-related problems in the United States: on the rise?
Are drinking problems on the rise in the U.S. general population? Surveys of drinking practices and problems conducted in the United States in 1967, 1969, 1979 and 1984 included numerous questions on alcohol-related problems that were identical or nearly identical in wording. Using data from these surveys, we tested for ordered increases over time in the prevalence of an indicator of multiple problems, considered on both a current (1-year) and lifetime basis. We studied prevalence in men and women between the ages of 22 and 59 in all four surveys. Prevalence of the multiple problem indicator was rare, especially when considered on a current basis. However, relative increases in prevalence ranging from 53% to over 200% were found from 1967 to 1984 in the multiple problem indicator for men and women, for lifetime as well as current problems. With the exception of current problems in women (a very rare condition even in the 1984 survey), these changes were all statistically significant or showed a trend toward significance. When respondents were subgrouped by age, all subgroups still showed increases since 1967, although sample sizes decreased and significance tests of ordered increases over time were not so consistent.
Adult↗
Self-help materials for anxiety: a randomized controlled trial in general practice.
The efficacy of a self-help package in treating chronic anxiety was evaluated in a randomized controlled trial in which the intervention group received self-help materials in the form of an audiotape and booklet, in addition to their current treatment. The intervention was successful in terms of mean depression scores (P = 0.01), anxiety scores (P = 0.04) and general health questionnaire scores (P = 0.02) which were significantly lower for the intervention group than for the controls. In addition, the depression scores fell faster for the intervention group than for the controls. The overall mean reduction in three months in adjusted depression scores was approximately two points greater for the intervention group than for the controls (P = 0.02). Clinicians welcomed the package as a valuable addition to the therapies available for managing chronic anxiety problems. Further studies should include larger sample sizes, taking into account the non-response to postal questionnaires over time.
Adolescent↗
Treated and untreated suicide attempts in substance abuse patients.
Suicidal behavior is a relatively common and serious problem in those with alcohol and drug problems. We compared demographic and clinical characteristics of 123 alcohol rehabilitation patients with and without a history of suicide attempts, using the Schedule for Affective Disorders and Schizophrenia-Lifetime version. Younger age was significantly related to suicide attempts, as were drug disorders, panic attacks, antisocial symptoms, and alcohol-related problems such as violence, withdrawal symptoms, and personal or occupational loss. Untreated suicide attempts were characterized by less serious suicidal intent and medical threat to life. However, alcohol- or drug-abusing individuals who have not sought treatment for suicidal behavior but who continue to drink or use drugs may be at special risk for completed suicide.
Adult↗
Cimetidine modulates natural killer cell function of patients with chronic lymphocytic leukemia.
Peripheral blood natural killer (NK) activity in patients with B-cell chronic lymphocytic leukemia (B-CLL) is frequently low or absent. Because cimetidine (a histamine-2 antagonist) has been shown to alter human lymphocyte function in vitro, we decided to study cimetidine's effect on peripheral blood NK activity of patients with B-CLL and controls. We administered cimetidine orally (1.2 gm per day) to seven patients with B-CLL and 12 controls for up to 28 days. Peripheral blood NK activity of patients with B-CLL rose from a pretreatment level of 0.7 +/- 0.5 (mean +/- SEM) lytic units/10(6) cells (LU) to 8.7 +/- 2.4 LU (P less than 0.05) at day 28. Peripheral blood NK activity of controls decreased after 14 days of cimetidine treatment but returned to pretreatment levels by day 28. When peripheral blood cells from controls were exposed to cimetidine during in vitro incubation (10 micrograms/ml), mean NK activity was increased at 48 hours (54% +/- 22% increase over controls, n = 5, P less than 0.05). Single cell cytotoxicity assays revealed increased killing of target cells (but not effector-target conjugation) with cimetidine-exposed effector cells. These data suggest that cimetidine may be useful to augment peripheral blood NK activity for patients with B-CLL.
B-Lymphocytes↗
Interactions of medroxyprogesterone acetate with estrogen on the calcium-parathyroid axis in post-menopausal women.
We studied the effect of medroxyprogesterone acetate (MPA) as a single agent and in combination with conjugated equine estrogens (E), on the calcium-parathyroid axis in healthy post-menopausal women. Twenty-six subjects, 2-22 yr post-menopause, were studied under basal conditions, and then following 10 days of MPA (10 mg/day), 30 days of E (0.625 or 1.25 mg/day), and an additional 10 days of E + MPA. As predicted, E decreased urinary excretion of calcium and hydroxyproline. MPA did not alter these excretion variables, either when given alone, or when added to E. Cyclic administration of MPA for 10 days is currently advocated to avoid the adverse endometrial consequences of unopposed estrogen. These data indicate that such a program does not interfere with the beneficial effect of estrogen on the calcium-parathyroid axis.
Adult↗
Alterations in coagulation and hemograms of horses given endotoxins for 24 hours via hepatic portal infusions.
This experiment was designed to establish a model for the study of gastrointestinal disturbances as a result of prolonged endotoxin uptake in the horse. The hepatic portal vein of 7 horses was catheterized (through flank incisions) to give chronic hepatic portal infusions of lipopolysaccharide (LPS, endotoxin). Lipopolysaccharide was infused at a rate of 1 microgram/kg of body weight/hr for 24 hours. Two of the horses were infused with saline solution for 12 hours before LPS infusions were given. Lipopolysaccharide was shown to affect behavior and hematologic and coagulation values. The 1st hour was critical for the LPS-infused horses; yet by 4 hours, the horses had apparently become refractory to continued infusion of LPS. During the 1st hour, all horses collapsed without an accompanying hypotension. A decrease in polymorphonuclear leukocytes (neutrophils) was seen during this time and was accompanied by a shortening of the recalcification tests, 1-stage prothrombin time, and activated partial thromboplastin time. There was an increased concentration of circulating fibrinogen/fibrin degradatory products. All of the LPS-infused horses showed signs of hoof discomfort and either stood with the 4 feet together beneath the body or continually shifted their weight from one front foot to the other. Hoof temperature decreased approximately 3 degrees (C) during this time and remained decreased for the duration of the experiment.
Animals↗
Computed tomographic scanning in Listeria monocytogenes meningitis.
Seven adults with Listeria monocytogenes infection of the central nervous system had computed X-ray tomography of the head performed. One patient had a normal scan, three had hydrocephalus; cerebral edema, an arachnoid cyst and hyperemia were each noted in one patient. Atrophy of the vermis of the cerebellum was demonstrated on follow-up scans in two patients. Further studies are necessary to determine whether such atrophy is a frequent sequelae of L. monocytogenes central nervous system infection.
Adult↗
Human anti-lymphoma responses generated in vitro and in vivo following sensitization with allogeneic leukocytes.
Peripheral blood lymphocytes (PBL) from a patient with poorly differentiated lymphocyte lymphoma (PDLL), after stimulation for 7 days with X-irradiated allogeneic lymphocytes pooled from three or ten donors (poolx), were cytotoxic for autologous lymphoma cells. Some clones lytic for autologous lymphoma cells, that were derived from this patient's pool-stimulated cells, resembled cytotoxic T lymphocytes (CTL), while other clones resembled natural killer (NK)-like cells in that they also lysed NK-sensitive HLA-negative K562 cells. In a second patient with more advanced PDLL, PDL cultured with T-cell growth factor (which is produced following stimulation with mitogens or alloantigens) lysed autologous lymphoma cells. On the basis of these in vitro findings, we asked whether IV transfusions with X-irradiated allogeneic leukocytes would result in anti-lymphoma responses in vivo. Ten days after transfusions with X-irradiated leukocytes from four unrelated donors, the first patient's two previously palpable nodes were no longer palpable and he remained in complete clinical remission for 6 months. The second patient had a temporary partial remission with dramatic reduction in size of multiple cervical and axillary nodes within 2 weeks after receiving the leukocyte transfusions.
Cells, Cultured↗
Panic disorder.
Panic disorder is a subtype of anxiety manifested by discrete periods of apprehension or fear and at least four of the following somatic symptoms: dyspnea, palpitations, chest pain, choking, dizziness, depersonalization or derealization experience, paresthesias, hot and cold flashes, sweating, faintness, trembling, and fear of dying, going crazy, or doing something uncontrolled during an attack. Because the patient with panic disorder often selectively focuses on one of these somatic symptoms and may minimize or deny psychosocial distress, panic disorder is frequently misdiagnosed. As a result of the frightening nature of the symptoms, a pattern of overutilization of medical care systems frequently ensues. Panic disorder is usually precipitated by stressful life events, most commonly separation or loss, in a patient with a genetic or acquired vulnerability. As with other psychophysiologic illness (depression, duodenal ulcer) resolution of the acute stressful life event may not lead to resolutions of the physiologic changes. Two specific tricyclic antidepressants, imipramine and desipramine, have been shown to be effective therapeutic agents in treating panic disorder.
Adolescent↗
Crisis in biocommunications--dangers and opportunities.
Explore the source record for details and available documents.
Communication↗
The safe-neighborhood hypothesis of junk DNA.
Explore the source record for details and available documents.
Chromosome Aberrations↗
Cyclic nucleotides of canine antral smooth muscle. Effects of acetylcholine, catecholamines and gastrin.
1. The effects of acetylcholine, catecholamines and gastrin on the intracellular content of cyclic AMP and cyclic GMP in antral circular muscle have been determined. 2. Acetylcholine results in a significant but transient increase in intracellular cyclic GMP. 3. Isoproterenol and norepinephrine increase intracellular cyclic AMP. Based on half-maximal effective doses, isoproterenol is 2.7-times more effective than norepinephrine. The increase in intracellular cyclic AMP by both agents is inhibited by propranolol but not phentolamine, indicating that both agents act on the muscle cell by a beta-receptor-coupled mechanism. 4. Gastrin has no demonstrable effect on either cyclic AMP or cyclic GMP. This suggests that while gastrin and acetylcholine can produce a like myoelectric response in the muscle cell, the action of gastrin is mediated by a separate receptor, presumably on the muscle cell, and not by a release of acetylcholine.
Acetylcholine↗
Depot neuroleptics in a community mental health service.
Explore the source record for details and available documents.
Clopenthixol↗