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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 937 records · Page 52Linked to original sources
PubMed1987

Production of mycoplasma-specific antisera in rabbits immunologically tolerized at birth to mycoplasma medium constituents.

Neonatal rabbits were injected intraperitoneally (i.p.) within 12 h of birth followed by similar injections every day for 10 consecutive days and then every second day for a further 8 weeks, with mycoplasma broth medium (tolerogen), to induce immune tolerance. The rabbits were then immunized with the porcine mycoplasmas, M. hyopneumoniae or M. hyorhinis at 9 weeks of age. Immune sera obtained from these rabbits and from normal control rabbits were tested for antibodies against both mycoplasma antigens and for antibodies to medium components by double immunodiffusion in agarose and by enzyme-linked immunosorbent assay (ELISA). Antisera obtained from the tolerized rabbits contained no antibodies to medium components as evidenced by lack of reactivity in both assays. In immunofluorescence tests the antisera obtained from tolerized rabbits permitted specific staining of colonies of the homologous mycoplasma grown on mycoplasma agarose medium. In contrast the antisera obtained from normal rabbits produced strong reactions in all of the tests and non-specific background fluorescence due to reactions with components of the culture medium.

Animals↗
PubMed1987

Reactive T cells in the immune repertoire: self-restricted and allo-restricted helper T-cell clones to Epstein-Barr virus.

Helper T-cell clones were generated by stimulation with autologous or allogeneic lymphoblastoid B cells (B-LCL) transformed by the Epstein-Barr virus (EBV). Some of these T-cell clones were allo-reactive and others were specific to EBV-transformed B-LCL. Helper T-cell clones specific to EBV-transformed B-LCL were restricted either by class-I or by class-II HLA molecules of self. T-cell clones restricted by class-I HLA molecules were stained by OKT3 and OKT8 monoclonal antibodies (MAbs), whereas class-II-restricted clones stained with OKT3 and OKT4. Not all helper T-cell clones specific to EBV-transformed B-LCL were restricted to self: one clone restricted by allo-HLA antigen was established. This finding suggests that in humans, as in mice, some T cells in the T-cell repertoire can be allo-restricted. This allo restriction may represent cross-reactivity of T cells, whereby "self + X" equals "allo + Y." Activation of these cross-reacting T cells restricted by allogeneic HLA molecules during infectious mononucleosis will give a T-cell response which may appear unrestricted by self HLA molecules. This mechanism helps to explain, at least in part, the HLA unrestricted cytotoxicity to B-LCL observed in infectious mononucleosis.

Antigens, Surface↗
PubMed1987

Detection of abnormality of fetal urinary tract as a predictor of renal tract disease.

Over three years all infants in this hospital found to have an abnormality of the urinary tract on antenatal scanning were followed up after delivery with contrast radiography. Disease of the renal tract was confirmed in 17 of 20 infants. Of the 15 survivors, 12 underwent surgery in the first year of life. Abnormality of the fetal urinary tract detected by ultrasound scanning seems to be an important indicator of disease of the renal tract. Before its use is extended, however, further assessment of the benefit of antenatal diagnosis and of the best time to scan is required.

Female↗
PubMed1987

Ion-molecule calculation of the abundance ratio of CCD to CCH in dense interstellar clouds.

Laboratory measurements and calculations have been performed to determine the abundance ratio of the deuterated ethynyl radical (CCD) to the normal radical (CCH) which can be achieved in dense interstellar clouds via isotopic fractionation in the C2H2+ (HD) = C2HD+ (H2) system of reactions. According to this limited treatment, the CCD/CCH abundance ratio which can be attained is in the range 0.02-0.03 for the Orion molecular cloud and 0.01-0.02 for TMC-1. These ranges of numbers are in reasonable agreement with the observed values in Orion and TMC-1. However, the analysis of the CCD/CCH abundance ratio is complicated via the presence of competing fractionation mechanisms, especially in the low-temperature source TMC-1.

Acetylene↗
PubMed1987

A phase I study of recombinant interferon gamma administered by s.c. injection three times per week in patients with solid tumours.

Human recombinant DNA interferon gamma (IFN-G), with a specific activity of 2 X 10(6) IU/mg protein, was administered s.c. 3 days per week for 2 months to patients with solid tumors. The maximum tolerated dose (MTD) was 10 X 10(6) IU/m2 (5.0 mg/m2) per injection, and six patients were treated at the MTD. Two of these ceased treatment because of severe subjective toxicity (headache, rigors and pyrexia) and three patients developed WHO grade 3 leucopenia. Subjective toxicity varied considerably between patients and some patients at low dose levels experienced severe constitutional symptoms whilst others treated at the MTD had few side effects. These differences were unrelated to pharmacokinetic parameters. Bioavailability of this IFN-G administered s.c. was very variable from one patient to another at the same dose level. We therefore counsel caution in using this IFN-G preparation s.c. in phase II studies.

Adult↗
PubMed1987

Failure to preserve fertility in patients with Hodgkin's disease.

The hypothesis that the "down-regulated" gonad is less vulnerable to the effects of cytotoxic chemotherapy for advanced Hodgkin's disease has been investigated. Thirty men and eighteen women were randomly allocated to receive an agonist analogue of gonadotrophin-releasing hormone prior to, and for the duration of, cytotoxic chemotherapy. Buserelin (d-Ser-[TBU]6 LHRH ethylamide) was prescribed in two different dosage schedules to twenty men, and in a single dosage schedule to eight women. A standard gonadotrophin-releasing hormone test (GnRH 100 micrograms) was performed 1 week prior to and on day 1 of each cycle of chemotherapy. In all patients peak luteinizing hormone responses to GnRH were suppressed throughout treatment. The higher of the two dosage schedules used in the men caused more effective suppression of luteinizing hormone, and both regimens led to an initial suppression of peak follicle-stimulating hormone responses to GnRH, which was not maintained. At follow-up assessment up to 3 years from the completion of treatment, all men treated with buserelin were profoundly oligospermic and four of the eight women were amenorrhoeic. All ten male controls were profoundly oligospermic, and six of nine female controls were amenorrhoeic. In the dosages and schedules investigated, buserelin was ineffective in conserving fertility.

Amenorrhea↗
PubMed1987

A phase I study of rDNA alpha-2b interferon as a 6-week continuous intravenous infusion.

Sixteen patients with advanced malignancy were treated with rDNA alpha-2b interferon using a continuous 6-week i.v. schedule. Patients received 1 microgram, 3 mu [corrected], 5 mu and 7 mu/m2/day via a portable infusion pump system, all therapy being on an outpatient basis. The dose-limiting toxicity occurring at 7 mu/m2/day [corrected] was lethargy and somnolence. Five million units (mu) was the maximum tolerated dose but significant nausea, anorexia and lethargy affected 4/5 patients at this level. A dose of 3 mu/m2/day was well tolerated, producing little disturbance of normal activity in the majority of patients. Suppression of WBC and platelets was seen at all doses but was not dose-limiting. There was increasing severity of derangement of hepatic transaminases with increasing dose, and the occurrence of liver toxicity appeared to correlate with nausea, anorexia and lethargy. Assay of serum interferon during the infusion showed that this system maintained a constant level of interferon in the blood. However, the increase did not show a linear pattern with increasing dose, suggesting saturation of metabolic inactivation at 7 mu/m2/day. We recommend that a dose of 3 mu/m2/day be used in future studies of prolonged infusions of alpha-2 interferon.

Adult↗
PubMed1987

Correlates of fantasy-induced and film-induced male sexual arousal.

Penile circumference and subjective arousal were recorded while 66 men attempted to achieve erection by engaging in fantasy. Similar measures were taken while the same men viewed an erotic film. Not only was fantasy-induced sexual arousal relatively unrelated to film-induced sexual arousal, but the two sets of measures had different correlates. Over and above the contribution attributable to demographic and state variables, the subjects' rated level of fantasy during masturbation and their scores on the Betts QMI Scales predicted significant variance in subjective and physiological arousal. Subjects with low and high levels of fantasy-induced sexual arousal were differentiated on the basis of the vividness of their mental imagery as well as the frequency with which they used the most erotic sexual fantasies when attempting to achieve erection. In contrast to fantasy-induced arousal, film-induced arousal levels were independent of a person's capacity to form images.

Adolescent↗
PubMed1987

The CaATPase activity of rat-incisor odontoblast vesicles.

An homogenate of rat incisor odontoblasts had Ca2+ and Mg2+ ATPase activity and suitable storage conditions kept it stable for several days. Over 90 per cent of the activity was retained in a vesicle-rich microsomal fraction that removed about 85 per cent of the total material from the homogenate. This fraction was further characterized: the resolved Ca2+-activated ATPase activity, above the basal MgATPase activity, was 0.30 mumol Pi/min-mg total protein, and 50 per cent activated at free [Ca2+] equal 0.8 microM. This calcium dependency is consistent with an intracellular Ca2+-regulated enzymatic activity. The calcium ionophore, A23187, had no measurable effect on the CaATPase activity, which suggests that the odontoblast vesicles do not concentrate Ca2+ in a lipid bilayer compartment. Direct measurement of the uptake of 45Ca2+ by the filtration method and parallel measurements of CaATPase activity on the same preparations under identical conditions indicated that the odontoblast-derived vesicles have a coupling ratio of 0.024 Ca2+/ATP. This low coupling ratio and the lack of detectable compartmentalization of calcium indicate that the CaATPase activity of the odontoblast microsomes is not associated with a calcium pump. The [Ca2+] dependence of the activity suggests the CaATPase is under intracellular Ca2+ control, but its function is unknown.

Animals↗
PubMed1987

In vivo glucose metabolism in the awake rat: tracer and insulin clamp studies.

The goals of this study were twofold: (1) to determine the in vivo dose-response relationship in the conscious, unstressed rat between the plasma insulin concentration and total body glucose uptake, and between plasma insulin and suppression of endogenous glucose production; and (2) to develop a physiologic compartmental model to describe the kinetics of plasma glucose in the rat in the basal state. In order to perform repeat insulin clamp studies in the same rat, chronic catheters were implanted in the aortic arch (via the carotid artery) and in the cardiac atrium (via the jugular vein), exteriorized, and fixed to the back of the skull with a dental cement cap. Insulin was infused at rates of 1.2, 2.4, 4.8, 12, and 24 mU/min.kg, and the plasma glucose was held constant at the basal level by a variable glucose infusion (euglycemic insulin clamp). The resulting steady-state plasma insulin concentrations ranged from 40 to 1,300 microU/mL. The dose-response curve for glucose uptake was sigmoidal in shape: in the basal state, total glucose utilization averaged 6.8 mg/min.kg at an insulin concentration of 9 microU/mL, half-maximal glucose uptake (18.3 mg/kg.min) occurred at a plasma insulin concentration between 70 and 80 microU/mL, and maximal uptake (36.6 mg/kg.min) was seen at an insulin level in excess of 100 microU/mL. Residual endogenous glucose production was evaluated by a prime-continuous infusion of (3-3H)-glucose. The dose-response curve for suppression of endogenous glucose output also was sigmoidal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

GABA, benzodiazepine and serotonergic receptor development in the dorsal raphe nucleus: electrophysiological studies.

To assess potential differences in the functional responsiveness of GABAergic and serotonergic receptors during postnatal development, extracellular recordings were made in in-vitro midbrain slices containing the dorsal raphe nucleus (DRN). Pacemaker-like activity analogous to that observed in vivo was induced by superfusing the slices with 2.5 microM phenylephrine. GABA (0.001 M) and 5-HT (0.004 M) dissolved in 0.1 M NaCl were applied microiontophoretically for 1-min intervals using a range of iontophoretic currents. The current required to produce a 50% inhibition in firing was determined using logit and regression procedures. Iontophoretically applied picrotoxin, baclofen, and bicuculline were applied alone and in combination with GABA to characterize the neonatal GABA receptor site. The pharmacology of the GABA responses observed in early postnatal DRN neurons was that associated with the GABAA subtype. No significant changes in sensitivity to iontophoretically applied 5-HT or GABA were observed at any time during postnatal development. The application of the benzodiazepine, clonazepam, in the perfusion fluid at doses between 10(-8) and 10(-7) potentiated the inhibitory effects of GABA in the slices, but produced no consistent inhibitory effect by itself. The increased potentiation of GABA's effects by benzodiazepine was greatest in neonatal animals. This finding is consistent with previous literature showing enhanced coupling of the GABA-benzodiazepine complex at early postnatal ages.

Action Potentials↗
PubMed1987

Effects of long-term Org OD 14 administration on blood coagulation in climacteric women.

98 post-menopausal women were randomly allocated to either Org OD 14 [(7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one] 2.5 mg/day or placebo. Treatment was continued for up to 6 yr. Any thromboembolic episode that occurred was recorded. Prothrombin time (PT), partial thromboplastin time (PTT), factor VII level and factor X level were measured prior to treatment and at yearly intervals. Antithrombin III level was measured in the last two yr of the study. There was one cerebrovascular accident after 3 months of placebo therapy but no other thromboembolic episodes. No significant difference was found between the effects of Org OD 14 and placebo with regard to any clotting factors at any time interval, although factor VII and factor X levels were consistently lower in the OD 14 group than in the placebo group. Antithrombin III levels measured after 5 and 6 yr were significantly higher (P less than 0.01) in the OD 14 group, suggesting a reduced risk of thrombosis in the treatment group.

Blood Coagulation↗
PubMed1987

Effect of aryl 4-guanidinobenzoates on the acrosin activity of human spermatozoa.

Certain aryl 4-guanidinobenzoates (AGs; inhibitors of proteinases, including the sperm enzyme acrosin) have been shown to be more potent vaginal contraceptives in rabbits and less toxic than nonoxynol-9, the active ingredient of most marketed vaginal contraceptive formulations. To determine if these AGs can contact sperm and inhibit acrosin when mixed with the entire human ejaculate for a short period of time (roughly imitating clinical conditions), the inhibitors were added to semen at various concentrations for 2 min, after which the seminal plasma and unbound inhibitor were removed from the sperm by Ficoll centrifugation. Subsequently, the total arginine amidolytic activity of the spermatozoa was determined spectrophotometrically after a combined treatment that resulted in extraction, proacrosin activation, and reaction with substrate. Dose-response curves were prepared. All AGs studied were effective inhibitors of the amidolytic activity under these conditions, with ED50 values (the dose levels at which half of the acrosin associated with 10(6) sperm is inhibited) ranging from 10(-5) to 10(-7) M. To determine the effect on the proteolytic activity of individual spermatozoa, the experiment was repeated with 4'-acetamidophenyl 4-guanidinobenzoate (AGB), and the protease released from the sperm was measured by the gelatin-plate assay. The inhibition results were similar to those obtained by extraction of the spermatozoa and measurement of amidolytic activity. Thus, when mixed with the human ejaculate, AGs interact rapidly with spermatozoa to inhibit both their arginine amidolytic and proteolytic activity (probably due primarily or only to inhibition of acrosin) and remain bound even after removal of the seminal plasma. These data encourage further study of the compounds for contraceptive purposes.

Acrosin↗