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Biomedical subjects

A M Williams

Publications and source records attributed to A M Williams.

At least 91 records · Page 5Linked to original sources
PubMed1989

Dissipation mechanisms for 5-hydroxytryptamine in the coronary circulation of the isolated perfused heart of the rat.

1. The contribution of uptake into vascular endothelial cells, of neuronal uptake and of extraneuronal uptake in the dissipation of 5-hydroxytryptamine (5-HT) perfused through the coronary circulation of the rat heart was examined. 2. Hearts from reserpine-pretreated rats were isolated and perfused in vitro with 5-HT, in the absence or presence of inhibitors, and rates of appearance of the deaminated metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in the venous effluent were measured using an h.p.l.c. assay. 3. The steady-state rates of 5-HIAA appearance in the venous effluent in hearts perfused with 1 microM 5-HT (422 +/- 8.48 pmol g-1 min-1, n = 12) were reduced by pretreatment of the rats with 6-hydroxydopamine (22% inhibition), and by inclusion in the perfusion solution of 30 microM cocaine (28% inhibition), 100 microM 3-O-methylisoprenaline (64% inhibition), 100 microM corticosterone (58% inhibition), or 30 microM cocaine and 100 microM 3-O-methylisoprenaline (87% inhibition). 4. The extraneuronal deamination of 5-HT in the heart was saturable (Km = 101 microM, Vmax = 31.2 nmol g-1 min-1). The neuronal deamination of 5-HT was saturated by about 50 fold lower concentrations of 5-HT than was extraneuronal deamination, but Km and Vmax values could not be determined. 5. In the coronary circulation of the rat heart, 5-HT was dissipated by the uptake processes for catecholamines, extraneuronal uptake (predominantly) and neuronal uptake, and subsequent metabolism by monoamine oxidase. There was no evidence that a cocaine-sensitive uptake of 5-HT into vascular endothelial cells made any significant contribution to 5-HT dissipation in the heart.

Animals↗
PubMed1988

Immunosuppressive treatment of aortic allografts.

Immunosuppression with cyclosporine (CsA) was explored as a means of preventing arterial allograft rejection and failure. Aortic allografts across the major histocompatibility barrier were studied in Brown-Norway and Lewis inbred rats. Grafts 1 cm long were interposed into the infra-abdominal aorta of Lewis recipients; five groups included two groups of untreated isograft and allograft control animals and three groups had allograft-CsA treatment regimens. The grafts were examined at 30, 60, and 100 days for patency, aneurysmal dilation, gross structural changes, inflammatory responses, and infiltration of W3/25- and OX8-positive lymphocytes. Only three allograft controls became occluded; the rest showed significant dilation (p less than 0.01), medial thinning and necrosis, intimal proliferation, and prominent cellular infiltration at 30 days. With all CsA regimens, aneurysmal dilation was significantly reduced or prevented (p less than 0.01), correlating with medial smooth muscle cell preservation. Cellular infiltration was delayed by an average daily dose of 5 to 10 mg/kg subcutaneous CsA for 30 days and was suppressed at 100 days by a continuous 5 mg/kg dose every 4 days. Intimal thickening in the graft was delayed but not prevented. We conclude that a low maintenance dose of CsA provides effective immunosuppression, thereby preventing aneurysm formation, and that the potential use of arterial allografts in vascular surgery may need to be readdressed.

Animals↗
PubMed1987

Anti-T cell monoclonal antibodies in vivo. I. Inhibition of delayed hypersensitivity but not cutaneous basophil hypersensitivity reactions.

As part of a study of the therapeutic potential of anti-T cell monoclonal antibodies, we studied the biologic effects of 8BE6, a mouse anti-guinea pig (GP) pan-T cell monoclonal antibody, on blood and tissue T cells and on the prototypic T cell-mediated reactions, classic delayed hypersensitivity (DH) and cutaneous basophil hypersensitivity (CBH). 8BE6 reacts to a 68,000 m.w. protein probably homologous with human CD5 (T1) and murine Lyt-1. A single dose of 1.8 to 3.4 mg 8BE6 caused lymphopenia and greater than 90% depletion of 8BE6+ peripheral T cells 1 to 72 hr later, and a significant but lesser decrease of lymphocytes reacting with another pan-T cell monoclonal antibody (p less than 0.02 at 24 hr). Free serum 8BE6 was detected for up to 48 hr after administration. Immunoperoxidase stains of tissue revealed that lymphocytes in lymph nodes and spleen were coated with mouse immunoglobulin 1 hr after antibody treatment and displayed in situ capping. Subsequently, there was a loss of T cells in all tissues (spleen, lymph node, liver, and kidney) except the thymus, with normal 8BE6 antigen staining returning by 72 hr. Areas of induration of DH reactions to PPD were reduced in 8BE6-treated GP, compared with pretreatment reactions in the same GP or in control-treated GP (p less than 0.001 for both). The numbers of infiltrating T cells and fibronectin-receptor-positive macrophages were also reduced. In contrast, 8BE6 had no effect on CBH reactions, as judged by erythema and basophil counts in 1-micron sections, although fewer T cells were found in reaction sites. There were no differences in IgM, fibronectin, or Ia staining between 8BE6-treated GP and controls. In vivo administration of a single dose of anti-T cell monoclonal antibody results in a transient, highly specific depletion of T cell populations in peripheral blood and tissues except the thymus. This treatment inhibits DH but not CBH reactions by systemic and local depletion of T cells.

Animals↗
PubMed1987

Anti-T cell monoclonal antibodies in vivo. II. Modulation of acute and chronic experimental allergic encephalomyelitis (EAE) in guinea pigs.

To determine the effects of anti-T cell monoclonal antibody-induced systemic T cell depletion in neuro-autoimmune disease, we studied the in vivo effects of 8BE6, a mouse anti-guinea pig (GP) pan-T cell monoclonal antibody, on the course and immunopathology of the disease model experimental allergic encephalomyelitis (EAE) in adult Strain 13 GP. Central nervous system (CNS) tissues were studied by routine histology and by an immunoperoxidase staining technique using monoclonal antibodies to T cells, IgM, and macrophages. From 3 days before to 10 days after sensitization with GP spinal cord and complete Freund's adjuvant, the GP were given one or two i.p. doses of 3.4 mg 8BE6 or MOPC 21, the parent mouse myeloma ascites, or normal saline. Eighteen of 18 control-treated GP developed typical acute, paralytic EAE 11 to 21 days after sensitization, whereas acute EAE was prevented in 33 of 49 8BE6-treated GP (67%), and the onset was delayed and disease progression was slowed in the others. Five GP treated with 8BE6 from days 11 to 14 after sensitization, at the onset of neurologic signs, rapidly deteriorated within hours after treatment and had loss of T cell staining, and lymphocytolysis in the CNS. 8BE6-treated GP which did not develop acute EAE were observed daily for up to 700 days (mean = 213 days). Twenty-nine of 39 (74%) had from one to six relapses or fixed neurologic deficits. GP in relapse were additionally treated with 8BE6 (22), MOPC-21 (5), or saline (6) in a cross-over protocol. Clinical scores were improved from days 2 to 12 after treatment (p less than 0.05), and complete recovery within 30 days occurred more frequently (p = 0.046) and more rapidly (p less than 0.01), after 8BE6 as compared with control treatments. Recoveries occurred more often if 8BE6 was given early in the relapse. Multiple treatments led to dose-dependent levels of serum antibodies to mouse immunoglobulin detected by an ELISA. There were no differences between acute and chronic EAE in numbers of inflammatory foci or numbers of macrophages and T cells in CNS infiltrates, but GP with chronic EAE had more extensive demyelination and vascular fibrosis and more numerous IgM+ B cells in parenchymal and meningeal infiltrates than in acute EAE (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1987

Radical radiation and oral and intra-vesical misonidazole for bladder cancer.

Patients with T2 grade 3 and T3 bladder cancer were entered into studies to evaluate the efficacy of 40 Gy in 2 Gy fractions (5/week) to the whole pelvis followed by 12 Gy in 6 Gy fractions (1/week) to a coned down volume plus oral and intravesical misonidazole (MISO). In a pilot study of 22 patients the complete response rate at cystoscopy at 6 months was 73% and the 5-year survival rate (life-table) with and without bladder preservation was 48% and 54% respectively. The 5-year bowel major complication rate (life-table method) was 8%. These results are statistically significantly improved over that seen in a series of historical controls. A prospective randomized trial has been completed comparing the above regimen with 40 Gy to the whole pelvis followed by 20 Gy to the coned down volume in 2 Gy fractions (5/week). Fifty-eight patients were entered and 53 are evaluable. The complete response rate at cystoscopy at 6 months is 69% (18/26) in the patients treated with MISO and 63% (17/27) in those treated without MISO. As this is an important prognostic indicator, it is unlikely that there will be an advantage in either group and this is supported by the initial follow-up data. The complete response rate at cystoscopy at 6 months is higher in both arms of this study than in the historical series.

Administration, Oral↗
PubMed1986

The effects of thyroxine treatment of rats on neuronal and extraneuronal uptake and metabolism of catecholamines in the heart.

The effects of thyroxine (T4) treatment of rats on the neuronal and extraneuronal uptake and subsequent metabolism of catecholamines in the heart were examined, to determine whether changes in the local dissipation of catecholamines might contribute to the enhanced sympathetic cardiac responses that occur when thyroid hormone levels are elevated. T4-treated rats were injected subcutaneously with L-thyroxine sodium 1 mg kg(-1) on days 1, 3 and 5, and controls were injected with the normal saline vehicle on the same days. The experiments on isolated, perfused hearts were carried out on day 8. The T4-treated rats had only 50% of the growth rate of the controls and their heart weights were 18% greater than the controls. The experimental data were adjusted to allow for the increase in heart weight caused by the T4 treatment. The initial rates of neuronal uptake of noradrenaline and of extraneuronal uptake of noradrenaline and isoprenaline in the hearts from T4-treated rats were not significantly different from those in hearts from control rats. The steady-state rates of extraneuronal O-methylation of isoprenaline and of extraneuronal deamination of noradrenaline in hearts from T4-treated rats were not significantly different from those in hearts from control rats. The steady-state rate of neuronal deamination of noradrenaline was significantly lower and the accumulation of unmetabolized noradrenaline in the hearts was significantly greater in T4-treated rats than in the controls. These findings could be explained by a decrease in neuronal monoamine oxidase activity or by an increase in intraneuronal binding of noradrenaline in hearts from T4-treated rats. 6 The study has shown that it is unlikely that increased plasma thyroid hormone levels cause cardiac supersensitivity to catecholamines by affecting the local dissipation processes for those amines in the heart.

Animals↗
PubMed1984

Radical irradiation and misonidazole for T2 grade III and T3 bladder cancer: 2 year follow-up.

Patients with T2 grade III and T3 bladder cancer were treated in a Phase II trial of radical irradiation plus Misonidazole (MISO). Forty Gy in 2 Gy fractions (5 per week) to the whole pelvis were followed by 12 Gy in 6 Gy fractions (1 per week) plus oral and intravesical MISO to a coned down volume. Twenty-two patients were treated and the results compared with historical controls. The cystoscopic complete tumor response between 6 and 12 months post therapy were 73 and 43%, respectively. The patient two year survival was 81 and 51%, respectively, and the patient 2 year survival with bladder preservation was 61 and 48%, respectively--4 patients in the MISO study having undergone salvage cystectomy. Complications that may be radiation related in the MISO study are wound sepsis after salvage cystectomy in 2 patients, rectal stenosis requiring colostomy 16 months after salvage cystectomy in 1 patient and the development of a contracted bladder in 1 patient with a history of prior extensive endoscopic therapy. No misonidazole neurotoxicity seen. These findings are being further evaluated in a prospective randomized trial.

Adult↗
PubMed1983

Factors determining the frequency content of the electromyogram.

The contribution of central and peripheral factors to the frequency content of the electromyogram was examined in 10 subjects performing maximal 45-s contractions of thenar muscles. The median frequencies (Fm) of surface-recorded electromyograms and compound action potentials were similar early (P greater than 0.6) and late (P greater than 0.5) in the contractions. There was a mean decrease in the Fm during contraction of 39% for electromyograms and 35% for compound potentials (P greater than 0.1). The Fm of electromyograms increased 11% (P less than 0.02) in only the 1st s of contraction as force was raised from 25 to 100% of maximum. Only one of five subjects showed evidence of increasing synchronization of motor unit discharge during contraction. There was no evidence that delay or dispersion of action potential propagation in terminal nerve fibers or at the neuromuscular junction had a significant effect on frequency content. The findings indicated that the spectral content of muscle electrical activity, and its shift during contraction, primarily reflects intrinsic muscle properties.

Adult↗
PubMed1982

The clearance of 131I-human plasma ferritin in man.

Ferritin was purified 33,000-fold from the plasma of patients with idiopathic hemochromatosis. The plasma ferritin was labeled with 131I and injected into 2 normal men. Clearance was found to be relatively slow, with 50% 131I-ferritin remaining in the plasma at 27-30 hr. The fraction of plasma ferritin that bound to concanavalin-A was found to be cleared more slowly than the nonbinding fraction. These findings confirm our previous suggestion that glycosylation is a major factor prolonging the survival of ferritin in the plasma, but differ from the results of earlier studies in experimental animals and preterm infants, which indicated very rapid plasma ferritin turnover.

Animals↗
PubMed1981

Membrane dynamics in the parotid acinar cell during regranulation: a stereological study following isoprenaline-induced secretion.

Recently weaned male rabbits were injected either with 150 micrograms/kg isoprenaline in saline containing 0.01 M ascorbic acid or simply with the drug vehicle. Groups of drug-injected animals were killed at various time after injection. Parotid gland tissue samples from all animals were fixed, embedded and thin sectioned, and micrographs were prepared at standard magnification. Estimations of membrane areas of each membrane type in parotid acinar cells were made. It was found that in animals killed 2 hours after induced secretion apical area was larger than in controls. In animals killed at successively later times the apical area was progressively less. No elevation of any internal smooth membrane areas was ascertained at any sampling time, though the areas of rough endoplasmic reticulum in 2-12 hour samples were larger. It is suggested that excess apical membrane, though probably removed by interiorization, is afterwards disassembled in side the cell to create fresh macromolecular building units (protein molecules), perhaps after passing through the Golgi apparatus. This cryptic pool of building units can provide about 900 micrometers2 of secretion granule membrane per cell, the supply apparently being exhausted in the first eight hours after degranulation, whilst granule numbers are being increased. Thereafter, apparently, limited granule fusion occurs, so that ultimately the cellular complement of secretion granule membrane comes to enclose a greater volume of secretory product, though the average granule number per cell is small.

Animals↗
PubMed1981

Occupational exposure to asbestos fibers resulting from use of asbestos gloves.

To assess the magnitude of fiber emission from asbestos gloves, 10 pairs were compared in an isolation chamber during simulation of a sterilization procedure; 176 air samples were collected. Means of time weighted average (TWA) concentrations ranged from 0.95 to 11.74 fibers (greater than 5 micrometers)/cm3 of air. Well-worn/clean gloves emitted significantly more fibers than did brand-new gloves, but fiber emission decreased with increased surface soiling. Eighty air samples were collected during simulation of the sterilization procedure in a well-ventilated room. The range of mean TWA concentrations was 0.07-0.99 fiber/cm3 for breathing zone samples and 0.06 to 0.60 fiber/cm3 for area samples. Thirteen samples were collected at actual workplaces; the range of TWA concentrations was 0.07-2.93 fibers/cm3 for breathing zone samples and 0.04-0.74 fiber/cm3 for area samples. Five of seven breathing zone samples from workplaces exceeded the proposed TWA concentration limit of 0.1 asbestos fiber/cm3. Hand contamination also was assessed. Four samples collected after touching the worktable ranged from 9953 to 13 108 fibers (greater than 5 micrometers)/cm2 of hand surface area; seven samples collected immediately after taking off gloves ranged from 741 to 3860 fibers/cm2. Available substitutes for asbestos gloves are discussed, and adoption of these substitutes is recommended strongly.

Air Pollutants↗
PubMed1980

Myasthenic syndrome: effect of choline, plasmapheresis and tests for circulating factor.

In a patient with myasthenic syndrome neuro-muscular transmission was characterised by depression and facilitation. The relative extent of these two processes varied between muscles, and in the one muscle with time. Guanidine HCl treatment corrected the electrophysiological defect. Oral choline increased muscle action potential amplitude in response to single shocks. Intravenous choline produced features indicating cholinergic autonomic stimulation. Pimozide and plasmapheresis had no effect. Animal in-vivo and in-vitro studies performed to detect a circulating factor which interferes with neuro-muscular transmission were negative.

Action Potentials↗
PubMed1979

The role of glucocorticoids, unstressful labor, and atraumatic delivery in the prevention of respiratory distress syndrome.

A 37 month review of the effects of glucocorticoids and uncompromised labor with atraumatic delivery on the incidence of respiratory distress syndrome (RDS) is presented. The incidence of RDS in the control and study population is not significantly different; however, the incidence of RDS in the control and study groups is markedly lower than the published figures for the same age and weight range. The low incidence of RDS in the control population is attributed to the avoidance of intrapartum hypoxia and stress during an uncompromised labor and atraumatic delivery.

Cesarean Section↗
PubMed1979

The quantity and quality of marital interaction related to marital satisfaction: A behavioral analysis.

An assessment instrument is presented for the evaluation of the quantity and quality of dyadic interaction, as well as for the daily recording of behaviors presented and omitted which influence marital satisfaction. Comparison of data from ten happy couples and from ten couples entering therapy indicated two distinct dysfunctional patterns among distressed couples, with significantly different patterns of time-together and positive/negative ratios differentiating the happy versus therapy groups. Independent behavioral recording for 14 consecutive days significantly increased husband-wife agreement on a traditional adjustment questionnaire without significantly increasing or decreasing the level of satisfaction being assessed. There was no difference between groups as to interspousal agreement on amount of time together. However, the happy couples agreed on daily quality ratings of the 72 15-minute segments significantly more often than did the distressed couples. Couples at the extremes of the happy-distressed continuum reported rewarding and punishing, respectively, in response to the partners presence, regardless of behaviors emitted. Midrange happy couples defined "pleasant" as positive behaviors presented; midrange distressed couples defined "pleasant" as negative behaviors omitted. Theoretical and clinical implications of behavioral analysis of sequential patterns are discussed.

Journal Article↗
PubMed1977

Validity of the Peabody Picture Vocabulary Test as a measure of hearing vocabulary in mentally retarded and normal children.

The Peabody Picture Vocabulary Test (PPVT) and the auditory and visual subtests of the Illinois Test of Psycholinguistic Abilities (ITPA) were administered to 48 normal and 48 retarded subjects. Results suggested that the PPVT is not an adequate measure of hearing vocabulary for mentally retarded subjects. Half of each group was given the visual reception subtest of the ITPA in a form which had been modified to control the visual memory variable. No differences were found as a function of that variable. It was concluded that caution should be exercised when using the PPVT as a clinical diagnostic procedure in the assessment of receptive auditory vocabulary.

Child↗