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Biomedical subjects

C Black

Publications and source records attributed to C Black.

At least 163 records · Page 9Linked to original sources

Factor VIII related antigen in connective tissue disease patients and relatives.

This study assayed serum levels of FVIII Rag as a marker of endothelial injury in patients not only with frank connective tissue disease but also in those presenting with Raynaud's phenomenon and in families of those with systemic sclerosis. Elevated levels of FVIII Rag were found in 62% of patients with systemic sclerosis (SS), 38% with systemic lupus erythematosus (SLE), 67% with mixed connective tissue disease (MCTD) and in 17% with primary Raynaud's phenomenon. Twenty per cent of first degree relatives of patients with SS also demonstrated high levels of FVIII Rag and certain antibodies, namely those reacting with U1RNP and the centromere. The association between elevated FVIII Rag and antibodies linked to Raynaud's and vasculitis lends support to antibody involvement in pathogenesis. High levels of FVIII Rag in family members may reflect an increased susceptibility of endothelium to injury particularly since relatives also have a higher frequency of clinical features such as Raynaud's phenomenon.

Antibodies↗

HIV infection among lower socioeconomic strata prostitutes in Nairobi.

A cohort of 418 lower socioeconomic strata prostitutes were enrolled in a study of the epidemiology of sexually transmitted diseases (STDs) between January and April 1985. Sixty-two per cent of the women were seropositive for HIV infection at enrollment. Significant associations were found between HIV seropositivity and Tanzanian origin (OR = 2.12, CI 95% = 1.18-3.81, P less than 0.03), younger age, a shorter duration of prostitution, reduced fecundity, use of oral contraceptives (OR = 1.8, CI 95% = 1.1-2.9, P less than 0.05) and genital ulcer disease (OR = 3.32, P less than 0.00001). No associations were noted with other STD. Stepwise logistic regression analysis confirmed independent associations between HIV infection and Tanzanian origin (OR = 2.27, CI 95% = 1.25-4.14, P less than 0.007), reduced fecundity (OR = 0.83, CI 95% = 0.74-0.94, P less than 0.003), oral contraceptive use (OR = 2.02, CI 95% = 1.22-3.35, P less than 0.006) and duration of prostitution (OR = 0.39, CI 95% = 0.23-0.65, P less than 0.004). Oral contraceptives may increase susceptibility to HIV or may be a marker for other factors which increase risk of acquisition. Further studies are necessary to confirm this association.

Acquired Immunodeficiency Syndrome↗

IgG heavy-chain subclass restriction of thyrotropin-binding inhibitory immunoglobulins in Graves' disease.

The IgG subclass composition of antibodies is an important determinant of their function. Thyrotropin receptor antibodies cause the hyperthyroidism of Graves' disease but their subclass distribution has been incompletely investigated. We have therefore purified IgG subclasses from Graves' sera by passage over affinity columns designed to deplete all but a single subclass, and then assayed those pure subclass fractions for their ability to displace radiolabelled thyrotropin from its solubilized receptor as a measure of thyrotropin receptor antibody activity. Sufficient activity was recovered for analysis in nine of 10 Graves' patients, in five of whom activity was almost completely (97-100%) restricted to the IgG1 subclass; in the remaining four patients the response was predominantly IgG1 and IgG4 with marked under-representation of the IgG2 subclass. This contrasts with the unrestricted subclass response, in the same fractions, for autoantibodies against thyroglobulin and microsomes. These results suggest that there may be a primary defect at the B-cell level in Graves' disease.

Autoantibodies↗

Characterization of mucous cell synthetic functions in a new primary canine gastric mucous cell culture system.

Mucin is a critical component of the protective layer secreted by gastrointestinal mucous cells. A detailed understanding of the molecular processing of gastric mucin and the physiology of its secretion has been limited by the lack of an adequate model for their study. We have developed a primary culture system of canine gastric mucous cells that has permitted us to study their synthetic and secretory functions. It was found that [3H]glucosamine used for metabolic labeling studies was incorporated into both mucin and lipid components of gastric mucus. To measure mucin with this model, a new immunoassay was developed to quantitate canine gastric mucin. Mucin was purified from the canine stomach, a polyclonal antibody was generated, and an enzyme-linked immunosorbent assay for gastric mucin was established. Mast cells were frequent contaminants of the gastric mucous cell preparation, and two methods were developed to limit their contamination. A new culture system has been developed for the study of gastric mucous cells. These cells synthesize and secrete both mucin and phospholipids. This system will permit us to study the molecular processing of mucin and the physiology of its production and release.

Animals↗

Geographical clustering of scleroderma in south and west London.

Anecdotal observation suggested a local increase in the occurrence of scleroderma within a borough in close proximity to a major airport. Ascertainment of all living cases was attempted within that borough and adjacent boroughs as well as a similar exercise in two further boroughs in close proximity to another major airport. The results showed a higher prevalence of scleroderma in all three study areas compared to that expected based on a population survey in another part of the United Kingdom adopting similar methodology. Further, within the boroughs there was a suggestion that the cases were not uniformly distributed but tended, in part, to cluster in those parts of the study areas that were in fact near to the airports under investigation. The increase in absolute risk was not sufficiently high to be consistent with a major environmental hazard. There is also no biologically plausible hypothesis for these observations. Nevertheless, the observation is of interest and might suggest further lines of inquiry for aetiological research.

Adolescent↗

Normal immune responses in systemic sclerosis.

Cellular and humoral immune responses were assessed in 24 patients with systemic sclerosis and matched controls by immunization with a thymus dependent (TD) antigen, keyhole limpet hemocyanin (KLH), a and thymus independent (TI) antigen, dinitrophenylated Ficoll (DNP-Ficoll). Cell mediated immunity in the patients with systemic sclerosis expressed as delayed cutaneous hypersensitivity to KLH, as well as the primary T dependent and T independent antibody responses were normal. Our findings suggest that there is no generalized defect in the immune responsiveness of patients with systemic sclerosis. There is however evidence that specific defects may occur in certain subsets of patients with systemic sclerosis.

Adult↗

Ketanserin and capillary flow in Raynaud's phenomenon.

The serotonin (S2) antagonist ketanserin has been proposed as a useful therapy for Raynaud's phenomenon. The present study was designed to investigate the effects of 8 weeks therapy with oral Ketanserin (40 mg tds for the last 6 weeks) on finger nailfold capillary flow velocity at rest and following cold challenge and symptom score in 30 patients with Raynaud's in a double-blind, placebo-controlled, parallel design study. The ketanserin treated group reported a 16.7% improvement in symptom score (p less than 0.05) relative to the end of the run-in phase compared with a 2.4% (NS) improvement in the placebo group. Improvement in capillary flow was confined to a significant (p less than 0.02) rise in rest flow in the ketanserin treated group but no beneficial changes were observed following cold challenge. The disparity between the subjective and objective benefits demonstrated for this drug suggest the possibility of a central action rather than one that involves the correction of a local vascular fault.

Adult↗

Genetic factors in scleroderma.

1. In no ethnic group is the overall association between SSc and the MHC, T-cell receptors, or drug metabolism phenotypes strong enough for direct clinical use. 2. Indications are that associations between specific subsets of SSc patients and genetic markers will assume greater importance both diagnostically and prognostically. The lung fibrosis group may be a prime candidate. 3. Genetic markers are useful means of relating chemically induced SSc-like disorders with the classical disease. Vinyl chloride disease is an example. 4. Evidence is emerging of strong associations between certain genetic markers and autoantibody production; a similar story has emerged in SLE. We believe that genetic testing will influence therapy in at least a subset of SSc patients, but that a dramatic breakthrough will not be made until we know how the genetics of the disease relate to the primary biochemical disease characteristic, that is the overproduction of collagen. In this respect, it has been suggested that the 5' flanking DNA of dermal collagen genes is particularly susceptible to the binding by Scl-70 (topoisomerase I). A problem is how to combine this and the other observations discussed above. Chromosomal instability can be linked to both the MHC and SSc-inducing chemicals, and the association of autoantibodies to topoisomerase I provides a tentative link between the MHC and collagen gene expression. Although the role and reason for anti-Scl 70 in SSc is unknown, humoral autoimmunity, at least in SLE, appears to be strongly dependent on specific HLA genes.

Chromosome Aberrations↗

Neuronal modulation of Schwann cell glial fibrillary acidic protein (GFAP).

Adult rat sciatic nerves contain cytoskeletal peptides that resemble CNS glial fibrillary acidic protein (GFAP) in immunoreactivity and molecular weight. Immunohistological examination of teased nerve fascicles indicated that these peptides are expressed selectively by Schwann cells related to small axons. Radiolabelled mouse and rat CNS GFAP cDNA probes hybridized with a single, 2.7 kb RNA band in Northern blots prepared from total RNA from both rat sciatic nerve and rat brain. Sciatic nerve GFAP mRNA was detectable by this means in adult, 2 month, or 21 day postnatal rats, but not in 3,6, or 10 day postnatal rats. Sciatic nerve transection caused a marked reduction in the level of GFAP mRNA in the axotomized distal stump. We conclude that Schwann cell synthesis of GFAP is developmentally regulated and that Schwann cells, unlike astroglia, require continued trophic input from small axons in order to express GFAP.

Aging↗

A prospective study to identify the fall-prone patient.

A prospective study in 16 patient care units in two institutions was conducted to assess patients' risk of falling. Three types of patient care units were utilized (acute medical and surgical, long term geriatric and rehabilitation areas), with 2689 patients over a 4-month period rated daily for fall risk using the Morse Fall Scale. Differences in mean fall score were evident between the acute care areas and the long term and the rehabilitation areas. Examination of the scores in the acute care institution by length of stay, showed different patterns of fall risk; the mean score of the long term patients showed less variation and higher scores. Patients' falls were analyzed by fall score and type of fall. All types of falls (anticipated physiological, unanticipated physiological and accidental), and the severity of injuries increased, with increasing scores indicating clinical validity of the scale.

Accidental Falls↗

Identification by cell electrophoresis of a subpopulation of polymorphonuclear cells which is increased in patients with rheumatoid arthritis and certain other rheumatological disorders.

Two and occasionally three electrophoretic subpopulations of polymorphonuclear cells (PMNs) were identified in the blood of normal healthy subjects and patients with rheumatoid arthritis (RA). Most of the PMNs from both groups of subjects were found in the population with the highest surface charge; the remainder being in the other distributions, which were collectively termed the slow cell population. There was a significant increase in the percentage of rheumatoid PMNs (mean 42%) ascribed to the slow population when compared with PMNs from normal subjects (mean 17%). A similar increase in the slow cell population was also seen in patients with Felty's syndrome (mean 38%) and scleroderma (mean 51%), but not in patients with Behçet's syndrome (mean 18%). Synovial fluid aspirated from the knee joints of patients with RA contained PMNs with the lowest surface charge. With nylon fibre as an adherence substrate cells of a low surface charge were found to be more adherent than those of a high surface charge. An alteration in the electrophoretic distribution of PMNs may represent changes that are related to the expression of functionally related membrane ionogenic groups.

Arthritis, Rheumatoid↗

Increased incidence of spontaneous abortion and infertility in women with scleroderma before disease onset: a controlled study.

A postal questionnaire was used in a nationwide case control study of women with scleroderma to investigate whether there was an increased rate of spontaneous abortion before the onset of the disease. The results from 155 case control pairs studied showed that the women with scleroderma had twice the rate of spontaneous abortion and three times the rate of fertility problems (no successful pregnancy by the age of 35) of the control women. Previous uncontrolled studies have suggested that established scleroderma is associated with an adverse reproductive history. The results from this investigation suggest that the adverse reproductive history may antedate the clinical diagnosis of scleroderma by many years and may possibly have an aetiological role. Such a hypothesis is consistent with the, as yet unexplained, marked female excess in incidence of the disease, with the peak age of onset occurring shortly after the reproductive period.

Abortion, Habitual↗

In vivo exposure to ozone causes increased in vitro responses of small airways.

We examined the effects of in vivo exposure to 3 ppm ozone on in vitro reactivity of large and small airways from dogs. No effects in large airways were detected. However, small airways exposed to O3 had larger responses to receptor-mediated stimuli and similar responses to KCl plus phorbol ester. These results suggest that small airways are more vulnerable to O3 inhalation than are large airways and that receptor-mediated pathways reflect that sensitivity. Another possible explanation is that O3 exposure prevents the epithelium from playing its normal dampening role in responses to contractile agonists.

Animals↗

The effect of Medicaid criteria on pediatric emergency department visits.

The use of the emergency department by children on Medicaid was documented, and the effect of new adult Medicaid criteria on a pediatric emergency department was investigated. Eight percent of daytime visits by all patients were nonemergencies, compared to 15% by Medicaid patients. More Medicaid patients required admission than other children (16% v 10%) seen in the emergency department. Emergency department use by Medicaid patients was not decreased by the new criteria. Documentation of inappropriate denials of emergency care when criteria designed for adults were applied to pediatric patients was presented to state health officials and resulted in a change in the state Medicaid criteria for emergency care of children.

Arkansas↗

Medicare use and cost of short-stay hospital services by enrollees with cataract, 1984.

In this article, we present data on aged and disabled Medicare hospital insurance enrollees discharged with the principal diagnosis of cataract from short-stay hospitals. Medical technology has reduced the risk of cataract surgery and the time needed to perform the surgery. As a result, the number of enrollees undergoing cataract surgery has increased. Also, such surgery has been shifted from inpatient hospitals to outpatient facilities. However, outpatient reimbursement for cataract surgery often equals or exceeds inpatient payments. To address this inequity, Congress legislated payment limits for cataract surgery.

Aged↗

Autoantibodies and immunogenetics in 30 patients with systemic sclerosis and their families.

Clinical and serological evidence of connective tissue disease was found in a high proportion of 132 family members of 30 patients with systemic sclerosis. In 20 probands with the milder CREST form of the disease, 10 had HLA-DR5 and 12 had null alleles at the C4 loci. None of 11 probands with more severe systemic sclerosis had HLA-DR5; all 11 had null alleles at the C4 loci. All but two of the probands had either HLA-DR5 or a C4 null allele, and this was also the case for the majority of the relatives with autoantibodies. Genetic markers of the major histocompatibility complex, including HLA-DR5 and C4 null alleles, appear to be closely associated with markers of disease in these probands and their families.

Antibodies, Antinuclear↗