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Biomedical subjects

J S Beck

Publications and source records attributed to J S Beck.

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

Histometric studies on biopsies of tuberculin skin tests showing evidence of ischaemia and necrosis.

In a study of tuberculin skin tests in 216 consecutive untreated pulmonary tuberculosis patients, one showed central necrosis at 48 h: there was no effective blood flow at the centre of this lesion, but the periphery was markedly hyperaemic. Many dermal capillaries and venules contained deposits of fibrin, but none was occluded completely: the surviving cells in the dermal infiltrate were almost all macrophages. Five patients with strongly positive reactions at 48 h showed slower blood flow at the centre of the reaction than at the periphery (central relative slowing, CRS), possibly indicating central ischaemia short of necrosis: no fibrin deposits were seen in the dermal vessels of these skin test sites. The cellular infiltrate in the dermis was similar in distribution, but more abundant than that seen in uncomplicated positive reactions of comparable clinical size and with blood flow velocity maximal at the centre. At 48 h, lymphocytes were more numerous than macrophages in both groups, CD8 lymphocytes were more abundant in CRS reactions, but CD4 and CD25 (activated) T-lymphocytes and macrophages had a similar density in both groups. Epidermal CD1 cells were less frequent in CRS reactions than in uncomplicated positive reactions. Although CRS reactions showed more intense inflammation than the uncomplicated controls, none of the histometric measurements correlated with the extent of CRS. Follow-up studies showed that CRS reactions reverted to a normal hyperaemic blood flow pattern 5 days after antigen injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Effect of topically applied local anaesthesia on histamine flare in man measured by laser Doppler velocimetry.

The direct and indirect effects of histamine on the cutaneous microvasculature were measured by laser Doppler velocimetry. Histamine (6.51 x 10(-4) M) was injected intradermally into the forearms of eight healthy subjects following treatment with a topically applied local anaesthetic cream (EMLA) or equivalent placebo. The blood flow at the injection site (0 cm) and at 1 and 2 cm proximally was measured by laser Doppler velocimetry over 80 minutes. Analysis of the changes in magnitude of the hyperaemic responses with time showed no difference at the 0 and 1 cm sites, but a marked reduction was found at the 2 cm site following EMLA treatment (p less than 0.05). At all three sites the decay of the histamine-induced hyperaemia was faster following EMLA treatment than with placebo (p less than 0.04). The experiments showed that the indirect effect of histamine on the cutaneous microvasculature in the peripheral flare around the injection site was greatly diminished by prior application of EMLA cream and this supports the neurogenic hypothesis: pre-treatment with EMLA cream did not affect the development of hyperaemia and oedema at the site of histamine injection where the mediator acts directly on the cutaneous microvasculature.

Administration, Cutaneous↗
PubMed1989

Total and anti-mycobacterial IgE levels in serum from patients with tuberculosis and leprosy.

A radioallergosorbent assay (RAST) was developed and used to determine the levels of IgE antibodies to soluble antigens of Mycobacterium tuberculosis (BCG vaccine strain) in sera from patients with tuberculosis and leprosy and in healthy control subjects. Total IgE levels in the same sera were quantitated with a commercial radioimmunoassay kit. Patients with tuberculosis and leprosy had higher total and specific IgE levels than the control groups but the overlap of levels in patients and controls was too great to render the difference diagnostically useful. Specific IgE levels were elevated in both tuberculosis and leprosy patients, suggesting that this antibody response is towards the shared mycobacterial antigens. No differences in total or specific IgE levels were found between healthy hospital workers occupationally exposed to patients with tuberculosis and factory workers who are not exposed.

Antibodies, Bacterial↗
PubMed1989

Relationship between radiological classification and the serological and haematological features of untreated pulmonary tuberculosis in Indonesia.

Immunological and metabolic responses were studied in 110 patients with newly diagnosed pulmonary tuberculosis and 32 healthy controls from similar socioeconomic backgrounds. The severity of lung involvement was assessed radiologically, but this was not related to the current features of cell mediated immunity or to those of many aspects of the serological response to Mycobacterium tuberculosis. However, the patients with more extensive pulmonary tuberculosis showed higher titres of IgG2 antibody to whole killed M. tuberculosis and to the ML34 epitope shared by many species of mycobacteria. The patients with more extensive pulmonary tuberculosis showed a more marked metabolic response to infection as manifested by changes in serum levels of acute phase reactant proteins. Accordingly, the metabolic responses are considered to be more likely to prove of value in clinical monitoring of patients for severity of infection, or of reactivation of infection with M. tuberculosis, than immunological responses.

Acute-Phase Proteins↗
PubMed1989

Association of tuberculosis and M. tuberculosis-specific antibody levels with HLA.

In the search for HLA-linked immune response genes that control susceptibility to tuberculosis, we performed HLA typing and measured antibody titers to well-defined Mycobacterium tuberculosis antigenic determinants in 101 patients with sputum smear-positive pulmonary tuberculosis and 64 healthy controls from Surabaya, Indonesia. HLA-DR2 and DQw1 were associated with sputum smear-positive pulmonary tuberculosis (attributable risk = 36% and 39%, respectively), while DQw3 was associated even more strongly with the control group (preventive fraction = 57%). Antibody titers to the TB71 and TB72 epitopes of the 38-kDa protein, present only on tubercle bacilli, were strongly associated with DR2 (Pcorr = .001 and .024, respectively). The association of both the disease and the antibody response to the 38-kDa antigen of M. tuberculosis with Class II HLA genes HLA-DR2 indicates that Ir-gene-mediated regulation of the immune response to this antigen may be of pathogenic significance for the development of sputum smear-positive tuberculosis.

Antibodies, Bacterial↗
PubMed1989

Acetazolamide and transient responses of basolateral membrane potential of rabbit kidney proximal tubules perfused in vitro.

1. A study was made of the partial recovery of basolateral membrane potential that follows some depolarizing manoeuvres in cells of isolated perfused segments of rabbit proximal convoluted tubules. 2. Peritubular application of 10(-4) M-acetazolamide (a known inhibitor of the basolateral sodium-bicarbonate co-transporter) caused a hyperpolarization of both the basolateral membrane potential (Vbl) and the transepithelial potential (Vte). 3. Activation of electrogenic apical sodium co-transport caused a depolarization of the basolateral membrane followed by partial recovery of potential, and a sustained transepithelial hyperpolarization. The partial recovery of basolateral membrane potential was significantly smaller in the presence of 10(-4) M-acetazolamide applied to the peritubular fluid, although the magnitude of the initial depolarization was not significantly altered. 4. Addition to the bath of 0.5 mM-barium, a potassium conductance blocker, caused a transepithelial and basolateral membrane depolarization followed by partial recovery of potential. The partial recovery of basolateral membrane potential was significantly smaller in the presence of 10(-4) M-acetazolamide applied to the peritubular fluid, although the magnitude of the initial depolarization was again not significantly altered. 5. Increases in bath potassium concentration from 5 to 20 mM led to transepithelial and basolateral membrane depolarization followed by partial recovery of potentials. In paired experiments the partial recovery of basolateral potential was significantly reduced when 10(-4) M-acetazolamide was present in the bath. 6. These observations are consistent with the hypothesis that the basolateral sodium-bicarbonate co-transporter plays a role in the recovery of Vbl following these depolarizing manoeuvres.

Acetazolamide↗
PubMed1989

Histometric studies on cellular infiltrates of tuberculin tests in patients with haemophilia.

The number of microanatomical location of CD4 and CD8 lymphocytes, of cells bearing receptors for I12 and transferrin, and of monocyte/macrophages in the dermis at the site of a tuberculin test were measured in 13 patients with haemophilia (10 seronegative and three seropositive for human immunodeficiency virus (HIV]. The overall density of lymphocytes in the perivascular and diffuse parts of the infiltrate was similar to that reported in other groups of subjects without evidence of immunosuppression. The CD4:CD8 ratio of the infiltrating lymphocytes throughout the section showed an inverse relation with clotting factor consumption. There was no significant change in the CD4:CD8 ratio in the diffuse infiltrate at various levels into the dermis in tuberculin reactions in patients with haemophilia, unlike healthy controls and other groups with no evidence of immunosuppression, who have previously been shown to have increasing CD4:CD8 ratio with increasing depth into the dermis. The number of cells bearing receptors for I12 and transferrin and of monocyte/macrophages was related to total lymphocyte density in the infiltrate. There was no evidence of serious impairment of the cell mediated response to a long term recall antigen, but the relatively low preponderance of CD4 lymphocytes in the diffuse infiltrate, particularly in the deeper dermis, may be the earliest indicator of impending immunosuppression.

CD4-Positive T-Lymphocytes↗
PubMed1989

Observer variability in histopathological reporting of cervical biopsy specimens.

Sections from 100 cervical biopsy specimens were studied by 12 consultant histopathologists to determine the robustness of the existing pathology terminology and classification. Analysis by kappa statistics showed good agreement in the diagnosis of CIN 3 and squamous carcinoma but an inability to distinguish accurately between the lesser grades of CIN. It is recommended that the classification be changed to low grade (present CIN 1 and 2) and high grade (present CIN 3) categories alone. There was very poor agreement in the identification of cellular changes associated with human papilloma virus (HPV) infection.

Biopsy↗
PubMed1989

Suppress of the increase in free cytosolic calcium during the inhibition of T-cell activation by an autoantibody present in the serum of leprosy patients.

A serum factor, believed to be an IgG autoantibody, in certain patients with lepromatous leprosy inhibits the proliferation of mitogen-stimulated lymphocytes. To investigate which stage of the cell cycle was inhibited, we examined the effect of these sera on the kinetics of lymphocyte activation induced by several mitogenic agents: phytohaemagglutinin (PHA), the calcium ionophore A23187, the phorbol ester phorbol myristate acetate (PMA) and purified protein derivative of BCG (PPD). Seven out of 54 sera tested were found to inhibit PHA-stimulated proliferation. Inhibitory sera and to a lesser extent serum IgG from leprosy patients were capable of suppressing the increase in free cytosolic calcium normally observed immediately after PHA stimulation. Subsequent stages of the cell cycle, increase in cell size, the expression of the IL-2 receptor and increase in DNA were also suppressed. The inhibitory sera was not toxic and, if addition of the sera was delayed, would not inhibit lymphocytes that had already entered the cell cycle. Using mitogenic agents which act intracellularly, the normal early increase in cell size with A23187- and PMA-stimulated lymphocytes was not affected by inhibitory leprosy sera or serum IgG, but all subsequent steps in the cell cycle were suppressed; although the inhibition of proliferation in PMA-stimulated cultures was incomplete. The mechanism of action of the inhibitory sera and derived IgG, although acting through a cell surface antigen, appears to interfere with a fundamental process in activation since the effect was seen with all of the diverse stimuli examined in this study.

Autoantibodies↗
PubMed1988

Measurement of cutaneous blood flow velocity in delayed hypersensitivity reactions in guinea pigs.

The blood flow velocity in the skin of the flanks of guinea pigs can be measured precisely by laser Doppler velocimetry, provided the animal is mildly sedated. The probe holder can be attached to the shaved skin with cyanoacrylate glue and can be detached after completion of blood flow velocity measurements by application of acetone without harming the animal. The technique is pain-free and non-invasive: it can be used to make serial measurements on the same animal. The system has demonstrated hyperaemia in delayed-type responses to tuberculin PPD, ovalbumin and Keyhole Limpet Haemocyanin with immunological specificity. The time course of evolution and resolution of the vasomotor response accords with previous experience. The method can detect hyperaemia-inducing mediators in the supernatant of antigen or mitogen stimulated lymphocyte cultures and could be used for their bioassay.

Animals↗
PubMed1988

Measurement of phagocyte chemiluminescence in a microtitre plate format.

Previously described assays of phagocyte chemiluminescence have required large numbers of cells and have not been able to follow responses from a large number of samples in single experiments. Recently, sensitive luminometers which employ a 96 well microtitre plate format have become available. We describe the application of this equipment to the measurement of phagocyte chemiluminescence using lucigenin to enhance the response and the estimation of the opsonic activity of serum. It was found that as few as 5 X 10(4) cells (polymorphonuclear leukocytes or monocytes) per well and a ratio of 10:1 zymosan particles to cells gave good results when opsonised with 10% whole serum. This method allows assays of opsonic activity to be performed in triplicate on large numbers of sera with a relatively small number of phagocytes and should aid the investigation of the role of opsonisation in infectious disease.

Humans↗
PubMed1988

On internalization of hormone-receptor complex and receptor recycling.

Experimental evidence for recycling of receptors and for discontinuous internalization of the hormone-receptor complex by endocytosis, suggests a number of variations on this theme. Simulations based on models of these processes show the possible effects of the variations and suggest experimental strategies. Two examples from the experimental literature are explored. The new parameters associated with endocytosis are threshold for internalization of clusters of the complex, composition of clusters with respect to the complex and uncomplexed receptor and rate constant for cluster formation.

Asialoglycoprotein Receptor↗