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Biomedical subjects

J S Beck

Publications and source records attributed to J S Beck.

At least 19 recordsLinked to original sources
PubMed1995

Effects of treatment on the histopathology of leprosy.

AIMS: To identify the histological changes in leprosy skin lesions over the first few weeks after the start of leprosy treatment and to examine their relationship to reversal reaction. METHODS: Sequential skin biopsy during treatment with multiple drug therapy. In this study, a series of 28 patients was studied, from whom two or more biopsies were taken at two week intervals. Fourteen patients had paucibacillary leprosy (PBL) and 14 had multibacillary leprosy (MBL). RESULTS: In most cases, granuloma fraction and bacterial index fell during treatment, the bacterial index being less sensitive than the granuloma fraction. Since the biopsies were fixed in buffered formalin and processed through to paraffin wax, little immunohistochemistry was feasible. However, there was strong evidence of immune activation, with increased expression of HLA-DR in the granulomas of MBL and PBL cases: the epidermis also expressed HLA-DR in several patients. Such changes may reflect gamma IFN production from granuloma lymphocytes. Patients with reversal reaction often showed HLA-DR expression on admission which decreased with corticosteroid treatment. CONCLUSIONS: The results suggest that activation of cell mediated immunity in leprosy lesions occurs during treatment with multiple drug therapy and may not be restricted to those with clinical evidence of reversal reaction.

Adolescent↗
PubMed1995

Delayed hypersensitivity and HLA in smear-positive pulmonary tuberculosis.

Tuberculin responses were quantified by induration of the skin, velocity of blood flow in dermal microcirculation and composition of the cellular infiltrate in 125 patients with tuberculosis and 39 healty controls. The diameters of the tuberculin responses were greater in HLA-DR15-positive patients than in DR15-negative patients. The density of infiltrating CD(4+)-positive cells showed a positive correlation with induration in DR15-negative subjects (r = 0.54). A fraction of DR15-positive patients gave large tuberculin responses (> or = 15 mm) but with few CD4+ cells in the test site (< 500/mm2); these patients had a greater percentage of cells in the diffuse dermal infiltrate than in the perivascular region, greater blood flow velocities in the tuberculin response but more frequently with central relative slowing of blood flow and had higher total IgG and specific antimycobacterial antibody levels compared to other DR15-positive patients. If the inflammatory infiltrate in the lungs parallels that in the tuberculin skin test, the lack of immunocompetent cells and tissue hypoxia could permit pulmonary cavitation and explain the association of HLA-DR15 with smear-positive pulmonary tuberculosis.

Blood Flow Velocity↗
PubMed1994

Ca(2+)-activated K+ channels are involved in regulatory volume decrease in acinar cells isolated from the rat lacrimal gland.

The volumes of acinar cells isolated from rat lacrimal gland were measured on computer by video-imaging. Cells were found to swell on exposure to hypotonic solutions; they subsequently exhibited a regulatory volume decrease (RVD). RVD was inhibited in the absence of extracellular Ca2+, and by the K+ channel blocker tetraethylammonium chloride (2 mM TEA+). The possible involvement of K+ channels in RVD was further investigated in cell-attached patches. Exposing the cells to a hypotonic solution activated channels with a conductance of 141 +/- 6 pS (n = 11). These channels were partially blocked by 0.5 mM TEA+, and channel activation was not observed in the absence of extracellular Ca2+. Experiments in the inside-out patch configuration demonstrated that the channels activated by hypotonic stress were "maxi" Ca(2+)-activated K+ channels. It is concluded that the opening of these channels plays an important role in RVD, by facilitating K+ loss from the cell.

Animals↗
PubMed1994

Comparison of macro- and micro-lightguide spectrophotometric measurements of microvascular haemoglobin oxygenation in the tuberculin reaction in normal human skin.

The changes in haemoglobin oxygenation (SO2) occurring in the tuberculin reaction in human skin were measured using macro- and micro-lightguide spectrophotometry and the results compared. A significant difference was found between the measurements from the respective instruments, demonstrating that the micro-lightguide technique measures only in the most superficial capillaries. Laser Doppler flux (LDF) and transcutaneous oxygen (tcpO2) measurements were also obtained concurrently. At the height of the reaction, heating did not significantly change SO2 or LDF, showing that the vessels in the skin were maximally vasodilated. Although SO2 was increased in the reaction, tcpO2 decreased. This suggests that the infiltrating cells may present a diffusion barrier to oxygen between the capillaries and the tissue cells. This study has shown that micro-lightguide spectrophotometry gives a local picture of intracapillary oxygen supply, which is useful in elucidating the pathophysiological changes occurring during chronic inflammation.

Adolescent↗
PubMed1994

Observer variability in the histopathological reporting of abnormal rectal biopsy specimens.

AIMS: To study the consistency of reporting of abnormal rectal biopsy specimens, especially in the differentiation of inflammatory bowel disease from other causes of abnormality. METHODS: Sixty rectal biopsy specimens were identified from patients presenting with bloody diarrhoea. These were then circulated to the 11 consultant pathologists in the study who filled in a proforma with a list of 12 diagnostic categories and 22 features. RESULTS: Forty one of the 60 cases were examples of inflammatory bowel disease. In 33 of these cases nine or more pathologists had made the diagnosis. Further categorisation into ulcerative colitis and Crohn's disease showed better recognition of ulcerative colitis. In the 19 cases of non-inflammatory bowel disease recognition of pseudomembranous colitis and solitary rectal ulcer syndrome was good, but the results were poorer in the case of infective colitis. CONCLUSION: The findings suggest that a group of consultant pathologists can differentiate between inflammatory bowel disease and other causes of an abnormal rectal biopsy specimen and can also recognise pseudomembranous colitis and solitary rectal ulcer syndrome satisfactorily.

Biopsy↗
PubMed1994

Different modulation of hepatocellular Na+/H+ exchange activity by insulin and EGF.

Indirect evidence suggests that insulin, like epidermal growth factor (EGF), stimulates liver cell Na+/H+ exchange. We directly studied the effect of insulin on intracellular pH (pHi) and the Na+/H+ exchanger in isolated rat hepatocytes with the fluorescent probe, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). The effects of insulin were compared with those of EGF. Studies were carried out in the absence of HCO3- and in the presence of acetazolamide to isolate the Na+/H+ exchanger from other pH regulatory mechanisms. Insulin (9 nM) caused a reversible acidification of baseline pHi, whereas no significant effect was observed with EGF (30 nM). pHi was acidified by two different methods (NH4Cl pulse and external Na+ removal) to assess liver cell Na+/H+ exchange activity. In the NH4Cl pulse experiments, insulin had no significant effect on the Na+/H+ exchanger compared with the control (0.141 +/- 0.009 pH units/min, n = 14, and 0.122 +/- 0.023 pH units/min, n = 16, respectively). However, in the same conditions, EGF nearly doubled the rate of the Na+/H+ exchange activity (0.193 +/- 0.015 pH units/min, P < 0.05, n = 6). In the Na+ removal experiments, EGF again significantly increased the pHi recovery rate (0.542 +/- 0.032 pH units/min, n = 3) compared with the control (0.227 +/- 0.028 pH units/min, n = 5) and insulin (0.245 +/- 0.053 pH units/min, n = 5). Compared with control conditions, a subchronic administration of insulin (9 nM) in vitro had no significant effect on the Na+/H+ exchanger, nor did it affect baseline pHi.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride↗
PubMed1994

cAMP stimulates proximal convoluted tubule Na(+)-K(+)-ATPase activity.

The effect of adenosine 3',5'-cyclic monophosphate (cAMP) was examined on the electrophysiological properties of nonperfused proximal convoluted tubule in vitro. In 5 mM bath K+, the basolateral membrane potential (Vbl) was -66 +/- 1 mV (n = 26). Low bath K+ (0.1 mM) led to a transient hyperpolarization of Vbl followed by a sustained decrease to reach -48.6 +/- 5.0 mV. Return to 5 mM bath K+ produced a rapid and transient Vbl hyperpolarization of 24.6 +/- 1.4 mV (n = 5). This hyperpolarization was completely blocked by 100 microM strophanthidin (n = 4), demonstrating that the hyperpolarization was caused by reactivation of the Na(+)-K(+)-adenosinetriphosphatase (ATPase). Addition of 1 microM forskolin (forsk) + 100 microM 8-(4-chlorophenylthio)-cAMP (cp-cAMP) significantly increased this hyperpolarization to 30.8 +/- 10 mV (P < 0.005, n = 5). In a separate series of experiments, addition of 1 microM forsk + 100 microM 3-isobutyl-1-methylxanthine increased this hyperpolarization from 21.7 +/- 2.8 to 27.1 +/- 1.6 mV (P < 0.05, n = 5), which excludes any nonspecific effect of cp-cAMP. Forsk + cp-cAMP decreased the apparent partial conductance to Cl- (tCl) from 0.049 +/- 0.003 to 0.031 +/- 0.007 (P < 0.06, n = 6), decreased that to K+ (tK) from 0.56 +/- 0.05 to 0.43 +/- 0.03 (P < 0.05, n = 6), slightly decreased that mediated by the Na-HCO3 cotransporter (tNaHCO3) from 0.26 +/- 0.03 to 0.21 +/- 0.05, and had no effect on the absolute conductance mediated by the Na-HCO3 cotransporter. Forsk + cp-cAMP had no effect on tK when determined using bath K+ steps from 15 to 45 mM (tK = 0.84 +/- 0.02, n = 5) instead of K+ steps from 5 to 15 mM as previously done, and did not affect the value of tK measured in the presence of strophanthidin (tK = 0.41 +/- 0.03, n = 5). These results demonstrate that the decrease of tK by forsk + cp-cAMP observed using K+ steps from 5 to 15 mM is due to modulation by these agents of the stimulated hyperpolarizing Na(+)-K(+)-ATPase current produced by the bath K+ steps. Consequently, the increased Vbl initial recovery from low bath potassium observed when intracellular cAMP is increased could not be the result of modulation of passive basolateral membrane properties and represents a stimulation of the pump current. The present work thus demonstrates that the Na(+)-K(+)-ATPase is stimulated by cAMP.

Animals↗
PubMed1994

Coupling between transepithelial Na transport and basolateral K conductance in renal proximal tubule.

A common feature of sodium-reabsorbing epithelia is their ability to match salt entry to salt exit. It is recognized that a key strategy to perform this feat involves the coupling between basolateral sodium pump and potassium conductance (pump-leak coupling). In the renal proximal tubule this coupling is of major importance, as regions of this nephron segment are faced with ever-changing reabsorptive loads. An understanding of this coupling can be facilitated by critically examining those studies that have looked at the problem from the point of view of the whole cell (macroscopic studies) and of single channels (microscopic studies). An overview of such work suggests that the transduction mechanisms which are likely to effect pump-leak coupling in the renal proximal tubule involve cell volume, ATP, and pH (but not calcium). Although the relationship between ATP and potassium conductance may be relatively straightforward, the involvement of pH is likely to be only transient and that of volume remains controversial, occurring either directly though stretch-activated channels in amphibian preparations or indirectly through an as yet unidentified second messenger system in mammalian preparations.

Animals↗
PubMed1994

Effect of hyperoxia at 1 and 2 ATA on hypoxia and hypercapnia in human skin during experimental inflammation.

Transcutaneous PO2 and PCO2 measurements and estimates of skin respiration were monitored at different levels of inspired PO2 in 20 healthy adults during the first 4 days of the tuberculin reaction, a convenient model of acute inflammation. Hyperoxia at 1 and 2 ATA significantly increased transcutaneous PO2 levels in undisturbed and in inflamed skin but did not fully correct the relative hypoxia at the site of inflammation. Hypercapnia was reduced with O2 breathing at 2 ATA. The apparent rate of O2 consumption at the reaction site was raised during hyperoxia, most prominently at 2 ATA. The most intense reactions showed a central relative slowing of laser-Doppler blood flow indicative of microcirculatory impairment. The extent of the relative hypoxia and hypercapnia was greatest in these strongest reactions. The density of lymphocytes and monocytes in biopsies of 48-h reactions was loosely related to the corresponding transcutaneous PO2 measurements. The present study provides evidence that diffusion barriers, in addition to increased local respiration, can contribute to the apparent hypoxia and hypercapnia of this inflammatory model.

Adult↗
PubMed1994

Symptom differences in major depression, dysthymia, panic disorder, and generalized anxiety disorder.

OBJECTIVE: The authors compared symptom features of specific subtypes of depressive and anxiety disorders. METHODS: Psychiatric outpatients with moderate levels of psychopathology and DSM-III diagnoses of major depression, dysthymia, panic disorder, or generalized anxiety disorder were given five standard measures of symptoms of anxiety and depressive disorders. Most of the outpatients were white, and most were middle-class. RESULTS: Principal components analysis revealed 12 orthogonal symptom components. Discriminant function analysis indicated that anxiety was distinguished by specific autonomic arousal symptoms, threat-related cognitions, and subjective anxiety and tension. Discriminant function analysis also indicated that depression was distinguished by anhedonia, cognitions of personal loss and failure, and dysphoric mood. CONCLUSIONS: As nosological categories, major depression and panic disorder were better differentiated by specific symptom markers than dysthymia and generalized anxiety disorder.

Adult↗
PubMed1994

Circulation and sensation at the fingertips of claw hands.

Measurements of skin blood flow (by laser Doppler flowmetry) and temperature were made under environmental conditions promoting peripheral vasodilatation at the fingertips of a disfigured 'clawed' hand in 12 leprosy patients long-resident at Baba Baghi Leprosy Hospital, Tabriz, Iran. Sensory function was assessed by measuring the responses to light touch, pain and temperature of each finger, and peripheral autonomic function was gauged by estimating palmer sweating and by measuring skin vasomotor reflexes in response to inspiratory gasp. In 2 patients all measured fingers had laser Dopper flux (LDFlux) values and skin temperatures lower than the 95% confidence limits for the mean of 20 healthy controls, i.e. were impaired; in 2 patients all fingers had normal values for LDFlux and temperature; and in 8 patients there was a combination of impairment with most fingers normal for these parameters but with the small finger most commonly impaired. There were 10 (67%) fingers with impaired LDFlux and temperature values who had significant sensory impairment, whereas only 5 (18%) of the fingers with normal LDFlux values and temperatures had a similar sensory deficit. Overall, the fingers with the most impaired sensation had significantly (P < 0.05) lower LDFlux and temperature values than those with no sensory deficit. Microcirculatory impairment was not related to disordered skin vasometer reflexes or dysfunction of sweating. We concluded that the relationship between motor (skeletal muscle) nerve paralysis and any subsequent sensory neuropathy and/or microcirculatory impairment is more complex than might be expected from previous understanding of the disease.

Adult↗
PubMed1993

Dynamic thermographic imaging for estimation of regional perfusion in the tuberculin reaction in healthy adults.

A sensitive method for measurement of the volume of blood flow through the skin, based on the kinetics of reheating after localised cooling, is described in this paper. This method has been used to study the tuberculin reaction as a model of cutaneous delayed-type hypersensitivity (DHS) in man. Over the positive reaction there is accelerated reheating similar in kinetics and extent to that seen after maximal hyperaemia induced by intradermal injection of histamine or prostaglandin E2. The earlier phase of reheating (10-100 s) is more dependent on blood flow, whereas the later phase (100-300 s) is apparently more dependent on non-perfusion heat exchange mechanisms, including conduction. The reheat kinetic method is largely dependent on blood flow in the deep dermal vessels (diameter > 50 microns), whereas the alternative approach of measurement of the velocity of flow of erythrocytes in the microcirculation by laser Doppler (LD) flowmetry gives results biased towards the most superficial dermal circulation. Previous studies with LD flowmetry have shown that the blood velocity is greatest at the centre of weak and strong reactions, while in the most intense reactions it is raised at the centre but maximal at the periphery (central relative slowing, CRS) raising the possibility of central ischaemia. The reheat kinetics approach has now indicated that the deep dermal circulation is not impaired in CRS reactions. It is concluded that there must be partial obstruction of the parts of the microcirculation communicating between the deep and superficial dermal plexuses, presumably from the accumulation of exudate oedema in the most intense tuberculin reactions.

Adult↗
PubMed1993

Classification of suicidal and nonsuicidal outpatients: a cluster-analytic approach.

The revised Beck Depression Inventory (BDI), Hopelessness Scale (BHS), Anxiety Inventory (BAI), and Scale for Suicide Ideation (SSI) were administered to 1,172 outpatients diagnosed with mixed psychiatric disorders. The SSI then was used to classify the patients into 127 (10.8%) suicide ideators and 1,045 (89.2%) nonideators. Both agglomerative-hierarchical and nonhierarchical cluster analyses then were employed to identify three types of nonideators, who represented anxious depressed, hopeless depressed, and below-average overall symptomatology, and four types of ideators, who reflected hopeless, anxious depressed, severely suicidal, and below-average overall symptomatology. Implications of these classification systems for describing psychopathology were discussed.

Adult↗
PubMed1993

The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions.

Single-strand conformation polymorphism (SSCP) analysis has proven to be a simple and effective technique for the detection of single base substitutions. We have used SSCP to analyze 29 mouse globin mutations, 27 p53 mutations, and 8 rhodopsin mutations contained within different size PCR products. Our results indicate that the type of mutation (transition versus transversion) did not play a major role in determining whether a mutation was detected by SSCP analysis. The position of the base substitution was more important than the precise base substitution in determining whether a mutation was detected. We report that SSCP sensitivity varies dramatically with the size of the DNA fragment being analyzed. The optimal size fragment for sensitive base substitution detection by SSCP is approximately 150 bp. Our results illustrate the need to keep the size of the PCR fragment small when performing SSCP to detect mutations. Larger fragments can be analyzed when screening for polymorphisms when the need to detect every sequence variation is not as critical.

Animals↗