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Biomedical subjects

J S Beck

Publications and source records attributed to J S Beck.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

A denaturing gradient gel electrophoresis assay for sensitive detection of p53 mutations.

p53 is a tumor suppressor gene located on 17p, a region of the human genome frequently deleted in tumors. Mutation of the p53 gene is an important step leading to development of many forms of human cancer. To simplify the analysis of tumors for p53 point mutations, we describe a GC-clamped denaturing gradient gel assay for detecting single-base substitutions within highly conserved regions of the p53 gene. This assay allows for efficient screening of tumors for single-base substitutions within the p53 gene and can be used to facilitate sequence analysis of p53 point mutations.

Base Sequence↗
PubMed1993

Vasomotor reflexes in the fingertip skin of patients with type 1 diabetes mellitus and leprosy.

Fingertip skin blood flow was measured by laser Doppler flowmetry (as LDflux) under environmental conditions promoting vasodilation in Scottish patients with diabetes mellitus and Indian patients with leprosy. The reflex control of fingertip blood flow was assessed by measuring the reduction in LDflux induced by deep inspiratory gasp (IG) and cold challenge (CC) of immersing the contralateral hand in cold water. The uncomplicated diabetic patients showed normal vasomotor reflexes and an increased, though non significant, LDflux level (p < 0.06). The patients with diabetic neuropathy had resting LDflux levels significantly less than the uncomplicated group and also had substantial impairment of both IG and CC reflexes. Those with retinopathy (but no clinically apparent neuropathy) had LDflux within the normal range, but they showed minor evidence of impairment of the vasomotor reflexes. The uncomplicated newly registered leprosy patients had reduced LDflux and substantial impairment of CC reflexes. These changes were more marked in newly registered leprosy patients with clinical evidence of neuropathy. Leprosy patients with long-standing neuropathy requiring orthopaedic treatment had LDfluxes so greatly reduced that measurement of vasomotor reflexes was not practicable. The CC reflex was more severely affected than the IG reflex and more frequently absent in leprosy patients, possibly because of associated sensory neuropathy affecting the afferent limb of this response. Thus laser Doppler flowmetry can detect impairment of reflex control of fingertip blood flow in both diabetes mellitus and leprosy, but there are functional differences in the pattern of autonomic impairment between the diseases, suggesting differences in the pathogenesis of nerve damage.

Adult↗
PubMed1993

The effect of fenclofenac on the regeneration of lymphocytes in rats following total body irradiation.

The effect of fenclofenac on the regeneration of white blood cells in Sprague-Dawley rats following total body irradiation was investigated. The lowest dose of total body irradiation that would suppress the peripheral blood lymphocyte count by at least 50% was found to be 1.0 Gray in a preliminary experiment. Fenclofenac in a dose of 150 mg/kg/day retarded the regeneration of lymphocytes following total body irradiation of 1 Gray: this effect was also seen in the CD4, CD8 and B-lymphocyte subsets. This suppressive effect in vivo may be due to interference with replicative growth of white blood cells since previous in vitro experiments have shown suppression of lymphocyte growth at a stage later than activation in the cell cycle. The suppressive effects on leucocyte regeneration in vivo suggest that fenclofenac may have promise as an immunosuppressive drug with fewer serious side effects than the currently available immunosuppressive drugs.

Animals↗
PubMed1993

Departmental audit in histopathology.

Audit is now part of any laboratory service. Histopathology is no exception, and we have set up a system which allows us to review 4% of our specimens. These specimens are identified using a random number generator and reviewed by a consultant pathologist. Both slides and wet specimens are reviewed and graded according to a set scheme. The results from the first year of operation (1990) show a high rate of accuracy with no serious diagnostic disagreements between the auditor and the reporting pathologist. However, some errors which we would wish to prevent were detected and the audit has allowed us to take corrective measures. In our opinion, this form of audit is useful and necessary to maintain good clinical practice. The cost is considerable--histopathology is by its nature labour intensive. Recognition of this fact by health boards is essential if such systems are to continue.

Biopsy↗
PubMed1993

How fatal is breast cancer? A prospective study of breast carcinoma deaths in Tayside.

A prospective autopsy study of deaths of women who had been diagnosed previously as having cancer of the breast was performed between October 1986 and December 1990. During the study period 28 deaths occurred and nine of these (32%) were attributable directly to breast cancer; a figure similar to that found in our earlier retrospective study. In this study the autopsy findings in both the breast cancer and non-breast cancer deaths were recorded and five cases underwent post-mortem radiological skeletal survey to detect metastases. The findings confirm the role of the post mortem in modern medicine as a method of auditing clinical practice. Of particular importance, is the finding that the clinical presumption of disseminated breast cancer as a cause of 'terminal' illness in some patients may be misleading and dangerous, possibly denying some patients treatment of potentially remedial conditions by the institution of inappropriate terminal care.

Breast Neoplasms↗
PubMed1993

A preliminary assessment of laser Doppler perfusion imaging in human skin using the tuberculin reaction as a model.

Laser Doppler imaging is a new development in the field of laser Doppler flowmetry. We were recently loaned the Lisca laser Doppler perfusion imager (LDI) manufactured by Lisca Development, Linkoping, Sweden for assessment against other methods for assessment of skin perfusion. In order to evaluate the device, it was applied to imaging flux changes induced in human skin during the tuberculin reaction. Flux values were compared directly with those from conventional lightguide laser Doppler flowmetry, and parameters measured using two other methods for assessment of tissue perfusion, dynamic thermographic imaging and tissue spectrophotometry. The results showed very good correlations between the various methods. In addition, the LDI showed that very large differences in flux values (up to 5 V) could be found within distances of only 2 mm during the tuberculin reaction and that focal centres of low flux values surrounded by higher values ('craters') could be found not only at the centre, but elsewhere in the lesion. The LDI enables rapid non-invasive detailed analysis of blood flow patterns in skin and correlates well with other methods for measuring skin perfusion. Its use to examine heterogeneity of microvascular blood flow patterns may lead to further understanding of the local mechanisms for regulation of oxygen supply to tissue.

Female↗
PubMed1993

Heat-stable opsonins in tuberculosis and leprosy.

We have examined heat-stable opsonins to 4 species of gamma-irradiated mycobacteria (M. tuberculosis (H37Rv), M. avium (28A), M. scrofulaceum and M. leprae (cd 103)) in complement-depleted sera collected from Indonesian subjects with tuberculosis (106 patients),-leprosy (24 patients) and controls (40 hospital workers and 41 factory workers) indirectly by microtitre plate chemiluminescence (CL) assay and compared the results with antibody levels. The results indicate that there is a wide range of opsonic capacity for mycobacteria in complement-depleted sera. There was a poor correlation between the opsonic capacity as measured by CL and the anti-mycobacterial antibody content of sera measured by ELISA, suggesting that anti-mycobacterial antibody has little influence on the uptake of mycobacteria. However, a non-specific heat-stable opsonin appears to be present in some sera. Conversely, some sera from tuberculosis or leprosy patients suppress the production of reactive oxygen species from normal phagocytes in vitro when stimulated with M. tuberculosis. The relevance of this inhibition and the presence of heat-stable opsonins to the pathogenesis of tuberculosis have yet to be determined, but it is possible that the presence of opsonins may inhibit dissemination of tubercle bacilli to other organs.

Adolescent↗
PubMed1993

Basolateral K+, Cl-, and HCO3- conductances and cell volume regulation in rabbit PCT.

The relationship between changes in cellular volume, intracellular pH (pHi), basolateral membrane potential (VBL), and membrane partial basolateral conductances to K+ (tK) and Cl- (tCl) and mediated by the Na-HCO3 cotransporter (tNaHCO3) was determined in the collapsed proximal convoluted tubule (PCT) submitted to a 125-mosmol/kg hypotonic shock. The shock that produces a rapid swelling followed by partial volume regulation was accompanied by a rapid and transient VBL hyperpolarization of 10.0 +/- 1.5 mV and a second gradual hyperpolarization of 5.0 +/- 0.7 mV with respect to a control value of -44.0 +/- 4.6 mV.tK was 0.12 +/- 0.03 in control, increased transiently to 0.15 +/- 0.03, and then gradually increased to reach 0.32 +/- 0.06 at the end of hypotonic shock. In contrast, tCl was 0.03 +/- 0.01 in control, increased rapidly to a maximum of 0.16 +/- 0.01, and then decreased slowly to 0.08 +/- 0.02. During the same period, tNaHCO3 decreased rapidly from 0.41 +/- 0.04 to a minimum of 0.11 +/- 0.02 and slowly reincreased to reach 0.16 +/- 0.01.pHi increased transiently from 7.09 +/- 0.03 in control to 7.24 +/- 0.05 to come back gradually to 7.15 +/- 0.05 at the end of the hypotonic period. The membrane absolute conductance mediated by the Na-HCO3 cotransporter was found to increase only slightly in hypotonic conditions, whereas that to K+ and Cl-, GK and GCl, increased by at least factors of 8 and 17, respectively, with the increase of GCl being much faster than that of GK. In addition, the temporal variations in GCl followed closely those of the cellular water efflux. We conclude that the hypotonic swelling leads to important increases in the conductive pathways for K+ and Cl- and that the Cl- conductance pathway appears to be the rate limiting step in triggering and supporting regulatory volume decrease.

Animals↗