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J S Beck

Publications and source records attributed to J S Beck.

At least 55 records · Page 3Linked to original sources
PubMed1993

Regulation of basolateral K channels in proximal tubule studied during continuous microperfusion.

Potassium channel activity of the basolateral membrane of the collagenase-treated rabbit proximal convoluted tubule (PCT) was studied during continuous luminal microperfusion. In cell-attached patches (high-K pipette) an inwardly rectifying potassium channel was observed with an inward slope conductance of 60.8 +/- 3.3 pS (n = 12) and outward slope conductance of 17.1 +/- 2.7 pS (n = 6). Stimulation of transcellular sodium transport with luminal glucose and alanine increased channel activity [measured as single-channel open probability (NPo)] from 0.19 +/- 0.11 to 0.44 +/- 0.09 (n = 8). This increase in channel activity was not likely to be mediated by either cell depolarization or cell swelling, because channel activity was voltage insensitive over physiological potentials and because the channel was not activated by stretch. However, channel activity was pH sensitive; reducing luminal pH from 7.4 to 6.5 reduced NPo from 0.63 +/- 0.24 to 0.26 +/- 0.16 (n = 5). Our work demonstrates the feasibility of patch clamping the basolateral membrane of microperfused nephron segments. This has allowed us to follow the activity of this potassium channel during an increase in sodium transport and show that its activity does increase during this maneuver. We conclude that: 1) it is possible to patch clamp the basolateral membrane of microperfused nephron segments, and 2) basolateral membrane of the rabbit PCT contains an inwardly rectifying, pH-sensitive potassium channel. The behavior of this channel on stimulation of transcellular sodium transport could explain the macroscopic increase in basolateral potassium conductance observed under similar conditions.

Alanine↗
PubMed1993

Na+ pump inhibition downregulates an ATP-sensitive K+ channel in rabbit proximal convoluted tubule.

In several epithelial and nonepithelial tissues a functional link between the basolateral Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) and a basolateral K+ conductance has been established. However, the nature of this link is unclear. We have previously identified a K+ channel on the basolateral membrane of the proximal convoluted tubule perfused in vitro, the activity of which is increased by stimulation of Na+ transport [J. S. Beck, A. M. Hurst, J.-Y. Lapointe, and R. Laprade. Am. J. Physiol. 264 (Renal Fluid Electrolyte Physiol. 33): F496-F501, 1993]. In the present study we investigate whether basolateral membrane K+ channel activity is tightly coupled to Na(+)-K(+)-ATPase activity. In cell-attached patches (150 mM K+ pipette), following stimulation of channel activity by addition of Na(+)-cotransported solutes to the tubule lumen, mean channel open probability (NPo) was reduced from 0.35 +/- 0.09 to 0.14 +/- 0.06 (n = 7, P < 0.05) by blocking the Na(+)-K(+)-ATPase with 100 microM strophanthidin. In excised patches the channel was reversibly blocked by 2 mM ATP from the cytosolic face of the patch, such that NPo fell to 20.1 +/- 7.0% (n = 5, P < 0.001) of control and recovered to 52.2 +/- 11.2% (n = 5, P < 0.05) after washout of ATP. Diazoxide, a putative opener of ATP-sensitive K+ channels, when added to the bathing solution of an unstimulated tubule (microperfused in the absence of Na(+)-cotransported solutes), increased NPo from 0.046 +/- 0.035 to 0.44 +/- 0.2 (n = 6, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Hopelessness, depression, suicidal ideation, and clinical diagnosis of depression.

The relevance of a clinical diagnosis of depression for explaining the discrepant relationships of hopelessness and depression with suicidal ideation was studied. The Beck Depression Inventory (BDI), Hopelessness Scale (BHS), and the Scale for Suicide Ideation (SSI) were administered to 1,306 (72.8%) patients with at least one DSM-III-R mood disorder and 488 (27.3%) patients without any mood disorders. A multiple regression analysis was conducted, and hopelessness was 1.3 times more important than depression was for explaining suicidal ideation. The interactions of the BDI and BHS with diagnostic group were not significant.

Adult↗
PubMed1993

Biological zero in laser Doppler measurements in normal, ischaemic and inflamed human skin.

The Biological Zero (BZ) signal in laser Doppler flowmetry was recorded during temporary occlusion of the arterial circulation to the limb by a blood pressure cuff inflated suprasystolically for 2 min. The non-thermoregulatory skin at the ankle was compared with the thermoregulatory skin over the toe pad in patients with lower limb arterial obstructive disease, elderly controls without arterial disease and young healthy adults under cool (15-17 degrees C) and warm (25-27 degrees C) ambient conditions. The absolute BZ values did not differ significantly within the three groups at the two room temperatures. However the resting laser Doppler flowmetry signal (LDflux) was consistently higher under warm than cold room temperatures: these differences were much greater at the toe than at the ankle. Accordingly, the relative size of BZ, expressed as a percentage of the resting LDflux, was least over the toe in a warm room (5-10%) and greatest over the malleolus (59-83%) in the cold room. The changes during the evolution of a positive tuberculin skin reaction were followed as a model of chronic inflammation in man. The resting LDflux rose 10 fold (from 0.3 to 3.4V) while the change in the BZ was minor (0.16-0.2V). Thus the rise in LDflux in a fully developed tuberculin reaction was approximately 30X greater than that for the corresponding BZ. Concurrent measurements of the alternative output from the laser Doppler flowmeter (CMBC) showed in a similar pattern. Since the BZ signal can be a substantial proportion of the resting LDflux measurement, we support the recommendation that the BZ should be measured wherever possible and practicable, for subtraction from the observed LDflux to assess the true flow: 'raw' LDflux measurements should be interpreted with extreme caution, particularly at relatively low resting LDflux levels.

Adolescent↗
PubMed1992

Morphometric analysis of Mycobacterium tuberculosis infection in mice suggests a genetic influence on the generation of the granulomatous inflammatory response.

There is evidence in natural human disease and experimental infection in mice that host genetic factors influence susceptibility to infection with Mycobacterium tuberculosis and the progress of the disease. In mouse models, both H-2 and non-H-2 genes have been implicated. In this study, four inbred strains of mice (Balb/b, Balb/k, B10, B10.BR), selected for combinations of two different H-2 haplotypes on two different non-H-2 backgrounds, were inoculated with M. tuberculosis, strain H37Rv, by intraperitoneal injection. The histological features of the granulomatous inflammatory response in the liver and lungs were investigated during the first 18 weeks of the infection. Granuloma fraction, mean granuloma area, bacillary load, and the density of acid-fast bacilli within granulomata were measured. Animals of all four strains showed the same general pattern of infection with an early, and later self-limiting, infection of the liver and delayed onset, but progressive, infection of the lung. The non-H-2 related genetic background appears to influence the morphology of the granulomatous inflammatory response. In comparison, H-2 differences appeared to be small and inconsistent.

Animals↗
PubMed1992

Spectrophotometric measurements of haemoglobin saturation and concentration in skin during the tuberculin reaction in normal human subjects.

A non-invasive technique employing light-guide spectrophotometry is described for the measurement of haemoglobin concentration and oxygenation in human skin. Measurements were carried out in the visible wavelength range (500-620 nm) and a series of experiments were carried out in vitro and in vivo in order to calibrate the system. Indices were derived for the measurement of relative haemoglobin concentration and absolute oxygen saturation. The technique was applied to measure the changes in these parameters occurring during the course of the tuberculin reaction in human skin. The results are compared with those from laser Doppler flowmetry and transcutaneous oxygen measurements which were carried out concurrently. Divergence between the intracapillary and tissue oxygenation during the course of the reaction provides evidence for the existence of increased diffusion resistance for oxygen; a model is proposed. The study demonstrates the potential clinical usefulness of light-guide spectrophotometry for the non-invasive investigation of tissue oxygen supply.

Adult↗
PubMed1992

Specificity of antibodies and tuberculin response after occupational exposure to tuberculosis.

Specific antibody levels and delayed-type hypersensitivity skin responses to antigens of Mycobacterium tuberculosis in 39 hospital staff who were heavily exposed to tuberculosis (TB) were compared with those in 36 factory employees from Indonesia. Antibody levels to the TB68 epitope of the 14-kDa antigen were significantly greater, while titers to the TB23 (19-kDa) and TB72 (38-kDa) epitopes and lipoarabinomannan (LAM) were lower in exposed than in nonexposed subjects (all P less than .02). The intensity of tuberculin responses correlated positively with anti-LAM and negatively with anti-19-kDa antibody levels. Possible reasons for the selective humoral response of chronically exposed healthy subjects to the 14-kDa antigen, but not to other antigens immunogenic in patients with tuberculosis, are discussed.

Antibodies, Bacterial↗
PubMed1992

Potassium conductance regulation by pH during volume regulation in rabbit proximal convoluted tubules.

When rabbit proximal convoluted tubules were microperfused in the presence of bicarbonate, a 90 mosmol hypotonic shock hyperpolarized the basolateral membrane by 5.5 +/- 1.4 mV, increased basolateral potassium selectivity (tK) from 0.30 +/- 0.02 to 0.45 +/- 0.02, and reduced the basolateral membrane resistance from 4,887 +/- 821 to 2,836 +/- 602 omega.cm. These data show that the hypotonic shock increased absolute basolateral potassium conductance. The same hypotonic shock elevated intracellular pH from 7.18 +/- 0.04 to 7.31 +/- 0.04. When bath pH was increased by 0.2 pH units (by reduction of CO2), intracellular pH rose by 0.13 +/- 0.01. In separate experiments this maneuver hyperpolarized the basolateral membrane by 5.0 +/- 0.8 mV and augmented basolateral tK from 0.58 +/- 0.06 to 0.68 +/- 0.04, suggesting that the basolateral potassium conductance is sensitive to pH changes of a magnitude similar to that evoked by a hypotonic shock. In the nominal absence of bicarbonate or presence of 0.5 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) in the bath, the hypotonic shock caused a transient intracellular acidification, suggesting involvement of basolateral bicarbonate transport in the hypotonic shock-induced alkalinization. In the absence of bicarbonate, the hypotonic shock did not increase basolateral tK or induce hyperpolarization of the basolateral membrane. We conclude that the increase in potassium conductance observed during hypotonic shock is at least partly mediated by a bicarbonate-dependent, SITS-sensitive intracellular alkalinization.

Alkalosis↗
PubMed1992

Involvement and source of calcium in volume regulatory decrease of collapsed proximal convoluted tubule.

We examined the role of Ca2+ in the volume regulatory decrease (VRD) of rabbit collapsed proximal tubules. Reduction of bath osmolality by 125 mosmol/kgH2O led to an initial cell swelling of 62.3 +/- 7.5% followed by a partial regulatory phase bringing cell volume to a value of 13.3 +/- 2.9% above control (n = 5). This swelling was accompanied by a transient intracellular Ca2+ ([Ca2+]i) increase from 174 +/- 33 to 306 +/- 67 nM (P < 0.05, n = 8). In the same condition, but in absence of extracellular Ca2+ ([Ca2+]e) [1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)], VRD following hypotonic shock was identical to that observed in presence of [Ca2+]e (n = 5), and [Ca2+]i increased transiently from 136 +/- 29 to 161 +/- 31 nM (P < 0.05, n = 5). Addition of 100 microM 8-(N,N-dimethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an agent known to inhibit Ca2+ release from intracellular stores, did not affect the initial cell swelling (63.4 +/- 4.2%), and VRD occurred to the same extent (25.0 +/- 7.1%, n = 4), although at a lower rate. In these conditions, [Ca2+]i, which was 113 +/- 30 nM in the isotonic solution, decreased progressively to 81 +/- 20 nM over the 5-min hypotonic period (n = 5). Mere preincubation with 100 microM TMB-8 before hypotonic shock led to a VRD identical to that observed in presence of Ca2+ and absence of TMB-8 while still blocking the Ca2+ release, with cell Ca2+ decreasing progressively from 179 +/- 32 to 87 +/- 21 nM (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cold fingers in leprosy.

Under conditions of maximal thermoregulatory peripheral dilatation, most healthy subjects (both Indian and European) showed raised blood flow in the fingertips (measured by laser Doppler flowmetry) where the skin temperature is only slightly lower than the core body temperature. Most borderline lepromatous (BL) leprosy patients had much colder fingers and the blood flow was slow: borderline tuberculoid (BT) patients had skin temperatures similar to those seen in healthy subjects, but their fingertip blood flow was reduced relative to that in control subjects. The occurrence of cold fingers and slow blood flow was clearly associated with evidence of sensory impairment to light touch, pressure and temperature. Slower fingertip blood flow was strongly associated with impairment of vasomotor control in this anatomical region, suggesting that both may be a consequence of leprosy peripheral neuropathy, at least in patients with early leprosy, but it is likely that leprosy arteriopathy may contribute to the lowered peripheral perfusion in advanced cases. It is suggested that the simple clinical sign of cold fingers may be of value in the preliminary assessment of patients presenting at any leprosy control clinic in the tropics.

Adult↗
PubMed1992

Measurement of the immunoperoxidase staining of macrophages within liver granulomata of mice infected with Mycobacterium tuberculosis.

A quantitative image analysis technique developed for the measurement of the extent of macrophage activation and epithelioid cell differentiation was performed on mice infected experimentally with Mycobacterium tuberculosis. The granulomatous inflammatory response within the liver reached a peak at day 23 and declined by day 33. Animals of strain B10.BR (H-2k) showed an increased granuloma fraction as compared to Balb/k (H-2k) mice, thus confirming the influence of non-H2 genes in the control of granuloma formation in mice. Using a monoclonal antibody against CD11b/CD18 (Mac1;CR3), we observed two subpopulations of macrophages within the granulomata. The small, darkly staining cells at the periphery of granulomata appear to be newly recruited macrophages. Larger, paler staining cells toward the center of granulomata represent activated and mature epithelioid macrophages. Using a semiautomated image analyzer (Quantimet 970), we measured the relative numbers of these macrophage subpopulations. There were more activated macrophages (epithelioid cells) associated with the increased granuloma fraction in the B10.BR mice than in the Balb/k. However, similar numbers of newly recruited peripheral macrophages were found in both Balb/k and B10.BR strains. This technique has shown qualitative as well as quantitative differences in the granulomatous inflammatory response in this murine model of tuberculosis in strains of mice with quite different antibody repertoires to mycobacterial antigens.

Animals↗
PubMed1992

Measurements of blood flow and histometry of the cellular infiltrate in tuberculin skin test responses of the typical Koch type and the non-turgid variant form (Listeria-type) in pulmonary tuberculosis patients and apparently healthy controls.

The typical turgid Koch type and the non-turgid variant form (Listeria-type) of the tuberculin skin test responses were studied in 76 newly diagnosed pulmonary tuberculosis patients and 29 apparently healthy factory worker controls from Surabaya in Indonesia; in general, the patients had more intense responses than the controls. The blood flow velocity (RBCflux) at the centre of the reaction was similar in all groups, but central relative slowing (a presumed forme fruste of severe ischaemia) was much more common in the Koch-type reactions in tuberculosis patients. In both groups of subjects, the overall density of cellular infiltrate (and the major populations of inflammatory cells) was greater in the typical Koch-type reactions than in the non-turgid variant reactions. Thus the Koch-type reactions were indubitably more intense in inflammatory terms than the non-turgid variant form, but the results of this study do not exclude the possibility that there were underlying qualitative differences in pathogenesis between reactions of the two types as well as the obvious difference in severity.

Adult↗
PubMed1992

Circulatory adaptation to the increased metabolism in the skin at the site of the tuberculin reaction.

The sequence of changes at the site of a positive tuberculin test response were studied in 19 healthy young adults who had been immunised with BCG in childhood. The development of erythema preceded that of induration and both were most intense at 48-72 h. The strongest reactions showed higher laser Doppler (LD) flux at the periphery than at the center (central relative slowing). All showed a substantial reduction in steady-state (ss) tcpO2 from 24 h onwards and the oxygen consumption rate (mlO2.kg-1.min-1), calculated from the rate of fall in tcpO2 during temporary cuff occlusion of arterial input, was raised (greater than two-fold) throughout the period of study (to 96 h). The density of lymphocytes and macrophages in the inflammatory infiltrate in the dermis was related to the fall in tcpO2.ss and to the extent of thickening of the dermis. These experiments showed that the previously healthy dermal microcirculation can adapt to temporary increase in metabolic demands of leucocytes emigrated from the circulation into the tissue: in intense delayed hypersensitivity (DHS) reactions there is considerable hypoxia and respiratory debt, but maintenance of viability in the short-term. It is likely that similar adaptations occur in the period of establishment of microbial infection.

Adaptation, Physiological↗
PubMed1992

Detection of multiallele polymorphisms within gene sequences by GC-clamped denaturing gradient gel electrophoresis.

The ability to efficiently detect DNA polymorphisms is essential for the completion of a high-resolution polymorphic linkage map of the human genome. Currently the most informative polymorphisms are the multiallelic dinucleotide repeat polymorphisms. However, many gene sequences lack an associated dinucleotide repeat sequence. We used GC-clamped denaturing gradient gel electrophoresis to screen for DNA polymorphisms in the following six gene sequences: MCC, p53, prealbumin (transthyretin), rhodopsin, S-antigen, and TGF-alpha. A single-base sequence polymorphism was identified in each of these gene sequences. Some of these polymorphisms were multiallelic and highly informative. Our results demonstrate the value of denaturing gradient gel electrophoresis for both identifying and analyzing human DNA polymorphisms. The ability to detect highly informative polymorphisms within gene sequences will greatly contribute to a gene-based polymorphic linkage map.

Alleles↗