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Biomedical subjects

S Reid

Publications and source records attributed to S Reid.

At least 109 records · Page 6Linked to original sources
PubMed1995

Ca2+ versus Zn2+ transport in the gills of freshwater rainbow trout and the cost of adaptation to waterborne Zn2+

Previous work suggested that Ca2+ and Zn2+ share a common uptake pathway in rainbow trout gills. We here report on relationships between the kinetic variables for unidirectional Ca2+ influx and unidirectional Zn2+ influx during a 1 month exposure of freshwater rainbow trout to Zn2+ (150 &micro;g l-1=2.3 &micro;mol l-1 as total zinc, Zn). Initial exposure to Zn2+ caused a large competitive inhibition of Ca2+ influx, as indicated by a threefold increase in apparent Km for Ca2+ (measured in the presence of Zn2+). There was also a smaller non-competitive inhibition (50 % decrease in Jmax) of the Ca2+ transport system, which was abolished after 1&shy;2 weeks of exposure. The Km, measured in the absence of Zn2+, decreased dramatically (i.e. elevated affinity) on days 1&shy;4 but increased thereafter; both true and apparent Km finally stabilized significantly above control levels. However, the Km values for Ca2+ (<200 &micro;mol l-1) were low relative to the Ca2+ level in the water (1000 &micro;mol l-1), and therefore the changes did not influence the actual Ca2+ influx of the fish, which tracked Jmax. In contrast, water [Zn2+] (2.3 &micro;mol l-1 as total Zn) was close to the reported apparent Km (3.7 &micro;mol l-1) for Zn2+ influx in the presence of 1000 &micro;mol l-1 Ca2+. Unidirectional Zn2+ influx increased during the first week of exposure to waterborne Zn2+, followed by a persistent reduction to about 50 % of control levels, effects that may be largely explained by the observed changes in true Km for Ca2+. We speculate that the initial response of the fish to elevated [Zn2+] is to compensate for a reduced availability of Ca2+ by markedly increasing the affinity of a dual Ca2+/Zn2+ transporter. Once the Ca2+ influx is 'corrected' by restoration of functional transport sites (Jmax), the system is tuned to limit the influx of Zn2+ by a persistent reduction in the affinities for both ions. The changes in influx characteristics for Ca2+ and Zn2+ were correlated with internal physiological alterations indicative of adaptation to Zn2+ and increased metabolic cost. Depressed plasma [Ca] was corrected within 1 week, and there were no effects on whole-body [Ca] or [Zn]. A slight accumulation of Zn in the gills was associated with increased branchial metallothionein levels. Rates of protein synthesis and degradation in the gills were initially increased and whole-body growth was transiently impaired, effects which were reversed after 18 days of exposure. Sublethal challenge with Zn2+ (at 450 &micro;g l-1=6.9 &micro;mol l-1 as total Zn) always depressed plasma [Ca] in control fish, but by 1 month of exposure to Zn2+ at 150 &micro;g l-1 (as total Zn), experimental fish were resistant to challenge. However, the fish did not acquire increased survival tolerance (LT50) to a lethal concentration of Zn2+ (4 mg l-1=61 &micro;mol l-1 as total Zn).

Journal Article↗
PubMed1994

T helper cell regulation of normal and neoplastic B cell growth.

Following challenge with a thymus-dependent antigen T helper cells regulate B cell growth and differentiation in several ways. Initially, the T cells physically associate with antigen presenting B cells. While in conjugate, the two cells communicate with each other through the actions of cell surface receptors whose ligands are integral membrane proteins expressed on the surface of the apposed cell. The ensuing biochemical pathways regulate the expression of genes required for B cell cycle progression. As a consequence of this interaction, the T cells are induced to synthesize and secrete soluble mediators that also affect B cell proliferation, as well as determining the ultimate fate of the activated B cell. We also suggest a role for normal, Th cells during the development, and continued expansion of certain types of B cell lymphomas.

Animals↗
PubMed1994

Calcium alginate immobilized hybridomas grown using a fluidized-bed perfusion system with a protein-free medium.

Hybridoma SPO1 cells were immobilized in calcium alginate beads and were further grown in a fluidized-bed perfusion system with a protein-free medium. The presence of serum in the steps of entrapment was shown to be helpful for the preservation of cell viability. Each step during immobilization was investigated with respect to the extent of cell damage caused. The immobilization process using small beads caused a lower cell viability initially but allowed a higher rate of cell growth subsequently, compared to those in large beads. In a perfusion system for the continuous production of monoclonal antibodies (MAb), the viable cell density reached 2 x 10(7) cells per ml of beads with a viability of 40%. Compared with the cells in suspension culture, the immobilized SPO1 cells showed higher viable cell based specific rates of substrate uptake (glucose and glutamine) and of MAb production. A significant drop in the formation of lactate after the cell growth entered a steady state suggested a higher activity of the Tricarboxylic Acid Cycle in the cells when the cell density became high.

Alginates↗
PubMed1994

Hybridoma cells in a protein-free medium within a composite gel perfusion bioreactor.

A composite gel system has been developed combining the chemical and physical properties of calcium alginate and agarose gels. The results of growing composite gel immobilized hybridoma SPO1 cells in a protein-free medium within a fluidized-bed perfusion bioreactor are presented in this paper. During the continuous operation of this system, the total cell density reached 3.9 x 10(7) cells per ml of beads (viability 79.6%). The specific productivity of monoclonal antibody of the immobilized hybridoma cells reached more than 1.5 micrograms per 10(6) viable cells per hour, compared with 0.5 for non-immobilized viable cells grown in a one liter agitated bioreactor with the same medium. Significant increases in cell metabolic activities, including substrate utilization and byproduct formation, were also observed. Leaching of materials from the beads was evident and the major fraction of released materials was alginate.

Alginates↗
PubMed1994

Relationship between oxygen uptake rate and time of infection of Sf9 insect cells infected with a recombinant baculovirus.

Oxygen uptake rates (OUR) of Sf9 insect cells propagated in a serum-free medium (SF900II, Gibco) and of cells infected with a recombinant AcNPV were investigated before and after infection in a laboratory-scale bioreactor. The volumetric OURs of uninfected and exponentially growing cells were found to be proportional to the cell density. For infected cultures, the specific OUR of cells increased immediately after addition of virus and a maximum of 1.3 times the value of uninfected cells was noted for all the cultures between 8 to 30 hours post infection, which coincides with the period at which most viral replication and the majority of DNA synthesis takes place. It was observed that the rate of rise in the specific OUR decreased as the cell density at the time of infection increased, which meant that the later the infection, the later the maximum sOUR was observed. We therefore suggest that OUR measurement can be used to reflect the efficiency of a batch infection. Carbohydrate and amino acid consumption rates from an infected run were analysed in an effort to identify substrate(s) that may be used at increased rates to fuel the rise in oxygen demand observed early in the infection cycle. No observable rise in the consumption rates of glucose or glutamine, which are the major energy sources for animal cells, were seen after infection but an increase in the consumption rates of some amino acids suggests that infected Sf9 cells may utilise amino acids at an enhanced rate for energy post infection.

Amino Acids↗
PubMed1994

Investigations of the 'active' edge of plaque psoriasis: vascular proliferation precedes changes in epidermal keratin.

We have investigated markers of epidermal proliferation and differentiation in terms of keratin expression, the morphology of the cutaneous vasculature, and numbers of cutaneous mast cells, in patients with chronic plaque psoriasis. Using the phenomenon of the 'active edge', we have studied these features in the psoriatic plaque itself, and in the clinically normal active and inactive edges of the same plaque. Our results confirm the anticipated changes in keratin profiles, mast cell numbers and psoriatic morphology of the vasculature within the plaque itself. They further indicate that the vascular changes precede the epidermal and mast cell features at the active edge, and that the inactive edge is inactive for all of these variables. Mediators responsible for the vascular proliferation and elongation must be present in increased amounts at the active edge when compared with the inactive, and include locally produced and circulating factors.

Cell Count↗
PubMed1994

THE EFFECTS OF ACCLIMATION TEMPERATURE ON THE DYNAMICS OF CATECHOLAMINE RELEASE DURING ACUTE HYPOXIA IN THE RAINBOW TROUT ONCORHYNCHUS MYKISS

The response of cannulated rainbow trout (Oncorhynchus mykiss) to acute hypoxia was studied in fish acclimated to two temperatures (5 and 15 &deg;C). Blood/water respiratory variables and plasma catecholamine levels were measured before and 15 min after exposure to hypoxic water varying between 4.0 and 10.7 kPa (30&shy;80 mmHg) oxygen partial pressure (PwO2). Arterial blood PO2 (PaO2) and oxygen content (CaO2) fell during hypoxia in a similar manner at both temperatures, although the changes in CaO2 were often more pronounced in the fish acclimated to 15 &deg;C. Regardless of acclimation temperature, plasma catecholamine levels were consistently elevated at PwO2 values below 8.0 kPa (60 mmHg); the largest increases in plasma catecholamine levels occurred below PwO2=5.3 kPa (40 mmHg). Adrenaline was the predominant catecholamine released into the circulation. Adrenaline was released at PwO2 values of 8.0 kPa or below, whereas noradrenaline was released at PwO2 values of 6.7 kPa or below. The construction of in vivo oxygen dissociation curves demonstrated an obvious effect of acclimation temperature on haemoglobin (Hb) oxygen-affinity; the P50 values at 15 &deg;C and 5 &deg;C were 3.6 kPa (26.7 mmHg) and 1.9 kPa (14.0 mmHg), respectively. At 15 &deg;C, catecholamines were released into the circulation abruptly at a PaO2 threshold of 4.6 kPa (34.5 mmHg) while at 5 &deg;C the catecholamine release threshold was lowered to 3.3 kPa (24.5 mmHg). The difference in the PaO2 catecholamine release thresholds was roughly equivalent to the difference in the P50 values at the two distinct temperatures. Catecholamine release thresholds, calculated on the basis of arterial blood oxygen-saturation (expressed as CaO2/[Hb]), were similar at both temperatures and were approximately equal to 53&shy;55 % Hb O2-saturation. The results support the contention that the lowering of blood oxygen content/saturation rather than PO2 per se is the proximate stimulus/signal causing catecholamine release in rainbow trout during acute hypoxia.

Journal Article↗
PubMed1994

Some endurance measures in persons with chronic low back pain.

Muscle fatigue and lack of endurance are complaints of persons with chronic low back pain, but there are no standard ways to assess endurance in this population. The purposes of this study were to examine three measures of endurance; to determine relationships of these measures to each other; and to describe effects of gender, obesity, smoking, and self-reported fitness on the clinical measures. The measures of endurance selected were not dependent on maximal voluntary muscular contractions. They were the Sorensen test, median frequency decline of selected muscles, and a submaximal bicycle ergometer test. Thirty-five consenting individuals who were referred for treatment answered questions about their daily exercise prior to being tested. Repeatability of the Sorensen test holding time and of the slope measure of decline in the median frequencies was acceptable for subjects who reported a higher activity level. The decline of the median frequency in the biceps femoris muscles correlated with holding time of the Sorensen test. Smoking, gender, or obesity level did not affect test results on any of the endurance measures. Subjects who reportedly were more active achieved significantly higher scores on the Sorensen test. The importance of controlling for self-perception of activity in physical testing is discussed.

Adult↗
PubMed1994

Differential cytokine production associated with distinct phases of murine graft-versus-host reaction.

Previous studies which demonstrated that cytokines such as interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are essential for the development of graft-versus-host reaction (GvHR) did not establish whether the individual cytokines were responsible for distinct features of the disease. In this report, we show that IFN-gamma production is associated with the early proliferative phase of the disease, whereas the late, destructive phase correlates with production of TNF-alpha. These studies may assist in the development of specific immunotherapies aimed at individual aspects of immunologically mediated disease.

Animals↗
PubMed1994

Fecal occult blood testing: a false sense of security?

BACKGROUND: Recent screening studies with fecal occult blood testing (FOBT) report that one of three patients with colorectal cancer (CRC) can be cured of the disease; minimal attention has been given to the two of three patients who despite repeated screening go on to die of silent CRC. We report the known "miss rate" (known false negatives) of our 14-year ongoing program of FOBT that was organized in 1979 to detect early CRC. METHODS: From October 1979 through December 1993, 36,034 FOBT kits were distributed to patients who were without gastrointestinal complaints at Hines Veterans Affairs Hospital. The test was considered positive if at least one result of the six tests was positive and negative if the test result was equivocal. Patients with negative FOBT received a new test kit each year by mail. A positive test was followed by full colonoscopy or an air contrast barium enema if a full colonoscopy was not possible. RESULTS: The overall return rate was 47.8%. CRC was detected in 115 patients: 94 had a favorable and 21 had an unfavorable Duke's C or D or lymphoma prognosis. Of 21 patients 13 (62%) had initially tested FOBT negative (missed lesion). Of the 21 cases of advanced CRC 15 (71.43%) were in the descending, sigmoid, or rectosigmoid colon or rectum. CONCLUSIONS: (1) The majority (82%) of all CRC detected by FOBT screening are diagnosed at a favorable stage. (2) The majority of known advanced CRC (62%) escape early detection with FOBT. (3) Five (62.5%) of eight of the advanced CRC cases discovered on initial FOBT and 10 (76.9%) of 13 of advanced CRC cases missed on initial FOBT but detected in subsequent years were in the left colon and most likely in the range of the flexible sigmoidoscope. (4) FOBT as a sole screening test may provide a false sense of security, especially in patients with advanced left-side CRC.

Aged↗
PubMed1994

Electrocardiographic and cardiovascular effects of subconvulsive stimulation during titrated right unilateral ECT.

The American Psychiatric Association Task Force on ECT has recommended that electroconvulsive therapy (ECT) stimuli be dosed at "moderately suprathreshold" intensities. Empiric estimation of the convulsive threshold by stimulus dose titration may expose the patient to subconvulsive stimuli, and subconvulsive stimuli have been reported by some to carry serious cardiovascular risk. This study examines the electrocardiographic (ECG) and cardiovascular effects of subconvulsive stimuli. Forty consecutive inpatients (29 women, 11 men; mean age 68 years) with major depression received subconvulsive stimuli during titrated, right unilateral (RUL) ECT. Successively larger stimuli were administered until a convulsion began. The effects of subconvulsive stimuli on the ECG, heart rate (HR), and blood pressure (BP) were assessed with multivariate repeated measures analysis. Subconvulsive stimuli prolonged the R-R interval and decreased HR compared with baseline values immediately before the subconvulsive stimulus, but the changes were of questionable clinical significance. BP was not changed. In conclusion, subconvulsive stimuli are well tolerated in the context of titrated RUL ECT. If stimulus dose titration proves to be useful in optimizing efficacy with fewer cognitive side effects, then cardiovascular considerations should not be an obstacle in the application of stimulus dose titration in most patients.

Aged↗
PubMed1993

Dissociation between lymphoproliferative responses and virus replication in mice with different sensitivities to retrovirus-induced immunodeficiency.

Murine AIDS (MAIDS) is induced by a replication-defective virus (BM5d). In susceptible mice (C57BL/6J), inoculation with LP-BM5 murine leukemia virus, which consists of the BM5d virus and replication-competent B-tropic ecotropic (BM5e) and milk cell focus-inducing (BM5-MCF) helper viruses results in the polyclonal proliferation of T and B cells, immunodeficiency, and the expansion of B cells containing the BM5d provirus followed by the development of B-cell lymphomas. Several strains of mice that are resistant to LP-BM5-induced murine AIDS have been identified, and major histocompatibility complex genes as well as non-major histocompatibility complex genes were shown to play a role in this resistance. In the present study, we have examined and compared the replication of the BM5d and BM5e viruses after inoculation of LP-BM5 into sensitive (C57BL/6J) and resistant (C57BL/KSJ) mice. Using a specific polymerase chain reaction, we could detect the BM5d and BM5e proviruses as early as 1 week postinfection in the sensitive mice, and the levels of both viruses increased significantly with the progression of the disease. In contrast, in the resistant C57BL/KSJ mice, replication of BM5d and BM5e was restricted and no BM5d and only very low levels of the BM5e provirus could be detected either at early or late times postinoculation with the LP-BM5 virus mixture. Inoculation with LP-BM5 did not lead to the production of antibodies that could recognize the BM5d-encoded Pr60gag in either the sensitive or resistant mice; however, production of antibodies recognizing the env-related proteins of the helper virus was detected in the resistant but not in the sensitive mice at late times postinfection. Interestingly, inoculation with LP-BM5 increased polyclonal stimulation of spleen cells and decreased mitogen stimulation in both strains of mice. This stimulation of splenocytes persisted in the sensitive mice but decreased after a few weeks in the resistant mice. These results show an early block in BM5d and BM5e replication in the resistant C57BL/KSJ mice and indicate that resistance is a consequence of the inhibition of an onset of the BM5d virus infection and its expansion. However, initial responses to virus infection such as proliferation of spleen cells and response to mitogen are similar in both strains of mice and are therefore not necessarily related to the development of the disease.

Animals↗