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Biomedical subjects

J Gamble

Publications and source records attributed to J Gamble.

At least 73 records · Page 4Linked to original sources
PubMed1992

Myocardial stretch alters twitch characteristics and Ca2+ loading of sarcoplasmic reticulum in rat ventricular muscle.

OBJECTIVE: The aim was to determine the influence of diastolic muscle length on force development and timing parameters of cardiac muscle twitch contraction and to determine whether a length dependency exists for the calcium loading capacity of the sarcoplasmic reticulum. METHODS: Right ventricular papillary muscles and trabeculae were isolated from hearts of female Wistar rats weighing 220-280 g. Papillary muscles were stretched to diastolic lengths of 90, 95, and 100% Lmax and paced at 1.0 Hz. Individual twitch profiles were characterised by their peak force and the maximum rate (dF/dt) of the positive and negative force changes. Intrinsic timing was identified through waveform analysis that divided the twitch profile into time domains for the ascending limb (T0-T1; T1-T2) and the descending limb (T2-T3; T3-T4). Each domain was compared at three muscle lengths. The sarcoplasmic reticular calcium content at short (1.88 microns) and long (2.11 microns) sarcomere lengths was characterised by rapid cooling contractures after 1 s and 60 s of diastolic rest. RESULTS: Peak developed force and the maximum rate of positive and negative force development decreased as diastolic muscle length was reduced from Lmax to 90% Lmax. The intrinsic timing for the segment that reflects the relaxation phase of the twitch (T1-T4) was shortened as muscle length was reduced. The time domain that reflects the combined effects of calcium release and the early phase of contraction (T0-T1) was insensitive to diastolic muscle length. The fractional release of sarcoplasmic reticular calcium at different muscle lengths was approximately 32-35% of the total sarcoplasmic reticulum calcium pool. CONCLUSIONS: The data on the intrinsic timing of the twitch characteristics coupled with rapid cooling contracture analysis suggests a fractional calcium release that is approximately 32-35% of the total sarcoplasmic reticular capacity at either long or short muscle lengths. However, the loading capacity of the sarcoplasmic reticulum is greater when the muscle operates at a shorter diastolic length. This can be interpreted as meaning that diastolic muscle length differentially influences sarcoplasmic reticular calcium storage and release processes.

Animals↗
PubMed1992

Mercury in silastic strain gauge plethysmography for the clinical assessment of the microcirculation.

We have used the mercury in silastic strain gauge plethysmography (MSG) system, which is wholly non-invasive, to obtain values (mean +/- s.e.m.) for the following parameters in the legs of supine control subjects: venous pressure (Pv) 9.89 +/- 0.88 mmHg, vascular compliance (Comp) 3.50 +/- 0.29 ml 100 g-1 mmHg-1 x 10(-2), microvascular hydraulic conductivity (Kf) 4.10 +/- 0.16 ml min-1 100 g-1 mmHg-1 x 10(-3) and isovolumetric venous pressure (Pvi) 22.12 +/- 0.82 mmHg. On passive foot-down tilting of control subjects through about 45 degrees, both Pv and Pvi rose to 28.00 +/- 2.33 and 36.58 +/- 2.29 mmHg respectively. The increases in both parameters were highly significant, P < 0.0001. We found that the time course of the vascular compliance component was short if small pressure steps were used. The value increased markedly if large steps were used. We also observed that none of the microvascular parameters studied in the arms differed from those in the legs of the same subjects. We observed that the mean value Kf in the arms of 12 young, non-neuropathic diabetics (9.08 +/- 6.12 x 10(-3)) was significantly greater than that of age and sex-matched controls (P < 0.001). Studies on 14 venous ulceration patients indicated that the values for Kf and Pv were unchanged, whilst those of vascular compliance (5.60 +/- 0.58 x 10(-2) ml 100 g-1 mmHg-1) and Pvi (37.30 +/- 2.25 mmHg) were significantly greater than those found in age-matched controls (P < 0.002 and 0.001, respectively). We feel that Pvi is a useful index of microvascular perfusion. We attribute the pressure-dependent difference, in the time course of the vascular compliance response, to the veni-arteriolar reflex. We feel that the pressure dependency of this response might form the basis for the assessment of peripheral autonomic neuropathy. We believe that the MSG system offers a means of monitoring the development of pathologies resulting from microvascular under-perfusion and, of course, the improvement in response to therapeutic interventions.

Adult↗
PubMed1991

The assessment of the microcirculatory effects of dobutamine using mercury in silastic strain gauge plethysmography in man.

Adverse changes in the microcirculation are currently considered as the most likely common pathway of organ failure, dramatically manifest in the multiple organ failure syndrome. We have investigated 28 patients presenting with gross cardiovascular instability due to septic shock or haemorrhage, using standard invasive methods of monitoring (Physiological Profile). We combined this study with a computer assisted mercury-in-rubber strain gauge plethysmography (MSG) measurement, for a parallel (non-invasive) assessment of peripheral microcirculatory function. We started the investigation on patient arrival in ICU and continued it during their resuscitation regime, which essentially consisted of fluid loading together with inotropic support, where necessary. We found highly significant changes in isovolumetric venous pressure (Pvi), determined by the MSG technique, when we compared survivors (27.29 +/- 1.65 mmHg, mean +/- s.e.m.) with non-survivors (39.5 +/- 2.97 mmHg, P less than 0.001). To investigate the role of dobutamine in patient improvement we compared the Pvi values obtained from the MSG studies and demonstrated a significant decrease from the initial value (38.2 +/- 2.4 mmHg) to the final one (25.4 +/- 2.4 mmHg), obtained after weaning the patients off dobutamine. Marked cyclic changes in limb circumference (vasomotion) were also observed and their appearance correlated well with accepted parameters of cardiovascular instability. We propose that changes in both Pvi and Vm are useful indices of microvascular hypoperfusion which is probably the underlying cause of pathology in both patient groups.

Dobutamine↗
PubMed1989

p53 is associated with a 35 kD protein in cells transformed by simian virus 40.

The p53 protein is functionally implicated in the normal control of cell proliferation and, abnormally, in cell transformation. p53 is believed to function via specific cellular target proteins and activated mutants of p53 are associated with proteins of the hsp/hsc 70 heat shock family. However, cellular target proteins of wild type p53 have not, as yet, been described. With the aim of detecting such targets we have screened for cellular protein(s) that co-precipitate with wt p53. We now describe a 35 kD protein co-precipitated with p53 from SV40-transformed cells (a similar protein is detectable in non-viral transformed cells). The 35 kD protein does not appear to be a degradation product of p53. In sequential immunoprecipitations the 35 kD protein was depleted in parallel with p53, with which it appeared to be physically associated. This was substantiated by dissociation experiments in which the 35 kD protein was dissociated under conditions that also dissociate p53 from SV40 large T antigen. Thus wt p53 appears to interact with a cellular protein of 35 kD, the identity of which is under investigation.

Antigens, Polyomavirus Transforming↗
PubMed1988

Evidence that immunological variants of p53 represent alternative protein conformations.

In normal murine lymphocytes the cellular oncoprotein, p53, exists as two immunologically distinct species which are reciprocally expressed in quiescent (p53-Go) and mitogenically stimulated (p53-G divided by) cells. More recently, we have identified discrete forms of p53, immunologically similar to p53-Go and p53-G divided by, in 3T3 cells transformed by simian virus 40 (SV40). In this report, we demonstrate that immunologically distinct p53 species can also be expressed in vitro, from a single murine p53 cDNA clone. The p53 variants expressed in vitro and in SV40-transformed 3T3 cells have been studied by immunoprecipitation and Western blotting. Immunoprecipitation data indicated that, in their native conformations, the p53 variants react with either the PAb421 or RA3.2C2 monoclonal antibodies, but not with both. When analyzed by Western blotting, however, the denatured proteins were found to react with both monoclonal antibodies. This suggests that the p53 protein is flexible and can fold in alternative conformations so as to expose or mask different epitopes. We propose, therefore, that immunologically distinct p53 species are generated, at least partly, by conformational changes in a single polypeptide species.

Antibodies, Monoclonal↗
PubMed1988

Filtration coefficient and osmotic reflection coefficient to albumin in rabbit submandibular gland capillaries.

1. The isolated perfused submandibular salivary gland of the rabbit has been used in order to make estimates of the filtration coefficient (Kf) and reflection coefficient (sigma d) of the capillary wall to albumin. 2. An isogravimetric preparation was used and in paired experiments the value for Kf obtained in glands perfused with albumin-Krebs solution, 0.96 +/- 0.086 (mean +/- S.E. of mean) ml min-1 mmHg-1 100 g-1, was not significantly different from that in blood-perfused glands, 0.90 +/- 0.15. 3. On analysing the data for reflection coefficient, it was concluded that the above values underestimated Kf by about 30%; using corrected values for Kf, osmotic reflection coefficients were determined from the weight changes following a sudden change in the oncotic pressure of the perfusate. The value for sigma d to albumin lay between 0.79 and 1.0, the lower value being obtained after the Kf correction. 4. The high hydraulic conductivity, combined with sieving properties comparable to those in continuous capillaries, is consistent with other data on fenestrated capillaries. 5. Finally, it was observed that, while the Kf value calculated from the initial flux rate was similar whether measured during fluid efflux from or influx into the microvasculature, on returning to the initial conditions after raising osmotic pressure, efflux was now more rapid than influx. This phenomenon is discussed in relation to readjustment of Starling forces and the possible existence of an asymmetric double membrane in the capillary, interstitium system and cells of the salivary gland.

Albumins↗
PubMed1987

Epidemiological-environmental study of diesel bus garage workers: acute effects of NO2 and respirable particulate on the respiratory system.

Personal samples of nitrogen dioxide (NO2) and respirable particulate (RP) were collected over the shift on 232 workers in four diesel bus garages. Response was assessed by an acute respiratory questionnaire and before and after shift spirometry. Measures of exposure to NO2 and RP were associated with work-related symptoms of cough; itching, burning, or watering eyes; difficult or labored breathing; chest tightness; and wheeze. The prevalence of burning eyes, headaches, difficult or labored breathing, nausea, and wheeze experienced at work were higher in the diesel bus garage workers than in a comparison population of battery workers, while the prevalence of headaches was reduced. Mean reductions in forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak flow, and flows at 50 and 75% of FVC were not obviously different from zero. There was no detectable association of exposure to NO2 or respirable particulate and acute reductions in pulmonary function. Workers who often had respiratory work-related symptoms generally had a slightly greater mean acute reduction in FEV1 and FEF50 than did those who did not have these symptoms, but these differences were not statistically significant.

Adolescent↗
PubMed1987

Epidemiological-environmental study of diesel bus garage workers: chronic effects of diesel exhaust on the respiratory system.

Two hundred and eighty-three (283) male diesel bus garage workers from four garages in two cities were examined to determine if there was excess chronic respiratory morbidity related to diesel exposure. The dependent variables were respiratory symptoms, radiographic interpretation for pneumoconiosis, and pulmonary function (FVC, FEV1, and flow rates). Independent variables included race, age, smoking, drinking, height, and tenure (as surrogate measure of exposure). Exposure-effect relationships within the study population showed no detectable associations of symptoms with tenure. There was an apparent association of pulmonary function and tenure. Seven workers (2.5%) had category 1 pneumoconiosis (three rounded opacities, two irregular opacities, and one with both rounded and irregular). The study population was also compared to a nonexposed "blue-collar" population. After indirect adjustment for age, race, and smoking, the study population had elevated prevalences of cough, phlegm, and wheezing, but there was no association with tenure. Dyspnea showed a dose-response trend but no apparent increase in prevalence. Mean percent predicted pulmonary function of the study population was greater than 100%, i.e., elevated above the comparison population. These data show there is an apparent effect of diesel exhaust on pulmonary function but not chest radiographs. Respiratory symptoms are high compared to "blue-collar" workers, but there is no relationship with tenure.

Age Factors↗
PubMed1987

Transcapillary transport during secretion by the rabbit submandibular salivary gland.

Fluid exchange in the rabbit submandibular gland has been studied with a view to improving understanding of the mechanisms underlying transcapillary transport during salivation. Using maximally vasodilated glands perfused in vitro, we found that acetylcholine had no significant effect on either hydraulic conductance (filtration coefficient, Lp) or reflection coefficient to albumin (sigma alb) of the gland microvessels. In vivo, parasympathetic nerve stimulation increased blood flow 20-fold, interstitial fluid production (total fluid efflux - saliva flow) increased approximately 10-fold, while filtration fraction remained constant. At the same time, isogravimetric capillary pressure increased about six-fold. There are several possible explanations for these findings, and it is argued that they are likely to include capillary recruitment. Thus, during salivation, parasympathetic nerve stimulation does not lead to a change in capillary permeability as such, but rather produces a relaxation of resistance vessels and a fall in precapillary resistance, accompanied by an increase in available capillary surface area. This leads to a rise in capillary blood flow and pressure, which in turn increase fluid filtration. These changes are self-limiting due to the resulting dilution of interstitial protein and rise in interstitial pressure, but during salivation, since the secretion is pumped out of the interstitium, this fluid transport has no net effect on transcapillary gradients.

Acetylcholine↗
PubMed1987

Back pain and spinal deformity in cystic fibrosis.

Back pain is a common complaint of individuals with cystic fibrosis (CF). We studied back pain in our patient population in three ways: a questionnaire, an orthopedic evaluation, and a survey of chest roentgenograms. Forty-seven patients with CF reported back pain as compared with seven controls. Patients with CF showed decreased muscle strength and mobility in the trunk, chest, and shoulders. The incidence of structural kyphosis was only 8.7%, but many had vertebral wedging. Much of the back pain may be due to postural abnormalities or to vertebral wedging, not fixed structural kyphosis.

Adolescent↗
PubMed1985

The SV40 large T-p53 complex: evidence for the presence of two immunologically distinct forms of p53.

The transforming protein of SV40 is the large T antigen. Large T binds a cellular protein, p53, which is potentially oncogenic by virtue of its functional involvement in the control of cell proliferation. This raises the possibility that p53 may mediate, in part, the transforming function of SV40 large T. Two immunologically distinct forms of p53 have been identified in normal cells: the forms are cell-cycle dependent, one being restricted to nondividing cells (p53-Go) and the second to dividing cells (p53-G divided by). We have now dissociated and probed the multimeric complex of SV40 large T-p53 for the presence of immunologically distinct forms of p53. Here we present evidence for the presence of p53-Go and p53-G divided by complexed with SV40 large T.

Animals↗
PubMed1984

Epidemiological-environmental study of lead acid battery workers. I. Environmental study of five lead acid battery plants.

Industrial hygiene measurements were taken at five lead acid battery plants. The average of all personal samples for H2SO4 was 0.18 mg/m3 with a range of "nondetectable" to 1.7 mg/m3. Highest levels of acid were found in the charging and forming areas of the plants. Stibine and arsine were also detected in the charging and forming areas (means = 0.44 and 0.042 mg/m3, respectively). Arsenic in particulate form was also detected, but levels were low (means = 0.00083 mg/m3). The average mass median aerodynamic diameter of the acid mist as measured by cascade impactors was approximately 5 micron. Air lead results were variable with an overall average of 0.072 mg/m3 and a standard deviation of 0.11 mg/m3.

Air Pollutants, Occupational↗
PubMed1984

Epidemiological-environmental study of lead acid battery workers. II. Acute effects of sulfuric acid on the respiratory system.

Two hundred and twenty-five (225) workers in five lead acid battery plants were administered a questionnaire containing work-related symptoms, underwent spirometry, and had personal samples for H2SO4 taken over the shift. Most personal samples were less than 1 mg/m3 H2SO4. Mass median aerodynamic diameter of H2SO4 from area samples in the formation areas was 2.6-10 micron. Workers with a higher exposure to acid did not have an increased rate of acute work-related symptoms. Changes in pulmonary function over the shift were not related to levels of airborne lead or airborne acid, sex, age, or smoking status. In acclimated workers, there is no evidence of acute symptoms or reductions in pulmonary function over the shift at concentrations less than 1 mg/m3.

Adult↗
PubMed1984

Epidemiological-environmental study of lead acid battery workers. III. Chronic effects of sulfuric acid on the respiratory system and teeth.

The effects of long-term exposure to sulfuric acid mist on the teeth and respiratory system were studied in 248 workers in five plants manufacturing lead acid batteries. The prevalence of cough, phlegm, dyspnea, and wheezing as determined by questionnaire were not associated with estimates of cumulative acid exposure. There was only one case of irregular opacities seen on the chest radiographs. There was no statistically significant association of reduced FEV1, peak flow, FEF50, and FEF75 with acid exposure although the higher exposed group had lower mean values. FVC in the high exposure group showed a statistically significant reduction compared to the low exposure group, but there was no significant association when exposure was analyzed as a continuous variable. The ratio of observed to expected prevalence of teeth etching and erosion was about four times greater in the high acid-exposure group. The earliest case of etching occurred after 4 months exposure to an estimated average exposure of 0.23 mg/m3 sulfuric acid.

Adult↗
PubMed1984

On the molecular basis of T helper cell function. III. B-lymphocyte promotor factors: production by T hybridoma and tumour cells; preliminary biochemical characterization.

B-lymphocyte promotor factors (B-LPF) are defined as T-cell-derived, released molecules that trigger polyclonal induction of B-cell differentiation into antibody-forming cells. B-LPF activity is independent of antigen, and it apparently induces only IgM-producing B cells. B-LPF was discovered as products of an antigen-specific, I-Ab-restricted T-cell line. We here show that B-LPF is produced also by lymphoma cells derived from this T-cell line or by T-cell hybrids constructed by fusing the T-cell line with BW5147 thymoma cells. A chicken gamma globulin-specific T-cell hybridoma clone also produced B-LPF. Biological assays demonstrated that B-LPF-containing supernatants did not contain IL-1, IL-2, B-cell growth factor, or allogeneic effector factor. Biochemical studies showed that B-LPF was precipitated by 50% (NH4)2SO4 saturation and that at least three types of molecules were involved in B-LPF activity: molecules with molecular weights of greater than 90,000, 50,000-90,000 and 10,000-25,000. The relationship between B-LPF and antigen-specific helper/inducer factors is discussed.

Animals↗