HepG2 cell binding activities of different hepatitis b virus isolates: inhibitory effect of anti-HBs and anti-preS1(21–47)

The antigenic relationships among different hepatitis B virus (HBV) isolates were investigated by using monoclonal antibodies (MAbs) specific for HBs, preS2 (pHSA binding site), and preS1 (hepatocyte receptor-binding site) epitopes in a double immunoradiometric assay. In order to define possible functional differences resulting from structural and antigenic differences in the HBV env protein, the HBV isolates were compared in an in vitro cell-binding assay based on the attachment of 125I-labeled HBV to human hepatoma HepG2 cells. We provided evidence for a variability of the expression of preS1 and preS2 specificities in the peplomer (glyco)protein of HBV depending on d/ysubtype of HBsAg, which could affect the viral infectivity. We showed that the integrity of the HBV envelope structure associated with a large expression of preS1(21–47) epitopes is an essential factor for effective binding to HepG2 cells. Interestingly, the HBs-specific MAbs directed to disulfide-bond-dependent epitopes were found to be the best inhibitors of the preS1-HepG2 cell interaction (>50% at the final concentration of 0.5 μg/ml). The MAb F35.25 directed to the preS1(21–47) sequence corresponding to the hepatocyte receptor recognition site was, however, also found to inhibit binding. Thus, our results demonstrate the abilities of both anti-HBs and anti-preS(21–41) to block the attachment of complete HBV particles to HepG2 cells, suggesting that these antibodies should be virus neutralizing and would be expected to confer protection against reinfection.     

Chronic bronchitis in textile workers

BACKGROUND: Exposure to cotton is known to produce a specific occupational disease known as byssinosis. A large population of textile workers was investigated to determine whether such exposure was also associated with chronic bronchitis once other possible aetiological factors had been accounted for. METHODS: A total of 2991 workers were investigated for the presence of symptoms compatible with chronic bronchitis. An MRC adapted respiratory questionnaire and MRC definition of chronic bronchitis were used for diagnostic labelling. Current and lifetime exposure to dust was estimated by personal and work area sampling, and the use of records of retrospective dust levels previously measured over the preceding 10 years. Airborne endotoxin exposure was measured using a quantitative turbidometric assay. Lung function tests were performed to measure forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A control group of workers exposed to man-made fibre textiles was identified. The comparative prevalence of chronic bronchitis in the two populations was assessed, allowing for sex, age, smoking habit, and ethnic origin. Two case referent studies were also performed; cases of chronic bronchitis were separately matched with controls from the cotton and control populations to determine the effect of the symptomatic state on lung function. RESULTS: After controlling for smoking (pack years), workers in a cotton environment were significantly more likely to suffer from chronic bronchitis and this was most marked in workers over 45 years of age (odds ratio 2.51 (CI 1.3 to 4.9); p < 0.01). Regression analysis of all possible influencing parameters showed that cumulative exposure to cotton dust was significantly associated with chronic bronchitis after the effects of age, sex, smoking, and ethnic group were accounted for (p < 0.0005). In the intra-cotton population case control study a diagnosis of chronic bronchitis was associated with a small decrement in lung function compared with controls: percentage predicted FEV1 in cases 81.4% (95% CI 78.3 to 84.6), controls 86.7% (84.9 to 88.5); FVC in cases 89.9% (95% CI 87.0 to 92.9), controls 94.6% (92.8 to 96.4). After controlling for cumulative past exposure and pack years of smoking the effect of the diagnostic state remained significant for both FEV1 (p < 0.01) and FVC (p < 0.05). CONCLUSIONS: Chronic bronchitis is more prevalent in cotton workers than in those working with man-made fibre and exposure is additive to the effect of smoking. The diagnosis of chronic bronchitis is associated with a small but significant decrement in lung function.


     

Intraaortic balloon tamponade during hemorrhagic shock in sheep

Two groups (n = 10 in each) of adult sheep were exposed to hemorrhagic shock resulting in mean arterial pressure (MAP) below 25 mmHg for 10 min. Following that, group A received crystalloids (8% of body wt) during one hr together with supraceliac intraaortic balloon tamponade during the first 30 min, while group B (controls) received crystalloids only. The central circulation was rapidly restored in group A, as indicated by increased MAP and increased systemic vascular resistance (SVR). After deflation of the balloon MAP dropped to the same value as in the control group, while cardiac index increased gradually with volume replacement and was significantly higher at the end of the resuscitation period (60 min) than in the control group (P less than 0.05). Despite a more rapid restoration of central hemodynamics in group A, lactic acidosis was more severe, acute renal failure and neurological complications more frequent, and mortality higher than in the control group. It was concluded that continuous supraceliac aortic occlusion for 30 min had deleterious effects on organs dependent on aortic blood flow distal to the aortic tamponade and may contribute to the development of multiple organ failure after resuscitation from hemorrhagic shock. Further studies are needed to evaluate the effects of intermittent intraaortic balloon tamponade in hemorrhagic shock.     

Successful treatment of failed AID cases by use of gamete intra-fallopian transfer using donor semen (GIFT (D)).

Over a 13-month period in a newly opened assisted conception unit at the Women's Hospital, Liverpool, gamete intra-fallopian transfer using donor semen, GIFT (D) was offered to eighteen couples who had failed to conceive after numerous cycles of treatment with artificial insemination by donor semen (AID). The indication for the use of donor semen was either azo- or severe oligoaesthenospermia, and, in addition, the female partners have been exhaustively investigated with no major cause found to account for the couple's infertility. Using a basic clomiphene citrate and human menopausal gonadotrophin protocol it was possible to achieve a pregnancy rate of 56% per GIFT (D) cycle. As a consequence of these results it is now our policy to treat couples whose infertility is due to an unresolvable male factor with AID for 12 cycles only. If they have been unsuccessful in achieving a pregnancy after this time, they are offered GIFT (D).     

Adrenal magnetic resonance imaging in addison’s disease

Magnetic resonance imaging of the adrenal glands was performed in 9 patients with Addison’s disease to evaluate the role of magnetic resonance (MR) in this entity. All patients had bilateral adrenal masses demonstrated by computed tomography (CT); etiologies included adrenal hemorrhage (2 patients), granulomatous disease (1 patient), adrenal lymphoma (3 patients), and adrenal metastases (3 patients). Spin-echo axial images were obtained at repetition times (TR) 0.5, 2.0 s and TE 28, 56 ms, using a Diasonics superconducting magnet operating at 0.35 T. In the patients with lymphoma, metastases, and granulomatous disease, the adrenal masses appeared hypointense or isointense with liver on the T₁-weighted images (TR 0.5 s, TE 28 ms). In cases of adrenal hemorrhage, areas of hyperintensity were seen on TR 0.5, TE 56 ms sequences, due to shortening of T₁ values. In both groups of patients the masses were hyperintense on T₂ weighted sequences. Mean calculated T₁ of the hemorrhagic glands was 449 ms, compared with a mean of 782 ms for mestastases and lymphoma. While MR is not capable of distinguishing between acute inflammatory and metastatic disases of the adrenal glands, it may be equally efficacious as CT in suggesting the diagnosis of adrenal hemorrhage in patients with Addison’s disease.     

Receptors for angiotensins I and II: their relevance to renal haemodynamics, blood pressure control and hind-limb blood flow.

The well established differential pulmonary handling of angiotensins I and II indicates the possibility that vascular receptors for the deca- and octa-peptides do not necessarily involve common sites in the renal vasculature either. Experimental findings involving haemodynamic changes within the kidney in anaesthetised and conscious sheep, with utilization of the angiotensins, and also of noradrenaline, are briefly presented; the implications of the intra-renal water and creatinine transfers are discussed, especially as they concern the possible location of angiotensin receptors in the renal blood vessels. Other aspects of the relationships between the peptides are also taken into account particularly with regard to a postulated angiotensin I [NaCl] dependent peritubular capillary antidiuretic action, angiotensin converting enzyme inhibition, Goldblatt clamp induced hypertension and blood flow through the hind-limbs.     

Effect of acclimation on resting energy expenditure measurements.

BACKGROUND: Development of an acclimation protocol for use when measuring resting energy expenditure (REE) would simplify and standardize data collection. The purpose of this study was to determine if our 2 metabolic carts could be used interchangeably and to determine if excluding the first 3 or 5 minutes of data collected as an acclimation period would significantly improve the coefficients of variation (CVs) for oxygen consumed (VO(2)) and carbon dioxide produced (VCO(2)) when performing REE assessments with our metabolic cart systems. METHODS: Thirteen healthy, nonsmoking adults ranging in age from 32 to 45 years, with activity levels ranging from sedentary to highly active, participated. Indirect calorimetry was performed twice in the morning after 30 minutes of supine resting. Subjects had fasted for 12 hours, and did not exercise within the last 24 hours. The system order for testing was randomized for the first measurement. When the first measurement was completed, subjects were crossed over for measurement using a second metabolic cart. RESULTS: The CVs for VO(2) and VCO(2) were significantly lower when excluding the first 3 (VO(2), p = .0005), (VCO(2), p = .0024) or 5 minutes (VO(2), p = .0001, VCO(2), p = .0021) of data compared with no exclusions. No significant differences in CVs between the 3- and 5-minute exclusions were found for VO(2) (p = .3224) or VCO(2) (p = .2255). CONCLUSIONS: Clearly, our machines cannot be used interchangeably within a study. An acclimation period improves CVs of VO(2) and VCO(2.) The similarities in CVs led us to adopt a 3-minute acclimation period for measuring REE.     

Preliminary assessment of the Dex Frame for assisting children with specific learning difficulties

A device called the Dex Frame has recently been marketed as an aid for children with specific learning difficulties. Using a test of reading speed and a test of reading accuracy we have attempted to evaluate the device. Two groups of children with learning difficulties were used, one having sole use of the device and being allowed to carry it with them and a second group who only used the device when attending for remedial tuition and assessment. The results show that no significant improvement occurred in reading performance of the groups with learning difficulties using the Dex Frame as compared with a control group. The teachers of the groups did, however, feel that on an individual basis some children (< 10%) expressed that they felt more comfortable using the device.