Biomedical subjects
Publications and source records attributed to J Gilbert.
Twenty-five (37%) patients with cystic fibrosis attending our clinic have experienced acute meconium ileus equivalent. In one year 37 of 40 episodes were treated with single dose oral Gastrografin with an 81% success rate, 75% being treated as outpatients. Patients found this treatment preferable to other recommended treatment.
The monoclonal antibodies HMFG-1 and HMFG-2 are directed against different epitopes on a large molecule in the human milk fat globule and are also expressed on breast tumors. Here we examine the relative intensity of staining of the two antibodies in formalin fixed paraffin embedded tissue sections from malignant and benign mammary lesions. Most ductal carcinomas and their lymph node metastases stained more strongly with HMFG-2 whereas primary lobular carcinomas are more variable but the majority of their lymph node metastases stained more strongly with HMFG-1. Western blots of gel separated extracts of formalin fixed, paraffin embedded tumor tissue, stained with the antibodies in an ELISA assay, show that the molecular weight of components expressing the antigenic determinants varies. Smaller molecular weight components recognised by HMFG-2 and present in metastatic tumors may be lost during tissue processing. To assess the importance of the molecular weight parameter in tumor classification and prognosis it will be necessary to use frozen tissue.
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Rats and dogs chronically treated with high doses of sulbactam are known to sequester protein-bound glycogen in their hepatocytes. As a result, previous UK studies of sulbactam/ampicillin excluded patients suffering from diabetes mellitus. This study examined the effects of sulbactam/ampicillin compared to flucloxacillin/ampicillin on diabetic control, the ability to mobilize glycogen and the pancreatic beta cell response to glucagon, in diabetic patients suffering from soft tissue infection. There was no significant effect between treatment groups on any of these parameters. Sulbactam/ampicillin is unlikely to have an adverse effect on diabetic control in clinical practice when used short term in the doses employed in this study.
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An instrument providing cyclic stress to cells cultured in vitro has been developed. The unit uses a vacuum to deform a plastic Petri dish yielding 0.13% compression to cells on the inner surface, measured by strain gauge recordings. A regimen of 25 s stress and 5 min relaxation induced no significant change in synthesis of a 45 X 10(3) Mr protein that comigrates with actin, whereas a 52 X 10(3) Mr protein that comigrated with tubulin decreased from 12.7 +/- 0.451% of the total protein synthesized in control, static cells to 8.53 +/- 0.182% in stressed cells. The unit may have a broad application in monitoring biochemical changes in response to stress in cells such as muscle, lung, tendon, ligament and bone that are normally subjected to tension or compression.
Several cryosurgical techniques for freezing hepatic parenchyma have been developed. To assess the efficacy of sonographic monitoring of hepatic cryosurgery, an experimental animal model was devised. Real-time sonography was used to monitor the in vivo evolution of hypothermically induced hepatic cryolesions in four mongrel dogs. The results suggest that sonography is an effective and accurate means of monitoring the entire freezing and thawing cycle in hepatic cryosurgery.
A monoclonal antibody (D5) raised against affinity-purified cytosol estradiol receptor (REC) from human myometrium has been used to stain human tissues by means of an indirect immunoperoxidase method. Good staining was obtained with ethanol-, glutaraldehyde-, or Carnoy's-fixed material but not with formalin or Bouin's fixation. Cytoplasmic staining of human breast tumors exhibited a highly significant correlation (P less than 0.001) with REC assayed by conventional estradiol-binding assay provided that allowance was made for both staining intensity and cellularity of the tumor; no correlation existed with soluble progesterone receptor content. Both patient age and tumor differentiation influenced staining patterns in the same way as did REC content. Cultured REC-positive human breast tumor cell lines (MCF-7, ZR-75-1, and CA-2) showed positive staining as did cultured epithelium from human milk. Epithelia in normal breast and fibroadenoma exhibited variable staining that rarely reached the intensity seen in REC-positive tumor cells. The staining patterns of human normal endometrium, myometrium, fallopian tube, ectocervix, endocervix, and ovary and neoplastic endometrium and ovary are described. In every situation thus far examined only cytoplasmic staining has been observed.
Four cases of amiodarone-induced restrictive, hypoxaemic lung disease are described. The cumulative dosages of amiodarone were relatively low (30 to 100 g). Alveolar lavage studies showed a lymphocytosis and study of the lymphocytic sub-populations showed an increase in the OKT8 group, and an inversion of the OKT4/OKT8 ratio. The outcome was favourable on withdrawal of amiodarone and steroid therapy. The immunological origin of this form of lung disease was confirmed. Two patients had renal failure; in the first case, hypercalcaemia, hyperphosphoremia and renal calcification were observed. The second patient had endo- and extracapillary glomerulonephritis with C3 deposits and circulating immune complexes. Renal failure regressed in both cases on withdrawal of amiodarone and with steroid therapy.
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Twelve homologous triphenyl acrylonitrile derivatives with a p-OH or p-CH3 group on one or more of the phenyl rings were synthesized in order to assess the relative influence of each position on binding to the estrogen receptor (ER) and on inhibition of prostaglandin synthetase (PGS). Their relative binding affinities (RBAs) for [3H]estradiol (E2)-labeled ER were compared at 0 and 25 degrees C in mouse and rat uterus cytosol with those of tamoxifen derivatives, cyclofenil and diethylstilbestrol. RBAs in both species were closely correlated (r = 0.92) although the RBAs were about twice as high in the mouse as in the rat. The unsubstituted skeleton had an RBA of much less than 0.1 (estradiol = 100). An OH-group in R1 or R2 (Fig. 1) engendered very low affinity whereas an OH-group in R gave rise to a compound with an RBA equivalent to that of E2, emphasizing the importance of this position in the interaction with ER. Compounds with an additional OH-group in R1 or R2 were significantly better competitors than E2. No further increase in RBA was noted with the trihydroxy derivative. The effect of the introduction of a hydrophobic CH3-group decreased affinity as expected in R, but also in position R1 unless a second OH-group was present in R2. None of the 12 test-compounds competed significantly for binding to the "anti-estrogen binding site" in rat kidney supernatant. Although polar groups were not necessary for inhibition of PGS, inhibition was enhanced by the presence of a hydroxy group in R or R1 (but not R2). Even greater inhibition was obtained by the further introduction of a CH3-group in R1 or R respectively. The conformations of these derivatives are compared to those of known estrogen ligands and anti-inflammatory agents in order to obtain further information on these protein recognition sites.
We have studied the effect of nearly 90 arylacrylonitrile derivatives, and several related compounds, on the biosynthesis of prostaglandins from bovine seminal vesicle microsomes. This effect was compared to that of triarylacrylonitrile derivatives known for their inhibiting properties. Several arylacrylonitrile derivatives have also proved good inhibitors, especially certain N-trisubstituted compounds: trans (dimethylamino-4 phenyl)-3 (methoxy-4' phenyl)-2 acrylonitrile was the best inhibitor of the group, with an IC50 of 0.07 microM. The absence of carboxy groups in these derivatives precludes the application of any of the site-models proposed to date. We suggest that the electronic charges carried especially by the three aromatic rings play an important role in the inhibiting mechanism.
A study was designed to evaluate the adequacy of gas exchange during continuous flow apneic ventilation (CFAV) in dogs. Seventeen dogs (average weight 22.9 kg) were divided into three experimental groups. Group I (n = 7) was anesthetized, paralyzed and ventilated with air using intermittent positive pressure ventilation (IPPV) through a tracheal tube. The tube was removed and each main stem bronchus was cannulated with a 2.5 mm i.d., 4 mm o.d. polyethylene catheter using a fiberoptic bronchoscope. The tracheal tube was replaced to hold the catheters in place. Heated, humidified air was continuously delivered equally to each catheter. Total flows ranged from 8 to 28 l/min (0.4-1.4 l X kg-1 X min-1). Airway pressure (Paw) in the trachea did not exceed 2 mmHg (0.27 kPa). Adequate gas exchange in terms of arterial oxygen and arterial carbon dioxide tension (Pao2 and Paco2) was found after 30 min at flows greater than 16 l X min-1. Group II (n = 7) was managed similarly to the first group, insufflating endobronchial air using the optimal flow of 1.0 l X kg-1 X min-1 obtained from Group I. CFAV continued for 5 h in all animals. Blood gas samples and measurements of systemic blood pressure, heart rate (HR), pulmonary artery blood pressure, pulmonary artery wedge pressure, cardiac output (Qt), and temperature were taken every 30 min. Group III (n = 3) was anesthetized similarly to the other groups. Pulmonary gas distribution was evaluated in relation to catheter placement using Xe133. Results showed significant differences between Pao2 values during CFAV and IPPV; however, all animals were adequately oxygenated.(ABSTRACT TRUNCATED AT 250 WORDS)
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Deliberate metallic paint inhalation, paint sniffing, has recently become the focus of community concern in central California, as numbers of recalcitrant young abusers have entered the overloaded Mental Health and Juvenile Justice systems. This study, based on an extension of psychological, sociological and anthropological explanations of inhalant abuse, describes the adolescent paint sniffer and proposes that a combination of interacting factors both differentiates him/her from other-drug abusing youth, and predisposes him/her to inhalant use. The experimental hypothesis was tested by a stepwise discriminant analysis performed on 50 subjects, equally divided into two groups, paint and other-drug. Six variables, in combination, were found to significantly differentiate the groups, and the derived function accounted for 56% of the between group differences. The following conclusions can be drawn from this investigation. Firstly, the adolescent paint sniffer is demonstrably and meaningfully different as discriminated by a combination of personal, familial and sociocultural variables. Secondly, these identified factors have predisposed the sniffer to abuse, and cannot be considered simply the consequence of said abuse. Finally, it can be concluded that the paint sniffer is a youth disengaged from the symbols and traditions of his/her culture of origin and concomitantly rejected by the majority culture. Inhalant intoxication provides a "cheap" and effective escape from his/her isolation. Recommendations for prevention, early intervention and treatment are addressed.