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Biomedical subjects

A Paul

Publications and source records attributed to A Paul.

At least 217 records · Page 12Linked to original sources

Phorbol ester-induced protein kinase C translocation and lysosomal enzyme release in normal and cystic fibrosis fibroblasts.

The ability of the tumor-promoting phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) to induce protein kinase C (PKC) translocation and lysosomal enzyme release was examined in skin fibroblasts from normal subjects and from patients with cystic fibrosis (CF). As compared to normal fibroblasts, those CF exhibited: (i) an increased sensitivity to the effect of PMA on the disappearance of PKC from cytosolic fractions as well as a greater and earlier recovery, in the membrane fraction, of the PKC activity lost in the cytosolic fraction; (ii) an earlier response to PMA for its effect on beta-N-acetylglucosaminidase release. In contrast, the inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD) proved ineffective in inducing PKC translocation and beta-N-acetylglucosaminidase release in both normal and CF fibroblasts. The data suggest a defect in the regulation of PKC activity in CF fibroblasts, which may lead to altered secretion.

Acetylglucosaminidase↗

Glycoconjugates secreted by bovine tracheal serous cells in culture.

Glycoconjugates secreted by bovine tracheal gland serous cells in culture were characterized after incorporation of radioactive precursor [1-14C]glucosamine and stimulation with isoproterenol. Under dissociative conditions, glycoconjugates eluted in both the void and included volumes on Sepharose Cl-4B. Fractionated by anion-exchange chromatography, the high-molecular-weight (Sepharose Cl-4B; V0) glycoconjugates gave two acidic fractions eluting at 0.5 and 2.0 M NaCl; low-molecular-weight glycoconjugates of the included volumes gave a neutral fraction and two acidic fractions eluting at 0.5 and 2.0 M NaCl. Based on chemical analysis and specific enzymatic digestions, the material eluting in the void volume was shown to contain hyaluronic acid and chondroitin sulfate proteoglycan. In addition, the presence of small amounts of galactose, fucose, sialic acid, glucosamine, and galactosamine suggest the presence of O-glycosidically linked glycoproteins in the void volume. The identification of galactosaminitol in beta-eliminated oligosaccharides from this material confirms this notion. The material eluting in the included volume was shown to contain N-linked glycoproteins with glycans of complex type in the neutral fraction and chondroitin sulfate proteoglycans in the two acidic fractions. Significant N-sulfation of amino sugars was detected in the 0.5 M acidic fraction, indicating the presence of heparan sulfate. Hyaluronic acid and chondroitin sulfate proteoglycan have recently been identified in tracheal secretions; our results suggest that these components originate at least in part from tracheal gland serous cells.

Animals↗

Rank relations of juvenile and subadult natal males of Barbary macaques (Macaca sylvanus) at Affenberg Salem.

Rank relations of more than 100 juvenile and subadult natal Barbary macaque males were analyzed. Hierarchical relations among individuals of the same age were established early during the first year of life. With few exceptions concerning infants from very high-ranking genealogies, males dominated female peers regardless of maternal rank. Males started to outrank females from older cohorts during the second year of life and completed the process of rank reversal with adult females at 5-6 years of age. An age-graded dominance pattern existed among males from different birth cohorts. Only 3 rank reversals between males from different cohorts were observed. Rank reversals among males of the same birth cohort occurred more frequently. Rank position of a male among his male peers was influenced by birth order, by maternal rank, and by the presence of juvenile brothers. Most males without juvenile brothers had low positions, regardless of maternal rank. Males born late in the birth season were also low-ranking, even when juvenile brothers were present. There was no cohort where ranking among males was determined by maternal rank alone, as is the case in rhesus monkeys and Japanese macaques. Adult/subadult male carriers had no noticeable effect on rank positions of 'their' infants. It is suggested that a weaker influence of Barbary macaque mothers on rank of their sons is related to very early integration of male infants in male social/play groups.

Age Factors↗

Percutaneous endoscopic duodenostomy (PED). Case report.

Surgeons are increasingly using endoscopy to place transabdominal feeding tubes for enteral nutrition or gastric decompression. A possible extension for the application of this new technique is the direct placement of the feeding tube into the duodenal bulb. Two patients are presented in whom percutaneous endoscopic duodenostomy was successfully performed, although percutaneous endoscopic gastrostomy was not possible. It shows that this new method is technically possible. In both patients the positive influence of this technique on the patient's quality of life could be shown using the Spitzer Quality of Life Index and the Karnofsky Performance Status. Enteral nutrition was maintained for more than 6 weeks.

Aged↗

Nonsurgical management of esophageal cancer: report of a study of combined radiotherapy and chemotherapy.

Between October 1980 and December 1985, 50 patients with esophageal cancer were treated with combined radiotherapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin C). Thirty patients with stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 h) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Twenty patients received palliative treatment (5,000 cGy plus chemotherapy) for stage III or IV disease (extraesophageal spread or distant metastases). All patients treated in this program had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Of the 30 definitively treated patients, 23 had squamous cell cancer, while seven had adenocarcinoma. Follow-up ranged from 6 months to 63 months. The complete response rate at 1 to 3 months following completion of treatment was 87% (26 of 30) documented by barium swallow and endoscopy (+/- biopsy). The actuarially determined local relapse-free rate at 1 year and beyond was 73%, and the actuarial survivals at 1, 2, and 5 years were 68%, 47%, and 32%, respectively. Of the 20 palliatively treated patients, ten had squamous cell carcinoma, eight had adenocarcinoma, and two had undifferentiated carcinoma. Seventeen patients were evaluable for freedom from dysphagia 1 or more months following completion of treatment. Eighty-two percent of evaluable patients (14 of 17) had no dysphagia posttreatment, while 64% (11 of 17) remained free of dysphagia until death or last follow-up, emphasizing the significant local control of those patients. The median survival for this group was 8 months. Treatment was well tolerated, and acute toxicity included esophagitis, stomatitis, oral candidiasis, and hematologic toxicities of thrombocytopenia and neutropenia. Late toxicities were predominantly manifested as a mild to moderate benign stricture, which required dilatation in four patients. One patient developed a perforation into the mediastinum in the absence of tumor, while two patients with persistent local disease developed tracheoesophageal fistula, and radiation pneumonitis was observed in two patients. This combination of radiation therapy with infusional 5-FU and mitomycin C is an effective and relatively well-tolerated regimen in the treatment of esophageal cancer. Surgical resection may not be necessary when high-dose radiation and chemotherapy are used.

Adenocarcinoma↗

Studies of tracheal secretion using serous cell cultures and monoclonal antibodies.

The glycoconjugate composition of tracheal secretions varies with physiological and pathophysiological parameters. Believing that these differences might be explained by metabolic or regulatory modifications of particular cell types, we have developed strategies for biochemical analysis at the cellular level. We have produced monoclonal antibodies whose determinants are restricted to a single secretory cell type (serous, mucous, or goblet cell granules, or ciliated cell glycocalyx). By enzyme immunoassay (ELISA), we have characterized four of the antibodies biochemically, and have also used the antibodies as quantitative molecular probes to detect release of antigen from mixed cell explants. Four of the antigens are carried by carbohydrate moieties of high molecular weight glycoproteins. Western blot analysis shows their molecular weight in reducing gels (SDS-PAGE) to exceed 200 kD. When used in parallel with pulse-chase labeling studies, the antibodies are both more sensitive and specific (than bound radioactivity) in detecting gland or goblet cell secretion in response to autonomic drugs or proteases. We have also isolated and cultured serous gland cells for physiological and biochemical studies. These cells express serous cell phenotype as reflected by ultrastructure, histochemistry, and lysozyme activity. Biochemical analysis of their secretory products reveals glycoconjugate components which are heterogeneous with respect to both molecular weight and charge. Radiolabeled secretory products eluting in the void volume of Sepharose C1 4B were completely degraded by chondroitinase ABC. This indicates that the major glycoconjugate produced by serous cell is a proteoglycan resembling chondroitin sulfate.

Animals↗

Effect of enprostil, a synthetic prostaglandin E2 on 24 hour intragastric acidity, nocturnal acid and pepsin secretion.

We have studied the effect of a prostaglandin E2 analogue (enprostil), on intragastric acidity, gastric acid and pepsin outputs during a 24 hour period in nine patients with duodenal ulcer in remission. Enprostil 35 micrograms bd dose inhibited 24 hour intragastric acidity by 38% and a 70 micrograms nocturnal dose by 33%. Decrease in nocturnal pepsin secretion was both volume and concentration related.

Adult↗

Carbonic anhydrase II deficiency syndrome: recessive osteopetrosis with renal tubular acidosis and cerebral calcification.

Four new Saudi Arabian cases of the carbonic anhydrase II deficiency syndrome from two families are described. This autosomal recessive syndrome includes osteopetrosis with renal tubular acidosis and cerebral calcification. Additional features are mental retardation, growth failure, typical facial appearance, and abnormal teeth. Two patients showed evidence of restrictive lung disease, a finding not previously described. One of the patients reported represents the first neonate reported to be affected with this syndrome. Intrauterine growth was normal, but metabolic acidosis was already evident in the neonatal period. Radiographic evidence of osteopetrosis was probably absent at birth but appeared during the late neonatal period. Carbonic anhydrase II deficiency was demonstrated in erythrocyte hemolysates from the older two siblings of this neonate, and a 50% normal level of carbonic anhydrase II was demonstrated in the erythrocyte hemolysate from their father.

Acidosis, Renal Tubular↗

A pilot study of combined radiotherapy and chemotherapy for esophageal carcinoma.

Between 9/80 and 9/83, 20 patients with esophageal carcinoma were treated with combined radiotherapy and chemotherapy (5-FU and mitomycin). Thirteen patients with Stages I or II disease received definitive treatment consisting of 6000 rad in 6-7 weeks and 5-FU (1000 mg/m2/24 hours) as a continuous I.V. infusion for 96 hours starting on days 2 and 28. Mitomycin (10 mg/m2) was administered as a bolus injection on day 2. Palliative treatment (5000 rad plus above chemotherapy) was delivered to six patients with Stage III disease (two with extra-esophageal spread, four with distant metastases) and to one patient with an anastomotic recurrence following resection. Two of 13 definitively treated patients were not evaluable due to early death from intercurrent disease. Ten of 11 evaluable patients treated definitively are alive from 4-32 months; the median survival has not been reached at 17 months. Four of 11 evaluable patients treated definitively have relapsed, with only one relapsing within the irradiated field. Among the palliative and definitively treated patients, relief of dysphagia was seen in 16/17, and continued until the time of last follow-up or until death in 13/17. The treatment was well tolerated and no significant hematologic problems were incurred. This combination of radiation therapy with infusional 5-FU and mitomycin appears to be an effective and well-tolerated regimen in the treatment of esophageal carcinoma and is worthy of further study.

Aged↗

Female reproductive characteristics in semifree-ranging Barbary macaques (Macaca sylvanus L. 1758).

Mating activities in a group of 178 Barbary macaques were studied during the breeding season 1982/83. Copulations were observed between the middle of August and the end of March. More than 80% of all copulations were recorded from October to December. Number of estrous periods ranged from 1 to 5, most females (67%) had 2 estrous periods. Most females (87%) conceived during the first estrus. Postconceptional bleedings and 1 postconceptional estrus were observed regularly. Mean interval between the end of conceptional estrus and the end of postconceptional estrus was 28 days. Mean interval between the end of conceptional estrus and the onset of bleeding was 18.2 days. Conception rate was 79%. Conceptions occurred between the end of September and the middle of February. Most females (60%) conceived between the middle of November and the middle of December. Mean gestation length for a viable infant was 164.7 days. Consequences of the strong breeding seasonality are discussed.

Age Factors↗

Evaluation of mebendazole used concurrently with piperazine monohydrochloride in horses.

Forty horses from a herd known to have benzimidazole-resistant small strongyles were treated with mebendazole (8.8 mg/kg) or combinations of mebendazole and piperazine monohydrochloride (25, 40, or 55 mg of piperazine base/kg). Pretreatment and 7-day posttreatment fecal examinations were done. Fecal cultures and strongyle egg per gram (epg) counts, and in vitro testing for benzimidazole resistance were performed. Results of fecal examinations prior to treatment were similar in all horses, and results of testing were positive for benzimidazole resistance. Horses treated with mebendazole and piperazine at all dosages had much lower geometric mean strongyle epg counts (2 to 4) and greater percentage reduction in geometric mean strongyle epg counts (99.7 to 99.9) at 7 days after treatment, compared with those measurements for horses treated with mebendazole alone. Adverse reactions to treatment were not observed.

Animals↗

Cimetidine or vagotomy? Comparison of the effects of proximal gastric vagotomy, cimetidine and placebo on nocturnal intragastric acidity and acid secretion in patients with cimetidine resistant duodenal ulcer.

Nocturnal pH, acid output and volume of gastric secretion have been measured in a group of patients who were referred for surgery because of a poor clinical response to cimetidine. Patients were studied after no treatment, cimetidine 1 g/day and proximal gastric vagotomy. Although pH and acid output were controlled better with cimetidine than no treatment this was not true for volume of secretion. Vagotomy was significantly better than cimetidine in controlling pH, acid output and volume of gastric secretion. The results suggest that cimetidine non-responders should have a good result from proximal gastric vagotomy, making more radical forms of gastric surgery unnecessary.

Adult↗

Evoked potential estimates of visual accommodation in infants.

Pattern reversal visually evoked potentials (VEPs) were recorded from infants between 2 and 5 months of age in order to measure their accommodative performance over a 9 diopter range (10-150 cm). Accommodation was stimulated by placing minus spherical lenses of increasing power in front of the infant's eyes and by changing the infant's distance from the stimulus. VEP latency measurements indicated that the infant's ability to maintain a zone of clear vision changes with age and pattern element size. For large checks (60 min arc), most 2- to 4-month old infants were able to maintain clear vision over the range of 9 diopters. When small checks (15 min arc) were used, the majority of 4- to 5-month old infants were unable by VEP measures to accommodate beyond 5-6 diopters. This decline in the infant's zone of clear vision with decreasing check size is due primarily to the relatively large depth of focus and poor visual resolution of the infant eye. In a small group of infants, accommodation was assessed both electrophysiologically by VEP recording and behaviorally using a preferential looking technique. Results indicated better accommodation by VEP estimates than by behavioral measures.

Accommodation, Ocular↗

Single nocturnal dose of an H2 receptor antagonist for the treatment of duodenal ulcer.

Twenty four hour intragastric acidity and nocturnal acid output have been measured over five separate 24 hour periods in each of 12 patients with duodenal ulcer receiving either placebo, cimetidine 400 mg bd, cimetidine 300 mg nocte, ranitidine 150 mg bd, or ranitidine 300 mg nocte. In these doses ranitidine was significantly more effective at decreasing intragastric acidity and nocturnal acid output than cimetidine. There was no significant difference between twice daily ranitidine and night time ranitidine or between twice daily cimetidine and night time cimetidine in the reduction of intragastric acidity. Nocturnal acid output was controlled significantly better with ranitidine at night, twice daily dosage of ranitidine, and cimetidine at night, than by the twice daily dosage of cimetidine. It is suggested that a single nocturnal dose of cimetidine or ranitidine should be evaluated in a clinical trial.

Cimetidine↗