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Biomedical subjects

J Kennedy

Publications and source records attributed to J Kennedy.

At least 181 records · Page 10Linked to original sources
PubMed1985

Direct pituitary effects of testosterone and luteinizing hormone-releasing hormone upon follicle-stimulating hormone: analysis by radioimmuno- and radioreceptor assay.

The present studies examine the effects of testosterone (T) and LHRH, alone or in combination, on the amount of FSH secreted by pituitary cells in culture. FSH was quantified by RIA and radioreceptor assay (RRA). Half of the cultures were exposed to T for 3 days. The remainder served as controls. Each of these two groups was divided in half and exposed to medium only or LHRH (10(-8) M) for 4 h. Medium was collected from all cultures after 3 days +/- T (medium 1) and after 4 h +/- LHRH (medium 2). After medium 2 collection, cell homogenates were prepared. In a second study, T-treated cell cultures also received 0, 0.5, or 5.0 micrograms/dish tunicamycin for the last 16 h of the 3-day incubation. During the 3 days of culture, the T-treated group secreted greater amounts of immunoactive FSH than controls. However, LHRH-induced FSH release measured by RIA was blunted as a result of T exposure compared with untreated controls. T treatment elevated intracellular immuno-FSH stores. Each sample was quantitated for FSH activity by RRA, and the FSH RRA/RIA was calculated. T and/or LHRH treatment, while eliciting FSH hypersecretion, caused a reduction in the RRA/RIA of secreted FSH. Changes in the RRA/RIA are thought to occur as a result of alterations in the glycosylation of FSH. To test this hypothesis, T-treated cells were exposed to tunicamycin, a drug that reduces the rate of glycosylation of secreted proteins. Exposure of cells to this drug prevented the reduction in the RRA/RIA of secreted FSH caused by T and/or LHRH. FSH secreted from control, T-treated, or T-treated plus tunicamycin-exposed cells was examined by isoelectric focusing. T-Treated cells released a greater proportion of FSH forms with lower isoelectric points (indicative of a greater degree of glycosylation) compared with controls. Tunicamycin exposure reversed T's effect upon the isoelectric profile. These studies demonstrate a direct pituitary action of LHRH and T upon the type of FSH released. During times of hormonally induced increases in the rate of FSH secretion, the pituitary releases FSH forms that are more heavily glycosylated, exhibit a lower isoelectric point, and show a reduced RRA/RIA. FSH secreted after T treatment would be expected to have an increased plasma half-life due to the protective effects of the sugar residues. Thus, the existing hormonal milieu exerts a multidimensional effect upon FSH released by pituitary cells in culture that cannot be appreciated by RIA assessment alone.

Animals↗
PubMed1984

Purification and structures of oligosaccharide chains in swine trachea and Cowper's gland mucin glycoproteins.

Mucin glycoproteins were purified from extracts of swine trachea mucosa and Cowper's gland. The gelatinous extracts were solubilized by reduction and carboxymethylation and then purified by chromatography on Sepharose CL-6B and DEAE-Sepharose. The structure of some of the carbohydrate units in these glycoproteins were determined and compared. Alkaline borohydride treatment indicated that more than 85% of the carbohydrate chains in these glycoproteins were linked to serine or threonine residues in the polypeptide chain through O-glycosidic bonds with N-acetylgalactosamine. Reduced oligosaccharides released by treatment with alkaline borohydride were isolated by gel filtration on Bio-Gel P-6 and chromatography on DEAE-cellulose and paper. The structures of the oligosaccharides were established by methylation analysis, gas chromatography, and sequential hydrolysis with specific exoglycosidases. The major oligosaccharides in Cowper's gland mucin glycoproteins were sialylated short chains: NeuAc alpha 2,6GalNAcol and NeuAc alpha 2,3Gal beta 1,3(NeuAc alpha 2,6)GalNAcol. In marked contrast, branched chains containing a Gal beta 1,3(GlcNAc beta 1,6)GalNAc core unit were the major components of trachea mucin glycoprotein. Ten of these chains had the following structures: (Formula: see text).

Amino Acids↗
PubMed1984

Synthesis of mucin glycoproteins by epithelial cells isolated from swine trachea by specific proteolysis.

Mucus-producing cells were isolated from swine trachea mucosa by a method that included enzymatic digestion of the epithelial surface with Dispase, a neutral protease from Bacillus polymyxa, and differential attachment of the washed cells to culture flasks coated with collagen. Epithelial cells were the major cell type isolated by these procedures. Ciliated cells that did not attach to the flasks were removed by decantation , and fibroblasts were destroyed by the bacterial protease. The isolated cells synthesized respiratory mucins and the rate of secretion was increased about threefold when tracheas were exposed to sulfur dioxide. The cultured cells incorporated both [35S]O4 and [I-14C]N-acetylglucosamine into secreted mucin glycoproteins. The secretion of glycoprotein increased for about 3 d until the cells became confluent, and then a constant rate was observed for a period of at least 7 d. This increase in the output of mucin glycoprotein during the initial 3 d of culture was accompanied by a corresponding increase in the number of mucus-producing cells in the flasks. The results obtained in these and subsequent studies suggest that the rate of formation of mucus-producing cells may be a rate limiting step in the regulation of mucin glycoprotein synthesis in tracheal epithelium. The chemical, physical, and immunological properties of the glycoprotein secreted by isolated tracheal epithelial cells were very similar to the mucin glycoprotein purified from washes of swine trachea epithelium. The purified mucin glycoproteins showed complete cross-reaction with antibodies to trachea mucin glycoprotein. They were eluted near the void volume during gel filtration of Sepharose CL-6B columns. The glycoprotein isolated from culture media under the standard assay conditions had nearly the same carbohydrate composition as samples purified from washes of trachea epithelium. Reduced oligosaccharides released by beta-elimination with dilute alkaline borohydride showed similar elution profiles during chromatography on Bio Gel P-6 columns. Taken collectively, these results suggest that the isolated epithelial cells secreted mucin glycoproteins that were very similar to those synthesized by the intact trachea epithelium under standard incubation conditions.

Animals↗
PubMed1984

Treatment of advanced ovarian cancer with combination chemotherapy using cyclophosphamide, adriamycin and cis-platinum.

Fifty-four patients with advanced ovarian cancer have been treated with combination chemotherapy using cyclophosphamide, adriamycin and cis-platinum. The toxicity of the regimen was manageable but few patients were prepared to tolerate more than 6 months of treatment. Those in complete clinical remission at that time were offered second-look laparotomy and if apparently free of disease, therapy was discontinued. Forty-seven patients could be assessed of whom 33 had had no previous therapy. Twenty-two of these were clinically free of disease after completion of chemotherapy of whom 12 had no detectable disease at second-look laparotomy. Of 14 patients who had failed previous therapy only one remains clinically free of disease. The results in the untreated patients demonstrate the primary importance of bulk reduction at initial laparotomy. The use of the regimen in patients who have failed on previous treatment or in patients with bulk disease seems to be palliative and the toxicity should be assessed in this context.

Adult↗
PubMed1983

Determinants of defibrillation: prospective analysis of 183 patients.

Previous studies have suggested that a number of factors may influence the ability to defibrillate: the transthoracic resistance and resultant current flow, the paddle electrode size, the duration of preshock ventricular fibrillation (VF) and cardiopulmonary resuscitation, metabolic abnormalities, body weight, the shock energy selected, and whether the patient is receiving lidocaine. To examine the effect of these variables, a prospective study was conducted of 183 patients who received direct-current shocks for VF. Overall defibrillation rates approached 90%, even in patients with secondary VF, but rates of successful resuscitation and survival were much lower. Patients who never defibrillated despite multiple shocks had a prolonged duration of cardiopulmonary resuscitation preceding the first shock (21 +/- 14 minutes) and systemic hypoxia and acidosis. These conditions tended to occur in patients who initially had cardiac arrest from causes other than VF: asystole, severe bradycardia and electromechanical dissociation. In such patients, VF developed only as a late event, which was then often unresponsive to attempted defibrillation. The other factors examined were not major determinants of defibrillation.

Body Weight↗
PubMed1983

Rapid conversion of newly-synthesized orotate to uridine-5-monophosphate by rat liver cytosolic enzymes.

It had been noted previously that the activity of mitochondrial dihydroorotate dehydrogenase was lower in crude tissue preparations containing cytosol than in isolated mitochondria. Closer examination reveals that the apparent lower enzyme activity is due to rapid conversion of newly-synthesized orotate to uridine-5-monophosphate by the cytosolic enzymes, orotate phosphoribosyltransferase and orotidylate decarboxylase.

Animals↗
PubMed1982

Rejection encephalopathy. An acute neurological syndrome complicating renal transplantation.

Fifteen episodes of encephalopathy have been studied in 13 renal transplant recipients. All episodes of encephalopathy occurred during an acute rejection crisis. Clinical and biochemical features were recorded during rejection crises associated with encephalopathy and in an equal number of uncomplicated rejection episodes in the same patients. Encephalopathy was related to the severity of the rejection crisis and not to other features such as blood pressure, fever, steroid therapy or plasma electrolytes. The definition of the syndrome of rejection encephalopathy and its relation to the severity of the rejection has important therapeutic implications. Steroid therapy should not be withdrawn or reduced because of acute neurological features. Control of hypertension, fluid overload and electrolyte imbalance, in addition to treatment of the rejection episode, are necessary to reverse the encephalopathy. The prognosis of this syndrome is excellent with no long-term sequelae.

Acute Disease↗
PubMed1982

Peritonitis due to a mycobacterium chelonei-like organism associated with intermittent chronic peritoneal dialysis.

Two outbreaks of peritonitis caused by a Mycobacterium chelonei-like organism--a previously unrecognized pathogen--occurred among patients receiving intermittent chronic peritoneal dialysis (CPD). In one center, five of 22 patients who had undergone CPD during a one-month period developed peritonitis caused by an M. chelonei-like organism acquired from a single contaminated automated CPD machine. In a second center, five of eight patients who had received CPD during a several-week period became infected, apparently as a result of cross-infection from contaminated machines. Seven sporadic cases of peritonitis due to an M. chelonei-like organism were also found. M. chelonei-like organisms can survive and proliferate in water and are relatively resistant to formaldehyde. Defects in the design of CPD machines and disinfection procedures were identified that may have permitted M. chelonei-like organisms to survive attempted disinfection.

Adult↗
PubMed1981

Elective cardioversion: influence of paddle-electrode location and size on success rates and energy requirements.

We compared the success rates and energy requirements of two electrode-paddle positions (anteroposterior vs. anterolateral) and different paddle sizes in the elective cardioversion of atrial arrhythmias. We prospectively studied 173 patients - 111 in atrial fibrillation and 62 in atrial flutter. The anterolateral paddles used were either two standard-size (8.5-cm diameter) paddles or one 13-cm diameter anterior paddle with one standard-size lateral paddle. The anteroposterior paddles used were either a standard-size or a 13-cm anterior paddle with 12-cm posterior paddle. Overall cardioversion success rates with either paddle position were similar (greater than 90 per cent). The larger paddles did not significantly reduce energy requirements for cardioversion of either arrhythmia. We conclude that anterolateral paddles are as effective as anteroposterior paddles for the elective cardioversion of atrial arrhythmias, and that there is no demonstrable advantage to using paddles that are larger than the standard size in either position.

Adult↗
PubMed1981

Prognosis in myocardial infarction--the benefits of exercise as seen in non-randomised trials.

Previous uncontrolled studies suggest that exercise rehabilitation reduces recurrence rates in post-myocardial infarction patients. Six hundred and ten consecutive post-coronary patients referred to an exercise rehabilitation programme have been followed for an average of 36.5 months (1-8 years). Total deaths amounted to 36 (1.89% p.a.) of which 23 were cardiac deaths, with an annual death rate averaging only 0.85% after the first year of conditioning had been completed. There were also a total of 21 non-fatal recurrences of infarction. comparison has been made with 700 patients enrolled in the Health Insurance Plan of New York. On the basis of smoothed probabilities for the risk factors reported in the New York series, we should have seen 89 deaths (P less than 0.001). Correcting for differences between the two groups (age and number of diabetics) gives a predicted mortality for the Toronto series of 63.5 deaths (3.42% p.a.). This discrepancy in favour of the exercised group is significant in terms of an infinitely large control population (P less than 0.001) and also sample sizes of 610 exercised and 700 control patients (0.01 greater than P greater than 0.001). Unfortunately, formally to prove such a 45% reduction in mortality by way of a randomised control trial would be extremely costly, possibly prohibitively so.

Canada↗
PubMed1981

Transthoracic resistance in human defibrillation. Influence of body weight, chest size, serial shocks, paddle size and paddle contact pressure.

Successful defibrillation depends on delivery of adequate electrical current to the heart; one of the major determinants of current flow is transthoracic resistance (TTR). To study the factors influencing TTR, we prospectively collected data from 44 patients undergoing emergency defibrillation. Shocks of 94-450 J delivered energy were administered from specially calibrated Datascope defibrillators that displayed peak current flow, thereby permitting determination of TTR. Shocks were applied from standard (8.5-cm diameter) or large (13 cm) paddles placed anteriorly and laterally. First-shock TTR ranged from 15-143 omega. There was a weak correlation between TTR and body weight (r = 0.45, p less than 0.05) and a stronger correlation between TTR and chest width (r = 0.80, p less than 0.01). Twenty-three patients who were defibrillated using standard 8.5-cm paddles had a mean TTR of 67 +/- 36 omega (+/- SD), whereas 21 patients who received shocks using paddle pairs with at least one large (13 cm) paddle had a 21% lower TTR of 53 +/- 24 omega (p = 0.05, unpaired t test). Ten patients received first and second shocks at the same energy level; TTR declined only 8%, from 52 +/- 19 to 48 +/- 16 omega (p less than 0.01, paired t test). In closed chest dogs, shocks were administered using a spring apparatus that regulated paddle contact pressure against the thorax. Firmer contact pressure caused TTR to decrease 25%, from 48 +/- 22 to 36 +/- 17 omega (p less than 0.01, paired t test). Thus, human TTR varies widely and is related most closely to chest size. TTR declines only slightly with a second shock at the same energy level. More substantial reductions in TTR and declines only slightly with a second shock at the same energy level. More substantial reductions in TTR and increases in current flow can be achieved by using large paddles and applying firm paddle contact pressure.

Animals↗