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Biomedical subjects

J Daly

Publications and source records attributed to J Daly.

At least 109 records · Page 6Linked to original sources
PubMed1984

Effect of corynetoxin isolated from parasitized annual ryegrass on albumin and transferrin synthesis and secretion by cultured fetal rat hepatocytes.

A group of glycolipid toxins, corynetoxin (CT), isolated from parasitized annual ryegrass, was shown to suppress the synthesis of both albumin and transferrin by cultured fetal rat hepatocytes. Based on [3H]leucine incorporation, inhibition of transferrin synthesis was greater than that of both albumin and total protein synthesis. As a result, the secretion of albumin and transferrin was decreased. The incorporation of [3H]N-AcGlc into cellular glycoproteins was only marginally affected by CT, although a dramatic reduction was observed with respect to the secreted proteins. Transferrin secreted into the culture medium was substantially non-glycosylated, judging by the absence of [3H]N-AcGlc. These studies suggested that the toxin preferentially affects the synthesis, and hence the secretion of glycoproteins, although it did not block the secretion of the proteins albumin and transferrin, as these did not accumulate intercellularly. Since transferrin labelled with [3H]leucine but not [3H]N-AcGlc is detected in the culture medium of hepatocytes exposed to CT, it was concluded that glycosylation of the protein is not required for secretion. This study shows that the effects of CT on protein synthesis and secretion in cultured hepatocytes are similar to those reported for tunicamycin (TM).

Albumins↗
PubMed1984

Hepatic artery pump infusion: toxicity and results in patients with metastatic colorectal carcinoma.

5-Fluorodeoxyuridine (FUDR) was infused continuously into the hepatic artery for 14 days a month at an initial dose of 0.3 mg/kg per day in 45 patients with liver metastases from colorectal carcinoma. In 41 adequately treated patients, partial responses (greater than 50% tumor regression) were observed in 12 (52%) of 23 previously untreated patients, and three (17%) of 18 previously treated patients. Severe gastrointestinal toxicity was endoscopically documented in 19 (46%) patients; 12 (29%) had discrete ulcers, and seven had diffuse gastritis or duodenitis. Significant hepatic-enzyme abnormality was seen in 29 patients (71%) and an elevated serum bilirubin in nine (22%). A significant factor influencing survival was the extent of tumor involvement in the liver; patients with less than 20% involvement have not yet reached a median survival at 13 months versus six months for patients with greater than 60% involvement (p less than 0.001). Studies comparing regional to systemic chemotherapy and stratifying patients according to the extent of hepatic tumor burden are needed to assess the true impact of hepatic infusion on response and survival.

Adenocarcinoma↗
PubMed1983

Intravenously administered amino acids with either dextrose or lipid as nutritional support in surgical patients.

The relative efficacy of exogenous fat or glucose in preserving lean body mass in surgical patients is controversial. In this study, peripheral intravenously administered amino acids with either lipid or dextrose were given to well nourished patients undergoing elective total cystectomy and ileal diversion. Patients were well matched for age, sex, nutritional status and degree of operative stress. Twenty-eight patients received 1.2 grams per kilogram per day of amino acids plus either dextrose (440 kilocalories per day) (17 patients) or 10 per cent fat emulsion (550 kilocalories per day) (11 patients) for three days preoperatively and seven days postoperatively. No significant differences between the groups were noted in mean nitrogen balances during the preoperative and postoperative periods or in the mean cumulative adjusted (for change in blood urea nitrogen and body weight) nitrogen balances for the total study time. Mean nitrogen excretion per 100 nonprotein calories infused was also similar. Changes in mean body weight, blood urea nitrogen, serum glucose and serum albumin were similar in the two groups. No deaths or major infectious complications occurred in either group. In well nourished patients matched for age, sex, nutritional status and degree of operative stress, the addition of either hypocaloric fat or dextrose to intravenously infused amino acid solutions resulted in an equivalent metabolic and clinical outcome.

Aged↗
PubMed1983

Systemic thermochemotherapy in a rat model.

The purpose of this study was to determine the effects of systemic hyperthermia, with and without Adriamycin, on two rat tumour models. Fischer rats were implanted subcutaneously with either a methylcholanthrene-induced sarcoma or a transitional cell carcinoma. In the first experiment, 32 rats with tumour volumes of 1 cm3 were divided into four groups of 8 rats receiving: (a) Adriamycin alone (2 mg/kg intraperitoneally) (group 1), (b) systemic hyperthermia alone (water bath immersion to a rectal temperature of 41.5 degrees C for 30 minutes) (group 2), (c) Adriamycin and systemic hyperthermia (group 3) or (d) immersion in water bath at 37 degrees C for 30 minutes (control group) (group 4). Serial tumour volume and animal survival were monitored. No differences were seen among the groups in either tumour system. In a second experiment, an identical protocol was used except that each animal received its respective treatment three times, at weekly intervals. In the rats implanted with methylcholanthrene-induced sarcoma, tumour volume was lower in group 3 than in control group 4, beginning at day 23 (37.5 +/- 8.2 cm3 vs. 52.3 +/- 9.6 cm3 [p less than 0.05]). Systemic hyperthermia or Adriamycin alone did not alter tumour growth in relation to the control group. In the transitional cell carcinoma system, tumour volume was decreased in both groups 1 and 3 at day 35 (group 1 = 32 +/- 5.4 cm3, group 3 = 28.1 +/- 12 cm3 vs. group 4 = 48.8 +/- 9 cm3 [p less than 0.05 for each]). Adriamycin with systemic hyperthermia was no more effective than Adriamycin alone. Tumour growth was similar in groups 2 and 4. These data demonstrate that multiple treatments with Adriamycin and systemic hyperthermia were effective in decreasing the rate of tumour growth in rat tumour models, whereas a single exposure had no effect.

Animals↗
PubMed1980

Correlation of estrogen and progesterone receptors with histologic differentiation in mammary carcinoma.

Using a modification of the histologic grading system of the NSABP, we observed a trend towards higher levels of estrogen (E2R) and progesterone receptor (PR) content in well (grade I) and moderately (grade II) differentiated mammary carcinomas. This relationship between receptor content and histologic grade is enhanced by considering estrogen and progesterone receptor simultaneously. The rank correlation between the quantitative levels of E2R and PR was 0.74 among histologic grade I tumors and 0.64 among histologic grade II tumors. Among the grade III carcinomas, the majority of tumors displayed either a paucity of measurable receptor or a divergence between levels of estrogen versus progesterone receptor (r = 0.19). The use of ultrastructural evaluation of features of differentiation is discussed in the evaluation of grade III tumors and in the evaluation of specific histologic types of mammary carcinoma.

Adenocarcinoma↗
PubMed1980

Chloroma (granulocytic sarcoma) without evidence of leukemia: facilitated light microscopic diagnosis.

Localized tumors composed of immature cells of the myelogenous series have been recognized for many years as an uncommon manifestation of granulocytic leukemia. The histologic diagnosis of chloroma (granulocytic sarcoma) may be extremely difficult when the myeloblastic cells are poorly differentiated and the tumor lacks the characteristic green color. The diagnostic difficulty may be further compounded when the granulocytic sarcoma develops before there is peripheral blood or bone marrow evidence of leukemia. Previous criteria for the diagnosis of chloroma have been ambiguous because of the capricious nature of the hydroperoxidase activity and the lack of definitive histochemical criteria. In this case, a combination of Sudan black B and myeloperoxidase histochemical staining and ultrastructural evaluation was applied. The light microscopic histochemical studies suggested the presence of Phi bodies and rods both in the formalin-fixed tumor and in the cells derived from the subsequent pleural effusion; this was confirmed by electron microscopy, which demonstrated the peridicity of the crystalline rod substructure. These observations show that light microscopic histochemical studies can facilitate the diagnosis of granulocytic sarcoma or chloroma in the absence of peripheral blood or bone marrow manifestations of leukemia.

Adult↗
PubMed1978

Biopsy of apparently normal urothelium in patients with bladder carcinoma.

We obtained 246 cold cup biopsies from pre-selected sites of apparently non-tumor-bearing bladder urothelium from 82 patients who presented with bladder cancer for the first time. Of 75 patients with transitional cell carcinoma 32 (43 per cent) suffered coincidental urothelial abnormalities, the most common being atypia. Significant abnormalities occurred more commonly (77 per cent) in association with high grade tumors than with low grade tumors (15 per cent).

Adenocarcinoma↗
PubMed1978

Gastric mucosal proteins in patients with chronic peptic ulcer.

As ulcerogenesis could be explained by a defect in the mucosal proteins, a study of soluble proteins extracted from human gastric mucosa was made. The proteins were fractionated by gel electrophoresis. 7--8 major bands and several minor bands were present on polyacrylamide tube gels and 30 bands were visible on isoelectric focusing gels. No reproducible differences were found between body and antral mucosa or between the mucosa of gastric ulcer, duodenal ulcer and gastric carcinoma patients.

Chronic Disease↗
PubMed1977

Ileal loop stenosis: a late complication of urinary diversion.

Stenosis of the ileal conduit was a late complication in 12 patients (10 adults) who underwent urinary diversion by this means at our hospital. The duration of the ileal loop at diagnosis ranged from 4 to 14 years, averaging 9 years. Loop stenosis was generally without symptoms and was suggested only by routine excretory urography, while loopography confirmed the diagnosis. The etiology of the condition is not clear. A variety of possible factors is considered, including microvascular ischemia, urine-borne toxic material, infectious and allergic stimuli and an immunologic defect. The pathogenesis of the condition appears to be based upon a chronic inflammatory reaction, with progressive fibrosis in the mucosa and submucosa of the ileal segment.

Adolescent↗
PubMed1975

Norepinephrine uptake sites in cardiac tissue. Lack of affinity of 6-hydroxynorepinephrine and related compounds.

The effects of a series of phenethylamines and the corresponding phenethanolamines on (i) rate of uptake of radioactive norepinephrine into cardiac tissue in vivo and (ii) the rate of efflux of radioactive norepinephrine from prelabeled cardiac storage sites have been determined. The results indicate that m- and p-hydroxuphenethylamines and the corresponding phenethanolamines have high affinities for uptake into cytoplasm and storage vesicles of noradrenergic terminals in the heart. o-Hydroxyphenethylamines such as 2-hydroxyphenethylamine and 2,4,5-trihydroxyphenethylamine (6-hydroxydopamine) also have moderate to high activity as inhibitors of norepinephrine uptake and as releasing agents for norepinephrine, but o-hydroxyphenethanolamines such as 2-hydroxyphenethanolamine, 2,5-dihydroxyphenethanolamine, and 2,4,5-trihydroxyphenethanolamine (6-hyproxynorepinephrine) have little or no activity as inhibitors of uptake or as releasing agents. 2,6-Dihydroxyphenethylamines have little or no activity as inhibitors of uptake or as releasing agents. The results are consonant with significant binding of the gauche conformers of 2-hydroxyphenethylamines to uptake sites. Such conformers would be preferred because of stabilization by hydrogen bonding between nitrogen and phenolic oxygen. Apparently a hydrophobic region of the site prevents binding of such stabilized gauche conformers of 2-hydroxyphenethanolamines and 2,6-dihydroxyphenetylamines.

Animals↗
PubMed1975

The pharmacology of batrachotoxin. VII. Structure-activity relationships and the effects of pH.

The effects of the depolarizing agent, batrachotoxin (BTX), and of various analogs were studied on rat phrenic nerve-diaphragm muscle preparations at 37 degrees C. The structural modifications of BTX included: 1) replacement of the 20alpha-pyrrole-3-carboxylate moiety; 2) alterations of substituents on the pyrrole moiety; 3) clevage of the 3alpha, 9alpha-hemiketal linkage; and 4) quaternization of the tertiary nitrogen of BTX. All of the compounds except batrachotoxinin A (BTX-A), which lacks the 20alpha-substituent, depolarized the postsynaptic membrane, transiently increased the frequency of spontaneous transmitter release to 400 to 600 sec- minus 1 and finally produced blockade of the directly and indirectly elicited muscle twitches. Of the compounds tested, only BTX-A potentiated the muscle twitches. The concentration which elicits a 50% depolarization of the muscle membrane in 1 hour was determined for all the compounds except for BTX-A and for dihydrobatrachotoxin which lacks the 3alpha, 9alpha-hemiketal linkage; these two analogs never depolarized the postsynaptic membrane by more than 10 to 15%. BTX, the 20alpha-2, 4, 5-trimethylpyrrole-3-carboxylate of BTX-A and the 20alpha-ester of BTX-A with 2-ethyl-4-methylpyrrole-3-carboxylic acid (homobatrachotoxin) were the three most potent toxins with doses of 4.5, 12 and 18 times 10- minus 9 M eliciting a 50% membrane depolarization in 1 hour. The quaternary derivative of BTX, the 20alpha-4, 5-dimethylpyrrole-3-carboxylate of BTX-A and 20alpha-2,4-dimethyl-5-acetylpyrrole-3-carboxylate of BTX-A were 24-, 65- and 110-fold less potent than BTX as depolarizing agents, whereas the 20alpha-p-bromobenzoate of BTX-A was 220-fold less potent. Each of these derivatives had the ability to increase sodium permeability since the increase in spontaneous miniature end-plate potential frequency and membrane depolarization were reversed by tetrodotoxin or by reducing the external sodium concentration. BTX was found to be more effective at alkaline pH (pH 9.0), at which it exists almost entirely in the un-ionized form, than at physiological or acidic pH(6.0). The results indicate that the analogs of BTX act by a mechanism similar to that of the parent compound, but that their potency differs and certain compounds may have a more selective action on either the pre- or postsynaptic membrane. For maximal depolarizing activity, a substituted pyrrole moiety is necessary at the 20alpha-position of BTX-A and 3alpha, 9alpha-hemiketal linkage must remain intact providing rigidity for the pentacyclic steroid nucleus.

Animals↗