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T Donnelly

Publications and source records attributed to T Donnelly.

49 records · Page 3Linked to original sources
PubMed1983

Modification of pancreatic carcinogenesis in the hamster model. 7. Inhibitory effect of bethanechol chloride.

Experiments were designed to investigate in the hamster model the effect on pancreatic carcinogenesis of bethanechol chloride (BC), which is known to increase pancreatic protein synthesis in rats. Hamsters received a single (15 mg/kg body weight) dose of BC either before, simultaneously with, or after a single dose of N-nitrosobis(2-oxopropyl)amine (BOP; 20 mg/kg body weight). A second group was treated daily with BC (7.5 mg/kg body weight) for 24 weeks, following BOP. The control groups consisted of animals treated with BOP only, with BC only, and with solvent only. The surviving hamsters were killed 46 weeks after BOP treatment. BC, whether given before, simultaneously with, or after BOP, significantly reduced the incidence of pancreatic ductal/ductular carcinomas. The multiplicity, size, and latency of carcinomas were also affected by BC. A more pronounced inhibition of cancer induction occurred in the group treated daily with BC after BOP. The possible mechanisms involved in the inhibitory action of BC on pancreatic carcinogenesis are discussed.

Animals↗
PubMed1983

Modification of pancreatic carcinogenesis in the hamster model. 2. The effect of partial pancreatectomy.

The effect of partial pancreatectomy (PP) on the pancreatic carcinogenicity of N-nitrosobis (2-oxopropyl)amine (BOP) was investigated in Syrian golden hamsters by subcutaneous injection of a single dose of BOP (20 mg/kg, body weight) given 30 minutes after (Group 1), 1 week after (Group 2), or 1 week before 70% PP (Group 3). Additional groups consisted of animals with PP alone (Group 4), sham operation (laparotomy) followed 30 minutes later by BOP treatment (Group 5), and BOP treatment only (Group 6). The experiment was terminated 46 weeks after BOP administration in each group. The pancreas and extrahepatic bile ducts, including the common duct and gallbladder, were examined histologically. Tumor patterns were compared in hamsters with PP and in the corresponding segments of the pancreas in BOP-treated control groups. The pancreatic cancer incidence was highest (31%) in Group 2 and lowest in Group 1 (3%), a difference that was statistically significant (P less than 0.01). Also, a statistically highly significant larger number of tumors occurred in Group 2, compared with group 1, 3, or 5 (P less than 0.0005). In a comparison of the number of carcinomas per tumor-bearing hamster, there were greater numbers of carcinomas in Group 2 (2.6 carcinomas) than in Groups 1, 3, 5, and 6 (1.0, 1.0, 1.3, and 2.6 tumors, respectively). Moreover, pancreatic tumors in Group 2 hamsters were larger (average diameter, 10 mm) than in Group 1 (4 mm), Group 3 (3.5 mm), Group 5 (4 mm), and Group 6 (average, 9mm). The incidence of extrapancreatic tumors did not vary among the PP groups but was equally lower than those in BOP-treated control groups. The data indicated BOP carcinogenesis was inhibited by surgery (regardless of whether PP was per formed) when the carcinogen was given 30 minutes after the surgery but was significantly enhanced when BOP was administered 1 week after PP. The possible reasons for these conflicting results are discussed. Morphologically all tumors were of ductular, ductal, and mixed ductular-insular patterns and most developed at the resected margins, where proliferation of islets, ducts, and ductules, but not of acinar cells, occurred. The results confirm our view that the ductal and ductular cells are the progenitor cells for BOP-induced pancreatic tumors in hamsters.

Animals↗
PubMed1983

Modification of pancreatic carcinogenesis in the hamster model. IX. Effect of pancreatitis.

The effect of acute and recurrent pancreatitis was investigated in pancreatic cancer induction by N-nitrosobis(2-oxopropyl)amine (BOP) in Syrian golden hamsters. For the correlation of the cellular alteration with carcinogenesis, BOP (20 mg/kg body wt) was injected once sc into hamsters at day 3 (group 2), week 1 (group 3), and week 8 (group 4), corresponding to cellular degeneration, regeneration, and healing, respectively. Additional groups received BOP 30 minutes before common duct ligation for 48 hours (group 1) or before repeated induction of pancreatitis at 4 weekly intervals for 4 weeks (group 5). Group 6 was a pancreatitis control. Two groups of hamsters received BOP only, at the age of 8 weeks (group 7, which served as a BOP control for groups 1-3 and 5) or at the age of 16 weeks (group 8, the control for group 4). Hamsters were killed 46 weeks after BOP injection (with the exception of group 1 animals, which were killed 52 wk after BOP) to guarantee the same postcarcinogen exposure time in each group. The results showed that BOP, when given during cellular degeneration (group 2) and healing (group 4), induced significantly fewer carcinomas than in the control groups, whereas the tumor pattern was not affected when BOP was given before pancreatitis induction (group 1) or at the time of cellular regeneration (group 3). Recurrent pancreatitis (group 5), however, resulted in carcinomas significantly larger in number and size than those in control group 8. A significantly higher incidence of carcinomas occurred in group 8 controls (treated with BOP at the age of 16 wk) compared to the incidence in group 7 controls (treated with BOP at the age of 8 wk).

Acute Disease↗
PubMed1983

Modification of pancreatic carcinogenesis in the hamster model. 6. The effect of ductal ligation and excision.

The effect of ligation and excision of the pancreatic duct in pancreatic carcinogenesis was examined in the hamster model. Animals were treated with a single dose (20 mg/kg body weight) of N-nitrosobis(2-oxopropyl)amine (BOP) either immediately (Group 1) or on Days 1 (Group 2), 3 (Group 3) or 7 (Group 4) after ligation and excision of the duct of the splenic lobe. Group 5 received BOP shortly after laparoscopy, and Group 6 consisted of BOP-treated controls. All hamsters were killed 46 weeks after BOP treatment. The results showed that despite advanced atrophy of the splenic lobe distal to the excised duct in Groups 1-4, some hamsters in Groups 2, 3, and 4 showed hyperplasia, dysplasia, and increased mitotic activities of ductal and ductular cells. However, carcinomas in the duct-excised atrophic lobe were found only in Groups 1-3. These data indicate that BOP carcinogenesis is mediated through blood circulation, and that cancer development is not inhibited in the duct-excised lobe for up to 3 days after surgery. However, in the entire pancreas, a significant reduction in tumor incidence was seen when the carcinogen was given immediately, or to a lesser extent, 1 day after surgery, regardless of whether or not excision was made. On the contrary, BOP, when given 3 and 7 days after duct excision, enhanced tumor development in the nonexcised (intact) pancreas, compared with other test groups and with BOP controls. Both inhibition and enhancement seemed due to a proportional decrease and increase, respectively, of BOP-responsive cells throughout the intact pancreas.

Animals↗
PubMed1983

Antibody classes and subclasses in circulating immune complexes isolated from mice infected with lactic dehydrogenase virus.

A chronological study of circulating immune complexes (CIC) in lactic dehydrogenase virus (LDV)-infected mice has been performed. The results demonstrate that CIC containing immunoglobulin of the IgM class were isolated between days 3 and 9 post-LDV infection and corresponded to an increase in serum IgM. IgG1-containing CIC were also transient in the serum of LDV-infected mice in that they were isolated only between days 5 and 13. The occurrence of IgG1 CIC did correlate with an increase in total IgG1 in the serum, however, it did correlate with a small (1:10) increase in IgG1 anti-LDV activity. In contrast, CIC containing immunoglobulin of the serum IgG2 subclass were not isolated from LDV-infected serum until 15 days post infection. This chronological appearance of IgG2 CIC did not correlate with the observed increase in total IgG2 concentration in LDV-infected mice on day 7, however, was analogous to the rapid increase in free serum LDV-specific antibody. We propose that the non-specific suppression of the immune response and tumour enhancement during the acute phase of LDV infection could be due to the immunoregulatory properties of IgG1 CIC.

Animals↗
PubMed1980

Effect of nifedipine on glucose tolerance and insulin secretion in diabetic and non-diabetic patients.

The effect of the acute and long-term oral administration of nifedipine on glucose and insulin levels during a standard oral glucose tolerance test was studied in a total of 8 diabetic and 8 non-diabetic patients. No significant effect weas found on either glucose or insulin levels or on serum calcium and phosphate concentrations. The drug was withdrawn in 2 patients because of side-effects and failure of response, respectively. When used in standard recommended oral dosage nifedipine has no significant effect on glucose tolerance.

Adult↗
PubMed1979

The morphologic and biologic patterns of chemically induced pancreatic adenocarcinoma in Syrian golden hamsters after homologous transplantation.

A pancreatic adenocarcinoma induced by N-nitrosobis(2-oxopropyl)amine in the Syrian golden hamster was successfully transplanted to a homologous host by subcutaneous inoculation through 10 successive passages. The rate of 'tumor take' increased progressively with each generation from 60% to 100%, and the latency period after inoculation was reduced simultaneously from 6 weeks to 1 week in the second and following passages. The tumors grew rapidly, ulcerated the overlying skin, and metastasized to the regional lymph nodes and lungs. The animals usually died with multiple lung metastases between the 5th and 20th weeks. All transplanted tumors and their metastases retained the pattern of the original, well-differentiated adenocarcinomas.

Adenocarcinoma↗
PubMed1978

Effect of cholecystoduodenostomy and choledochostomy in pancreatic carcinogenesis.

The pancreatic carcinogen N-nitrosobis(2-oxopropyl)-amine was administered to Syrian golden hamsters after cholecystoduodenostomy and choledochostomy to investigate a possible bile reflux mechanism as a factor in pancreatic carcinogenesis. The induced lesions were similar in morphology, multiplicity, and distribution to those of animals in other studies without surgery. Hence the findings contraindicate the importance of biliary reflux in pancreatic tumor induction. Other possible mechanisms are discussed.

Adenocarcinoma↗
PubMed1977

The pancreas of the Syrian hamster (Mesocricetus auratus). I Anatomical study.

An anatomical study was made of the pancreas of the Syrian hamster (Mestocricetus auratus). The pancreas was found to consist of a head and three well-defined segments: the duodenal, gastric, and splenic lobes. The duct systems from each of the three lobes converge at the head region of the pancreas and develop into two major ducts which enter the distal portion of the common bile duct to form a common duct. The tails of the gastric and splenic lobes are connected by a string of omental fat which contains the major blood vessels of the two lobes. The gross anatomy of the hamster pancreas differs to some extent from that of the mouse and rat, but the principal structure of the ducts is similar.

Animals↗
PubMed1977

Sequential alteration of the pancreas during carcinogenesis in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine.

A systematic histological-pancreatographic study indicated that, during pancreatic carcinogenesis by N-nitrosobis(2-oxopropyl)amine, the ductular cells (cells of intercalated or intralobular ductules and especially those of peri-and intrainsular ductules) are most responsive. The initial proliferation (multiplication) and distension of ductules seemed due to primary hyperplasia of ductular cells, followed by metaplasia, atypia, and malignant alteration. Among 75 induced adenocarcinomas, most were of ductular origin, whereas only a few seemed to arise from ductal epithelium (interlobular, secondary, and main ducts). There was no preferential segment for tumor development. However, about one-third of the adenocarcinomas in the head of the pancreas had a periampullary location, while most neoplasms in other pancreatic lobes arose along the main pancreatic ducts. There was evidence of "leaking" of pancreatic juice through altered epithelium of main ducts, and this may have caused a marked periductal chronic inflammatory reaction.

Adenocarcinoma↗
PubMedDate not supplied

No effect of gliclazide on gastric inhibitory polypeptide (GIP) in type II diabetes.

Seven subjects with non-insulin-dependent diabetes mellitus were studied prior to and after 1 month of treatment with gliclazide, 80 mg twice daily. Individuals attended for a standard breakfast test meal (10 kcal/kg) on three occasions--prior to therapy, first day of therapy, and 30th day of therapy. Blood samples were collected between 0 and 240 min post-prandially and assayed for glucose, insulin, C-peptide, glucagon, pancreatic polypeptide, gastric inhibitory polypeptide (GIP), and gastrin. Following gliclazide, fasting and post-prandial glucose levels were significantly improved. An increase in post-prandial insulin and C-peptide levels was noted on the first treatment day and values remained elevated for the study period. GIP and other measured peptide hormones were unchanged. These data suggest that gliclazide asserts its hypoglycaemic effects by promoting insulin release, and has no detectable effect on other enteropancreatic hormones.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

Effect of indapamide on blood pressure and glucose tolerance in non-insulin-dependent diabetes.

Ten hypertensive non-insulin-dependent diabetic patients were treated with the antihypertensive drug indapamide to assess its effect on glucose tolerance over 1 year. Both systolic and diastolic blood pressures fell significantly (p less than 0.001) over the first month of treatment, and no change in plasma glucose or plasma insulin levels during an oral glucose tolerance test occurred at any time. Indapamide is an effective antihypertensive drug and, in contrast to thiazide diuretics, has no adverse effect on glucose tolerance in non-insulin-dependent diabetic patients.

Adult↗