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D McKay

Publications and source records attributed to D McKay.

At least 55 records · Page 3Linked to original sources
PubMed1992

Simultaneous measurement of cholecystokinin-stimulated amylase release and cholecystokinin receptor binding in rat pancreatic acini.

In the past, isolated-dispersed pancreatic acini have been used to examine either cholecystokinin-stimulated amylase release or pancreatic acinar cholecystokinin receptors. We have developed and validated a method for simultaneous measurement of synthetic cholecystokinin octapeptide-stimulated (CCK8-stimulated) pancreatic amylase release and cholecystokinin receptors. After an 18-hour fast, rats were killed and their pancreatic acini isolated. Three-milliliter aliquots of acinar suspension were incubated for 60 minutes in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-Ringer buffer containing graded doses of CCK8 and a constant amount (7 pmol/L) of iodine 125-labeled CCK8 (by the Bolton-Hunter method) ([125I]BH-CCK8). A 1 ml sample was removed from each flask for determination of amylase release, and the remaining 2 ml were used to determine cholecystokinin receptor capacities and affinities. The median effective dose for amylase release was 16 pmol/L, and release was maximal at 100 pmol/L CCK8 plus 7 pmol/L [125I]BH-CCK8, a dose that released 28% +/- 3% of total cellular amylase content. High affinity (equilibrium dissociation constant of high-affinity receptors = 58 +/- 8 pmol/L, receptor density of high-affinity receptors = 4 +/- 1 fmol/mg protein) and low affinity (equilibrium dissociation constant of low-affinity receptors = 7 +/- 2 nmol/L, receptor density of low-affinity receptors = 313 +/- 108 fmol/mg protein) cholecystokinin receptors were measured. The results demonstrate that CCK8-stimulated amylase release and cholecystokinin receptor binding in pancreatic acini can be measured concurrently and that the parameters of amylase release and cholecystokinin receptor binding are strikingly similar to those previously observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1991

Rat liver mitochondrial malate dehydrogenase: purification, kinetic properties, and role in ethanol metabolism.

Malate dehydrogenase was purified from the mitochondrial fraction of rat liver by ion-exchange chromatography with affinity elution. The kinetic parameters for the enzyme were determined at pH 7.4 and 37 degrees C, yielding the following values (microM): Ka, 72; Kia, 11; Kb, 110; Kp, 1600; Kip, 7100; Kq, 170; Kiq, 1100, where a = NADH, b = oxalacetate, p = malate, and q = NAD+. Kib was estimated to be about 100 microM. The maximum velocities for mitochondrial malate dehydrogenase in rat liver homogenates, at pH 7.4 and 37 degrees C, were 380 +/- 40 mumol/min per gram of liver, wet weight, for oxalacetate reduction and 39 +/- 3 mumol/min per gram of liver, wet weight, for malate oxidation. Rates of the reaction catalyzed by mitochondrial malate dehydrogenase under conditions similar to those in vivo were calculated using these kinetic parameters and were much lower than the maximum velocity of the enzyme. Since mitochondrial malate dehydrogenase is not saturated with malate at physiological concentrations, its kinetic parameters are probably important in the regulation of mitochondrial malate concentration during ethanol metabolism. For the mitochondrial enzyme to operate at a rate comparable to the flux through cytosolic malate dehydrogenase during ethanol metabolism (about 4 mumol min-1 per gram liver), the mitochondrial [malate] would need to be about 2 mM and the mitochondrial [oxalacetate] would need to be less than 1 microM.

Animals↗
PubMed1991

An epoxygenase metabolite of arachidonic acid mediates angiotensin II-induced rises in cytosolic calcium in rabbit proximal tubule epithelial cells.

Previous studies from this and other laboratories have shown that angiotensin II (AII) induces [Ca2+]i transients in proximal tubular epithelium independent of phospholipase C. AII also stimulates formation of 5,6-epoxyeicosatrienoic acid (5,6-EET) from arachidonic acid by a cytochrome P450 epoxygenase and decreases Na+ transport in the same concentration range. Because 5,6-EET mimics AII with regard to Na+ transport, it effects on calcium mobilization were evaluated. [Ca2+]i was measured by video microscopy with the fluorescent indicator fura-2 employing cultured rabbit proximal tubule. AII-induced [Ca2+]i transients were enhanced by arachidonic acid and attenuated by ketoconazole, an inhibitor of cytochrome P450 epoxygenases. Arachidonic acid also elicited a [Ca2+]i transient that was attenuated by ketoconazole. 5,6-EET augmented [Ca2+]i similar to that seen with AII, but was unaffected by ketoconazole. By contrast, the other regioisomers (8,9-, 11,12-, and 14,15-EET) were much less potent. [Ca2+]i transients resulted from influx through verapamil- and nifedipine-sensitive channels. These results suggest a novel mechanism for AII-induced Ca mobilization in proximal tubule involving cytochrome P450-dependent arachidonic acid metabolism and Ca influx through voltage-sensitive channels.

8,11,14-Eicosatrienoic Acid↗
PubMed1991

Tissue and plasma levels of immunoreactive gastrin and cholecystokinin in chickens with and without bombesin.

Immunoreactive gastrin and immunoreactive cholecystokinin were measured in chicken tissue extracts obtained from the gut and brain. In contrast to that found in mammals, immunoreactive gastrin found in chickens was higher in the brain than in gut tissues, and it was highest in the ileum when compared with other gut tissues. Dose-response curves of tissue extracts from the brain and ileum and of serum were parallel to the dose-response curve of synthetic human gastrin, suggesting the existence of gastrin or a peptide immunologically similar to gastrin in those chicken tissues. Immunoreactive cholecystokinin in tissues was highest in the duodenum, followed by the jejunum, ileum, and cortex; lesser amounts of cholecystokinin were found in other tissues. Influence of bombesin on the release of immunoreactive gastrin and immunoreactive cholecystokinin in the blood of chickens was also studied. Bombesin doses of 3 micrograms/kg per hour significantly increased immunoreactive gastrin in serum and immunoreactive cholecystokinin in plasma, whereas gastrin did not increase with a bombesin dose of 0.6 micrograms/kg per hour. The results confirm the existence of immunoreactive gastrin and immunoreactive cholecystokinin in the tissue of chickens and indicate that they are released into circulation in response to bombesin.

Animals↗
PubMed1990

Phase I and pharmacology study of intravesical mitoxantrone for recurrent superficial bladder tumors.

A phase 1 study of intravesical mitoxantrone was done in patients with superficial bladder tumors recurrent after previous intravesical therapy. Mitoxantrone (5 to 10.5 mg.) was instilled in the bladder via catheter and was left in situ for 2 hours. Each patient received 6 treatments at 1-week intervals. Pharmacology studies were conducted in a subset of consenting patients. Dysuria, urinary frequency and hematuria were dose-limiting at 10 to 10.5 mg., the dose recommended for our phase 2 studies. One patient treated with 7.5 mg. mitoxantrone had bladder contracture after severe bladder injury caused by the drug. The interval free of recurrence increased in 5 of 8 patients treated with 10 to 10.5 mg. mitoxantrone and in 6 of 19 treated at lower dose levels. One patient who had residual evaluable tumor in the bladder at treatment experienced a complete remission for 16 months. Only 1 of 18 patients who underwent pharmacology studies had any mitoxantrone detectable in the blood after intravesical administration. This patient had severe irritative symptoms at treatment. No systemic toxicity was noted in any patient. Of the mitoxantrone instilled into the bladder 33 to 100% (mean 75%) was recovered in the specimen voided at the end of treatment. In summary, intravesical mitoxantrone is reasonably well tolerated and should be studied further at a dose of 10 mg. per week for 6 weeks. Caution should be exercised, since bladder contracture was seen in 1 patient. Systemic absorption and toxicity are negligible.

Administration, Intravesical↗
PubMed1990

Lymphomatoid granulomatosis presenting as sudden blindness.

Lymphomatoid granulomatosis is an uncommon clinical problem and even more rarely presents to the ophthalmologist. A case is described in which a 60-year-old Fijian woman presented with sudden, sequential, complete visual loss in association with signs of scleritis. Direct eyewall biopsy and nasal mucosal biopsy confirmed the diagnosis of lymphomatoid granulomatosis. Despite intensive high-dose oral prednisone therapy her vision remained at no light perception and she developed recrudescence of disease necessitating the use of radiotherapy. All systemic investigations failed to show any other organ involvement by the disease process and she remains well. This is the first report of lymphomatoid granulomatosis presenting as sudden blindness.

Biopsy↗
PubMed1989

Total small bowel resection inhibited bombesin-stimulated release of cholecystokinin and pancreatic polypeptide in anesthetized cats.

In anesthetized cats, immunoreactive cholecystokinin (CCK), pancreatic polypeptide (PP), and gastrin were released in response to bombesin both before and after small bowel resection. Total small bowel resection significantly decreased bombesin-stimulated release of cholecystokinin and pancreatic polypeptide without affecting the release of gastrin. Integrated analysis showed that CCK, pancreatic polypeptide, and gastrin were released in significant quantities after small bowel resection. The results show that total small bowel resection caused significant inhibition of bombesin-stimulated release of cholecystokinin and pancreatic polypeptide; in contrast, gastrin release remained unaffected. The data further indicate that extra bowel sources of cholecystokinin exist in cats and the release of CCK from those sources occurred following bombesin stimulation.

Anesthesia↗
PubMed1989

Mechanism of action of nicotine on amylase release by isolated pancreatic acini.

The effects of nicotine on the pH of acinar suspension, amylase release and on amylase response stimulated by carbachol were examined in isolated rat pancreatic acini. Additions of nicotine at concentrations ranging from 10 microM to 30 mM caused dose-dependent increases in pH of acinar suspension with simultaneous amylase release (p less than 0.05). There was no increase in amylase release when acinar cells were incubated with nicotine adjusted to pH 7.40. Carbachol alone released amylase whereas nicotine (pH 7.40) at a concentration of 10 mM caused a significant and nonparallel inhibition of amylase release in response to graded doses of carbachol. At concentrations ranges between 3 microM and 10 mM, nicotine at pH 7.40 inhibited amylase release stimulated by 1 microM carbachol, with a half maximal inhibition at 0.8 +/- 0.2 mM. These results indicate that in isolated rat pancreatic acini nicotine at pH 7.40 has no effect on basal nonstimulated amylase release but it inhibits carbachol-stimulated amylase response in a noncompetitive manner. These observations may have direct implications in underlying mechanism of pancreatic disorders.

Amylases↗
PubMed1989

Effect of L-364,718 on GRP-stimulated pancreatic and gastric secretions and GI peptides in conscious dogs.

The effect of L-364,718, a cholecystokinin (CCK) receptor antagonist, on exocrine pancreatic secretion, gastric secretion, and plasma levels of gastrointestinal (GI) peptides stimulated by gastrin-releasing peptide (GRP) was examined in five conscious dogs. Intravenous infusion of graded doses of synthetic porcine GRP (18, 36, and 178 pmol/kg/h) caused significant and dose-dependent increases in pancreatic and gastric juice secretion and in plasma levels of pancreatic polypeptide (PP), CCK, and gastrin. Intravenous injection of L-364,718 (20 nmol/kg) significantly inhibited GRP-stimulated pancreatic outputs of juice volume, protein, and amylase and plasma PP release. L-364,718, however, did not affect gastric juice volume and plasma levels of CCK and gastrin. The results suggest that endogenously released CCK is, at least in part, responsible for GRP-stimulated pancreatic protein and enzyme secretions and PP release in dogs. The results further suggest that GRP-stimulated pancreatic secretion might be, in part, a direct response of GRP to exocrine pancreas.

Animals↗
PubMed1988

Flexor tendon ruptures in patients with rheumatoid arthritis.

One hundred fifteen flexor tendon ruptures were reviewed in 43 hands with rheumatoid arthritis, one hand with psoriatic arthritis, and one hand with lupus erythematosis. Ninety-one tendons were ruptured at the wrist, four ruptures occurred at the palm, and 20 ruptures occurred within the digits. At the wrist level, 61 ruptures were caused by attrition on a bone spur and 30 were caused by direct invasion of the tendon by tenosynovium. All ruptures distal to the wrist were caused by invasion of the tendon by tenosynovium. Patients whose ruptures were caused by attrition regained better motion than those whose ruptures were caused by invasion by tenosynovitis; however, motion overall was poor. Patients with isolated ruptures in the palm or at the wrist had the best functional results. Those patients with multiple ruptures within the carpal canal had a worse prognosis. Ruptures of both tendons within the fibro-osseous canal had the worst prognosis. The severity of the patient's disease and the degree of articular involvement had a great effect on the outcome of surgery. Prevention of tendon ruptures by early tenosynovectomy and removal of bone spurs should be the cornerstone of treatment.

Adult↗
PubMed1988

Effect of L364718, a new CCK antagonist, on amylase secretion in isolated rat pancreatic acini.

We examined the effect of L364718, a new cholecystokinin (CCK) receptor antagonist, on amylase release stimulated by CCK or different secretagogues in isolated rat pancreatic acini. L364718 caused a parallel rightward shift of the dose-response curve of CCK8. Schild plots showed a slope of 1.05 +/- 0.15 and a pA2 value of 10.01 +/- 0.31. L364718 inhibited maximally stimulated amylase release by CCK in a dose-dependent manner, with half maximal inhibition (ID50) at 1.7 nM and complete inhibition at 30 nM. Asperlicin, a prototype compound of L364718, also caused dose-dependent inhibition, but L364718 was approximately 400 times more potent than asperlicin (ID50 = 761 nM). L364718 significantly inhibited amylase release in response to CCK33 and CCK8 but had no effect on amylase release stimulated by other receptor secretagogues or agents by passing receptors. The results indicate that L364718 acts as an extremely potent, competitive, and specific antagonist of CCK's action on pancreatic acini.

Amylases↗
PubMed1987

Acquired immune deficiency syndrome presenting as bone marrow and mediastinal cryptococcosis.

Disseminated cryptococcosis developed as the first manifestation of the acquired immune deficiency syndrome in a previously healthy Haitian man. Following presentation with a febrile illness that included massive mediastinal and peripheral lymphadenopathy, the patient died of overwhelming pulmonary, visceral, and meningeal cryptococcosis.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Intra-arterial cisplatin treatment of unresectable or medically inoperable invasive carcinoma of the bladder.

Five patients between 72 and 82 years old received 5 to 6 treatments of 50 to 75 mg. per m.2 cisplatin by bilateral internal iliac artery infusion for unirradiated invasive transitional cell carcinoma of the bladder. Of the patients 3 also were diabetics and 1 had congestive heart failure. Treatment was tolerated extremely well, although most courses were associated with moderate to severe nausea and vomiting lasting several hours. Of 4 evaluable patients 3 achieved complete remission and 1 achieved a good partial remission. An additional 55-year-old woman with a large invasive bladder carcinoma fixed to surrounding structures was treated with 4 courses of 100 mg. per m.2 intra-arterial cisplatin. This patient had a marked decrease in tumor size, permitting surgical resection of all known residual tumor. A 49-year-old patient with large pelvic lymph node metastases from a squamous cell carcinoma of the bladder achieved only minimal decrease in tumor size after 3 courses of 100 mg. per m.2 intra-arterial cisplatin. We conclude that intra-arterial cisplatin can be highly effective for localized invasive bladder cancer even when relatively low doses are used. With proper care the regimen can be used safely and effectively in elderly patients with medical contraindications to an operation.

Age Factors↗
PubMed1982

High pressure liquid chromatographic determination of mono- and disaccharides in presweetened cereals: Collaborative study.

A collaborative study was conducted using a modified AOAC method (sugars in chocolate) for the determination of fructose, glucose, sucrose, and maltose in presweetened cereals by high pressure liquid chromatography (HPLC). Eight samples consisting of 6 products were analyzed in duplicate by the HPLC method and the AOAC Lane-Eynon method. The AOAC method was modified to use water-alcohol (1 + 1) and Sep-Pak C18 cartridges for sample cleanup. The HPLC results indicate precision comparable to the lane-Eynon method and the chocolate method. The modified HPLC method has been adopted official first action.

Chromatography, High Pressure Liquid↗