Bezafibrate lowers VLDL concentrations without modifying its structure.
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Aged↗
Biomedical subjects
S Baba
Publications and source records attributed to S Baba.
Effect of a new cholecystokinin receptor antagonist CR 1392 on caerulein-induced acute pancreatitis in rats.
The effects of cholecystokinin receptor antagonist CR 1392 was studied in a model of mild acute pancreatitis induced in rats by four subcutaneous injections of the secretagogue caerulein. A single subcutaneous injection of 50 mg/kg body weight of CR 1392 caused a dramatic reduction in serum amylase concentration and pancreatic wet weight as well as histologic improvement of the caerulein-induced acute pancreatitis when given 30 min before the first caerulein injection. CR 1392 was also effective in reducing the elevated serum amylase activity, pancreatic weight, and histologic alterations even when administered after the pancreatitis had been induced. These present observations suggest that CR 1392 remains active for more than 3 h and blocks the action of caerulein on the pancreas.
Acute Disease↗
Hydrocortisone treatment increases the sensitivity and responsiveness to cholecystokinin in rat pancreas.
The effects of hydrocortisone treatment on the secretory abilities of pancreatic acini to various secretagogues were studied. Rats were given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, or 5.0 mg/kg body wt once daily for 7 days. Hydrocortisone led to a small dose-dependent increase in pancreatic wet weight per 100 g body wt, which was associated with an increase in both total protein and DNA contents. In acini prepared from hydrocortisone-treated rats, both the responsiveness and the sensitivity to cholecystokinin octapeptide (CCK-8) was increased. The concentration dependence of cellular Ca2+ mobilization in response to CCK-8 was also shifted to lower concentrations in acini from hydrocortisone-treated rats compared with control rat acini. In vivo administration of hydrocortisone caused a significant increase in the affinity of 125I-CCK-8 binding to high-affinity receptors. The secretory responsiveness to carbamylcholine and bombesin, but not to secretin, was also increased but without any change in the sensitivity. Moreover, the hydrocortisone treatment increased the secretory responsiveness of acini to the Ca2+ ionophore A23187 and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate but did not to an adenosine 3',5'-cyclic monophosphate analogue, 8-bromoadenosine 3',5'-cyclic monophosphate. The present observations suggest that in vivo glucocorticoid administration affects both the CCK receptors and a postreceptor loci.
8-Bromo Cyclic Adenosine Monophosphate↗
Putative mechanisms involved in excitatory and inhibitory effects of somatostatin on intestinal motility.
The mechanism of action of somatostatin on the motility of intestine was examined in the entire preparation and the longitudinal muscle attached with Auerbach's plexus (LA) preparation of guinea pig ileum, in relation to the cholinergic neuron and gamma-aminobutyric acid (GABA)ergic neuron. Somatostatin produced a transient potentiation of electrical stimulation-induced twitch contractions followed by an inhibition. The excitatory effect of somatostatin was associated with an increase in the release of [3H]acetylcholine (ACh) from the preparations preloaded with [3H]choline. Bicuculline, a GABAA antagonist, inhibited the somatostatin-induced excitatory effect. Somatostatin inhibited the electrical stimulation-induced twitch contraction and release of [3H]ACh, and the inhibition was greater in the entire preparation than in the LA. Phaclofen, a GABAB antagonist, prevented the inhibitory effects of somatostatin. Somatostatin induced a Ca2+ -dependent, tetrodotoxin-sensitive release of [3H]GABA from the preparations preloaded with [3H]GABA. Therefore somatostatin exerts excitatory and inhibitory effects on the cholinergic neuron due to the stimulation of the GABAergic neuron, and the motility of the intestine is regulated.
Acetylcholine↗
Effect of cholecystokinin octapeptide analogues on food intake in the dog.
Cholecystokinin octapeptide, administered into the third cerebral ventricle (icv), suppresses feeding in sheep, pigs, chicken, rats, and dogs. Because of the species differences in the feeding response to cholecystokinin (CCK), we studied the pharmacological characterization of this peptide on feeding in 16-h-fasted dogs. We examined the effects of CCK-(26-33)-NH2 (CCK-8) and a variety of its analogues, nonsulfated CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(26-33)-OH (deamidated CCK-8), (Nle28,31)-CCK-(26-33)-NH2 [(Nle28,31)-CCK-8], succinyl-CCK-(27-33)-NH2 (Suc-CCK-7) succinyl-Thr28, Leu29, MePhe33-CCK-(27-33)-NH2 [Suc-Thr28, Leu29, MePhe33)-CCK-7], CCK-(29-33)-NH2 (CCK-5), and CCK-(30-33)-NH2 (CCK-4) on food intake after iv injection. Systemic dose-response studies appeared to reveal the following rank order of potencies: Suc-CCK-7 = Suc-(Thr28, Leu29, MePhe33)-CCK-7 greater than CCK-8 = (Nle28,31)-CCK-8 greater than desulfated CCK-8 greater than deaminated CCK-8 greater than CCK-5 = CCK-4 = 0. Smaller COOH-terminal fragments acted as antagonists to the satiety effects of CCK-8. These data demonstrate in the dog that the structural requirements for the behavioral activity of CCK-8 are the COOH-terminal amide group, the sulfate ester of the tyrosine moiety, and the conformational constraints observed in CCK-7.
Animals↗
Effects of a new proglumide analogue CR 1392 on pancreatic exocrine secretion in the rat.
The effects of proglumide analogue. CR 1392, on pancreatic exocrine secretion were studied in the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, CR 1392 caused a parallel rightward shift of the dose-response curve for amylase secretion stimulated by cholecystokinin octapeptide (CCK-8). CR 1392 inhibited maximally stimulated amylase release by CCK-8 (100 pM) in a concentration-dependent manner, with a half maximal inhibition (ID50) at 8.0 +/- 0.6 microM. CR 1409, another proglumide analogue, also caused a concentration-dependent inhibition (ID50: 3.2 +/- 0.4 microM). Although CR 1409 was about 2.5-fold more potent than CR 1392 in inhibiting the stimulated amylase release, 1 mM CR 1409 caused 107.4 +/- 0.9% increase in amylase release, suggesting acinar cell damage. CR 1392 (1 mM) also caused 19.9 +/- 2.3% increase in amylase release, but was less toxic than CR 1409. The antagonism produced by CR 1392 was selective for CCK and had no effect on amylase release stimulated by other receptor secretagogues or by agents bypassing receptors. CR 1392 added 20 min after the CCK-8 stimulation rapidly abolished pancreatic exocrine secretion in both isolated acini and isolated perfused pancreas. Although the inhibitory effect of CR 1392 was fully reversible in the isolated acini, the pancreata perfused with 100 microM CR 1392 for 20 min did not respond to the subsequent stimulation with CCK-8 for more than 20 min. These results indicate that CR 1392 is a potent, competitive, specific and long acting antagonist of CCK in rat pancreas.
Amylases↗
Renal cell carcinoma presenting as Budd-Chiari syndrome.
Herein a case of renal cell carcinoma presenting as Budd-Chiari syndrome is reported. Ten percent of patients with renal cell carcinoma have shown inferior vena cava invasion. However, Budd-Chiari syndrome is a relatively rare condition where the hepatic venous outflow into the inferior vena cava is blocked by tumor thrombus, and the prognosis is very poor.
Budd-Chiari Syndrome↗
Characterization of peptide YY receptors in the brain.
We studied the pharmacological and structural characteristics of peptide YY (PYY) receptors in porcine brain. PYY and neuropeptide Y (NPY) bound with high affinity to crude membrane preparations from the hippocampus, but their C-terminal fragments bound with 30- to 450-fold lower affinity Guanine nucleotides, especially the nonhydrolyzable GTP analog GTP gammas inhibited the binding of [125I]PYY, but other transmitters, hormones, and central nervous system-acting drugs did not, except for gangliosides at high concentrations. These results suggest that PYY receptor binding resides in the N-terminal part of the PYY molecule and is coupled to a guanine nucleotide regulatory protein. To elucidate PYY receptor structure, we used the cross-linking reagent disuccinimidyl suberate to covalently attach [125I]PYY to its receptors in the hippocampus membrane. Gel electrophoresis followed by autoradiography revealed a band centered at the mol wt of 50,000. Competitive inhibition of binding by unlabeled PYY resulted in a parallel inhibition of labeling of the 50,000 mol wt protein. The reducing agent 2-mercaptoethanol did not affect the appearance of this band, suggesting that the PYY receptor does not have subunits connected by sulfhydryl bonds. Furthermore, cross-linking [125I]NPY to its receptors in the porcine hippocampus produced the same 50,000 mol wt band regardless of 2-mercaptoethanol. The identity in the size of NPY and PYY receptors together with their similarities in binding properties including regional distribution and peptide specificity, indicate that NPY and PYY regulate brain function through interaction at a common receptor site.
Animals↗
Biological properties of an initial degradation product of insulin by insulin-degrading enzyme.
We previously reported on the degradation of monocomponent porcine insulin by affinity-purified pig skeletal muscle insulin-degrading enzyme (IDE) and on the detection and HPLC separation of the initial degradation product (peak VI). Using relatively high concentration of insulin, peak VI appeared rapidly at 30 sec of incubation, whereas other peaks were not detected within 5 min of incubation. Performate oxidation studies suggested that peak VI is composed of a cleaved A-chain and an intact B-chain. To assess whether the initial degradation product of insulin generated by IDE preserves biological properties, we analyzed several insulin-like activities of peak VI. It had a hypoglycemic effect on rats. In vitro, it bound to the insulin receptors of rat adipocytes and stimulated glucose oxidation there. It also strengthened insulin receptor kinase activity in insulin receptors from rat liver and human placenta. Its biological potency, however, was 1/40th to 1/160th that of insulin itself. This is probably due to reduced affinity for the insulin receptor, since it had 2.5% of insulin's ability to both bind to the receptor and stimulate glucose oxidation. Moreover, peak VI had all of insulin's agonistic effect on glucose oxidation when used at a higher concentration. On the other hand, cross-linking analysis suggested that peak VI preserves almost the same affinity for IDE as does insulin. These results suggest that pig skeletal muscle IDE may cleave peptide bonds within the A-chain early in insulin degradation, generating peak VI; this then serves as the next substrate of IDE while exerting reduced insulin-like activity, and peak VI is converted to several relatively low mol wt products.
Adipose Tissue↗
Endogenous and exogenous testosterone levels after administration of deuterium-labelled testosterone propionate in hypogonadotropic hypogonadism.
A gas chromatography-mass spectrometry-selected ion monitoring technique was employed to determine simultaneously the plasma concentrations of endogenous and exogenous testosterone in three patients with hypogonadotropic hypogonadism after a single i.m. dose of testosterone propionate-19,19,19-d3. The plasma levels of testosterone-19,19,19-d3 derived from testosterone propionate-19,19,19-d3 were maintained above the normal testosterone levels (greater than 4 ng/ml) for 48 h, while the plasma levels of endogenous testosterone changed little.
Adult↗
Effects of pancreastatin on insulin and pancreatic polypeptide secretion in the dog.
Porcine pancreastatin (1.19 nmol) was administered into the peripheral vein (i.v.) or the third cerebral ventricle (i.t.v.) of dogs and its effect on the secretion of insulin and pancreatic polypeptide (PP) studied. Neither means of administration had any effect on basal and glucose-induced insulin or PP secretion. However, i.v. pancreastatin did inhibit the i.v. CCK-8-induced insulin but not PP release. Pancreastatin may thus play a role in the regulation of insulin secretion in the canine pancreas.
Animals↗
Natural killer cell activity and recycling capacity of natural killer cells in patients with carcinoma of the prostate.
Natural killer (NK) cell activity and recycling capacity of NK cells in patients with carcinoma of the prostate (CaP) was determined by combining the 51Cr-release cytotoxicity assay and single cell cytotoxicity assay in agarose. The NK cell activity in patients with advanced CaP (stage D) was significantly lower than the NK cell activity of normal controls and that of patients with localized CaP (stage B and C). The number of active NK cells in the peripheral blood lymphocytes was similar in all groups tested including normal controls, patients with localized CaP, and patients with advanced CaP. Maximal killing potential (Vmax) and maximal recycling capacity (MRC) were significantly reduced in patients with advanced CaP as compared to patients with localized CaP or normal controls. Obtained results indicated that the depressed NK cell activity in advanced CaP was not due to a reduced number of active NK cells but due to the decreased recycling capacity of the individual NK cells.
Adult↗
Increased beta-cell secretory responsiveness to ceruletide and TPA in streptozocin-induced mildly diabetic rats.
We examined the effects of various stimuli on immunoreactive insulin (IRI) and glucagon (IRG) release from perfused pancreases isolated from control and streptozocin-induced diabetic (STZ-D) rats. Diabetes was induced by injecting 30 mg/kg STZ into rats fasted for 16-18 h 12-17 days before our experiments. Glucose (11.1 mM) caused a distinct biphasic pattern of IRI release from the control pancreas, whereas the first phase was marginal and the second phase was absent in the diabetic pancreas. Arginine (20 mM)-induced IRI release was similar in both groups, whereas IRG release was greater in the control rats than in the diabetic rats. Thus, this model of STZ-D simulates a certain class of non-insulin-dependent diabetes mellitus (NIDDM). In these diabetic animals, the cholecystokinin (CCK) analogue ceruletide (620 pM) caused a significantly greater increase in IRI release in the presence of 5.6 mM glucose than in the control rats, but ceruletide caused a similar IRG release in both groups. Because CCK and ceruletide stimulate phosphoinositide turnover in pancreatic islets, we examined the effects of carbachol and phorbol ester TPA on IRI release in the presence of 5.6 mM glucose. Carbachol (10 microM), which is thought to generate similar second messengers as ceruletide, induced greater IRI release in diabetic than in control rats. TPA (100 nM) caused a significantly greater increase in IRI release from the diabetic than the control pancreas. Our results demonstrate that the insulin-releasing mechanism involved in protein kinase C activation is enhanced in this model of NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Contralateral hearing and tympanoplasty].
The relationship between the contralateral hearing threshold in the operated ear and the type of tympanoplasty and the hearing threshold in the operated ear was investigated in this report. The subjects of analysis were 863 ears that received tympanoplasty during the past nine years at the Nippon Medical School Main Hospital. Patients who had good hearing in the contralateral ear received type I tympanoplasty more frequently than did those who had poor hearing on the contralateral ear. On the other hand, patients who had poor hearing in the contralateral ear received a modified type III tympanoplasty more frequently. Patients who had good hearing in the contralateral ear tended to have better hearing in the operated ear compared to those who had poor hearing in the contralateral ear. The hearing threshold in patients who had normal contralateral hearing on the average had 20 dB better hearing than did those who had profound hearing loss in the contralateral ear. More than one third of the patients whose hearing thresholds were worse than 30 dB in the operated ear also had a contralateral hearing loss of 30 dB or more. The decision to perform tympanoplasty in cases of the better hearing ear or the only hearing ear must be made very carefully. The contralateral hearing in patients with chronic otitis media, however, is frequently not normal as was evidenced in this investigation. Also, patients who had poor hearing or were deaf in the contralateral ear received more benefit by tympanoplasty than did those who had good hearing in the contralateral ear.(ABSTRACT TRUNCATED AT 250 WORDS)
Auditory Threshold↗
[Flow cytometric DNA analysis of normal adrenal tissues and adrenal tumors].
Flow cytometric DNA analysis (FCM) of adrenal tumors was studied to evaluate whether FCM will be a useful examination for differentiating between benign and malignant adrenal tumors. 10 specimens of surgically resected (for renal cell carcinoma confined within the middle or lower pole) normal adrenal glands and 20 specimens of surgically resected adrenal tumors were submitted for the study. Hyperplastic adrenal cortex as well as normal adrenal gland showed normal diploid pattern. On the other hand, some of the cortical adenomas showed tetraploid patterns, which has been known to be an index of malignancy in most of the flow cytometric intervention to other solid tumors. Conn adenomas were especially apt to show this tendency, in which as much as 86% showed tetraploid pattern. Proliferation Index (PI) (ratio of S + G2 +M cells for the whole population of analyzed cells) were as much as 9.45 +/- 6.97% in normal adrenal cells, whereas it was much higher in cortical adenomas (17.75 +/- 8.53%). As a matter of fact, PI of hyperplastic adrenal cortex was within the same range as that of the normal adrenal glands. In pheochromocytomas, aneuploid pattern, which has been believed to be a definite index of malignancy, was shown in 60% of the cases, tetraploid pattern in 20%, and normal diploid pattern in only 20%. As a matter of fact, a case of non functioning cortical adenocarcinoma and a case of malignant pheochromocytoma were judged to show typical aneuploid pattern. Thus, the application of the flow cytometric diagnosis for adrenal tumors was supposed to require some refinement in understanding the significance of aneuploidy or tetraploidy.
Adrenal Gland Neoplasms↗
[Clinical experience with Ureteromat in transurethral ureterorenoscopy].
By September 1988, we performed 58 ureterorenoscopies (52 for primary ureteral calculi, 3 for ureteral biopsy, 2 for ureteral stricture and 1 for ureteral foreign body) using a Ureteromat (Uromat Storz, West Germany). Continuous saline irrigation with the Ureteromat has obviated mechanical dilation of the ureteral orifice in 93.1% of the cases, which made this endoscopy as easy as the conventional cystourethroscopy. In 4 cases (6.9%), however, balloon dilation of the ureteral orifice was necessary for the passage of a rigid ureterorenoscope. Of 52 ureteral calculi, 37 were assigned for transurethral ureterolithotripsy (TUL), whereas transurethral ureterorenoscopy (TUURS) was indicated to flush the remaining 15 calculi up into renal pelvis for later extracorporeal shock wave lithotripsy. TUL was successful in 81.1% (30/37). The causes of failure were stone migration in 6 cases and ureteral avulsion by electrohydraulic lithotripsy necessitating open surgery in 1 case. The irrigation with the Ureteromat facilitated the manipulation of intraluminal ureteral lesions always under clear vision; by-passing the impacted stone with a guide wire and flushing-up of the calculi were successfully performed in 100%, in spite of the co-existing edematous and inflammatory mucosal changes. In 7 cases where ureteroscope could not be advanced well up to the lesion because of spasm in the iliac ureter, the irrigation pressure was transiently increased up to 200 mmHg to allow safe and easy dislodgement of impacted calculi under fluoroscopic guidance. This procedure was also effective to introduced a ureteral stent over a guide wire in 2 cases of ureteral stricture, which could not be achieved by conventional cystoscopic procedure. Immediate postoperative complications were fever in 8.6% and gross hematuria lasting for more than 4 days in 8.6%.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Studies on biological characteristics of transitional cell carcinoma of the bladder in patients under 30 years of age].
The incidence of transitional cell carcinoma (TCC) of the bladder has been increasing in men with a peak incidence occurring in the sixth decade. However, development of tumors under the age of 30 is relatively rare. In this regard, it has been reported that vesical tumors in the young group is less malignant and rare to recur when compared with those in the elderly group. Recently, flow cytometric DNA histograms (FCM) provides quantitative and objective informations for detection and evaluation of malignant potential of bladder neoplasms. Here we report patients with tumor of the bladder under 30 years old and assess the clinical properties and biological characteristics of their tumors based on FCM. A total of 11 patients from 1975 through 1988 were reviewed. Their mean age at the diagnosis was 22.6 years old (range from 22 to 29 years old). Male/female ratio was 2.7:1. The mean follow-up period was 4 years and 7 months (range from 8 months to over 13 years). An asymptomatic gross hematuria was found in all of the patients, which is the most common sign. Filling defects of the bladder on excretory urograms were observed in six out of the 11 patients (54.5%). Cystoscopically, the size of tumors was less than 2 cm in diameter. Ten patients had a single tumor and one patient had multiple tumors at the time of the initial diagnosis. Endoscopically tumors were papillary in all but one patient, who had a non-papillary tumor. Their urine cytology showed class I in one, class II in eight, class III in one, class IV in one and class V in none.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Comparative study on prophylactic intravesical instillation of bacillus Calmette-Guerin (BCG) and adriamycin for superficial bladder cancers].
In this study we evaluated 77 patients with superficial bladder cancer who were treated with either intravesical bacillus Calmette-Guerin (BCG) (44 patients) or doxorubicin hydrochloride (Adriamycin, ADR) (33 patients) for prophylaxis of tumor recurrence after transurethral resection. The estimated actuarial probability of non-recurrence rate at three years for the BCG group was 73.0%, and the actuarial non-recurrence rate for the ADR group was 27.3%; a statistically significant difference (p = 0.0013). A comparison between the two groups was also made according to the patient's background, including whether the tumor was initial or recurrent, solitary or multiple, and the tumor grade. In all areas of the study, except for grade-1 tumors, the BCG group was significantly superior to the ADR group. The efficacy of BCG therapy as a result of different BCG treatment protocol was evaluated for six weekly instillations 1) without further maintenance instillation, 2) followed by 12 months of maintenance, and 3) followed by more than 18 months of maintenance. Long-term maintenance BCG instillation group (more than 18 months) showed the most favorable results, however, the differences were not statistically significant. These results indicate that intravesical BCG instillation was significantly superior to ADR in the prevention of bladder cancer recurrence and that six weekly intravesical BCG instillations may provide adequate prophylactic effects against recurrence of superficial bladder cancers.
Actuarial Analysis↗