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Biomedical subjects

H Uehara

Publications and source records attributed to H Uehara.

At least 145 records · Page 8Linked to original sources

Inhibition by somatostatin of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of somatostatin on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and s.c. injections of 200 micrograms/kg body wt of somatostatin every other day from the beginning of the experiment until the end of week 16. Pre-neoplastic and neoplastic lesions staining for gamma-glutamyl transpeptidase (GGT) or placental type glutathione-S-transferase (GST-P) were examined histochemically. Administration of somatostatin for 16 weeks resulted in significant reduction in the percentage volume of GGT-positive and GST-P-positive lesions. The incidence, number and size of hepatocellular carcinomas were significantly less in rats treated with somatostatin than in untreated rats. Administration of somatostatin significantly decreased the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that somatostatin inhibits hepatocarcinogenesis and that this effect may be related to its effect in decreasing cell proliferation in pre-neoplastic lesions.

Animals↗

Enhancing effects of calcium-deficient diet on gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of ad libitum feeding of calcium-deficient diet on the incidence, number and histological types of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in male Wistar rats. Rats were fed standard pellet diet containing 0.5% (normal-calcium diet) or 0.01% calcium (calcium-deficient diet) after oral treatment with MNNG for 25 weeks. Oral administration of the calcium-deficient diet resulted in a significant increase in the incidence, but not the number, of gastric cancers in experimental Week 52. However, it did not affect the histological types of cancer. The calcium-deficient diet also caused a significant increase in tissue norepinephrine concentration of the antral portion of the gastric wall and in the labeling index of the antral epithelial cells. These findings indicate that the calcium-deficient diet enhanced gastric carcinogenesis and suggest that its effect may be related to increase in norepinephrine in the gastric wall and consequent stimulation of proliferation of antral epithelial cells.

Adenocarcinoma↗

Surgical resection of potentially curable pancreatic cancer with improved preservation of endocrine function--further evaluation of intraoperative cytodiagnosis.

Very early detection of pancreas cancer is most desirable, since it permits less invasive surgery which has a correspondingly greater chance of success. The present study investigated both surgical outcome and postsurgical quality of life in 8 patients whose occult neoplasms were successfully treated. In all 8 patients, cytology of the pancreatic secretion obtained during endoscopic retrograde pancreatography (ERP) was positive, although no pancreatic tumor was detected by ERP, other examinations or intraoperative inspection. In these 8 patients, our method of intraoperative cytodiagnosis to locate occult neoplasms of the pancreas (Surgery 1992; 111: 294-300) was used (1). Using this method of cytodiagnosis, we were able to avoid total pancreatectomy in 6 patients (75%; 3 pancreatoduodenectomies and 3 caudal pancreatectomies), but not in the other 2 patients. Histopathological study of the resected specimens indicated that the extent of pancreatic resection was quite appropriate in all 8 patients. There were 6 minimally invasive carcinomas, one carcinoma in situ and one borderline lesion. Neither nodal involvement nor severe invasion was found on microscopic inspection, and all have been disease-free for 23 +/- 13 months after surgery. In the 6 patients with partial pancreatectomies, both postoperative quality of life and general health were good, with no insulin-dependent diabetes developing. Thus, our cytology-guided surgical technique is very useful not only for locating occult and potentially curable neoplasms, but also for avoiding blind resection of the entire pancreas, permitting better preservation of pancreatic endocrine function.

Aged↗

Reevaluation of the usefulness of serum free hydroxyproline as a parameter for assessing renal osteodystrophy.

Hydroxyproline (HYP) is an amino acid which is highly specific for bone collagen. Measurement of HYP provides an index of bone resorption, although the usefulness in this respect of the serum free HYP, which is the easiest HYP fraction to determine, has not yet been established. In the present study, the serum free HYP was measured using the method of Dabev et al., and the data were compared against other parameters of renal osteodystrophy (ROD). In comparison with values for the normal control group (n = 10), the serum free HYP was significantly elevated in the patient group with conservatively treated end-stage renal failure (n = 14) and in the patient group on chronic hemodialysis (n = 107), with the latter group showing the highest value. Also, in the group with radiographic evidence of bone resorption, the free HYP exhibited a significant elevation. Significant positive correlations were noted between the free HYP and both the parathyroid hormone (PTH) and alkaline phosphatase (Al-P) levels. When the subjects undergoing bone biopsy were divided according to their histological findings into an increased osteoid group and an increased osteoid + resorption group, the latter displayed a significantly higher free HYP value. In addition, the free HYP values were low in the group administered 1 alpha-OH-D3 and showing only slight bone resorption. These results suggest that since the free HYP closely reflects accelerated bone resorption in ROD and is easier to measure than non-protein-bound HYP, it can serve as a clinically useful index of ROD.

Adult↗

[Vasculitis-related acute abdomen in systemic lupus erythematosus--ultrasound appearances in lupus patients with intra-abdominal vasculitis].

Although an acute abdomen often occurs in lupus patients, definitive treatment is commonly delayed due to the difficulty in diagnosis. We performed an abdominal ultrasound (US) in two patients with severe abdominal pain and recognized mural thickenings of intestinal walls. In the first case high dose prednisone was given for severe abdominal pain, with subsequent perforation of sigmoid colon. Pathological specimens showed a thrombotic vasculitis in the mesenteric artery and arteriole of intestinal walls. In the second case physical examination elicited a rebound tenderness. An abdominal X-ray demonstrated a gasless ileus and US also showed marked thickening of intestinal walls, 16 mm in thickness. A CT scan revealed the same findings in the entire bowel. After high dose methylprednisolone was administered, her symptoms markedly improved. The mural thickenings disappeared within 10 days as seen by abdominal ultrasound examination. The US is very useful in order to make an early diagnosis of intestinal vasculitis, showing as edema (but non-specific) of intestinal wall and we can use it safely and repetitively without exposure to radiation, compared with other examinations, such as CT scan and gastrointestinal contrast study etc. The US is not only useful in diagnosis, but also helpful for follow up of patients after the initiation of treatment.

Abdomen↗

[Clinical experience of endopyelotomy].

From July 1986, percutaneous endopyelotomy was performed on a total of 12 patients (13 kidneys) including 8 males and 4 females with ureteropelvic junction (UPJ) obstruction. Of the 13 kidneys, 9 had primary UPJ obstruction and 4 had secondary UPJ obstruction. A rigid urethrotome (cold knife) was employed in 12 cases and a flexible electorotome (hot knife) in one case. A stent ureteral catheter was placed for 3 to 31 weeks after the procedure. The outcome was evaluated by radiography and urodynamic examinations. A successful outcome was obtained in 8 of 9 kidneys with primary UPJ obstruction and in 1 of 4 kidneys with secondary UPJ obstruction. These findings suggest that percutaneous endopyelotomy is useful in the treatment of primary UPJ obstruction.

Adolescent↗

Protection by muscimol against gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in spontaneously hypertensive rats.

The effects of prolonged administration of the gamma-aminobutyric acid receptor agonist muscimol on enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in spontaneously hypertensive rats (SHR), and on the norepinephrine concentration in the gastric wall and the labeling index of gastric mucosa were investigated. SHR and normotensive Wistar Kyoto (WKY) rats as controls were given a solution of MNNG (25 micrograms/ml) for 25 weeks and then i.p. injections of 0.5 mg/kg body weight of muscimol every other day. In control WKY rats, gastric cancers were found in 1 (7%) of 14 rats examined at week 52. In SHR treated with NaCl solution only, the incidence of gastric cancers was significantly increased to 50% compared with that in control WKY rats. However, treatment of SHR with muscimol significantly increased its incidence to 12% compared with the value in SHR treated with NaCl solution only. The norepinephrine concentration in the gastric wall and the labeling index of the gastric mucosa were significantly greater in SHR than in WKY rats. Prolonged administration of muscimol to SHR significantly reduced the norepinephrine concentration in the antral portion of the gastric wall or the labeling index of the antral epithelial cells. These findings indicate that long-term treatment of SHR with muscimol attenuated the enhancement of gastric carcinogenesis in SHR.

Analysis of Variance↗

Cytologic examination of pure pancreatic juice in the diagnosis of pancreatic carcinoma. The endoscopic retrograde intraductal catheter aspiration cytologic technique.

BACKGROUND: Although cytologic examination of pure pancreatic juice obtained with a duodenofiberscope has been useful for the diagnosis of pancreatic carcinoma, the rate of false-negative results is reported to be high. To eliminate these false-negative results, the authors developed a new technique, endoscopic retrograde intraductal catheter aspiration cytology, especially for an accurate cytologic diagnosis of carcinoma of the body or tail of the pancreas. METHODS: The accuracy of conventional cytologic examination of pure pancreatic juice was assessed in 25 patients with pancreatic carcinoma, 29 patients with pancreatitis, and 52 control subjects. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a videoimaging duodenoscope after intravenous administration of secretin. The new endoscopic retrograde intraductal catheter aspiration technique was used in four patients with carcinoma of the body or tail of the pancreas and five patients with localized pancreatitis in whom a correct diagnosis was not made by previous cytologic examination of pure pancreatic juice. RESULTS: Positive cytologic findings were obtained in 76% of the patients with pancreatic carcinoma. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail. By the new technique, positive cytologic results were obtained in all of the patients with pancreatic carcinoma. This technique caused no severe complications. CONCLUSIONS: This procedure of endoscopic retrograde intraductal catheter aspiration cytology seems useful for diagnosis of pancreatic carcinoma.

Catheterization↗

Mucin gene expression in colonic tissues and cell lines.

Complementary DNA clones encoding four different mucin core peptides have been isolated. However, the expression of these mucin genes in the colon has not been systematically studied. The present investigation used Northern blot analysis to study the expression of MUC1, MUC2, MUC3, and MUC4 mRNA in paired normal and cancerous colonic tissues, and nine colon cancer cell lines. Results were correlated with the clinicopathological features of the tumors and with the immunohistochemical expression of several carbohydrate tumor-associated antigens that may reside on mucins. MUC1 mRNA was expressed in all colonic tissues, and levels in paired normal and cancer tissues were similar in most cases. MUC2 and MUC3 mRNAs were expressed in both normal and cancer tissues, but levels were often decreased in the cancers. MUC4 mRNA was present in normal mucosa with comparable or sometimes greater expression in cancers. There was no apparent correlation between the expression of any particular mucin gene or pattern of mucin genes and the site, stage, or histological type of tumor. In addition, the expression of mucin-associated carbohydrate antigens did not correlate with any individual mucin gene or group of mucin genes. In colon cancer cell lines all four MUC genes were expressed rather weakly or not at all. These results indicate that the human colon expresses a broad repertoire of mucin genes which are differentially regulated in malignancy. Whether this differential regulation of mucin genes affect the behavior of the tumor and results in the altered glycosylation commonly seen in these requires further investigation.

Aged↗

A prospective trial of early detection of pancreatic cancer by ultrasonographic examination combined with measurement of serum elastase 1.

The accuracy of ultrasonographic examination combined with measurement of elastase 1 levels for early detection of pancreatic cancer was evaluated prospectively. Abdominal ultrasonographic examination and measurement of serum elastase 1 levels were done within 2 weeks after the initial visit to the clinic in a total of 2098 patients older than 35 years of age with symptoms suggesting pancreatic disease. Those in which one or both of these examinations had abnormal results underwent additional tests such as endoscopic retrograde cholangiopancreatography and computed tomography. Of those with pancreatosonograms with abnormal results with or without abnormally high serum elastase 1 levels, 19 patients eventually were found to have pancreatic cancer. No patients with pancreatic cancer, a normal level of serum elastase 1, and a pancreatosonogram with normal results were found, but follow-up studies revealed one pancreatic cancer in 189 patients after technically unsatisfactory ultrasonographic examination. In 9 (45%) of the 20 cases detected in this study, the pancreatic cancers were resectable, and two (10%) were less than 2.0 cm in longest diameter. These findings indicate that this combined examination is useful for early detection of pancreatic cancer. However, no pancreatic cancer was found in patients with abnormally high serum elastase 1 levels without a pancreatosonogram with abnormal results. Moreover, a combination of ultrasonographic examination and measurement of the elastase 1 level did not raise the diagnostic accuracy over that of ultrasonographic examination alone. These findings indicate that ultrasonographic examination alone is useful in screening for early pancreatic cancer.

Adult↗

Effect of gamma-butyrolactone on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of gamma-butyrolactone (GBL) on inhibition by baclofen of gastric carcinogenesis was investigated in Wistar rats. In week 52, baclofen significantly decreased the incidence of gastric cancers. Concomitant treatment with GBL significantly increased gastric acid secretion but had no influence on the inhibition by baclofen of gastric carcinogenesis. This finding suggest that GBL significantly increased the sensitivity of gamma-aminobutyric acid (GABA) receptor to GABA mimetics in gastric acid secretion but not in the inhibitory effect of gastric carcinogenesis.

4-Butyrolactone↗

A new method of intraoperative cytodiagnosis for more precisely locating the occult neoplasms of the pancreas.

We have done endoscopic retrograde pancreatography-aspiration cytology for 81 consecutive patients in whom there had been neither pancreatic mass nor duct stenosis; cancer cells were detected in four cases (5%). This report reviews a new method of intraoperative cytodiagnosis, which was done for these four cases, to locate the original lesion of the cancer cells. This method involved dividing the pancreatic neck at a right angle to the main pancreatic duct. A catheter was then inserted in both the caudal and cranial ducts of Wirsung. With the aid of an intravenous injection of secretin, pure pancreatic secretions were collected separately and used for intraoperative cytodiagnosis. With this method, all four occult neoplasms of the pancreas were correctly identified as to whether they were located in the cranial, caudal, or both portions. In one case in which carcinoma in situ extended throughout the entire pancreas, total pancreatectomy had been indicated by the positive results obtained from both portions. Likewise, in the other three cases in which, the occult neoplasms were limited to the cranial or caudal pancreas, either a Whipple procedure (one case) or a caudal pancreatectomy (two cases) had been quite correctly indicated. Since this method is simple, safe, and reliable, it is beneficial to the patient with occult neoplasm, because it prevents blind resection of the entire pancreas without any fear of leaving the neoplastic lesion behind.

Adenocarcinoma↗

Enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats fed a low-protein diet.

The effects of ad libitum feeding of synthetic, low-protein diets on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats. Rats were fed synthetic diets of equal calorie content containing 25% casein (normal protein diet), 10% casein (low-protein diet), or 5% casein (very-low-protein diet) after treatment with N-methyl-N'-nitro-N-nitrosoguanidine p.o. for 25 weeks. Administration p.o. of a very-low-protein diet containing 5% casein resulted in a significant increase in the incidence and number of gastric cancers in experimental Week 52. However, it did not affect the histology of the cancers. The very-low-protein diet also caused a significant increase in tissue norepinephrine concentration of the antral portion of the gastric wall and in the labeling index of the antral epithelial cells. These findings indicate that a very-low-protein diet enhances gastric carcinogenesis and that this effect may be related to its effect in increasing norepinephrine in the gastric wall and stimulating proliferation of antral epithelial cells.

Animals↗

Inhibition by putrescine of experimental carcinogenesis in rat colon induced by azoxymethane.

The effects of putrescine on the incidence and number of colon tumors induced by azoxymethane, and on the labelling index and the activity of ornithine decarboxylase (ODC) in the colon mucosa were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of azoxymethane and i.p. injections of 300 mumol/kg body weight of putrescine every 2 days until the end of the experiment at week 40. This prolonged treatment with putrescine significantly reduced the incidence and number of colon tumors. Administration of putrescine also significantly decreased the labelling index and the ODC activity in the colon mucosa during, but not after, treatment with the carcinogen. These last effects may be related to the action of putrescine in inhibiting the development of colonic tumors.

Adenocarcinoma↗

Enhancement by sulpiride of the inhibitory effects of cysteamine on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of sulpiride on cysteamine inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the BUdR labelling index of gastric mucosa were investigated in inbred Wistar rats. After 25 weeks of oral treatment with MNNG, rats received one of the following alternate-day injections: cysteamine (2 doses), cysteamine (2 doses) plus sulpiride or sulpiride. At week 52, prolonged administration of cysteamine significantly reduced the incidence of adenocarcinomas of the glandular stomach. Cysteamine at low dose had no effect on the incidence of gastric cancers, but a combination of low-dose cysteamine and sulpiride caused a significantly greater reduction in the incidence of gastric cancers. Administration of sulpiride alone had no influence on gastric carcinogenesis. The labelling index of the antral mucosa was significantly lower in rats treated with high but not low doses of cysteamine. However, a combination of low-dose cysteamine and sulpiride significantly decreased the labelling index of the antral mucosa. Our findings indicate that cysteamine suppressed gastric carcinogenesis and that sulpiride enhanced this inhibition. Because sulpiride is a dopamine antagonist, these findings also indicate that dopamine may play an important role in cysteamine inhibition of gastric carcinogenesis.

Animals↗

Several testis-expressed genes in the mouse t-complex have expression differences between wild-type and t-mutant mice.

The t-complex of the mouse occupies the proximal half of chromosome 17 and contains genes which have profound effects on spermatogenesis. Mutations of several loci in the t-complex appear to interact to cause male sterility or transmission ratio distortion (TRD). By cDNA screening or chromosomal walking we have identified seven genes, which are expressed in the germ cells of testis and map to various regions of the t-complex. These genes were named t-complex testis-expressed (Tctex) genes. An analysis of their expression patterns in testes from +/+, +/t, and t/t mice was done by in situ hybridization and by northern blotting. Six genes begin to be expressed at the pachytene stage: Three of them are more abundant at pachytene stage, while three others are more abundant at postmeiotic stages. One gene is expressed at all the stages of spermatogenesis. Interestingly, four Tctex genes show differences in the amount of transcript between wild-type and t-mutant testes. The chromosomal location and expression pattern imply that Tctex genes might be candidate genes for sterility or TRD.

Animals↗

Molecular organization of the D-Qa region of t-haplotypes suggests that recombination is an important mechanism for generating genetic diversity of the major histocompatibility complex.

We have determined the molecular maps of the H-2D and Qa regions of the t-complex haplotypes t12 and tw5 by chromosomal walking. Analysis with class I probes and other probes unique to the H-2D:Qa subregion indicates that the class I gene organization of t12 is: D1-D2-Q1-Q2-Q3-Qx-Q4-Q5-Q10, while that of tw5 is: D1-D2-Q1-Q2-Q4-Q5-Q10. Thus, the absence of the Q6-Q9 genes suggested previously in t-haplotypes was confirmed. A comparison of the molecular maps of the t12 and tw5 chromosomes revealed an extremely mosaic pattern of diversity: The regions between D1 and D2, and between Q4 and Q10, are very similar in both chromosomes. However, their Q1 to Q3 regions are strikingly different. Further comparisons of wild-type chromosomes and additional t-haplotypes by molecular mapping and genomic Southern blot hybridization with probes to the Q1-Q3 region showed a high level of polymorphism among both wild-type chromosomes and among t-haplotypes. The characteristics of the polymorphisms suggest that recombination may play an important role in generating this genetic diversity. Furthermore, recombination between wild-type and t-haplotype chromosomes may be involved.

Animals↗