Biomedical subjects

H Uehara

Publications and source records attributed to H Uehara.

At least 73 records · Page 4Linked to original sources

PubMed1998

"Facilitated" amino acid transport is upregulated in brain tumors.

The goal of this study was to determine the magnitude of "facilitated" amino acid transport across tumor and brain capillaries and to evaluate whether amino acid transporter expression is "upregulated" in tumor vessels compared to capillaries in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non-metabolized [14C]-labeled amino acid, and a reference molecule for passive vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga-DTPA), were used in these studies. Two experimental rat gliomas were studied (C6 and RG2). Brain tissue was rapidly processed for double label quantitative autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA. Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA, microL/min/g) produced from the autoradiograms and the histology were obtained from the same tissue section. These three images were registered in an image array processor; regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images to obtain mean values. The facilitated component of ACPC transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and paired comparisons between tumor and contralateral brain were performed. ACPC flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this difference was largely (approximately 90%) due to facilitated ACPC transport. Substantially higher K1ACPC values compared to corresponding K1DTPA values were also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values for RG2 gliomas was not significantly higher than that of contralateral cortex, although a approximately 2-fold difference in facilitated transport is obtained after normalization for differences in capillary surface area between RG2 tumors and contralateral cortex. K1ACPC, deltaK1ACPC, and K DTPA were directly related to tumor cell density, were higher in regions of "impending" necrosis, and the tumor/contralateral brain ACPC radio-activity ratios (0 to 10 minutes) were very similar to that obtained with 0 to 60 minutes experiments. These results indicate that facilitated transport of ACPC is upregulated across C6 and RG2 glioma capillaries, and that tumors can induce upregulation of amino acid transporter expression in their supporting vasculature. They also suggest that early imaging (e.g., 0 to 20 minutes) with radiolabeled amino acids in a clinical setting may be optimal for defining brain tumors.

Amino Acids↗

PubMed1998

Adenosarcoma of the uterine cervix presenting as a cervical polyp.

A case of adenosarcoma arising from the uterine cervix of a 55-year-old female who complained of vaginal discharge is reported. A polyp, 6 x 2 x 1.5 cm in size, identified in the cervical canal was clinically diagnosed as benign cervical polyp and resected. Histologically, the polyp was composed of benign epithelial components and sarcomatous stroma wherein periglandular hypercellularity and some mitoses including atypical ones were noted. Immunohistochemically, stromal cells were positive for muscle-type actins, desmin and estrogen receptor. Adenosarcoma is a rare, biphasic tumor of the uterus and usually presents as a polypoid mass in the endometrial cavity. When they arise from the cervix, adenosarcomas may be confused with benign cervical polyps clinically and pathologically. As the former often recurs, microscopic differentiation is crucial for further treatment.

Actins↗

PubMed1998

Basic studies on hydroxy apatite cement: I. Setting reaction.

Self-setting cements, alpha D-Cement and alpha DT-Cement, were prepared. They consisted of only the calcium phosphates alpha-TCP, TTCP and DCPA. These cements reacted and hardened in a moist environment at 37 degrees C. The powder X-ray diffraction patterns were taken to examine the conversion of their reactions as a function of time. The cements reacted and produced hydroxyapatite. The optimum powder/liquid ratio of alpha D-Cement was 2.0 and that of alpha DT-Cement was 1.8. The initial setting time of alpha D-Cement was 87.5 m and that of alpha DT-Cement was 107.5 m. The component and the product of these cements are calcium phosphates which are the putative minerals in teeth and bones. Therefore, these cements are useful for oral surgery as bone-filling materials.

Bone Substitutes↗

PubMed1998

Hepatosplenic gamma delta T-cell lymphoma associated with hepatitis B virus infection.

Hepatitis B virus (HBV) infection has been implicated in the development of hepatocellular and hematopoietic malignancies. We describe a patient with chronic hepatitis B who developed hepatosplenic gamma delta T-cell lymphoma. A 45-year-old woman presented with marked hepatosplenomegaly and hepatic failure during the course of chronic hepatitis B. Peripheral blood examination revealed 57% abnormal lymphoid cells which expressed the gamma delta T-cell receptor. The cytogenetic analysis of tumor cells showed an abnormal karyotype; 47, XX, -13, +2mar in all 20 metaphases examined. A clonal rearrangement of the T-cell receptor genes was demonstrated by Southern blot analysis, showing monoclonal expansion of tumor cells. A liver biopsy specimen showed fibrosis of the portal areas and sinusoidal infiltration of tumor cells. HBV infection was documented by the presence of IgG anti-HBc and anti-HBs antibodies in serum. Although HBV-DNA was not detected in tumor cells by polymerase chain reaction analysis, there is a possibility that proliferation of gamma delta T cells in response to HBV infection played a role in the pathogenesis of hepatosplenic gamma delta T-cell lymphoma.

Chronic Disease↗

PubMed1998

[A measure to continue intra-arterial infusion chemotherapy long-term for locally advanced pancreatic cancer].

For locally advanced non-resectable cancer of the pancreas, we have routinely performed intra-arterial chemotherapy: Each catheter is placed in the splenic artery and gastroduodenal artery during laparotomy, and a mixture of Methotrexate and Angiotensin-II is infused within 30 minutes. This treatment is repeated weekly at our outpatient clinic as long as possible. However, obstruction of the catheter or corresponding artery is the major cause of interruption of treatment. The present paper reports a case in which intra-arterial chemotherapy was possible by repeated catheterization for the catheter obstruction. A 54-year-old woman with non-resectable pancreatic cancer underwent catheter placement during laparotomy, but they became occluded one month later. Another catheter was placed into the common hepatic artery by the Seldinger method. After this catheter was occluded again, another catheter was placed into the inferior pancreaticoduodenal artery via the superior mesenteric artery by the Seldinger method. By repeating this catheter placement, we succeeded in continuing the intra-arterial chemotherapy, and the patient has remained alive (30 postoperative months) without losing her quality of life.

Angiotensin II↗

PubMed1997

Hyperinsulinemia but no diabetes in transgenic mice homozygously expressing the tyrosine kinase-deficient human insulin receptor.

We generated transgenic mice homozygous for the tyrosine kinase-deficient human insulin receptor (hIRK1030M(+/+)) under control of the insulin receptor promoter. Similar growth patterns and results of glucose tolerance tests were observed among normal, heterozygous, and homozygous mice. Insulin tolerance test indicated no significant difference in the hypoglycemic response to insulin among the three genotypes. However, the serum insulin levels of the homozygous mice before and after glucose loading (201.42 +/- 58.15 pg/ml to 578.57 +/- 49.03 pg/ml) were significantly higher than in the control mice (100.92 +/- 19.55 pg/ml to 356.36 +/- 55.08 pg/ml; p < 0.01 and p < 0.01, respectively) and heterozygous mice (74.46 +/- 18.55 pg/ml to 352.33 +/- 52.43 pg/ml; p < 0.005 and p < 0.01, respectively). Immunohistological evidence of pancreatic islets showed no significant difference among the three genotypes. Taken together, these results suggest that the tyrosine kinase-deficient insulin receptor causes hyperinsulinemia but not diabetes in these homozygous transgenic mice.

Animals↗

PubMed1997

Ornithine decarboxylase inhibitor lessens the rat gastric carcinogenesis enhancement caused by tyrosine methyl ester.

The effects of combined administration of a catecholamine precursor, tyrosine methyl ester (TME), and an ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the norepinephrine (NE) concentration and ODC activity of the gastric wall, and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received s.c. injections of TME, 512 mg/kg body weight, every other day and drinking water with or without 2.5 g/l of DAP after 25 weeks of oral administration of MNNG. At week 52, administration of TME resulted in significant increases in the incidence of gastric cancers, in the NE concentration and the ODC activity of the antral portion of the gastric wall, and in the labeling index of antral epithelial cells. Administration of both TME and DAP significantly reduced the enhancements by TME of gastric carcinogenesis, NE concentration and ODC activity of the antral wall, and the labeling index of the antral mucosa. Our results suggest that ODC inhibition lessens enhancement by TME of gastric carcinogenesis and that the enhancement by TME of gastric carcinogenesis is mediated in part by polyamine biosynthesis.

Animals↗

PubMed1997

d-Limonene inhibits N-nitrosobis(2-oxopropyl)amine induced hamster pancreatic carcinogenesis.

The effect of d-limonene on pancreatic carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine (BOP) was investigated in Syrian golden hamsters. During and after 5 weekly injections of BOP, each hamster was fed diet containing d-limonene. In week 26, quantitative histological analysis showed that prolonged treatment with d-limonene significantly reduced the number of pancreatic carcinomas. Administration of d-limonene did not cause a significant increase in the apoptotic index, but caused a significant decrease in the BrdU labeling index of carcinoma. These findings indicate that d-limonene inhibits the development of pancreatic carcinoma not by enhancing tumor cell loss through apoptosis, but rather by inhibiting cell proliferation.

Animals↗

PubMed1997

Reduction in NaCl-enhanced gastric carcinogenesis in rats fed a high-protein diet.

The effect of a purified, high protein diet on enhanced gastric carcinogenesis induced by oral administration of NaCl was investigated in Wistar rats. Rats were fed on a purified diet with an equalized caloric content, containing 8% NaCl and 25% casein (normal protein diet), or 50% casein (high protein diet) after oral treatment with N-methyl-N'-nitro-N-nitrosoguanidine for 25 weeks. In week 52, oral administration of NaCl had significantly increased the incidence and size of gastric cancer in rats fed a normal protein diet. However, NaCl had no significant effect on gastric carcinogenesis in rats fed a high protein diet. Oral administration of NaCl also caused a significant increase in tissue norepinephrine concentrations in the antral portion of the gastric wall, and increased the labeling indices of the antral epithelial cells of rats fed on a normal protein diet. However, in rats fed a high protein diet, administration of NaCl had no significant influence on these two parameters. These findings indicate that a high protein diet attenuates enhanced gastric carcinogenesis induced by the administration of NaCl, and that this effect may be related to its ability to decrease norepinephrine concentrations in the gastric wall, which subsequently decreases the proliferation of antral epithelial cells.

Animals↗

PubMed1997

Enhancement by ethyl alcohol of experimental hepatocarcinogenesis induced by N-nitrosomorpholine.

The effects of ethyl alcohol (EtOH) during or after treatment with N-nitrosomorpholine (NNM) on hepatocarcinogenesis, ornithine decarboxylase (ODC) activity and the labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received i.p. injections of 1 g EtOH/kg body weight every other day during or after treatment with NNM. Pre-neoplastic and neoplastic lesions staining positively for glutathione-S-transferase, placental type (GST-P), were examined immunohistochemically. At the end of experiment at week 16, administration of EtOH after NNM treatment had no significant effect on the number and size of GST-P-positive hepatic lesions, whereas administration of EtOH during NNM treatment significantly increased the number and percentage area but not the mean area of GST-P-positive hepatic lesions. EtOH caused significant increases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and the adjacent hepatocytes after the cessation of EtOH administration but not during EtOH treatment. Our findings indicate that EtOH enhances hepatocarcinogenesis and suggest that this effect may be closely related to the increases in ODC activity and cell proliferation in enzyme-altered lesions and the adjacent liver after EtOH treatment.

Animals↗

PubMed1997

Diagnosis of carcinoma in situ of the pancreas by peroral pancreatoscopy and pancreatoscopic cytology.

BACKGROUND: Most pancreatic carcinomas are unresectable at the time of diagnosis, but recently the diagnosis of carcinoma in situ of the pancreas has become possible. This diagnosis can be made by the detection of cancer cells in pancreatic juice and the radiographically demonstrated lack of a mass lesion. It has greatly improved the effectiveness of surgery. Carcinoma in situ remains within the pancreatic ductal epithelium and has not yet invaded the parenchyma. However, it has often been difficult to locate carcinoma in situ by conventional diagnostic methods, such as ultrasonography, endoscopic ultrasonography, computed tomography, and endoscopic retrograde pancreatography. METHODS: Peroral pancreatoscopy and a new method of cytodiagnosis, pancreatoscopic cytology, were used to analyze 11 patients with carcinoma in situ of the pancreas, 10 with disease in the main duct of the pancreas and 1 with disease in the branch ducts. The results of pancreatoscopic cytology were compared with those of conventional pancreatic juice cytology. RESULTS: Under peroral pancreatoscopy, carcinoma in situ of the pancreas in the main duct appeared as papillary mucosa, irregular mucosa, or nodular mucosa. Using pancreatoscopic cytology, cancer cells were obtained from all the lesions, allowing a more thorough analysis than pancreatic juice cytology. CONCLUSIONS: Peroral pancreatoscopy and pancreatoscopic cytology are useful for locating and diagnosing carcinoma in situ of the pancreas.

Aged↗

PubMed1997

Enhancement by monochloramine of the development of gastric cancers in rats: a possible mechanism of Helicobacter pylori-associated gastric carcinogenesis.

The effects of cytotoxic monochloramine on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats. After oral administration of drinking water containing the carcinogen and regular chow pellets for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without s.c. injection of taurine, until the end of the experiment in week 52. Treatment with both ammonium acetate and sodium hypochlorite significantly increased the incidence of gastric cancers in week 52, while the concomitant use of taurine with ammonium acetate and sodium hypochlorite significantly attenuated the enhanced gastric carcinogenesis. Spectrophotometric examinations revealed that taurine scavenged monochloramine. These findings suggest that Helicobacter pylori-associated gastric carcinogenesis may be mediated by monochloramine.

Animals↗

PubMed1997

Inhibition by ginsenoside Rg3 of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats.

The effects of concomitant use of bombesin and ginsenoside Rg3 on the incidence of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane were investigated in male inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 microg/kg body weight) every other day, and from week 20, s.c. injections of ginsenoside Rg3 (2.5 or 5.0 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of a higher dose of ginsenoside Rg3 with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth pattern, labeling and apoptotic indices and tumor vascularity of intestinal cancers, it significantly decreased the incidence of cancer metastasis. These findings indicate that ginsenoside Rg3 inhibits cancer metastasis through activities that do not affect the growth or vascularity of intestinal cancers.

Adenocarcinoma↗

PubMed1997

Usefulness of simple endoscopic aspiration cytology of pancreatic juice for diagnosis of early pancreatic neoplasm. A prospective study.

For detection of early cancer of the pancreas, endoscopic aspiration cytology of pancreatic juice without endoscopic retrograde pancreatography was performed in 64 consecutive outpatients who had symptoms or findings that suggested pancreatic disease. Patients with positive or suspicious cytologic results or abnormal US findings were admitted and underwent detailed examinations. Positive and suspicious cytologic results were obtained in 2 and 10 patients, respectively. Of those with positive and suspicious cytologic results, two, and one patient, respectively, were ultimately found to have pancreatic neoplasms. Of these three resected specimens, one was in situ carcinoma and two presented marked atypia. All patients were alive with no evidence of recurrence. No further cases of pancreatic neoplasm were found. Complications from the procedure did not develop in any patient. This technique is useful in the diagnosis of early neoplasms of the pancreas, because it is simple and safe to perform for outpatients.

Aged↗

PubMed1997

Low diastolic blood pressure, hypoalbuminemia, and risk of death in a cohort of chronic hemodialysis patients.

In a previous report, we showed that nutritional status and especially serum albumin had great predictive value for death in chronic hemodialysis patients, whereas blood pressure did not. In the present study, we analyzed the causes of death in consideration of the relationship between serum albumin and blood pressure. A total of 1,243 Okinawan patients (719 males, 524 females) undergoing hemodialysis in January 1991 were followed up through the end of 1995. Three hundred forty-two of the patients died, 45 received transplants, and 12 were transferred by the end of the follow-up period. The total duration of observation was 5,110.3 patient-years. Blood pressure as well as clinical and laboratory variables were determined immediately prior to the first dialysis session in January 1991. The crude death rate was 40.0% when the diastolic blood pressure (DBP) <70 mm Hg, 35.0% at 70 to 79 mm Hg, 25.0% at 80 to 89 mm Hg, 25.0% at 90 to 99 mm Hg, and 13.0% at >100 mm Hg. The death rate showed an inverse correlation with DBP. DBP showed a significant positive correlation with serum albumin (r = 0.137, P < 0.001) and age (r = -0.325, P < 0.0001). The adjusted odds ratio (95% confidence interval) of death was 0.84 (0.71 to 0.99) with 10 mm Hg increments in DBP when the reference DBP was less than 69 mm Hg. Low DBP may be a manifestation of malnutrition and/or cardiovascular disease in chronic hemodialysis patients. Target DBP levels may be higher levels in chronic hemodialysis patients than the general population.

Blood Pressure↗

PubMed1997

Imaging experimental brain tumors with 1-aminocyclopentane carboxylic acid and alpha-aminoisobutyric acid: comparison to fluorodeoxyglucose and diethylenetriaminepentaacetic acid in morphologically defined tumor regions.

The goal of this study was to evaluate the differences and define the advantages of imaging experimental brain tumors in rats with two nonmetabolized amino acids, 1-aminocyclopentane carboxylic (ACPC) acid and alpha-aminoisobutyric (AIB) acid compared with imaging with fluorodeoxyglucose (FDG) or the gallium-diethylenetriaminepentaacetic acid chelate (Ga-DTPA). 1-aminocyclopentane carboxylic acid, AIB, and FDG autoradiograms were obtained 60 minutes after intravenous injection to simulate positron emission tomography (PET) imaging, whereas the Ga-DTPA autoradiograms were obtained 5 or 10 minutes after injection to simulate gadolinium (Gd)-DTPA-enhanced magnetic resonance (MR) images. Three experimental tumors were studied (C6, RG2, and Walker 256) to provide a range of tumor types. Triple-label quantitative autoradiography was performed, and parametric images of the apparent distribution volume (Va, mL/g) for ACPC or AIB, relative glucose metabolism (R, micromol/100 g/min), vascular permeability to Ga-DTPA (K1, microL/min/g), and histology were obtained from the same tissue section. The four images were registered in an image array processor, and regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images. A comparative analysis of all measured values was performed. The location and morphologic characteristics of the tumor had an effect on the images and measurements of Va, R, and K1. Meningeal extensions of all three tumors consistently had the highest amino acid uptake (Va) and vascular permeability (K1) values, and subcortical portions of the tumors usually had the lowest values. Va and R (FDG) values generally were higher in tumor regions with high-cell density and lower in regions with low-cell density. Tumor areas identified as "impending" necrosis on morphologic criteria consistently had high R values, but little or no change in Va or K1. Tumor necrosis was seen consistently only in the larger Walker 256 tumors; low values of R and Va for AIB (less for ACPC) were measured in the necrotic-appearing regions, whereas K1 was not different from the mean tumor value. The highest correlations were observed between vascular permeability (K1 for Ga-DTPA) and Va for AIB in all three tumors; little or no correlation between vascular permeability and R was observed. The advantages of ACPC and AIB imaging were most convincingly demonstrated in C6 gliomas and in Walker 256 tumors. 1-aminocyclopentane was substantially better than FDG or Ga-DTPA for identifying tumor infiltration of adjacent brain tissue beyond the macroscopic border of the tumor; ACPC also may be useful for identifying low-grade tumors with an intact blood-brain barrier. Contrast-enhancing regions of the tumors were visualized more clearly with AIB than with FDG or Ga-DTPA; viable and necrotic-appearing tumor regions could be distinguished more readily with AIB than with FDG. [11C]-labeled ACPC and AIB are likely to have similar advantages for imaging human brain tumors with PET.

Aminoisobutyric Acids↗

PubMed1997

Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) stimulate interleukin-6 production through the third subtype of PACAP/VIP receptor in rat bone marrow-derived stromal cells.

Regulation of Interleukin-6 (IL-6) production in bone marrow (BM)-derived stromal cells by neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), was examined. Both forms of PACAP, PACAP-27 and PACAP-38, as well as VIP significantly increased IL-6 production by rat BM-derived stromal cells at physiological concentrations ranging from 10(-10)-10(-8) M. The three related peptides (PACAP-27, -38, and VIP) stimulated the production of both cAMP and inositol 1,4,5-trisphosphate (IP3) in rat BM-derived stromal cells with similar 50% effective concentrations. The stimulatory potency of the three related peptides for the production of IL-6, cAMP, and IP3 was almost consistent, suggesting that the dual signaling transduction pathways may be involved in PACAP/VIP-induced IL-6 production in rat BM-derived stromal cells. The messenger RNA (mRNA) for the third subtype of PACAP receptor (PVR3) was found to be abundantly expressed in both BM-derived stromal cells and the BM tissue, whereas little of the mRNA for type 1 (PVR1) nor type 2 (PVR2) was detected. Furthermore, the mRNAs for PACAP and VIP were detected in the BM tissue, suggesting that both PACAP/VIP and PVR3 are synthesized in vivo in the BM. The results shown in this paper suggest that PACAP/VIP and their receptor play an important role in the IL-6 production and perhaps in the hematopoiesis in the BM.

Animals↗

PubMed1997

L-Myc overexpression and detection of auto-antibodies against L-Myc in both the serum and pleural effusion from a patient with non-small cell lung cancer.

Non-small cell lung cancer patient was found to have auto-antibodies against L-Myc in both the serum and pleural effusion. The titer of anti-L-Myc antibodies was higher in the pleural effusion than in the serum. Overexpression of L-Myc without DNA amplification was observed in the tumor cells. L-Myc antigen was not detected in either the serum or the pleural effusion. Anti-nuclear antibodies were also detected in both the serum and pleural effusion, although this patient did not have collagen-vascular disease.

Aged↗