Biomedical subjects

Hitoshi Kohno

Publications and source records attributed to Hitoshi Kohno.

34 records · Page 2Linked to original sources

PubMed2003

Sequential changes of connexin32 and connexin26 in ischemia-reperfusion of the liver in rats.

Serial changes in expression of hepatic gap junction components, connexin32 and connexin26 expressions during ischemia (60 min)-reperfusion injury of the liver were evaluated by immunofluorescence staining and reverse transcription-polymerase chain reaction in rats. Hepatic tissue calcium content and liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase), were also examined. Connexin expressions were down-regulated during ischemia and steeply increased during the early reperfusion period. This upsurge in connexin was coincided with the augmentation in tissue calcium content level. And the mRNA levels of connexin changed in parallel with the connexin protein level until 60 min after reperfusion. Since it is known that the changes in intracellular Ca(2+) concentration controls the intercellular communication via gap junction, these findings suggest the possibility that gap junction may play a definitive role in reperfusion injury of the liver. Further studies may be necessary to clarify the exact role of connexins in hepatic ischemia-reperfusion injury.

Journal Article↗

PubMed2003

Binding site of novel 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine herbicides in the D1 protein of Photosystem II.

A series of replacement experiments of [(14)C]-triazines, [(14)C]-atrazine and [7-(14)C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine, bound to thylakoids isolated from wild-type and atrazine-resistant Chenopodium album (lambsquarters) were conducted. Replacement experiments of [(14)C]-triazines bound to wild-type Chenopodium thylakoids with non-labeled atrazine and 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine were carried out, to elucidate whether benzylamino-1,3,5-triazines use the same binding niche as atrazine. [(14)C]-Atrazine and [7-(14)C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine bound to wild-type thylakoids were replaced by non-labeled 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine and non-labeled atrazine, respectively. The above two replacements showed mutual competition. To clarify further whether benzylamino-1,3,5-triazines bind at the D1-protein to amino acid residue(s) different from atrazine or not, experiments to replace [7-(14)C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazines bound to atrazine-resistant Chenopodium thylakoids by non-labeled atrazine, 2-(4-bromobenzylamino)-4-methyl-6-trifluoromethyl-1,3,5-triazine, DCMU and DNOC were carried out. Although the bound [7-(14)C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine was difficult to be replaced even with high concentrations of atrazine, [(14)C]-labeled 1,3,5-triazine was competitively replaced by non-labeled 2-(4-bromobenzylamino)-4-methyl-6-trifluoromethyl-1,3,5-triazine, DCMU or DNOC. Thus, 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine herbicides are considered to bind to the same niche at the D1 protein as atrazine, but use amino acid residue(s) different from those involved with atrazine binding.

Journal Article↗

PubMed2002

Serum endostatin predicts tumor vascularity in hepatocellular carcinoma.

BACKGROUND: Tumor angiogenesis is a strong prognostic factor in patients with hepatocellular carcinoma (HCC). However, to the authors' knowledge, details regarding the serum levels of proangiogenic and antiangiogenic growth factors controlling this process are not yet known. METHODS: Serum endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) levels were measured by the enzyme immunoassay method in prospectively collected samples from 33 HCC patients who had received no preoperative therapy. The angiogenic score (AS) and endostatin localization were evaluated using immunohistochemistry. RESULTS: Significant decreases in serum endostatin (P = 0.0007) and bFGF (P = 0.0004) were observed in postoperative samples compared with the preoperative values. A very strong direct correlation was noted between VEGF and endostatin (P < 0.0001). Only the preoperative serum endostatin was found to have a significant (P = 0.0025) inverse correlation with the AS. Furthermore, the combined positivity for bFGF and VEGF and negativity for endostatin was found to have a significantly (P = 0.0069) positive correlation with AS. Significantly high levels of endostatin were noted in patients with trabecular-type tumors (P = 0.0446) and in patients with hepatitis B infection (P = 0.0183). The serum endostatin level was found to be significantly (P = 0.0166) higher in living patients and patients with high serum endostatin levels had a tendency (P = 0.0871) toward long survival. Tissue endostatin expression was found to have a direct correlation with the serum endostatin level (P = 0.0117). CONCLUSIONS: The measurement of serum endostatin can predict tumor vascularity and may serve as a promising tool in the antiangiogenic therapy for patients with HCC.

Carcinoma, Hepatocellular↗

PubMed2002

Impact of PTEN expression on the outcome of hepatitis C virus-positive cirrhotic hepatocellular carcinoma patients: possible relationship with COX II and inducible nitric oxide synthase.

PTEN, a novel tumor suppressor, functions as a regulator of both cell cycle progression and apoptosis. PTEN gene is frequently mutated or deleted in several malignancies including human hepatocellular carcinoma (HCC). The clinical significance and prognostic value of PTEN expression in HCC or in the surrounding non-cancerous parenchyma remain obscure. Using immunohistochemistry, we analyzed the PTEN protein expression in 46 tissue sections collected from surgically resected hepatitis C virus (HCV)-positive cirrhotic HCC patients. Although the surrounding normal liver tissue was strongly expressing PTEN in 42 cases (91.3%), the immunostaining intensity was low in 29 (63.1%) and high in 17 (36.9%) of the HCCs. Additionally a significant positive correlation was identified between low PTEN expression in the HCC and increased expression of iNOS and COX II in the surrounding liver. The overall survival was significantly longer for the HCC-patients with high PTEN expression than patients with low PTEN expression. Univariate analysis revealed PTEN expression as an independent prognostic factor for patients survival. By Western blot analysis we also found that the Akt/PKB signaling, which is negatively regulated by PTEN, was upregulated in the HCCs in comparison to its expression in the surrounding liver tissue. These results demonstrate that downregulation of PTEN in the tumor is an important step in HCV-positive cirrhotic hepatocarcinogenesis and might result in concomitant upregulation of iNOS and COX II in the surrounding liver in favor of tumor promotion.

Adult↗

PubMed2002

Association study of the NRAMP1 gene promoter polymorphism and early-onset type 1 diabetes.

Natural resistance-associated macrophage protein 1 (NRAMP1) has an important role in regulating macrophage functions that affect innate resistance as well as immune responses. We analyzed the microsatellite polymorphism in the promoter region of the human NRAMP1 gene in 206 type 1 diabetes patients and 200 normal children to determine whether this polymorphism might be associated with type 1 diabetes in the Japanese population. The frequency of allele 2 (180 bp) of the promoter microsatellite polymorphism of the NRAMP1gene was slightly lower in the early-onset population (2-10 years of age) of type 1 diabetes patients than in controls, although the difference did not reach statistical significance. The association study of the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene, located near the NRAMP1 gene, and type 1 diabetes showed that the CTLA-4 gene significantly contributed to the development of type 1 diabetes, whereas NRAMP1 had an additional effect on the onset of type 1 diabetes in the young population.

Abatacept↗

PubMed2002

Esophageal cancer patients surviving 6 years after esophagectomy.

BACKGROUND: Esophageal cancer is one of the most malignant tumors, with a dismal prognosis in spite of recent advances in early diagnosis and extended lymphadenectomy. These patients need to be stratified according to prognostic variables for precise identification of high-risk group. MATERIAL AND METHODS: Seventy-six patients with esophageal carcinoma were uniformly treated with curative intent between 1980 and 1992 with at least 6 years follow-up. Results and prognostic factors of long-term survival were analyzed by univariate and multivariate analyses. RESULTS: Thirty patients (39.5%) survived 6 years, and the remaining 46 patients died within 6 years: recurrent esophageal cancer in 27 and causes unrelated to esophageal cancer in 19. The 1-, 2-, 3-, and 6-year overall survival rates in all 76 patients were 77.6%, 57.9%, 53.9%, and 39.5%, respectively. The factors influencing survival rate verified by univariate analysis were Borrmann classification (0, 1 vs. 2, 3), size of tumor (< or =3.0 vs. >3.0 cm), depth of invasion (T1, 2 vs. T3, 4), pN category (pN0 vs. pN1), number of lymph node metastasis (< or =4vs. >4), metastatic lymph node ratio (< or =0.1 vs. >0.1), time of operation (< or =480 vs. >480 min), and amount of perioperative blood transfusion given (< or =2 vs. >2 U). Among the significant variables independent prognostic factors for survival determined by multivariate analysis were metastatic lymph node ratio and amount of blood transfusion. CONCLUSIONS: A significant number of patients can thus apparently be cured of esophageal carcinoma by extensive resection. Patients with many metastatic lymph nodes and much blood transfusion, on the other hand, should receive appropriate treatment against such esophageal carcinoma.

Aged↗

PubMed2002

The prognostic significance of lymph node size in patients with squamous esophageal cancer.

BACKGROUND: The prognosis of patients with esophageal cancer remains dismal, and their care poses a great challenge of customizing therapeutic strategies for individual patients. Lymph node staging is still less than ideal in esophageal cancer patients. Therefore, we investigated a new approach to lymph node analysis. METHODS: One hundred eighty-seven patients curatively resected for squamous cell cancer of the esophagus were studied. The long diameter of the largest metastatic lymph node (MLN) was measured on a histopathologic slide and was considered as the MLN size. RESULTS: Patient survival decreased with each millimeter increment in MLN size. By using MLN size as the lymph node classification criterion, patients with MLN <10 mm had both a significantly better overall and cancer-specific survival than those with MLN >or=10 mm. Patients with fewer than four MLNs were separated into prognostic groups according to the MLN size. Among the several prognostic factors, MLN size remained the strongest independent predictor of survival by multivariate analysis. This nodal analysis allowed stratification of patients into four stages with distinctly different survivals. CONCLUSIONS: This approach supplements traditional nodal staging strategies and therefore has potential for guiding the development of treatment strategies in this carcinoma.

Aged↗

PubMed2002

Surgical treatment for locally advanced (T4) squamous cell carcinoma of the thoracic esophagus.

It is still difficult to decide on the treatment modalities for advanced esophageal carcinoma when the prognostic factors of T4 esophageal cancer are not fully understood. In this article, we report that among 71 patients with T4 thoracic esophageal cancer, 49 underwent esophagectomy, 9 had curative resection (R0 group), and 40 had palliative resection (R1/2 group). A total of 22 patients had palliative treatments: bypass in 5 (bypass group), gastrostomy or jejunostomy in 6 (stoma group), and radiochemotherapy alone in 11 (nonoperation group). Clinicopathologic characteristics were retrospectively investigated. Treatment-related deaths occurred in 7 (10%): none in R0, 3 (8%) in R1/2, 3 (60%) in bypass, and 1 (17%) in stoma group. Swallowing was improved in 50 (70%) patients: 9 (100%) in R0, 30 (75%) in R1/2, 1 (20%) in bypass, 3 (50%) in stoma, and 7 (64%) in the nonoperation group. One-, two-, and three-year overall survival rates were 56%, 22%, and 22% in the R0 group and 35%, 19% and 6% in the R1/2 group, respectively (p = 0.19). In the bypass, stoma, and nonoperation groups, none survived 1.6 years. The factors influencing the survival rate of the 49 patients undergoing esophagectomy were grade of lymph node metastasis, amount of perioperative blood transfusion, lymph vessel, and blood vessel invasion. Among these, independent prognostic factors for survival were amount of blood transfusion (-6 units vs. -7 units, p <0.0001) and grade of lymph node metastasis [none- or peritumoral [lymph nodes adjacent to the main tumor or at a nearby location (<3 cm) from the tumor] metastasis vs. more distant metastasis [lymph nodes at a distant location (> 3 cm)], p = 0.016]. Bypass and stoma operation neither prolonged the survival nor improved the difficulty of swallowing compared with radiochemotherapy alone. Esophagectomy can achieve the best improvement of swallowing and the longest survival with an acceptable mortality rate. Esophageal carcinoma patients with T4 disease and distinct metastasis in the lymph nodes at a distant location (>3 cm) from the primary tumor may not benefit from an esophageal resection.

Adult↗

PubMed2002

Changes in adiposity and excess body weight correlate with growth responses but not with decreases in low-density lipoprotein cholesterol levels during GH treatment in GH-deficient children.

BACKGROUND AND AIMS: GH has profound effects on body composition and lipid metabolism in children as well as in adults. The relationship between such metabolic effects and the growth-promoting effects of GH has not been studied thoroughly in children with GH deficiency. This prospective study was designed to determine the relationship between growth and lipid metabolism during long-term GH treatment. PATIENTS AND METHODS: Twenty-two boys with idiopathic GH deficiency were studied. Height, per cent overweight (%OW), per cent body fat (%BF) and serum low-density lipoprotein (LDL) cholesterol levels were determined every 6 months during 3 years of GH treatment. RESULTS: After 3 years of GH treatment, the mean height SD score had increased significantly from -2.70 SD to -1.59 SD (P < 0.0001), while the mean %OW and LDL cholesterol level had decreased significantly from 7.0% to 1.3% (P < 0.0001) and from 2.69 mmol/l to 2.04 mmol/l (P < 0.0001), respectively. The mean %BF fell significantly from 15.5% to 11.1% during the first 6 months of GH treatment (P < 0.0001). The 6-month reduction in %BF correlated significantly with the 3-year increase in height SD score (r = -0.58, P = 0.008). The decrease in %OW also correlated negatively with the change in height SD score (r = -0.48, P = 0.03). However, there was no correlation between the changes in LDL cholesterol levels and those in %BF, %OW or height SD score. CONCLUSION: We conclude that the growth-promoting effects of GH correlate significantly with the reductions in %BF and %OW but not with the decrease in LDL cholesterol level in children with GH deficiency. The changes in LDL cholesterol did not correlate with any of the changes in body composition parameters, suggesting that the various actions of GH may have different mechanisms of regulation.

Adipose Tissue↗

PubMed2002

Prognosis of patients with T2N0 tumors in the alimentary tract: should they be considered as early cancers?

BACKGROUND: T1N0 tumor of the alimentary tract has an excellent long-term prognosis, however, the prognosis of T2N0 tumor has not been uniformly elucidated. MATERIAL AND METHODS: Between February 1981 and April 2000, 75, 424 and 327 patients with node-negative esophageal, gastric and colorectal carcinomas, respectively, underwent curative resection and were included in this study. Long-term prognosis of those node-negative patients stratified by the T-stage were evaluated retrospectively. RESULTS: The 5-year survival rates of patients with T1N0 and T2N0 esophageal tumors were 95.7 and 93.3%, respectively, however those with T3N0 tumor was only 47.6% (p < 0.01). Similarly, the 5-year survival rates of gastric cancer patients with T1-2N0 tumors was 100%, however those with T3N0 and T4N0 tumors were 55.6 and 44.4%, respectively (p < 0.01). The 5-year survival rates of colorectal cancer patients with T1N0 and T2N0 tumors were 97.3 and 97.5%, respectively. In contrast, those with T3N0 and T4N0 tumors were 78.6 and 58.3%, respectively (p < 0.05, T1N0, T2N0 vs. T3N0; p < 0.001, vs. T4N0). CONCLUSION: Patients with T2N0 tumors have an excellent long-term prognosis like T1N0 tumors and both categories could be classified as early cancer in the alimentary tract cancers.

Adenocarcinoma↗

PubMed2002

A case of growth hormone and gonadotropin deficiency associated with unilateral anophthalmia, microphallus, cryptorchidism, and mental retardation.

We report a rare case of growth hormone and gonadotropin deficiency associated with dysmorphic features. A 16-year-old boy had left anophthalmia, microphallus, bilateral cryptorchidism, and mental retardation. His chromosomal karyotype was normal, 46, XY. Endocrinological studies revealed growth hormone and gonadotropin deficiency, attributed to hypothalamic dysfunction. Magnetic resonance imaging scan of the head showed a hypoplastic pituitary gland, decreased high intensity signals in the pituitary posterior lobe, absence of the left eye, and a hypoplastic left optic nerve with no abnormality of the pituitary stalk, corpus callosum, or septum pellucidum. Although not completely consistent with the features of septo-optic dysplasia (SOD), his condition was considered within the spectrum of SOD. Despite similarities to the Hesx1 knockout mouse, a model of human SOD, mutation analyses revealed no mutations or polymorphisms in coding regions of any exons or intron-exon boundaries of the HESX1 gene. Further genetic studies of this patient may improve understanding of molecular mechanisms involved in pituitary development.

Adolescent↗

PubMed2002

COX-2 - a target for preventing hepatic carcinoma?

Hepatocellular carcinoma (HCC) is one of the most common reasons for malignancy-related death in Africa and Asia and is still recognised as the leading cancer in men in Taiwan. Despite enthusiastic efforts in early diagnosis, aggressive surgical treatment and application of additional nonoperative modalities, its prognosis is still dismal. This emphasises the necessity to develop new measures and strategies for its prevention. Inducible cyclooxygenease 2 (COX-2) is an immediate-early (IE) response gene and extensive studies conducted over the past few years have recognised its overexpression in several carcinomas and thus its implication in carcinogenesis. Recent studies have suggested that overexpression of COX-2 might be one of the leading factors in hepatic carcinogenesis. COX-2 can induce angiogenesis via vascular endothelial growth factor (VEGF) and prostaglandin production and can also inhibit apoptosis by inducing the antiapoptotic factor Bcl-2 as well as activating antiapoptotic signalling through Akt/PKB. Therefore, the use of selective inhibitors for the downregulation of COX-2 activity might be a target for preventing hepatic carcinoma development.

Angiogenesis Inhibitors↗

PubMedDate not supplied

Photosynthetic electron transport inhibition by 2-substituted 4-alkyl-6-benzylamino-1,3,5-triazines with thylakoids from wild-type and atrazine-resistant Chenopodium album.

The effect of 2-benzylamino-1,3,5-triazines on photosynthetic electron transport (PET) was measured with thylakoids isolated from atrazine-resistant, wild-type Chenopodium album, and spinach to find novel 1,3,5-triazine herbicides bearing a strong PET inhibition. The PET inhibition assay with Chenopodium (wild-type and resistant), yielded a resistance ratio (R/W = I50 (resistant)/I50 (wild-type)) of 324 for atrazine while for benzylamino-1,3,5-triazine derivatives of diamino-1,3,5-triazines a R/W of 11 to 160 was found. The compounds having a benzylamino group at one of the amino groups in the diamino-1,3,5-triazines have a resistant ratio down to one half to 1/30 of the atrazine value. The average resistance ratio of 21 benzylamino derivatives of monoamino-1,3,5-triazines was found to be about 4.0. The inhibition of 21 benzylamino-1,3,5-triazines assayed with atrazine-resistant Chenopodium thylakoids, indicated by pI50 (R)-values, correlated well with the PET inhibition pI50 (W) of wild-type thylakoids from Chenopodium.

Atrazine↗

PubMedDate not supplied

Expression and prognostic significance of S100A2 protein in squamous cell carcinoma of the esophagus.

The purpose of this study was to evaluate the expression of S100A2 Ca2+-binding protein and its prognostic significance in the management of squamous cell carcinoma of the esophagus. Changes in cytosolic Ca2+ concentration control a wide range of cellular responses including cellular apoptosis. Intracellular S100 Ca2+-binding proteins are key molecules in transducing Ca2+ signaling. Among these, S100A2 has recently attracted major interest due to its stable expression in normal epithelia and down-regulation in some tumors. As a candidate tumor suppressor, expression of S100A2 has been proposed as a valuable prognostic marker in different tumors. We examined the clinical significance of S100A2 expression in 116 resected specimens of esophageal squamous cell carcinomas (ESCC) using immunohistochemistry. S100A2 was positive in 49 cases (42.2%) and its expression was significantly higher in large (p=0.01) and well differentiated tumors (p=0.013). Lymph node-positive tumors had a lower expression of S100A2 protein in comparison to the corresponding lymph node negative equivalents in each of the T stages, but the difference was statistically significant (p=0.041) only for the T1b tumors. S100A2 status became an independent predictor of patient survival (p=0.026) in lymph node-negative cases but not in node-positive cases. Evaluation of S100A2 protein expression may play an important role in the management of ESCC. The node-negative ESCC patients without S100A2 expression might be a high-risk group with poor survival and will need further attention to design appropriate adjuvant therapy.

Aged↗

PubMedDate not supplied

Requisite role of VEGF receptors in angiogenesis of hepatocellular carcinoma: a comparison with angiopoietin/Tie pathway.

BACKGROUND: Tumor vascularity is an independent predictor of prognosis in HCC patients, however, the growth factors governing the angiogenesis remain obscure. MATERIALS AND METHODS: Multiple mRNA species of angiogenesis-related growth factors/receptors and CD31 were evaluated in 38 hepatocellular carcinomas (HCCs) and surrounding livers (SL) by a highly sensitive RNase protection assay. RESULTS: Significant increases in VEGF, VEGFR3, endoglin and CD31 mRNA expressions were noted in HCC rather than in SL. Only VEGFR1 had significant correlation with CD31 expression. VEGFRs and CD31 overexpressed in tumors with portal vein invasion and only VEGFR3- and CD31-positive patients had significantly shorter disease-free survival. Tie1 and Tie2 were overexpressed in large HCCs. The VEGF and Tie receptors expressed differentially in 28 tumors. CONCLUSION: The VEGF receptors might play the major role in HCC angiogenesis and prognosis. The differential expression of receptors might prove valuable in selected subsets of patients for tailored antiangiogenic therapy in HCC patients.

Angiopoietin-1↗

PubMedDate not supplied

Combination therapy with paclitaxel and thalidomide inhibits angiogenesis and growth of human colon cancer xenograft in mice.

BACKGROUND: Combination chemotherapy is increasingly practiced for treating malignancies with greater sensitivity and less toxicity. Paclitaxel is a potent anti-tumor agent but has dose-limiting side-effects, whereas thalidomide is an orally active anti-angiogenic drug but less than sufficient to exert anti-tumor effect as a single agent. MATERIALS AND METHODS: Nude mice bearing hypervascular (LS174T) and less vascular (HT29) colon carcinomas were challenged with either a non-cytotoxic dose of paclitaxel, thalidomide or a combination of paclitaxel and thalidomide. RESULTS: Significant growth retardation was noticed only in the combination treatment group of LS174T tumors. Microvessel density data indicated a significantly low count in the combination treatment group compared to the others. Trends of decreased expression of angiogenic growth factors and increased apoptotic index were noticed in the combination treatment group. CONCLUSION: The results of this study underscore the therapeutic efficacy of concomitant use of paclitaxel and thalidomide in the treatment of highly vascular colorectal tumors in a xenograft model.

Adenocarcinoma↗