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Biomedical subjects

Y Kanazawa

Publications and source records attributed to Y Kanazawa.

At least 37 records · Page 2Linked to original sources

Proliferating cell nuclear antigen and p53 protein expression in submucosal invasive colorectal carcinoma.

In some cases of early colorectal carcinoma, radical surgical resection might be required because of vessel invasion, distant metastasis, or inadequate surgical margin. To characterize submucosal invasive colorectal carcinoma, we investigated expression of PCNA and p53 protein. Sixty-seven patients who underwent curative resection of submucosal invasive colorectal carcinoma participated in this study. The PCNA labeling index (PCNA-LI) is determined at the deepest lesion of carcinoma. The expression of PCNA and p53 protein were analyzed according to clinicopathological factors. 1) The PCNA-LI was correlated to histological grade, depth of invasion or vessel invasion in polypoid type. 2) The flat type had significantly higher PCNA-LI (65.1+/-8.2%) and p53 protein expression (69.6%) than the polypoid type. 3) The PCNA-LI was higher in cases with lymph node metastasis than in these without lymph node metastasis. 4) Overexpression of the p53 protein was detected in all cases with liver metastasis. Our results suggest that in order to determine the treatment for the patients with submucosal invasive colorectal carcinoma, the expression of PCNA and p53 protein may be a useful biologic marker.

Aged↗

[Diabetes mellitus].

The thiazolidinedione compound is known as an insulin-sensitizing agent and is considered a very promising drug, because insulin resistance is a major component of type 2 diabetes. Many reports have demonstrated that the thiazolidinedione has the good hypoglycemic effect in monotherapy and in combination therapy with sulfonylureas, metformin, alpha-glucosidase inhibitors, or insulin. Furthermore, the thiazolidinedione has additional beneficial effects on serum lipids, arterial blood pressure, coagulation-fibrinolysis system, arterial wall cell function. These favorable effects suggest the thiazolidinedione may have inhibitory actions on both macroangiopathy and microangiopathy in patients with diabetes mellitus. However, some patients treated with troglitazone, the first available thiazolidinedione, have suffered from liver dysfunction; in some cases, patients have progressed to hepatic failure and death unfortunately. As the thiazolidinediones are clearly excellent drugs to diabetics with insulin resistance, we should check hepatic function and monitor symptomes of hepatic damage.

Blood Coagulation↗

Fatal hepatic failure caused by chemotherapy-induced reactivation of hepatitis B virus in a patient with hematologic malignancy.

A patient with hematologic malignancy and hepatitis B virus (HBV) infection received chemotherapy containing a glucocorticoid. The patient developed severe hepatitis after chemotherapy and, despite achieving complete remission of the malignancy, died of hepatic failure. We carried out a retrospective study of changes in the serological markers of HBV in this patient. Both serum hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) were negative on admission. During the course of chemotherapy, HBsAg gradually became positive, but no liver dysfunction was apparent until after completion of the chemotherapy. The patient showed no initial evidence of being a latent HBV carrier. Therefore, we believe that screening for HBsAg is insufficient for detecting latent HBV carriers, and that investigation for hepatitis B core antibody (HBcAb) is essential.

Aged↗

[Effect of dietary protein restriction and influence of proteinuria on progression of type 2 diabetic renal failure].

PURPOSE: This study investigated the effect of dietary protein restriction on disease progression and how it is influenced by proteinuria in patients with type 2 diabetic nephropathy(DN) and renal failure. METHODS: One hundred and six type 2 DN patients whose baseline creatinine clearance(Ccr) values were 29 +/- 12 ml/min/1.73 m2 were maintained on a diet containing 0.66 +/- 0.05 g/kg/day of protein. They were classified into 3 groups according to mean dietary protein intake(DPI) estimated from urinary urea nitrogen excretion during the follow-up period of 23 +/- 14 months(I, < 0.7 g/kg/day; II, 0.7-0.89 g/kg/day; III, > or = 0.9 g/kg/day). Furthermore, they were divided into 3 subgroups according to mean urinary protein excretion(UP) during the follow-up period (a, > or = 5.0 g/day; b, 2.0-4.99 g/day; c, < 2.0 g/day). Their rates of decline of Ccr(D-Ccr) and the changes in UP were examined. RESULTS: There were no significant differences in D-Ccr among Group Ia, IIa, and IIIa(1.1 +/- 0.6, 1.5 +/- 0.7, 1.2 +/- 0.6 ml/min/1.73 m2/month), among Group Ib, IIb, and IIIb(0.6 +/- 0.3, 0.7 +/- 0.4, 0.8 +/- 0.4 ml/min/1.73 m2/month), and also among Group Ic, IIc, and IIIc(0.1 +/- 0.3, 0.2 +/- 0.2, 0.2 +/- 0.6 ml/min/1.73 m2/month). On the other hand, significant differences were revealed in D-Ccr among Group Ia, Ib, and Ic, among Group IIa, IIb, and IIc, and among Group IIIa, IIIb, and IIIc. There were no significant differences in final UP and minimum UP during follow-up among 3 groups of different DPI levels in patients with 5.0 g/day < or = baseline UP(n = 49) and in patients with 2.0 < or = baseline UP < 5.0 g/day(n = 37). However, significant correlations were demonstrated between D-Ccr and the relative changes in UP between baseline and minimum during the follow-up period in both patients(r = 0.49, 0.48, p < 0.001, p < 0.01). CONCLUSIONS: Irrespective of the level of dietary protein restriction, proteinuria has a great influence on disease progression, and the reduction in UP correlates with retardation of renal function loss in patients with type 2 DN and renal failure.

Aged↗

An improved genetic linkage map of rat chromosome 20.

BACKGROUND AND PURPOSE: Rat chromosome 20 is one of special interest because it contains some diabetogenic genes, such as a major histocompatibilitiy complex (MHC)-linked genetic components and quantitative trait loci. We studied rat chromosome 20, using the backcross progeny between BB/Wor and PVG.R23 rats, and confirmed the genetic linkage map by use of another backcross panel. METHODS: Backcross panels were done between BB/Wor and PVG.R23 rats, and BN and KZC rats. Length variations of simple sequence length polymorphism markers were analyzed by use of polymerase chain reaction (PCR) analysis. Alleles of RT1-Bb and RT1-Db were analyzed by use of the PCR-restriction fragment length polymorphism method. Genetic maps of rat chromosome 20 were constructed, using the Map Manager computer program. RESULTS: Fifty-two loci were mapped on rat chromosome 20. Genetic length was 57.9 cM, with average spanning of 1.11 cM between markers. The positions of RT1-N1, Tnf, and RT1-Bb into the MHC region were separated and confirmed by results of two backcross panels in our linkage studies. CONCLUSIONS: The genetic linkage map of rat chromosome 20 was improved, and was a useful tool for genetic analysis of a diabetogenic gene(s) and for producing MHC congenic strains.

Animals↗

Structure-activity relationships in allergic contact dermatitis induced by methacrylates. Studies of the influence of side-chain length of methacrylates.

Some methacrylates are known to be strong contact sensitizers. To determine the effect of side-chain length on sensitizing potential, we examined 11 derivatives with linear side chains from C1 to C18 in an experimental sensitization test in guinea pigs. The results showed an increase in the sensitizing potential with increasing length of the alkyl side chain from C1 to C12. The C12 derivative, lauryl methacrylate, showed the strongest sensitizing potential. Further elongation of the alkyl side chain of methacrylates resulted in a decrease in the potential. With respect to the side-chain-length-dependent sensitizing potential, the present results correspond well with the findings obtained with other compounds like primin, catechols, phenols, hydroquinones, and gallates.

Administration, Topical↗

A preliminary study for clinical pharmacokinetics of oral fluorine anticancer medicines using the commercial MRI system 19F-MRS.

These preliminary studies of dynamic natural abundance 19F-magnetic resonance spectroscopy (19F-MRS) on 5-FU based medicines were performed in the human liver using commercial 1.5 T MRI equipment. A single tuned, custom-made circular shape surface coil with a diameter of 15 cm operating at 60 MHz was used for the 19F-MRS study. Localized proton shimming with a whole body coil was performed with adequate volume to include the observing area of the surface coil, and the line width of the water signal was less than 40 Hz. Very different spectroscopic appearance patterns of 5-FU were observed. We examined whether the pharmacokinetics in the liver of orally administered 1-hexylcarbamoyl-5-fluorouracil (HCFU) differ from those of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR). This preliminary study suggested the 19F-MRS technique could be a useful method of evaluating in vivo the metabolism of 5-FU based medicines.

Administration, Oral↗

[New classification of diabetes by ADA and WHO with special reference to pathogenesis].

New classification of diabetes mellitus was proposed by ADA international committee on the diagnosis and classification and by WHO consultation committee. The classification based on the pathogeneses of diabetes and also on the stages of diseases. Since our knowledge on causes of diabetic syndrome is not yet enough to classify diabetes in genetic bases, the classification had been carried out some sort of mixture of pathogeneses, genetic findings and clinical features of hyperglycemia. Stages of diseases based on the natural course of diabetes mellitus in reference to shortage of insulin effects and degree of chronic hyperglycemia. These two components of classification composed two dimensions of the field that expresses all the pathogeneses and metabolic conditions of all diabetic patients.

Diabetes Mellitus↗

[Evaluation of fat nutrition in the energy intake on low protein diets for patients with chronic renal failure].

Low protein diet has been proven to retard the progression of chronic renal failure. In this diet, the energy intake depends mainly on fats and carbohydrates instead of protein, and precautions should be taken against increasing risks of both lipid nephrotoxicity and atherosclerosis. In order to assess the adequacy of fat nutrition in a low protein diet for patients with chronic renal failure, we evaluated the total amounts of dietary fat intake, dietary individual fatty acid intake and serum individual fatty acid concentrations in 16 patients, whose mean creatinine clearance was 21.3 +/- 12.1 ml/m, serum creatinine 3.8 +/- 2.2 mg/dl and serum urea nitrogen 41.5 +/- 18.6 mg/dl. The percentage ratio of fat intake to total energy intake was 26.7 +/- 5.2%. The ratio of intake of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids was 1:2:1.8, and n-6/n-3 was 8.5 +/- 9.3. These were significant correlations between dietary intake and the serum concentrations in both EPA and the ratio of EPA/AA. Consequently, it might be considered that polyunsaturated fatty acids intake should be lowered and patients with chronic renal failure on a low protein diet should be advised about the proper selection of foods containing animal protein and plant-derived oil. It may be beneficial to recommend the intake of more EPA and lowering the ratio of n-6/n-3 intake might be useful in improving the fat nutrition to adequate levels in these patients.

Aged↗

True small lymphocytic T-cell chronic lymphocytic leukemia lacking the CD3 molecule and TCR-alpha beta on its cell surface.

We report a case of T-cell chronic lymphocytic leukemia (T-CLL) in which the lymphocytes were small and mature, did not have cytoplasmic granulation, and appeared to be similar to those of B-cell chronic lymphocytic leukemia (B-CLL). Immunophenotyping of the lymphocytes revealed CD2+, CD4+, CD5+, and CD25+ on the cell surface, but expression of the CD3 and TCR-alpha beta molecules was localized only in the cytoplasm. The clinical course was as indolent as that of B-CLL, and the patient was able to undergo open-heart surgery. Thus, we confirmed that true T-CLL is able to exist as a counterpart of B-CLL.

Aged↗

Ethidium bromide-induced inhibition of mitochondrial gene transcription suppresses glucose-stimulated insulin release in the mouse pancreatic beta-cell line betaHC9.

Recently, a mitochondrial mutation was found to be associated with maternally inherited diabetes mellitus (Kadowaki, T., Kadowaki, H., Mori, Y., Tobe, K., Sakuta, R., Suzuki, Y., Tanabe, Y, Sakura, H., Awata, T., Goto, Y., Hayakawa, T., Matsuoka, K., Kawamori, R., Kamada, T., Horai, S., Nonaka, I., Hagura, R., Akanuma, Y., and Yazaki, Y. (1994) N. Engl. J. Med. 330, 962-968). In order to elucidate its etiology, we have investigated the involvement of mitochondrial function in insulin secretion. Culture of the pancreatic beta-cell line, betaHC9, with low dose ethidium bromide (EB) (0.4 microg/ml) for 2-6 days resulted in a substantial decrease in the transcription level of mitochondrial DNA (to 10-20% of the control cells) without changing its copy number, whereas the transcription of nuclear genes was grossly unaffected. Electron microscopic analysis revealed that treatment by EB caused morphological changes only in mitochondria and not in other organelles such as nuclei, endoplasmic reticula, Golgi bodies, or secretory granules. When the cells were treated with EB for 6 days, glucose (20 mM) could no longer stimulate insulin secretion, while glibenclamide (1 microM) still did. When EB was removed after 3- or 6-day treatment, mitochondrial gene transcription recovered within 2 days, and the profiles of insulin secretion returned to normal within 7 days. Studies with fura-2 indicated that in EB-treated cells, glucose (20 mM) failed to increase intracellular Ca2+, while the effect of glibenclamide (1 microM) was maintained. Our system provides a unique way to investigate the relationship between mitochondrial function and insulin secretion.

Animals↗

Immunolocalization of fibronectin and its receptors integrin alpha 3 and alpha 5 subunits in the rat limb development.

In the rat hind limb bud aged between prenatal days 14 and 16, immunoreactions of fibronectin in the apical ectodermal ridge were localized on the plasma membranes of epidermal cells and cytoplasmic projections of the underlying mesenchymal cells, which are in contact with the basal lamina. Those of integrin alpha 3 and alpha 5 subunits also appeared on such areas. Definite immunoreactions of fibronectin and both integrin subunits were seen in cell to cell contact areas of mesenchymal cells which are associated with the marginal vein, or with each other forming solid cell cords, and appeared on the basal plasma membrane of endothelial cells of the growing capillaries arising from the marginal vein. These findings suggest that fibronectin may work as a ligand for alpha 3 beta 1 and/or alpha 5 beta 1 integrins expressed by the mesenchymal and vasoformative cells in developing limb bud.

Animals↗

Establishment of two substrains, diabetes-prone and non-diabetic, from Long-Evans Tokushima Lean (LETL) rats.

Diabetes mellitus in Long-Evans Tokushima Lean (LETL) rats closely resembles type 1 diabetes in human beings, e.g., no gender differences in the incidence of diabetes and no T lymphopenia. Although the LETL rats have been established as an inbred strain, the incidence of diabetes is only approximately 20%. In the present study, we established two substrains, one a diabetes-prone (KDP) and the other a non-diabetic (KND) from the original inbred LETL rats. The features of KDP rats are a high incidence of diabetes (over all approximately 70%) without lymphopenia and 100% development of mild to severe insulitis at 120-220 days of age. In contrast, the KND substrain is characterized by the complete absence of diabetes incidence. Among 165 SSLP marker loci throughout all rat chromosomes, no loci showed variation among KDP and KND substrains and their parental LETL rats. In this regard, the genetic background of these two substrains, KDP and KND, appears to be uniform except for the major gene(s) that is responsible for the diabetes. In this context, these two substrains of LETL rats should serve as useful tools for research on the pathogenesis and for the genetic analysis of type 1 diabetes. In this report, we have not only established, but also characterized these two substrains, and provided their fundamental data.

Age of Onset↗