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Biomedical subjects

K Ohtsuka

Publications and source records attributed to K Ohtsuka.

266 records · Page 15Linked to original sources
PubMedDate not supplied

Molecular chaperone function of mammalian Hsp70 and Hsp40--a review.

Virtually all organisms respond to up-shifts in temperature (heat shock) by synthesizing a set of proteins called heat shock proteins (HSPs). The HSPs are induced not only by heat shock but also by various other environmental stresses. Induction of HSPs is regulated by the trans-acting heat shock factors (HSFs) and cis-acting heat shock element (HSE) present at the promoter region of each heat shock gene. Usually, HSPs are also expressed constitutively at normal growth temperatures and have basic and indispensable functions in the life cycle of proteins as molecular chaperones, as well as playing a role in protecting cells from the deleterious stresses. Molecular chaperones are able to inhibit the aggregation of partially denatured proteins and refold them using the energy of ATP. Recently, there are expectations for the use of molecular chaperones for the protection against and therapeutic treatment of inherited diseases caused by protein misfolding. In this review, the focus will be on the mammalian Hsp40, a homologue of bacterial DnaJ heat shock protein, and the beneficial functions of molecular chaperones.

Animals↗
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Effects of mild hypercapnia on somatosensory evoked potentials in experimental cerebral ischemia.

In a previous report, the authors demonstrated the effectiveness of mild hypercapnia in enhancing decreased perfusion flow in ischemic, non-infarcted brain tissues. However, the previous work lacked in verification of improvement of suppressed brain function. Therefore, this report was attempted to evaluate the effect of hypercapnia on somatosensory evoked potential (SEP), using the similar ischemic model as previously. The results showed that mild hypercapnia of 43 to 55 mm Hg range was beneficial not only for enhancing decreased perfusion flow but also for restoring suppressed SEP. This report seems to be the first publication which verifies a presence of correlation between local cortical blood flow (LCBF) and SEP under mild hypercapnia in mildly to moderately ischemic brain tissues.

Animals↗
PubMedDate not supplied

Gut-associated lymphoid tissues in ulcerative colitis.

BACKGROUND: The main feature of ulcerative colitis (UC) is numerous infiltration of not only lymphocytes and plasma cells but also neutrophils and macrophages, indicating acute on chronic inflammation. Recent studies show that apoptosis may play an important role in the regulation of gut-associated lymphoid tissues (GALT). Therefore, this study was performed to clarify apoptosis of lymphocytes in the peripheral blood and colonic mucosa of UC. METHODS: Three-color flow cytometry was used to clarify apoptosis of lymphocytes in the peripheral blood and colonic mucosa of patients with active and inactive UC compared with controls using fluorescence-labeled monoclonal and polyclonal antibodies such as Fas (CD95), Fas ligand, CD4, CD8, CD45RO, etc. RESULTS: The ratio of Fas and CD45RO double-positive cells in the peripheral blood of UC patients was significantly increased in CD8 but not CD4 T cells when compared with controls. The ratio of Fas-positive and CD45RO-negative cells was significantly increased in CD4 and CD8 T cells of UC when compared with controls. There was unbalanced immunoregulation between CD4 and CD8 T cells in the colonic mucosa of UC probably due to apoptosis through Fas-Fas ligand system. CONCLUSIONS: Abnormal GALT system was found in UC probably due to dysregulation of T cells through Fas-Fas ligand system.

Antigens, CD↗
PubMedDate not supplied

Autoimmunity to heat shock protein 40 in ulcerative colitis.

Autoantibodies against heat shock protein 40 (HSP40) and their clinical significance in ulcerative colitis (UC) have not been evaluated before. Twenty-six tissue specimens of inflamed areas from patients with UC, 16 from patients with Crohn's disease (CD) and 16 endoscopically normal tissues were analysed for HSP40 expression. Sera from 47 patients with UC and 44 healthy volunteers were examined for the presence of autoantibodies against HSP40 by enzyme-linked immunosorbent assay test. Immunohistochemistry showed that 17 out of 26 specimens from UC patients, one specimen from a CD patient and one normal tissue specimen were positive for HSP40. Most HSP40-positive cells expressed CD68. Higher titres of anti-HSP40 autoantibodies were detected in sera from UC patients compared with healthy volunteers. In patients with inactive disease, those with proctitis or left-sided colitis had higher titres of anti-HSP40 autoantibodies than those with total colitis. Our study suggests that autoimmunity against HSP40 may have a beneficial effect in UC patients by limiting the extent of the disease.

Adolescent↗
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Intracellular distribution of 73,000 and 72,000 dalton heat shock proteins in HeLa cells.

Intracellular localization of 73,000 and 72,000 dalton heat shock proteins (HSP73/72) in HeLa cells that were heat shocked or treated with chemical stressors was investigated using indirect immunofluorescent staining. The antiserum used specifically recognized the HSP73/72 in HeLa cells, and HSPs were increased by heating cells at 42 degrees C for 2 or 4 h and by prior treatment with chemical stressors (sodium arsenite, cadmium chloride, 8-hydroxyquinoline and ethanol). There was diffuse cytoplasmic staining at 37 degrees C, whereas nucleoli were stained brightly when cells were heated at 42 degrees C for 2 h. This rapid accumulation of HSP73/72 in the nucleoli was not inhibited by cycloheximide (50 micrograms/ml). Translocation of HSPs to the nucleoli was specific for heat because no translocation was induced by treatment with chemical stressors. When the cells were returned to 37 degrees C after heating, the HSPs in their nucleoli disappeared rapidly and diffuse cytoplasmic staining was present after 6-9 h. Our results suggest that the transient accumulation of HSP73/72 in HeLa cell nucleoli that is induced by heat shock is not correlated with the development of thermotolerance obtained in other cell systems.

Animals↗
PubMedDate not supplied

Modification of the thermal sensitivity of the murine foot and tumour by prior hypoxic treatment.

The response of Furth's murine mastocytoma to heat and the effect of prior heating and hypoxic treatment by clamping on the thermal sensitivity of the murine foot and the tumour were investigated. Two different-sized tumours, with average diameters of 3-4 mm and 7-8 mm were used. The tumour response to heat was evaluated by tumour growth (TG) time. Thermotolerance developed in both the foot and tumour tissues by a prior heating for 5 or 10 min at 45 degrees C. Hypoxic treatment resulted in dual effects on tumours. A 10 or 20 min hypoxic pretreatment increased thermal sensitivity of the tumour, while more than a 30 min hypoxic pretreatment induced thermotolerance. In contrast, a 20 min hypoxic treatment induced thermotolerance in the normal tissues. These results indicate that an appropriate period of prior hypoxic treatment may lead to a differential response between normal and tumour tissues.

Animals↗
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Development of thermotolerance in hsp70 induction-defective mutant of NRK cells.

We investigated the relation between the synthesis of inducible form of heat-shock protein 70 (hsp70) and the development of thermotolerance using NRK (normal rat kidney) cells and their mutant cell line (39-1 cells). In NRK cells, hsp70 was clearly induced by conditioning treatments (42 degrees C for 2 h, 45 degrees C for 15 min or 100 microM sodium arsenite for 1 h). On the other hand, the induction of hsp70 in 39-1 cells was very low or not detectable by these treatments. Other high molecular weight hsps, hsc70 (constitutive form), hsp90 and hsp110 were induced in both cell lines. However, thermotolerance as defined by clonogenic survival was induced in both cell lines to a similar extent by the conditioning treatments. When cells were made thermotolerant by conditioning heating at 45 degrees C for 15 min, the inhibition of protein synthesis after challenge (second) heating was less in NRK cells than in 39-1 cells. This indicated that the extent of 'translational thermotolerance' was much higher in NRK cells than in 39-1 cells. From these results, it is suggested that the synthesis of inducible hsp70 is involved in the translational thermotolerance rather than the development of thermotolerance as defined by clonogenic survival.

Animals↗
PubMedDate not supplied

Characteristic synthesis and redistribution of 70 kd heat shock protein in thermotolerant Chinese hamster V79 cells.

Upon exposure to heat shock the increased rate of hsp70 synthesis decreased more rapidly in thermotolerant V79 cells than in the non-thermotolerant cells. However, the levels of hsp70 in the thermotolerant cells at 12 h after a heat shock were almost the same as those in the non-thermotolerant cells. On the other hand, the migration of hsp70 from cytoplasm to nucleoli after a heat shock was very rapid in both thermotolerant and non-thermotolerant cells, but hsp70 in the nucleoli disappeared faster in the thermotolerant cells than in the non-thermotolerant cells, and this coincided with the faster decline of hsp70 synthesis in the thermotolerant cells. For the characteristic distribution of hsp70, protein synthesis was not required. Furthermore, the induction and expression of thermotolerance by the cells were little affected by the inhibition of protein synthesis. Thus, the synthesis of hsp70 itself seemed not to be essential for the induction and expression of thermotolerance of the cells, although hsp70 may be essential for thermoresistance of cells. The rapid decrease of hsp70 synthesis and the rapid disappearance of hsp70 from the nucleoli after a heat shock may be essential for the expression of thermotolerance of the cells.

Animals↗
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Cytoskeletal thermotolerance in NRK cells.

We investigated the effect of heat shock on the cytoskeletons (actin stress fibres, intermediate filaments and microtubules) and the relation between thermotolerance of cytoskeletons and thermotolerance as defined by clonogenic survival in normal rat kidney (NRK) cells. Upon heating at 45 degrees C for 15 min, almost all actin stress fibres were disrupted. During the recovery period after heat shock the stress fibres were reorganized rapidly and returned to their preheated state by 16 h. When the cells were heated again at 45 degrees C for 15 min, the disruption of stress fibres was less severe, indicating thermotolerant state of stress fibres. However, the thermotolerant state of stress fibres induced by prior treatment with sodium arsenite or by heating at 42 degrees C for 2 h was less evident than that induced by prior heat shock at 45 degrees C. The intermediate filaments in NRK cells were very heat-resistant; no apparent changes were observed even after heat shock at 45 degrees C for 60 min, and prior conditioning treatments could not induce thermotolerance of microtubules. All prior conditioning treatments could induce heat shock proteins and thermotolerance as defined by clonogenic survival. From these results it is suggested that there is no correlation between cytoskeletal thermotolerance and either heat shock protein level or thermotolerance as defined by clonogenic survival in NRK cells.

Actins↗
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Hsp40, a possible indicator for thermotolerance of murine tumour in vivo.

The relationship between Hsp40/Hsp70 synthesis and the development of thermotolerance was investigated using mouse squamous cell carcinoma in vivo. To examine the thermotolerance, tumours were heated at 44 degrees C for 30 min as conditioning heating. After various intervals they were heated again at 44 degrees C for 90 min as challenge heating. The tumour response to heat was evaluated by the growth delay. Thermotolerance rapidly developed with increasing interval and reached a maximum at 12 h interval. Subsequently, thermotolerance gradually decayed and almost disappeared at 120 h interval. Under this condition, synthesis of Hsp40/Hsp70 increased after conditioning heating, reached a maximum at 12 h interval, then gradually decreased thereafter within 120 h. The kinetics of accumulation and decay of both Hsp40 and Hsp70 were very similar. The extent of thermotolerance was well correlated with the relative amount of Hsp40/Hsp70. These results obtained in vivo were very similar to those in vitro (Kaneko et al. 1995). Our findings suggest that Hsp40 could be a useful indicator of the degree of thermotolerance in addition to Hsp70 in vivo as in vitro.

Animals↗
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Initial histopathology of the autovein graft in late occlusion after arterial reconstruction.

Five patients developed local stenosis of autologous vein grafts implanted for femoro-popliteal arterial occlusive lesions. This stenosis occurred in the vein grafts 2 months to 5 years after the initial operation. Histopathologic study revealed that the stenotic segments had a thickened intima with a prominent proliferation of smooth muscle cells associated with fibrous extracellular matrix. There were no findings showing deposition of mural thrombi, as has heretofore been reported. The intimal thickening due to excessive fibromuscular proliferative response of the vein graft may possibly play an important role in the development of late graft occlusion.

Adult↗
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Occluded persistent sciatic artery.

The case of a patient with ischemic symptoms due to occlusion of a persistent left sciatic artery is presented. Femoral arteriography revealed a tapering hypoplastic superficial femoral artery terminating as small branches in the distal thigh and a hyperplastic profunda femoris artery. Also, translumbar aortography demonstrated an abrupt occlusion of a hyperplastic left hypogastric artery just distal to the inferior gluteal artery. The popliteal artery was found to be patent and perfused by collaterals. A bypass graft using a composite E-PTFE prosthesis and an autogenous vein graft was successfully performed.

Angiography↗
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Transformation by viral oncogenes increased sensitivity to heat in rat 3Y1 fibroblasts.

Sensitivity to the lethal effect of hyperthermia was compared using the rat 3Y1 fibroblastic cell line and its seven sublines transformed by various agents in vitro. The cell lines examined were those transformed by simian virus 40 (SV3Y1), mouse polyoma virus (Py3Y1), adenovirus type 12 (Ad3Y1), the E1A region of adenovirus type 12 (E1A3Y1), Rous sarcoma virus (SR3Y1), v-Harvey ras oncogene (HR3Y1) and N-methyl-N-nitro-N-nitrosoguanidine (NG3Y1). We also examined the intracellular amount and distribution of 70-kilodalton heat shock protein which has previously been shown to be associated with thermal tolerance in several experimental systems. There was a striking difference in heat sensitivity, as defined by a clonogenic assay, depending on the transforming agents. The parental untransformed 3Y1 cells were most resistant to heat, whereas the Ad-, E1A- or NG3Y1 cell lines were most susceptible to heat. The other 4 lines showed intermediate sensitivity. We detected translocation of hsp70 from cytoplasm to nucleoli shortly after the heat shock in all cell lines, as detected by indirect immunofluorescence. Western blotting experiment failed to show any difference in amount of hsp70 among the cell lines. We conclude that transformed cells were more susceptible to heat than untransformed cells, and that a mechanism other than hsp70 synthesis may operate on the heat sensitivity, at least in our system.

Adenovirus E1A Proteins↗