Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 163 records · Page 9Linked to original sources

PubMed2001

Dietary habits and risk of lung cancer death in a large-scale cohort study (JACC Study) in Japan by sex and smoking habit.

Lung cancer has increased and is the leading cause of cancer death among Japanese males. The associations of dietary habits with the risk of lung cancer death were evaluated by sex and smoking habits in this study. In the Japan Collaborative Cohort (JACC) Study, a cohort established in 1988 - 90 and consisting of 42 940 males and 55 308 females was observed for lung cancer deaths up to the end of 1997. During the observation period, 446 males and 126 females died of lung cancer. A self-administered food frequency questionnaire was used as the baseline survey. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. Among males, a high intake of ham and sausages, cheese, green-leafy vegetables, oranges, and other fruits significantly and dose-dependently decreased the risk of lung cancer death. Among females, a high intake of miso-soup, ham and sausages, and liver significantly and almost dose-dependently increased the risk. Vegetables and fruits rich in antioxidative and carcinogenic agents reduced the risk of lung cancer deaths among male smokers more than among female nonsmokers. The results among female nonsmokers were partially consistent with the hypothesis that high fat consumption increases the risk of lung cancer, especially that of adenocarcinoma.

Adult↗

PubMed2001

Chl12 (Ctf18) forms a novel replication factor C-related complex and functions redundantly with Rad24 in the DNA replication checkpoint pathway.

RAD24 has been identified as a gene essential for the DNA damage checkpoint in budding yeast. Rad24 is structurally related to subunits of the replication factor C (RFC) complex, and forms an RFC-related complex with Rfc2, Rfc3, Rfc4, and Rfc5. The rad24Delta mutation enhances the defect of rfc5-1 in the DNA replication block checkpoint, implicating RAD24 in this checkpoint. CHL12 (also called CTF18) encodes a protein that is structurally related to the Rad24 and RFC proteins. We show here that although neither chl12Delta nor rad24Delta single mutants are defective, chl12Delta rad24Delta double mutants become defective in the replication block checkpoint. We also show that Chl12 interacts physically with Rfc2, Rfc3, Rfc4, and Rfc5 and forms an RFC-related complex which is distinct from the RFC and RAD24 complexes. Our results suggest that Chl12 forms a novel RFC-related complex and functions redundantly with Rad24 in the DNA replication block checkpoint.

Cell Cycle Proteins↗

PubMed2001

Pie1, a protein interacting with Mec1, controls cell growth and checkpoint responses in Saccharomyces cerevisiae.

In eukaryotes, the ATM and ATR family proteins play a critical role in the DNA damage and replication checkpoint controls. These proteins are characterized by a kinase domain related to the phosphatidylinositol 3-kinase, but they have the ability to phosphorylate proteins. In budding yeast, the ATR family protein Mec1/Esr1 is essential for checkpoint responses and cell growth. We have isolated the PIE1 gene in a two-hybrid screen for proteins that interact with Mec1, and we show that Pie1 interacts physically with Mec1 in vivo. Like MEC1, PIE1 is essential for cell growth, and deletion of the PIE1 gene causes defects in the DNA damage and replication block checkpoints similar to those observed in mec1Delta mutants. Rad53 hyperphosphorylation following DNA damage and replication block is also decreased in pie1Delta cells, as in mec1Delta cells. Pie1 has a limited homology to fission yeast Rad26, which forms a complex with the ATR family protein Rad3. Mutation of the region in Pie1 homologous to Rad26 results in a phenotype similar to that of the pie1Delta mutation. Mec1 protein kinase activity appears to be essential for checkpoint responses and cell growth. However, Mec1 kinase activity is unaffected by the pie1Delta mutation, suggesting that Pie1 regulates some essential function other than Mec1 kinase activity. Thus, Pie1 is structurally and functionally related to Rad26 and interacts with Mec1 to control checkpoints and cell proliferation.

Amino Acid Sequence↗

PubMed2001

Comparable effects of adrenalectomy and C fiber depletion on delayed-type hypersensitivity in rats.

OBJECTIVE: To determine the influence of the hypothalamic-pituitary-adrenal (HPA) axis and sensory C fibers on cell-mediated immunity, the time course of allergic contact dermatitis (ACD) was examined in normal, adrenalectomized (ADX) and capsaicin (CAP)-treated rats. METHODS: Five days after sensitization with 2,4-dinitro-1-fluorobenzene (DNFB) onto the back, rats were challenged with DNFB on the pinna. ADX or CAP treatment was performed a week before the sensitization. RESULTS: Ear swelling in normal rats reached a peak 24 h after the challenge and subsided gradually to about half of this peak 72 h afterwards. Plasma ACTH levels increased about 9 times more than those of nonsensitized rats 72 h after the challenge. ADX rats, in which the plasma corticosterone level was significantly lower than that in sham-operated animals, exhibited more rapid development of ACD, which reached a peak 12 h after the challenge. However, the swelling returned to about half of the maximum within 48 h. In CAP-treated rats, ACD reached a peak 6 h after the challenge and recovered quickly as in ADX rats. Plasma ACTH levels in CAP- treated rats were significantly lower than those in vehicle-treated rats. CONCLUSIONS: The rapid development of and recovery from ACD in ADX and CAP-treated rats, both of which showed suppression of the HPA axis, indicated a biphasic action of the HPA axis on ACD, i.e. inhibitory in the early phase but augmentative in the late phase of ACD.

Adrenalectomy↗

PubMed2001

Transgenic CuZn-superoxide dismutase inhibits NO synthase induction in experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The expression of inducible NO synthase (iNOS) after experimental subarachnoid hemorrhage (SAH) has been postulated to play a critical role in the pathogenesis of SAH and subsequent cerebral vasospasm. The inhibitory effect of CuZn-superoxide dismutase (CuZn-SOD) on the induction of iNOS after SAH was examined by using transgenic mice overexpressing CuZn-SOD. METHODS: SOD-transgenic mice and nontransgenic littermates were subjected to SAH by endovascular perforation of the left anterior cerebral artery. The iNOS mRNA expression after SAH was determined by reverse transcription-polymerase chain reaction, and the distribution of iNOS-positive cells was immunohistochemically examined. The nuclear expression of activated nuclear factor-kappaB, a major transcription factor of iNOS gene, was also immunohistochemically examined. RESULTS: In nontransgenic mice, SAH-induced iNOS protein and mRNA expressions in the arteries of basal cistern as well as in the cerebral cortex were demonstrated by immunohistochemistry and reverse transcription-polymerase chain reaction. SAH-induced iNOS protein and mRNA expressions in those tissues were much reduced in SOD-transgenic mice compared with nontransgenic mice. Moreover, the nuclear expression of the activated form of nuclear factor-kappaB was immunohistochemically detected in the cerebral cortices of nontransgenic mice but not in those of SOD-transgenic mice. CONCLUSIONS: These results indicate that oxygen-derived free radicals, particularly superoxide, play an important role in the iNOS gene expression after SAH and provide a molecular basis for the protective role of SOD against vasospasm after SAH.

Animals↗

PubMed2001

Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport.

Expression of angiogenic factors such as VEGF under conditions of hypoxia or other kinds of cell stress contributes to neovascularization during wound healing. The inducible endoplasmic reticulum chaperone oxygen-regulated protein 150 (ORP150) is expressed in human wounds along with VEGF. Colocalization of these two molecules was observed in macrophages in the neovasculature, suggesting a role of ORP150 in the promotion of angiogenesis. Local administration of ORP150 sense adenovirus to wounds of diabetic mice, a treatment that efficiently targeted this gene product to the macrophages of wound beds, increased VEGF antigen in wounds and accelerated repair and neovascularization. In cultured human macrophages, inhibition of ORP150 expression caused retention of VEGF antigen within the endoplasmic reticulum (ER), while overexpression of ORP150 promoted the secretion of VEGF into hypoxic culture supernatants. Taken together, these data suggest an important role for ORP150 in the setting of impaired wound repair and identify a key, inducible chaperone-like molecule in the ER. This novel facet of the angiogenic response may be amenable to therapeutic manipulation.

Adenoviridae↗

PubMed2001

Natural killer type 2 bias in remission of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease characterized by clinical relapse and remission. Because of the potential role of natural killer (NK) cells in the regulation of autoimmunity, we have examined cytokine profile and surface phenotype of NK cells in the peripheral blood of MS. Here we demonstrate that NK cells in the remission of MS are characterized by a remarkable elevation of IL-5 mRNA and a decreased expression of IL-12Rbeta2 mRNA, as well as a higher expression of CD95. Moreover, the NK cells from MS in remission produced much larger amounts of IL-5 than did those from controls after stimulation with phorbol myristate acetate (PMA) and ionomycin. These features are reminiscent of those of NK type 2 (NK2) cells that can be induced in a condition favoring functional deviation of T cells toward Th2. Remarkably, the NK cells lose the NK2-like property when relapse of MS occurs, but regain it after recovery. We also found that NK2 cells induced in vitro inhibit induction of Th1 cells, suggesting that the NK2-like cells in vivo may also prohibit autoimmune effector T cells. Taken together, it is possible that NK cells play an active role in maintaining the remission of MS.

Adult↗

PubMed2001

Association of the TaqI A polymorphism of the dopamine D(2) receptor gene with predisposition to neuroleptic malignant syndrome.

OBJECTIVE: The pathophysiology of neuroleptic malignant syndrome is mainly explained by a central hypodopaminergic state. The familial occurrence of neuroleptic malignant syndrome suggests the involvement of a genetic mechanism in the predisposition to the syndrome. Therefore, the authors examined the association between the TaqI A polymorphism of the dopamine D(2) receptor gene (DRD(2)), which alters DRD(2) density and function, and the development of neuroleptic malignant syndrome. METHOD: The subjects were 15 psychiatric patients who had developed neuroleptic malignant syndrome (12 patients with schizophrenia and three with major depression) and 138 patients with schizophrenia who had never developed neuroleptic malignant syndrome. The TaqI A genotypes, A1 and A2 alleles, were determined by the polymerase chain reaction method. RESULTS: The frequency of the A1 allele was significantly higher in the patients who had developed neuroleptic malignant syndrome (56.8%) than in the patients who had not (35.1%). The proportion of the A1 carrier was significantly higher in the patients with neuroleptic malignant syndrome (14 [93.3%] of 15 patients) than in those without the syndrome (79 [57.2%] of 138 patients). CONCLUSIONS: These findings suggest that the TaqI A DRD(2) polymorphism is associated with the predisposition to neuroleptic malignant syndrome.

Adult↗

PubMed2001

Myopathic form of very-long chain acyl-coa dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.

In a 14-year-old Japanese girl, manifested recurrent myalgia with elevated serum creatine kinase after moderate exercise became evident, and she was diagnosed as having a myopathic form of very-long chain acyl-CoA dehydrogenase deficiency. Her first clinical symptom of the disease was evident when she was 6 y of age. She had never had hypoglycemic attacks, and hepatomegaly and cardiomyopathy were absent. The diagnosis was suspected on the basis of the urinary organic acid profile after a 36-h fast, long-chain fatty acid-loading test, and the blood acylcarnitine profile. Acyl-CoA dehydrogenase activity with palmitoyl-CoA as a substrate was severely decreased in her fibroblasts, and the amount of very-long chain acyl-CoA dehydrogenase protein was reduced. She was a compound heterozygote of A416T from her father and R450H from her mother. Transient expression of mutant A416T cDNA retained a significant residual acyl-CoA dehydrogenase activity of 10% and 20% normal at 37 degrees C and 30 degrees C, respectively. Specific activity of A416T mutant protein was calculated to be one fifth that of control. In the case of R450H mutant expression, a low residual acyl-CoA dehydrogenase activity of 5% normal was detected at 30 degrees C although significant activity was absent at 37 degrees C. The R450H protein was not detected at 37 degrees C but was clearly detected at one fourth the normal amount at 30 degrees C. These results indicate that both mutations were temperature-sensitive mild mutations, the result being the mildest phenotype of very-long chain acyl-CoA dehydrogenase deficiency.

Acyl-CoA Dehydrogenase, Long-Chain↗

PubMed2001

Activation-recovery intervals of 12-lead electrocardiograms before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

Preexcitation in Wolff-Parkinson-White syndrome (WPW) has been reported to induce long-lasting changes in ventricular recovery properties. However, there has not been a report concerning changes in the activation-recovery interval (ARI) in 12-lead ECGs before and after catheter ablation (CA) in patients with WPW syndrome. The present study compared changes in ARIs from 12-lead ECGs with those from body surface unipolar leads before and after CA to examine whether ARIs from limb leads of 12-lead ECGs provide useful information on changes in recovery properties in addition to the ARIs from precordial leads. The study population consisted of 27 manifest WPW patients with a left- (n=18, group A) or right-sided accessory pathway (n=9, group B). ARIs in leads I, II, and III were strongly correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. ARIs in leads aVR, aVL, and aVF showed a significant correlation with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. These correlations were maintained before and after CA. Furthermore, in group A, ARIs in lead V1 tended to increase on day 7 post CA compared with before CA and on day 1. In group B, ARIs in lead III significantly decreased on day 7 compared with before CA and on day 1. These findings suggest that ARIs from the limb leads of 12-lead ECGs may represent those from unipolar leads of a particular area over the body surface, and that ARIs from 12-lead ECGs may provide useful quantitative information on changes in recovery properties before and after CA in patients with manifest WPW syndrome.

Adolescent↗

PubMed2001

Size and composition changes in diaphragmatic fibers in rats exposed to chronic hypercapnia.

OBJECTIVE: To test the hypothesis that chronic hypercapnia changes the composition of the respiratory muscle by continuous augmentation of ventilation. MATERIALS AND METHODS: Eighteen male Wistar rats were housed in 10% CO(2) in air for 19 weeks, and their minute ventilation V(E) was measured every 6 weeks. The diaphragm, excited at 19 weeks of exposure, was classified as fiber type I, IIa, or IIb. Cross-sectional areas of individual fibers were measured. Fibers with a target-like appearance on reduced nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) stain also were counted. The data were compared with those of rats kept in room air. RESULTS: The mean (+/- SD) PaCO(2) after 19 weeks of sustained hypercapnia was 71.0 +/- 4.7 mm Hg. The V(E) remained at a high level until 12 weeks of exposure, and then it significantly decreased at week 18. In a comparison with the control rats, a larger number of type I fibers and a smaller number of type IIb fibers were found in the diaphragm of the chronically hypercapnic rats. In addition, the latter group's cross-sectional area revealed fibers of a significantly smaller diameter. Target-like fibers were observed in 5% of the NADH-TR-stained fibers in the chronically hypercapnic rats but were not seen in the control rats. CONCLUSION: By increasing the ratio of fatigue-resistant fibers, the diaphragm was able to adapt to a sustained load induced by hypercapnia. However, this adaptive process was accompanied by a degenerative change in the tissue.

Animals↗

PubMed2001

Difference in the occurrence of cardiovascular events according to class of antihypertensive agent, based on a follow-up study of Japanese hypertension patients.

We conducted a nested case-control study to evaluate the relationship between antihypertensive agent class and the incidence of initial cardiovascular events. A total of 7.443 patients being treated with an antihypertensive agent in 1985-1986 were enrolled for follow-up of up to 5 years. A total of 362 patients (186 males and 176 females) developed cardiovascular events. Age (5-year interval) and sex-matched controls were then randomly selected. A Multiple logistic regression analysis was done to control for the effects of confounding factors. The results showed that the use of diuretics and beta-blockers was associated with a reduced risk of cardiovascular events (odds ratio [OR] =0.65, 95% confidence interval [CI]: 0.49-0.86, and OR=0.75, 95% CI: 0.56-1.02, respectively), against a significantly raised risk associated with the use of calcium antagonists (OR=1.34, 95% CI: 1.03-1.80). However, as far as stroke was concerned, there was no significant association of risk with the use of any agent. The control group was found to be similar to the case group with respect to the changes in the treatment program during the follow-up period. The results suggest that the calcium antagonists used in Japan during the period of 1985-1990 constituted a potential risk for the occurrence of cardiovascular events.

Adrenergic beta-Antagonists↗

PubMed2001

Pulmonary fibrosis with intractable pneumothorax: new pulmonary manifestation of relapsing polychondritis.

Relapsing Polychondritis is a rare disease which causes the repetitive inflammation of cartilage and connective tissues. Although the large airway is sometimes involved and the stenosis of them often influences the prognosis of the patients, there have been few reports concerning the manifestation of the peripheral lung. A 60-year-old man with pulmonary fibrosis was admitted to a regional hospital due to sudden deafness, and then he suffered from relapsing polychondritis. During the steroid therapy, he also suffered from bilateral pneumothoraces. His computed tomogram revealed many bilateral bullae, emphysematous changes, and fibrotic changes in bilateral lungs. The mechanism of generating peripheral pulmonary manifestations is also discussed.

Blood Cell Count↗

PubMed2001

Postural tachycardia syndrome in a 28-year-old Japanese woman.

Postural tachycardia syndrome is defined as the development of orthostatic symptoms without orthostatic hypotension. We report a 28-year-old female patient with postural tachycardia syndrome who exhibited palpitation, low-grade fever and weight loss. Evaluation of autonomic nervous system functions showed that cardiovagal function was normal. Sweat response to acetylcholine was decreased. Excessive blood pressure elevation was seen in phase IV of the Valsalva maneuver. Pathophysiologic factors in this case were considered to be alpha adrenergic denervation and beta adrenergic hyperresponsiveness. It is important that this syndrome be widely recognized and properly diagnosed.

Adrenergic alpha-Agonists↗

PubMed2001

Primary lymphoma of spermatic cord.

Primary lymphomas of spermatic cord are extremely rare. In a review of the world medical literature, until now, only fourteen cases of spermatic cord lymphoma have been reported, and, furthermore, they have a poor prognosis even in patients with stage I disease. Herein, we report a new case of primary non-Hodgkin's lymphoma of the spermatic cord. In August, 1993, 76-year-old man visited an urological hospital with a compaint of a right intrascoral mass, and underwent orchiectomy. Macroscopically no invasive lesion in the testis was observed, and the tumorous lesion was restricted to the epididymis. The histopathological study indicated that he suffered from primary malignant lymphoma of the spermatic cord (B-cell, diffuse medium-sized cell type). As radiographic investigations showed no other invasive lesion, the patient was diagnosed to be in stage IE. He was followed only with clinical observation, and, in August, 1996, relapsed with extensive disease in the abdoninal cavity, and was transferred to our hospital. Fourty months after the orchiectomy, he died of progression of disease irrespective of the salvage radio-chemotherapies given to him.

Aged↗

PubMed2001

Diagnostic value of 201Tl-single-photon emission computerized tomography studies in cases of posterior fossa hemangioblastomas.

OBJECT: The 201Tl uptake index was evaluated for its usefulness in formulating a diagnosis of hemangioblastoma. Thallium-201-single-photon emission computerized tomography (SPECT) studies were performed in nine patients harboring hemangioblastomas in the posterior fossa and in five patients (six lesions) with gliomas in the posterior fossa. METHODS: The 201Tl uptake index was defined as the ratio of mean counts of isotope per pixel in the tumor to mean counts of isotope per pixel in the homologous region of the healthy brain. The 201Tl uptake indices of the early image (TlE) and that of the delayed image (TlD) were calculated. The isotope retention index (RI) was calculated as (TlE - TlD)/TlE. The TlE was 2.7 +/- 0.7 in hemangioblastomas and 2.9 +/- 1.7 in gliomas (mean +/- standard deviation). The TlD was 1.5 +/- 0.4 in hemangioblastomas and 2.4 +/- 1.6 in gliomas. There were no significant differences between hemangioblastomas and gliomas when TlEs and TlDs were compared. The isotope RI was 0.43 +/- 0.07 in hemangioblastomas and 0.15 +/- 0.1 in gliomas, showing a significantly higher RI in hemangioblastomas compared with gliomas (p < 0.01). CONCLUSIONS: Thallium-201 washout is significantly faster in hemangioblastomas. Hemangioblastoma is biologically benign, but contains a rich capillary network that forms a hypervascular tumor bed. Variations in its appearance on magnetic resonance images may cause difficulties in the differential diagnosis of hemangioblastoma. Thallium-201 SPECT studies can be used to distinguish hemangioblastomas from gliomas in the posterior fossa.

Adult↗

PubMed2001

Overexpression of platelet-derived growth factor B and downregulation of PDGF-receptor alpha in human immortalized fibroblasts.

Since immortalization of cells is critical in multistep carcinogenesis, efforts should be made to elucidate the mechanisms of the immortalization. To determine whether platelet-derived growth factor (PDGF) signal pathways play a role in immortalization of cells, we compared mRNA expressions of PDGFs and their receptors in three immortalized human fibroblast cell lines (SUSM-1, OUMS-24F, and KMST-6) with their normal parent cells. As a result, mRNA expression of PDGF-B (oncogene: c-sis) was upregulated in these immortalized cells. Unexpectedly, the expression of alpha- and beta-PDGF receptor genes was downregulated. PDGFR-alpha mRNA was remarkably decreased. When exogenous PDGFR-alpha was expressed transiently in the KMST-6 cells, the morphology of the cells resembled that of normal cells. These results suggest that the overexpression of PDGF-B (c-sis) and downregulation of PDGFR-alpha are related to the phenotypic characteristics of immortalized human cells.

Blotting, Northern↗

PubMed2001

[Thyroid tumor clinical path].

The need for improved medical treatment quality, efficient use of medical finances, and shortening of hospitalization have helped disseminate team medical care using a clinical path. In otorhinolaryngological head and neck surgery, medical facilities have created a clinical path for tonsillectomy, tympanoplasty, and radical sinus maxilectomy and ethmoidectomy. Such a path has not been made, however, for head and neck tumors. We created a clinical for thyroid tumor, then evaluated its advantages and disadvantages. We started the clinical path for benign thyroid tumors in April 2000 for 14 thyroid patients considered benign before surgery. In some cases, the clinical path was slightly changed to allow for delayed drain extraction or increasing the number of blood pressure measurements due to complications of hypertension. No variation was so major, however, that the clinical path had to be canceled. Its advantages were (1) average hospitalization shortened from 18.7 days to 14.5 days, and (2) the clinical path was useful for educating new staff. Since changes are more likely to occur in cases of tumors, medical staff and patients must understand that the clinical path basically represents the standard or average and may depend greatly on the individual condition. Since the clinical path represents the standard or average at a certain time point, it must be revised. A clinical path is, even so, useful in the treatment of tumor.

Adult↗