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Biomedical subjects

A Hanai

Publications and source records attributed to A Hanai.

At least 19 recordsLinked to original sources
PubMed2006

Sensory system-predominant distribution of leukotriene A4 hydrolase and its colocalization with calretinin in the mouse nervous system.

Leukotriene B4 is a potent lipid mediator, which has been identified as a potent proinflammatory and immunomodulatory compound. Although there has been robust evidence indicating that leukotriene B4 is synthesized in the normal brain, detailed distribution and its functions in the nervous system have been unclear. To obtain insight into the possible neural function of leukotriene B4, we examined the immunohistochemical distribution of leukotriene A4 hydrolase, an enzyme catalyzing the final and committed step in leukotriene B4 biosynthesis, in the mouse nervous system. Immunoreactivity for leukotriene A4 hydrolase showed widespread distribution with preference to the sensory-associated structures; i.e. neurons in the olfactory epithelium and vomeronasal organ, olfactory glomeruli, possibly amacrine cells, neurons in the ganglion cell layer and three bands in the inner plexiform layer of the retina, axons in the optic nerve and tract up to the superior colliculus, inner and outer hair cells and the spiral ganglion cells in the cochlea, vestibulocochlear nerve bundle, spinal trigeminal tract, and lamina II of the spinal cord. Double immunofluorescence staining demonstrated that most of the leukotriene A4-hydrolase-immunopositive neurons coexpressed calretinin, a calcium-binding protein in neurons. The ubiquitous distribution of leukotriene A4 hydrolase was in sharp contrast with the distribution of leukotriene C4 synthase [Shimada A, Satoh M, Chiba Y, Saitoh Y, Kawamura N, Keino H, Hosokawa M, Shimizu T (2005) Highly selective localization of leukotriene C4 synthase in hypothalamic and extrahypothalamic vasopressin systems of mouse brain. Neuroscience 131:683-689] which was confined to the hypothalamic and extrahypothalamic vasopressinergic neurons. These results suggest that leukotriene B4 may exert some neuromodulatory function mainly in the sensory nervous system, in concert with calretinin.

Animals↗
PubMed2001

Induction of apoptosis in human colon carcinoma cells HT29 by sublethal cryo-injury: mediation by cytochrome c release.

Cryosurgery is an emerging treatment for human solid tumors, notably colorectal liver metastasis. Cryosurgical procedures generate a thermal gradient of from at least -50 degrees C at the center of the tumor being treated to about 0 degrees C at the periphery. Cell death occurs by necrosis in the center, while the peripheral zone of frozen tumor harbors a mix of viable and dead tissue. In order to understand the mechanisms of cell death and survival in this peripheral area at risk for tumor recurrence, we have established an in vitro freezing system that mimics in vivo conditions of sublethal injury. HT29 colon cancer cells were subjected to freezing temperatures from -6 degrees C to -36 degrees C, thawed at room temperature for 30 min and rewarmed at 37 degrees C for a period of time. Post-freeze-thaw, cryolytic cells were evaluated by trypan blue exclusive assay. We also identified apoptotic cells after rewarming by cell shrinkage, nucleic condensation, TUNEL assay, DNA fragmentation and PARP degradation. The intensity of cryolysis and apoptosis was increased by lowering the freezing temperature. At -36 degrees C, all cells were dead immediately after freeze-thaw. A kinetic analysis of cryo-induced apoptosis showed that the commitment to enter apoptosis occurred right after the freeze-thaw period and lasted less than 8 hr after rewarming. We further demonstrated that freezing triggers one of the caspase cascade involved in apoptosis: release of cytochrome c from mitochondria to cytosol, followed by activation of caspase-9 and degradation of PARP. These results indicate the death of cancer cells under cryo-treatment at sublethal freezing temperature can be attributed 2 different modes, cryolysis as well as apoptosis. HT29 cells carrying p53 mutant have very quick response for induction of apoptosis by cryo-treatment and contain an intact pathway of caspase cascade. Further studies will address if mechanisms in cells with wild-type p53 will differ.

Apoptosis↗
PubMed2001

A new mouse model with cochleo-saccular type inner ear defects.

We found a new inner ear mutant exhibiting abnormal behavior, such as circling and head shaking, in a breeding stock of SJL/J mice. The traits are inherited in a simple autosomal-recessive fashion. Animals homozygous for the responsible gene, designated cosa, show no startle response to sounds and an inability to swim. In the inner ears of cosa/cosa homozygous, but not +/cosa heterozygous adults, histopathological features of severe damage that are typical for 'cochleo-saccular' or 'spotting' mutants have been demonstrated. We suggest here that the abnormal mice carry a mutation of a gene that is developmentally switched on in the early stages of development and is involved in endolymph homeostasis.

Animals↗
PubMed2000

Mouse myosin X: molecular architecture and tissue expression as revealed by northern blot and in situ hybridization analyses.

The structure of the coding region of mouse myosin X cDNA was determined. The predicted protein sequence indicated an approximately 240 kDa molecular mass with 2062 amino acids. When aligned with the structure predicted for calf myosin X (GenBank Accession No. U55042), extremely highly conserved pleckstrin homology domains and a myosin tail homology 4 domain were apparent in the tail region, suggesting their importance for myosin X's function. Northern blot analysis revealed the existence of a myosin X mRNA, 8.7 kb in size, in various mouse tissues, while a similar size of human type myosin X mRNA was recognized mainly in the testis. In addition to the adult-type transcripts in mice, a smaller embryo-specific mRNA, 4.8 kb in size, was identified in early to late embryonic stages, suggesting the presence of a shorter myosin X isoform in mouse embryos. In situ hybridization experiments with mouse testis revealed that myosin X mRNA was restricted to Sertoli cells at stages VIII-X of the spermatogenesis cycle, suggesting that myosin X is implicated in the supporting cells during the spermatid morphogenesis.

Amino Acid Sequence↗
PubMed2000

Reproducibility of diagnosis and its influence on the distribution of lung cancer by histologic type in Osaka, Japan.

The histologic types of lung cancer cases diagnosed in 1979-1980 (n=799) and 1987 (n=587) were independently reviewed by two pathologists in order to investigate the reproducibility of the diagnosis of the histologic type when the WHO classification (1981) was used. The specimens from 354 surgical cases and biopsy or cytology specimens from 1032 non-surgical cases were reviewed. The inter-observer agreement was 87.9% (kappa=0.79) for surgical cases and 81.4% (kappa=0.72) for non-surgical cases. When compared to the original diagnosis, the agreement was 86.8% (kappa=0.78) for surgical and 86.4% (kappa=0.79) for non-surgical cases in 1979-1980 and the agreement was 92.8% (kappa=0.87) for surgical and 89.1% (kappa=0.83) for non-surgical cases in 1987. By histologic type, no difference in the agreement was observed except for large cell carcinoma. The distribution of histologic types after the review differed only slightly (less than 6%) from the original distribution. This suggests that in Osaka, Japan, the diagnosis based on the WHO classification (1981) had only a limited influence on the distribution of histologic types, and is not a major reason for the changing trends in lung cancer incidence by histologic type.

Diagnosis, Differential↗
PubMed1999

Chromosomal localization of a gene responsible for vestibulocochlear defects of BUS/Idr mice: identification as an allele of waltzer.

Mice of the bustling mutant strain BUS/Idr have vestibulocochlear defects. bus/bus homozygotes, but not heterozygotes, are hyperactive and display an abnormal behavior such as circling, head bobbing and head tilting. To characterize BUS mice further, the auditory brain-stem response of the mutant was examined. In +/bus heterozygotes as well as control animals, the auditory brain-stem response was developmentally first recorded as early as 11 days of age and heterozygous and normal adults showed typical auditory brain-stem responses with five peaks in a threshold of 40-45 dB SPL. In contrast, bus/bus homozygotes showed no auditory brain-stem response at any age in response to stimuli up to 130 dB SPL, indicating that they are deaf throughout life. Linkage analysis revealed that the responsible gene, originally designated as bus, maps on chromosome 10, 1.09+/-0.9 cM distal to D10Mit127 and D10Mit59, and 0.72+/-0.51 cM proximal to three markers, D10Mit48, D10Mit112 and D10Mit258, at a site indistinguishable from that of the Albany waltzer, v(A/b). The results of allelism tests between BUS and Albany waltzer indicated that bus is allelic with v(Alb). From these data, we propose here that the bus mutation could represent another allele of waltzer, now designated v(bus).

Alleles↗
PubMed1999

Trends of lung cancer incidence by histologic type: a population-based study in Osaka, Japan.

We investigated trends of lung cancer incidence from 1974 to 1993 by histologic type, using data from the population-based cancer registry in Osaka, Japan. Since the proportion of cases with histologic types identified was not sufficiently high, sex- and age-specific incidence rates by histologic types were estimated assuming that the distribution of histologic types was the same across the same sex and age group regardless of reporting status. Cumulative risk from 0 to 74 years old for total lung cancer increased 1.3-fold from the period 1974-77 to 1986-89 and then plateaued in the period 1990-93 for both males and females. When divided into histologic types, cumulative risk for incidence of squamous cell carcinoma was almost constant during the study period for both males and females. During the same period, adenocarcinoma increased up to 1.4-fold for both males and females. This increase seemed to have reached a plateau recently for males, but not for females. Small cell carcinoma increased monotonously up to 1.6- to 1.7-fold for both males and females. Large cell carcinoma showed over 2-fold increase for both males and females; however, the estimates fluctuated due to the small number of cases. This study provides further evidence of a relative increase of adenocarcinoma compared to squamous cell carcinoma. Recent trends of tapering increase of lung cancer incidence should be confirmed by further observation.

Adenocarcinoma↗
PubMed1999

[UFT-E granule compliance in postoperative adjuvant chemotherapy].

UFT-E granules were administered as postoperative adjuvant chemotherapy to patients who had undergone surgery for gastric cancer, colorectal cancer or breast cancer. After treatment for one year, the dose conditions were investigated. The subjects were patients under 75 years of age in whom malignant tumors had been confirmed histologically, who had undergone curative resections, had no marked complications, and from whom personal informed consent had been obtained. As a rule, UFT-E granules were administered orally 450 mg (t.i.d.)/day continuously for one year beginning two weeks after surgery. The dose rate was studied from patient records and the tegafur blood concentrations on the 1st, 2nd, 6th, 8th and 12th month. The appearance of complications or clinical lab test abnormalities was also checked. A total of 19 cases were compliant among the 5 gastric cancer, 10 colorectal cancer, and 7 breast cancer patients. The mean administration period was 459 days (29-879 days), and the mean completion rate was 92.5%. The complications in 4 cases (21.1%) were relatively mild. A comparison of the prescribed dosage and patient records revealed a mean dose rate of 86.3%. From these findings, long-term administration of UFT-E granules with mild side effects is considered feasible. However, to achieve high compliance, it is considered necessary to gain a clear picture of dose conditions from patients records and other sources.

Administration, Oral↗
PubMed1997

Multivariate analysis of the prognostic factors of patients with unresectable synchronous liver metastases from colorectal cancer.

PURPOSE: It frequently is observed that widely varying prognoses are given for patients with the same extent of liver metastases from colorectal cancer, even though the same treatment is performed on these patients. One of the reasons for this variance is that prognostic factors for these patients have not been defined. This study was designed to elucidate which clinicopathologic factors were the most important in the prognosis of 73 patients with unresectable synchronous liver metastasis from colorectal cancer. METHODS: Univariate and multivariate analysis of 11 clinicopathologic factors were performed using the Cox proportional hazard model. Survival curves were generated using the Kaplan-Meier method. RESULTS: Extent of liver metastases was the most significant variable in this survival analysis, although the extent of lymph node metastases of the primary lesion also was significant. However, the method of treatment was not a significant determinant in the survival for patients with unresectable liver metastases. Median survival of patients with H1, H2, and H3 was 13, 12, and 6 months, respectively, and there was a significant difference between survival curves for patients with H1 and patients with H3. Median survival of patients with n0, n1, and n2 was 13, 7, and 7 months respectively, and there was a significant difference between survival curves for patients with n0 and patients with n2. Median survival of 6 patients with H1 and n0 and of 17 patients with H3 and n2 was 28 and 4 months, respectively. There was a significant difference in survival curves between these two groups. CONCLUSION: Longevity of patients with unresectable synchronous liver metastases from colorectal cancer is affected adversely by the presence of nodal metastases and extent of liver metastases. This should be considered in the planning treatment.

Adult↗
PubMed1997

Degenerative hairlets on the vestibular sensory cells in mutant bustling (BUS/Idr) mice.

The bustling mouse (BUS/Idr: bus) is a mutant mouse strain which exhibits deafness, bustling/hyperkinetic behaviour and functional disorders seemingly related to the vestibular system. This phenotype develops in homozygous (bus/bus) mice and has been shown from cross experiments to be genetically induced by a single autosomal recessive gene. We previously detected, with light and electron microscopy, post-natal degeneration of the inner ear sensory cells in homozygotes. In the present study, we examined, by electron microscopy, the development of pathological changes in the sensory epithelia of the macula acustica and crista ampullaris of homozygous mice of various ages, paying special attention to the detailed morphology of the sensory hairlets. The homozygous mice exhibited specific pathological changes: a decrease in the number of hairs; disarrangement of the kinocilium-stereocilia pattern; and, fused and/or very large stereocilia. Homozygotes also frequently exhibited apical cytoplasmic herniation, or bleb of hair cells, as well as a degenerated kinocilium in the sensory epithelium. Heterozygotes showed similar changes, but to a lesser degree and frequency. As for the vestibular organs, similar pathological changes had developed at day, 17 of gestation. These pathological findings and onset suggest that the BUS mouse may be a mutant mouse strain distinct from other reported strains which display similar behaviour, and may be a useful animal model for the study of human degenerative vestibular disorders.

Animals↗
PubMed1996

Present status and research activities of cancer registries in Japan.

Population-based cancer registries in Japan were first established in the cities of Hiroshima and Nagasaki in 1957-1958 for assessing radiation effects and in Miyagi in 1959 for promoting epidemiological researches, while most other prefectures in Japan set up cancer registries as a part of their own cancer programs. This resulted in the broader use of registry data in Japan. In 1975, the Research Group for Population-based Cancer Registration in Japan was first organized with a research grant under the National Cancer Research Promotion Program. Since then, continuous efforts have been made by the Group to improve the quantity and quality of registry data and to develop methodologies to utilize it. Studies being conducted using registry data cover (1) descriptive epidemiology, (2) analytical epidemiology, (3) evaluation of screening programs, and (4) evaluation of regional cancer medical care. In 1992, 32 regional cancer registries which were operating in Japan set up the Japanese Association of Cancer Registries. However, there are still many difficulties to overcome in order to achieve completeness of reporting in registries. Further improvement of reporting rate, together with standardization of registry data are left for future efforts.

Epidemiology↗
PubMed1996

[The effect of intraportal chemotherapy in terms of administered dose of 5-FU].

Forty-six patients with colorectal cancer were studied for the effects of intraportal chemotherapy in terms of the administered dose of 5-FU. No liver metastases occurred in patients with a total dose of more than 4 g of 5-FU. The five-year survival rate for patients with a total dose of more than 4 g of 5-FU was 98%, which was better than that for control (72%). In patients administered 500 approximately 600 mg/body/day of 5-FU, the concentration of 5-FU in the peripheral blood was 0.022 approximately 0.027 microgram/ml. Liver dysfunction occurred in 22%, 33%, and 80% of patients administered less than 4 g, 4 approximately 4.9 g, or more than 5 g of 5-FU, respectively, but almost all of them were grade 1. These results suggest that intraportal chemotherapy administered with a total of more than 4 g of 5-FU was effective for prevention of liver metastases after resection of colorectal cancer.

Colorectal Neoplasms↗
PubMed1995

Survival rates of childhood cancer patients in Osaka, Japan, 1975-1984.

Survival rates for childhood cancers were analyzed with a total of 2,209 cases who were registered in a population-based cancer registry in Osaka, Japan in 1975-1984. These cases were reclassified according to Birch's classification and the survival rate of each diagnostic group was calculated by Kaplan-Meier methods. Death certificate-only cases, which amounted to 3.9% of all incidence, were excluded from the calculation. The five-year cumulative survival rate for both sexes was 46% for all cancer children. Among 12 major diagnostic groups, the most favorable survival was seen in retinoblastoma (87.5%), followed by renal tumors, epithelial neoplasms, and gonadal and germ-cell tumors. The outcome was unfavorable in leukemias, sympathetic nervous system tumors, hepatic tumors and malignant bone tumors. Comparing the survival in 1975-1979 with that in 1980-1984, the rate for all childhood cancer rose from 41% to 51%. Improvement in survival was also observed in 4 groups; acute lymphocytic leukemia, acute non-lymphocytic leukemia, non-Hodgkin's lymphoma and osteosarcoma. One attributable factor for the rise of survival was proved to be improvement of medical treatment by Cox's hazard model analysis. Comparison of survival rates in Osaka with those in England and the U.S. revealed that the prognosis for acute lymphocytic leukemia and acute non-lymphocytic leukemia was less favorable in Osaka than in England and the U.S.

Adolescent↗
PubMed1995

[Pharmacokinetic study in biochemical modulation therapy of UFT with leucovorin tablet].

Preoperative oral treatment with UFT and leucovorin tablet was performed. Pharmacokinetics, degree of degeneration in the tumor tissue and side effects were studied in 34 patients with colorectal cancer preoperatively given 400 mg/day of UFT with 20 mg/day of leucovorin tablet or 400 mg/day of UFT alone. Results were as follows; 1) there was no significant difference between UFTL group and UFT group regarding concentration of FdUMP in the tumor tissue. In UFTL group, concentration of FdUMP was higher in the tumor tissue of moderately differentiated adenocarcinoma than that of well differentiated adenocarcinoma. No significant differences regarding concentration of FdUMP were obtained between diploid and aneuploid groups. 2) TS inhibition rate in the tumor tissue was 66.8% in UFTL group and 53.2% in UFT group, and there was a significant difference between these two groups. TS inhibition rate in the tumor tissue was higher than that in the normal tissue either in UFTL group or UFT group. However, there were no significant differences of TS inhibition rates regarding differentiation of tumor tissue or DNA ploidy pattern. 3) Degree of degeneration of more than Grade 2 was not obtained in any patients of either UFTL or UFT group. 4) There was no change in blood laboratory data between before and after medication. Only one patient complained Grade 1 pruritus in UFTL group. These results suggest that oral biochemical modulation therapy of UFT with leucovorin tablet is effective because of pharmacokinetically high anti-tumor effect and minimal side effects.

Adenocarcinoma↗
PubMed1994

Incidence of childhood cancer in Osaka, Japan, 1971-1988: reclassification of registered cases by Birch's scheme using information on clinical diagnosis, histology and primary site.

In 1971-1988, 4,021 malignant tumors occurring among children under 15 years of age were registered in the Osaka Cancer Registry, a population-based registry which covers Osaka Prefecture, Japan. These patients were reclassified into 12 diagnostic groups by Birch's scheme using information on clinical diagnosis, histology and primary site. The annual age-standardized incidence rate for childhood cancer per million children was 130.3 for males and 104.9 for females in 1971-88. Comparing the incidence rates for both sexes in 1981-88 with those in 1971-80 in Osaka, we observed a significant decrease of acute non-lymphocytic leukemia (ANLL) and a significant increase of all cancers, acute lymphocytic leukemia, non-Hodgkin lymphoma, sympathetic nervous system tumors, soft-tissue sarcomas, and gonadal and germ-cell tumors. Age-standardized incidence rates in around 1971-80 of the above-mentioned diagnostic groups were compared among 4 population-based registries; Osaka, Miyagi (Japan), SEER (U.S.), and the National Registry of Childhood Tumors (England and Wales). Rates for ANLL and gonadal and germ-cell tumors were higher and those for other diagnostic groups were lower in Osaka, especially for Hodgkin's disease. Thus, in 1980-88 in Osaka, rates for Hodgkin's disease remained low and rates for gonadal and germ-cell tumors increased, though rates for other cancers appeared to resemble the levels in caucasian populations. The incidence of childhood cancer in Japan was estimated according to the diagnostic groups in Birch's scheme.

Adolescent↗
PubMed1994

Incidence of second primary cancers in Osaka residents, Japan, with special reference to cumulative and relative risks.

This study was conducted to examine the incidence rates and cumulative risks of second primary cancers in Osaka and to compare the observed number of second primary cancers with the expected number calculated using cancer incidence rates among Osaka residents. Study subjects were all reported cases aged 0-79 who were first diagnosed as having a first primary cancer between 1966-86. Incidence of second primary cancer among the study subjects was examined through to the end of 1989. The total number of study subjects was 217,307. During the follow-up period (mean duration: 3.7 years), second primary cancers developed in 5,071 patients (2.3%). Incidence of synchronous (interval < 3 months) and metachronous (interval > or = 3 months) second primary cancers increased in the later years. Incidence rates of second primary cancers were significantly associated with gender (male), age and calendar year at diagnosis of the first cancer. Based on the incidence rates, cumulative risk of developing metachronous second primary cancer was calculated. The ten-year cumulative risk was estimated as 10% for those who developed their first cancer during their sixties in 1978-83. The observed number of second primary cancers (including synchronous) was compared with the expected number. The ratios of observed-to-expected numbers were generally lower than 1.0 among those who developed their first cancer in 1966-77, while these ratios were higher than 1.0 among those who developed their first cancer in 1978-86. The ratios were much higher than 1.0 among those who developed their first cancer in their childhood and youth. Patients who had developed cancer of the colon, larynx, lung, bladder, or breast (female) showed significantly higher risk of developing second primary cancer during the period 1-4 years after diagnosis of the first cancer.

Adult↗