Biomedical subjects

Kazuhiko Hoshi

Publications and source records attributed to Kazuhiko Hoshi.

At least 19 recordsLinked to original sources

PubMed2006

Commercial cows' milk has uterotrophic activity on the uteri of young ovariectomized rats and immature rats.

Cows' milk contains considerable quantities of estrogens, mainly in the form of estrone sulfate (ES). To determine whether the commercial milk has any biologically significant hormonal effects, 2 series of uterotrophic tests were performed, 1 with young ovariectomized rats and the other with sexually immature rats. Thirty-six rats were used for each test. They were divided into 3 groups of 12 animals each, and were kept for 7 days on powdered chow with 1 of 3 drinking solutions: low-fat milk (LFM), artificial milk (AM, negative control), or AM containing ES at 100 ng/ml (positive control). At autopsy, both the wet and blotted uterine weights were measured. The cell heights of uterine epithelia in ovariectomized rats were also determined. The significance of differences among groups was tested by Dunnett's multiple comparisons test. In each test, the weights of the uteri in the LFM group were significantly greater than those of the respective weights in the AM group (p < 0.01). Furthermore, in ovariectomized rats, the uterine epithelial-cell height in the LFM group was significantly greater than that observed in the AM group (p < 0.01). The uterotrophic effect of 100 ng/ml ES solution was greater than that of LFM in immature rats (p < 0.01), whereas the effect of the solution was almost comparable to that of LFM in young ovariectomized rats (p > 0.05). In conclusion, commercially available milk has uterotrophic effects in both young ovariectomized rats and sexually immature rats.

Animals↗

PubMed2005

Analysis of national representative opinion surveys concerning gestational surrogacy in Japan.

OBJECTIVE: Although gestational surrogacy offers several advantages, this procedure has given rise to some ethical and legal issues. We aimed to clarify the factors affecting the attitude of the Japanese toward gestational surrogacy. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Nationwide opinion surveys concerning assisted reproductive technologies (ART) were carried out in 1999 and 2003. Participants included 2568 and 3647 people from the general public surveyed in 1999 and 2003, respectively (1564 people received only the questionnaire, and 2083 people received a questionnaire and brochure about ART). MAIN OUTCOME MEASURE: Multivariate-adjusted odds ratio and 95% confidence interval from logistic regression models for factors affecting the attitude toward gestational surrogacy. RESULTS: In both surveys, approximately half of respondents approved of gestational surrogacy; 20-30% disapproved of the procedure. People with high socioeconomic status clearly expressed their opinion on this issue. A liberal attitude toward gender role promoted approval of gestational surrogacy; a liberal attitude toward family had the opposite effect. CONCLUSION: Our findings suggest that socioeconomic status affects people's expression of their opinion regarding this issue, while attitudes toward this procedure were influenced by individual belief. Considering socioeconomic status and diversity of individual belief is required for further discussion on this topic.

Attitude to Health↗

PubMed2005

Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats.

BACKGROUND: : Voglibose is an alpha-glucosidase inhibitor used to decrease postprandial hyperglycemia in diabetic patients. Although clinical concern has not yet been raised, hepatic dysfunction has been reported in a few patients taking this drug. METHOD: : In the present study, we studied the effects of voglibose on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP) in rats, since both of these agents exert their effects through isoforms of cytochrome P450. Male Sprague-Dawley rats were given a daily ration (20g) of powdered chow diet containing 0, 2.5, 5.0 or 10.0mg/100g of voglibose. Three weeks later, the rats were challenged with either 0.50g/kg CCl(4) orally or 0.75g/kg APAP intraperitoneally for biochemical examinations or killed for an in vivo metabolism study. RESULTS: : Voglibose at these three experimental doses potentiated CCl(4) and APAP hepatotoxicity, as evidenced by significantly increased levels of both plasma asparate transaminase (AST) and alanine transaminae (ALT). The glutathione (GSH) content was decreased while malondialdehyde (MDA) increased in the liver after CCl(4) or APAP administration. Hepatic cytochrome P450 2E1 (CYP2E1) concentration was increased at doses of 5.0 and 10.0mg/100g of voglibose and its activity increased in the three voglibose dosage groups, while hepatic cytochrome P450 3A (CYP3A) and cytochrome P450 1A2 (CYP1A2) were only slightly changed at any dose. CONCLUSION: : Our study demonstrated that voglibose can potentiate CCl(4) and APAP hepatotoxicity in rats by inducing hepatic CYP2E1.

Journal Article↗

PubMed2005

Novel human alpha-fetoprotein mRNA isoform lacking exon 1 identified in ovarian yolk sac tumor.

OBJECTIVE: Alpha-fetoprotein (AFP) is a major fetal serum protein, the biologic role of which has not been not fully elucidated. Recently, existence of a novel AFP mRNA isoform (del.1 AFP mRNA isoform), which is transcribed from the intron A (the intron between exons 1 and 2), has been reported in murine yolk sac and fetal liver. In the present study, we intended to identify the human homologue of the murine AFP mRNA isoform in the yolk sac tumor. METHODS: To investigate the existence of the mRNA isoform (which we termed the "AFP-C mRNA isoform"), reverse transcription-polymerase chain reaction (RT-PCR) was used. Moreover, the expression analysis of the AFP-C cDNA isoform using the AFP-negative human cell line was carried out. RESULTS: RT-PCR revealed the existence of the AFP-C mRNA isoform in the yolk sac tumor and human hepatocellular carcinoma cells. The expression analysis clarified that the molecular size of the AFP-C was approximately 65 kd, and that the protein was not secreted, in contrast to the traditional AFP. CONCLUSION: From these results, the existence of the AFP-C mRNA isoform has been demonstrated for the first time in humans. The AFP-C located in cytoplasm possibly plays physiologic/pathogenic roles distinct from those of the traditional AFP in the yolk sac tumor and hepatocellular carcinoma.

Adenocarcinoma↗

PubMed2005

Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia: a report of four cases with histochemical and immunohistochemical analyses.

We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia.

Adenocarcinoma↗

PubMed2005

Absence of human papillomavirus infection in minimal deviation adenocarcinoma and lobular endocervical glandular hyperplasia.

The human papillomavirus (HPV) is basically always detected in squamous cell carcinoma of the cervix and its precursors; a high incidence of HPV also has been reported in adenocarcinoma and adenocarcinoma in situ of the uterine cervix. Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci in 1999. It is difficult to differentiate minimal deviation adenocarcinoma (MDA) from LEGH preoperatively or postoperatively by clinical and pathologic features. The relationships between HPV and MDA or LEGH have not been studied well because of the rare incidence of the two diseases. To our knowledge, the HPV status in LEGH has not been reported. This study was designed to investigate HPV infection in MDA and LEGH, using the polymerase chain reaction (PCR) technique. Tumor tissue lesions were microdissected and the detection of HPV and its typing were analyzed by PCR-based assay. As the control, HPV DNA was detected in all cases of squamous cell carcinoma and three of five cases of adenocarcinoma. However, no HPV DNA was detected in any of the 10 cases of LEGH or in the 3 cases of MDA. These results suggest that MDA and LEGH are probably not related to HPV infection.

Adenocarcinoma↗

PubMed2005

Heterozygous hemophilia developed during pregnancy.

In rare cases, patients with heterozygous hemophilia show bleeding tendency due to a low factor VIII activity of <20%. Here we describe a case of heterozygous hemophilia that developed during pregnancy. The patient was a 33-year-old Japanese woman whose father and brother both showed elevated nasal bleeding tendencies. However, they had received no medication for this condition. At 26 weeks' gestation she experienced heavy nasal bleeding. The prothrombin time and platelet count were normal, but the activated partial thromboplastin time was prolonged. Premature rupture of the membrane occurred, and an emergency cesarean section was carried out at 28 weeks' gestation. A diagnosis of heterozygous hemophilia was made after the cesarean section. Hemophilia crisis and heterozygous hemophilia require special obstetric care, with close liaison with a hematologist. Guidelines for the management of such cases should be available and observed.

Adult↗

PubMed2005

Chromatoid bodies: aggresome-like characteristics and degradation sites for organelles of spermiogenic cells.

We investigated the localization of several markers for lysosomes and aggresomes in the chromatoid bodies (CBs) by immunoelectron microscopy. We found so-called aggresomal markers such as Hsp70 and ubiquitin in the core of the CBs and vimentin and proteasome subunit around the CBs. Ubiquitin-conjugating enzyme (E2) was also found in the CBs. In tubulovesicular structures surrounding the CBs, lysosomal markers were detected but an endoplasmic reticulum retention signal (KDEL) was not. Moreover, proteins located in each subcellular compartment, including the cytosol, mitochondria, and nucleus, were detected in the CBs. Signals for cytochrome oxidase I (COXI) coded on mitochondrial DNA were also found in the CBs. Quantitative analysis of labeling density showed that all proteins examined were concentrated in the CBs to some extent. These results show that the CBs have some aggresomal features, suggesting that they are not a synthetic site as proposed previously but a degradation site where unnecessary DNA, RNA, and proteins are digested.

Animals↗

PubMed2004

Low-fat milk promotes the development of 7,12-dimethylbenz(A)anthracene (DMBA)-induced mammary tumors in rats.

Commercial cow milk contains considerable amounts of estrogens. Our study assessed the effect of commercial low-fat milk on the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. Eighty 6-week-old female Sprague-Dawley rats received a single oral dose of 5 mg DMBA. Twenty-four hours later, the animals were divided into 4 groups of 20 animals each and given 1 of 4 test solutions for 20 weeks as their drinking liquid: low-fat (1%) milk (M), artificial milk (A), estrone sulfate solution (0.1 microg/ml, E), or tap water (W). The artificial milk was formulated to supply essentially the same calories as the milk. The low-fat milk contained 378 pg/ml estrone sulfate. Tumor incidence, the cumulative number of tumors and the sum of tumor diameters were higher in the M and E groups than in the A or W groups. Overall, the development of mammary tumors was in the order: M = E > A = W. Whereas the plasma 17beta-estradiol concentration in the M group was the 2nd highest after the E group, the plasma level of insulin-like growth factor (IGF-I) was significantly higher in the M group than in the other 3 groups. In conclusion, commercially available low-fat milk promotes the development of DMBA-induced mammary tumors in rats. The degree of the promotion is almost comparable to that of 0.1 microg/ml estrone sulfate. The high estrogen content in the milk may be responsible for the promotional effects, acting in concert with other hormones such as IGF-I.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2004

Estrogen: one of the risk factors in milk for prostate cancer.

Studies to elucidate the cause of prostate cancer have met with little success to date. Epidemiological studies suggested that milk consumption is probably as one of the risk factors for prostate cancer. The studies thus focused on the fat and calcium in milk, but reached no definitive conclusion. According to the measurements of estrogen levels in milk by different studies, it was suggested that estrogen in milk was a possible risk to cause prostate cancer. One reason supporting this hypothesis is that Western diet (characterized by milk/dairy products and meat) causes a trend of increasing levels of estrogens, and Western males show a higher incidence rate of prostate cancer than Asia males. Estrogen levels in prostate fluid are also correlated very well with the prostate cancer. During several decades, estrogens, together with testosterone, was commonly used to induce the rodent model of prostate cancer. Our hypothesis also was supported by the presence of estrogen receptors in the prostate gland and the genotoxic role of estrogens on the prostate gland, as possible mechanisms. Therefore, if modern milk consumption does expose consumers to high levels of estrogen and plays an adverse role in prostate cancer, action should be taken to produce the noncontaminant milk.

Animals↗

PubMed2004

Cytoplasmic transfer in the mouse in conjunction with intracytoplasmic sperm injection.

Cytoplasmic transfer (CT) from a donor to a recipient oocyte has been used clinically to facilitate human pregnancies. Data reported here describe the first characterization of CT coincident with intracytoplasmic sperm injection in the mouse system. Sibling oocytes were used to transfer 2, 4, or 6 pl of ooplasm to a recipient egg along with a sperm head using piezo-actuated injection. Survival and fertilization after CT were comparable to controls at 2 pl and 4 pl, but survival was significantly reduced with 6 pl volumes. Development to the blastocyst stage was also inversely related to CT volume, with some decline beginning with the 4 pl CT group. However, some blastocysts did develop in all of the groups. The results are in contrast with human eggs, which tolerate larger CT volumes. Results indicate that the mouse system can be used to characterize the transfer of exogenous materials concomitant with sperm injection, provided that the CT volume is not excessive.

Animals↗

PubMed2004

Oocyte mitochondria: strategies to improve embryogenesis.

Mitochondria play a central role to provide ATP for fertilization and preimplantation embryo development in the ooplasm. The mitochondrial dysfunction of oocyte has been proposed as one of the causes of high levels of developmental retardation and arrest that occur in preimplantation embryos generated using Assisted Reproductive Technology. Cytoplasmic transfer (CT) from a donor to a recipient oocyte has been applied to infertility due to dysfunctional ooplasm, with resulting pregnancies and births. However, neither the efficacy nor safety of this procedure has been appropriately investigated. In order to improve embryogenesis, we observed the mitochondrial distribution in ooplasma under the several conditions using mitochondrial GFP-transgenic mice (mtGFP-tg mice) in which the mitochondria are visualized by GFP. In this report, we will present our research about the mitochondrial distribution in ooplasm during early embryogenesis and the fate of injected donor mitochondria after CT using mtGFP-tg mice. The mitochondria in ooplasm from the germinal vesicle stage to the morula stage were accumulated in the perinuclear region. The mitochondria of the mtGFP-tg mouse oocyte transferred into the wild type mouse embryo could be observed until the blastocysts stage, suggesting that the mtGFP-tg mice oocyte is very useful for visual observation of the mitochondrial distribution in the oocyte, and that the aberrant early developmental competences due to the oocyte mitochondrial dysfunction may be overcome by transferring the "normal" mitochondria.

Animals↗

PubMed2004

Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies.

Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further.

Age Factors↗

PubMed2004

Ubiquitin signals in the developing acrosome during spermatogenesis of rat testis: an immunoelectron microscopic study.

The localization of ubiquitin (UB) signals in the acrosomes of rat spermiogenic cells was investigated by immunoelectron microscopy using two anti-UB antibodies: UB1, reacting with ubiquitinated proteins and free UB; and FK1, recognizing polyubiquitinated proteins but not monoubiquitinated proteins or free UB. Labeling of UB by UB1 (UB1 signal) was detected in the acrosomes at any stage of differentiation. In step 1 spermatids, UB1 signals were detected on the cytoplasmic surface and in the matrix of transport vesicles located between the trans-Golgi network and the acrosome. Weak signals were detected in acrosomal granules within acrosome vesicles that had not yet attached to the nucleus. In step 4-5 spermatids, the acrosome vesicles had enlarged and attached to the nucleus. Strong gold labeling was noted in a narrow space between the outer acrosomal membrane and the developing acrosomal granule, where a dense fibrous material was observed on routine electron microscopy, whereas the acrosomal granule was weakly stained by UB1 antibody. In step 6-8 spermatids, UB1 signals were detected in the fibrous material that expanded laterally to form a narrow electronless dense zone between the acrosomal granule and the outer acrosomal membrane. Labeling in the acrosomal granule increased. In step 9-11 spermatids, UB1 signals were confined to the narrow zone from the tip of the head to the periphery of the ventral fin. The matrix of the acrosome was weakly stained. In epididymal sperm, UB1 labeling in the acrosome decreased without any pretreatment, whereas staining was noted in a spot in the neck region and in the dorsal fin after trypsin digestion. On the other hand, the staining pattern with FK1 was quite different from that with UB1. The trans-Golgi network was weakly stained but the cis-Golgi network was strongly stained. The dense fibrous material just beneath the outer membrane was never stained with FK1. The results suggest that UB on the surface of transport vesicles is involved in anterograde transport from the Golgi apparatus to the acrosome. The physiological role of UB in acrosomes is not clear. Two candidates for monoubiquitinated proteins in the acrosome, which have a UB-interacting motif, were found by cyber screening.

Acrosome↗

PubMed2003

Transient decrease in the CD45RA expression on T lymphocytes in neonates with fetal distress.

To determine the expression of CD45 isoforms on T lymphocytes in neonates with fetal distress and to evaluate its diagnostic accuracy, peripheral blood samples were examined in 53 neonates who were classified into one of three groups: group I: 'control' group (n = 23), group II: 'mild distress' group (n = 15), and group III: 'moderate distress' group (n = 15). The expression of CD3 (mean +/- SD 24.2 +/- 10.1%), CD4 (23.0 +/- 5.7%), and CD45RA (27.3 +/- 9.6%) on total lymphocytes and the expression of CD45RA on CD4+ T lymphocytes (13.7 +/- 4.7%) in group III were significantly lower than in the other two groups 0-3 days after birth. Sensitivity and specificity of the CD45RA expression on CD4+ T lymphocytes for discrimination of group III were calculated as 0.79 and 1.0, respectively, when the cutoff value was 22.7%. The low CD3, CD4, and CD45RA expression returned to normal levels 10 days and more after birth. There were no differences in the CD8 and CD45RO expression between the groups. We conclude that CD4+ T lymphocytes from neonates with fetal distress show a transient decrease in the CD45RA expression without an increase in the CD45RO expression, and, therefore, analysis of the CD45 isoform expression is useful for laboratory evaluation of fetal distress.

CD3 Complex↗

PubMed2003

Spatiotemporal changes of levels of a moonlighting protein, phospholipid hydroperoxide glutathione peroxidase, in subcellular compartments during spermatogenesis in the rat testis.

We studied temporal changes in the subcellular localization and levels of a moonlighting protein, phospholipid hydroperoxide glutathione peroxidase (PHGPx), in spermatogenic cells and mature sperm of the rat by immunofluorescence and immunoelectron microscopy. The PHGPx signals were detected in chromatoid bodies, clear nucleoplasm, mitochondria-associated material, mitochondrial aggregates, granulated bodies, and vesicles in residual bodies in addition to mitochondria, nuclei, and acrosomes as previously reported. Within mitochondria, PHGPx moved from the matrix to the outermost membrane region in step 19 spermatid, suggesting that this spatiotemporal change is synchronized with the functional change of PHGPx in mitochondria. In the nucleus, PHGPx was associated with electron-lucent spots and with the nuclear envelope, and PHGPx in the latter region increased after step 16. In early pachytene spermatids, PHGPx signals were noted in the nuclear material exhibiting a very similar density to chromatoid bodies and in the intermitochondrial cement, supporting the previous proposal that chromatoid bodies originate from the nucleus and intermitochondrial cement. The presence of PHGPx in such various compartments suggested versatile roles for this protein in spermatogenesis. Quantitative immunoelectron microscopic analysis also revealed dynamic changes in the labeling density of PHGPx in different subcellular compartments as follows: 1). Total cellular PHGPx rapidly increased after step 5 and reached a maximum at step 18; 2). mitochondrial labeling density increased after step 1 and achieved a maximum in steps 15-17; 3). nuclear labeling density suddenly increased in steps 12-14 to a maximum; 4). in cytoplasmic matrix, the density remained low in all steps; and 5). the labeling density in chromatoid bodies gradually decreased from pachytene spermatocytes to spermatids at step 18. These spatiotemporal changes in the level of PHGPx during the differentiation of spermatogenic cells to sperm infer that PHGPx plays a diverse and important biological role in spermatogenesis.

Animals↗

PubMed2003

Isoform/variant mRNAs for sex steroid hormone receptors in humans.

The open reading frames of human sex steroid hormone receptors (hSSHRs) are composed of eight exons. In addition, the presence of various exons - including 5'-untranslated exons, alternative coding exons and novel 'intronic' exons - has been demonstrated in the genes encoding hSSHRs. The isoform/variant hSSHR mRNAs generated from thes e exons can be tentatively classified into seven types. In type 1, different mRNAs are generated with the use of alternative transcription start sites. In type 2, one or more exons are skipped. In type 3, one or more exons are duplicated. In type 4, distinct mRNAs containing different 5'-untranslated exon(s) are synthesized. In type 5, distinct mRNAs possessing different coding exon(s) are generated. In type 6, mRNA is synthesized by intronic exons and coding exons 4/5-8. In type 7, mRNA with insertion of intronic exon(s) is generated. Here, we review the isoform/variant hSSHR mRNAs and the structure of the genes encoding them.

Alternative Splicing↗

PubMed2003

The relationship between carbohydrate intake and glucose tolerance in pregnant women.

OBJECTIVE: We verified whether a misdiagnosis of gestational diabetes mellitus can result in pregnant women when glucose tolerance has deteriorated after a low-carbohydrate meal, and tried to elucidate the mechanism behind the different outcome of the test. STUDY DESIGN: Twenty-seven pregnant women were given directions for their evening meal the day before each of two 75-g oral glucose tolerance tests (OGTT). The evening meal was either a low-carbohydrate meal (carbohydrate, 6.7%; Low), or a high-carbohydrate meal (carbohydrate, 85.7%; High). RESULTS: The OGTT showed that the glucose tolerance was significantly impaired after Low than after High, with a significant increase of fasting plasma non-esterified fatty acids (NEFA) level. Moreover, the insulinogenic index (I-I) after High significantly decreased than that after Low. CONCLUSIONS: The present data suggests that there is a risk of misdiagnosis of impaired glucose tolerance with only one intake of this extremely low-carbohydrate meal on the evening before testing. The decrease of insulin secretion and the activation of glucose-fatty acid cycle may be considered as the mechanism.

Adult↗