Biomedical subjects
C Kaneko
Publications and source records attributed to C Kaneko.
Donor selection in Japan: a trial of new criteria with predonation haemoglobin testing.
BACKGROUND AND OBJECTIVES: In Japan, eligibility for blood donation depends on blood specific gravity, which does not directly measure blood haemoglobin. Additionally, the criteria are not based on normal values. Therefore, we investigated the feasibility of predonation screening by using actual haemoglobin levels, and adopted a new criterion based on the normal range for men. MATERIALS AND METHODS: Using a portable device, we measured haemoglobin in 1032 prospective blood donors, then applied this method to all blood donations. The criterion for men was set at the 95th percentile of haemoglobin distribution, namely 13.0 g/dl and 13.5 g/dl, respectively, for 200-ml and 400-ml donations. That for women remained unchanged. RESULTS: The percentage of men ineligible by these criteria increased from 0.6 to 1.5%, while that of women decreased from 16.5 to 14.6%. Donors with abnormal haemoglobin levels were referred to hospitals. CONCLUSION: Predonation measurement of haemoglobin concentration, combined with the referral of those with abnormal values, provided a health benefit to that population.
Spatial and topological distribution of progesterone receptor A and B isoforms during human development.
Progesterone receptor (PR) is a member of the nuclear receptor superfamily. To date, two isoforms of PR have been identified, PR-A and PR-B. In progesterone responsive tissues, the relative ratio of PR-A and PR-B is considered to contribute to the tissue-specific actions of progesterone. In this study, we examined the distribution of PR-A and PR-B in human fetal tissues ranging from 11 to 40 gestational weeks using immunohistochemistry and RT-PCR analysis. PR immunoreactivity was detected in a wide range of fetal tissues until 20 weeks of gestation, but gradually decreased towards the late gestational period. However, PR continued to remain positive throughout the gestational period in the interstitial cells of Cajal and endocrine tissues. PR-B was demonstrated as the predominant isoform in comparison to PR-A in all fetal tissues examined. These findings suggest that progesterone may be involved in the development of fetal organs throughout the gestational period.
Deafness due to degeneration of cochlear neurons in caspase-3-deficient mice.
Mice that lack caspase-3, which functions in apoptosis, were generated by gene targeting and shown to undergo hearing loss. The ABR threshold of the caspase-3(-/-) mice was significantly elevated compared to that of caspase-3(+/+) mice at 15 days of age and was progressively elevated further by 30 days. Distortion product otoacoustic emissions were not detectable in caspase-3(-/-) mice at 15 days of age. Caspase-3(-/-) mice exhibited marked degeneration of spiral ganglion neurons and a loss of inner and outer hair cells in the cochlea at 30 days of age, although no such changes were apparent at 15 days. The degenerating neurons manifested features, including cytoplasmic vacuolization, distinct from those characteristic of apoptosis. Spiral ganglion neurons and cochlear hair cells thus appear to require caspase-3 for survival but not for initial development. The mapping of both the human caspase-3 gene and the locus responsible for an autosomal dominant, nonsyndromic form of hearing loss (DFNA24) to chromosome 4q35 suggests that the caspase-3(-/-) mice may represent a model of this human condition.
Immunohistochemical distribution of 11beta-hydroxysteroid dehydrogenase in human eye.
11beta-hydroxysteroid dehydrogenase (11beta-HSD) regulates local actions of corticosteroids at glucocorticoid and mineralocorticoid receptors. Corticosteroids are thought to play important roles in ocular function. However, mechanisms of intraocular corticosteroid action are still unclear. Therefore, in this study, we examined the immunohistochemical localization of 11beta-HSD type 1 (11beta-HSD1), 11beta-HSD type 2 (11beta-HSD2), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in human ocular tissues from patients (6 months to 78 years of age; n = 10) retrieved from surgical pathology files. Both 11beta-HSD2 and MR immunoreactivity was detected only in non-pigmented epithelium of the ciliary body, but was undetectable in cornea, lens, iris, retina, choroid and sclera, in all the cases examined. GR was detected in all cell types in the human eye. 11beta-HSD1 immunoreactivity was not detected in the human eye in this study. These results suggest that 11beta-HSD2 play an important role in human ocular mineralocorticoid action, such as the production of aqueous humor, in the ciliary body. The widespread expression of GR suggests that glucocorticoids may play an important role in the function and homeostasis of the human eye.
5alpha-reductases in human breast carcinoma: possible modulator of in situ androgenic actions.
The expression of 5alpha-reductase types 1 and 2 was examined in human breast carcinoma using immunohistochemistry and RT-PCR. Immunoreactivity for 5alpha-reductase isozymes was also correlated with various clinicopathological parameters to examine possible local regulatory mechanisms of sex steroids, including progesterone and androgens, in human breast carcinoma tissues. Immunoreactivity for 5alpha-reductase type 1 was detected in the cytoplasm and possibly in the nuclear membrane of tumor cells in 35 of 60 invasive ductal carcinomas (58%), and type 2 signal was detected in 9 of these 60 cases (15%). The results from RT-PCR (n = 8) were consistent with those from immunohistochemistry. A significant positive correlation was detected between 5alpha-reductase type 1 immunoreactivity and androgen and progesterone receptor A or B labeling indexes, and immunoreactivities of 5alpha-reductase type 2, 17beta-hydroxysteroid dehydrogenase type 5, or 3beta-hydroxysteroid dehydrogenase, which recognizes both types I and II. An inverse correlation was detected between 5alpha-reductase type 1 immunoreactivity and tumor size, histological grade, or Ki-67 labeling index. 5alpha-Reductase type 2 immunoreactivity was significantly correlated with 17beta-hydroxysteroid dehydrogenase type 5 immunoreactivity, but not with other parameters. This study suggests that 5alpha-reductase type 1 is mainly expressed in human breast carcinoma, which may play an important role in the in situ production and actions of the potent androgen, 5alpha-dihydrotestosterone, including inhibition of cancer cell proliferation, in hormone-dependent human breast carcinoma.
Expression and cellular localization of estrogen receptors alpha and beta in the human fetus.
Estrogens exert various biological effects by acting through their native receptors, two of which have been identified to date: estrogen receptors alpha (ERalpha) and beta (ERbeta). In this study we examined the expression and cellular localization of ERalpha and ERbeta in various human fetal tissues by semiquantitative RT-PCR (13 and 20 gestational weeks) and immunohistochemistry (13, 20, and 38 gestational weeks), respectively, to study the possible effects of estrogens on human fetal tissues during development. Relatively high levels of ERbeta expression were detected in various human fetal tissues, whereas those tissues expressing ERbeta had markedly lower levels of ERalpha expression. ERbeta messenger ribonucleic acid expression was especially high in the adrenal gland. ERbeta-immunoreactive protein was localized to the definitive zone, but not in the fetal zone, of the adrenal cortex. Although low levels of ERbeta messenger ribonucleic acid were present in the brain, heart, lung, and kidney, ERbeta immunoreactivity was not detected in these tissues. These results suggest that the effects of estrogens in these tissues are predominantly mediated through ERbeta. ERbeta immunoreactivity was detected in Sertoli cells and spermatogonia in the male reproductive tract and in germ cells in the fetal testis and epididymis. In the female reproductive tract, both ERalpha and ERbeta were immunopositive in epithelium of the oviduct. The results of the present study have demonstrated the possible sites for estrogenic action in the human fetus and suggest that the effects of estrogen via ERbeta may play important roles in human fetal development, especially in the definitive zone of the adrenal cortex, and in the reproductive tissues of the developing fetus.
The analyses of 17beta-hydroxysteroid dehydrogenase isozymes in human endometrial hyperplasia and carcinoma.
Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of human endometrial adenocarcinoma. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone and thereby serve to modulate the tissue levels of bioactive E2. To elucidate the possible involvement of this enzyme in human endometrial carcinoma, we first examined the expression of 17beta-HSD type 1 and type 2 in 20 normal cycling human endometria, 36 endometrial hyperplasia, and 46 endometrial endometrioid adenocarcinoma using immunohistochemistry, and we then studied immunoreactivity of 17beta-HSD type 2 using immunoblotting analyses, the activity of 17beta-HSD type 1 and type 2 using thin-layer chromatography and their expression using RT-PCR in endometrial endometrioid adenocarcinoma. We correlated these findings with various clinicopathological parameters to examine the biological significance of 17beta-HSDs in human endometrial disorders. 17beta-HSD type 2 immunoreactivity in normal endometrium was present in all cases of secretory phase (n = 14), but not in any endometrial mucosa of proliferative phase (n = 6). In addition, 17beta-HSD type 2 immunoreactivity was detected in 27 of 36 (75%) endometrial hyperplasia and 17 of 46 (37%) carcinoma cases. 17beta-HSD type 1 immunoreactivity was not detected in all the cases examined. In both endometrial hyperplasia and carcinoma cases there were significant positive correlations between 17beta-HSD type 2 and progesterone receptor labeling index (LI). In carcinoma cases, a significant inverse correlation was detected between 17beta-HSD type 2 immunoreactivity and age. In addition, 17beta-HSD type 2 immunoreactivity was also correlated with 17beta-HSD type 2 enzymatic activity, and semiquantitative analyses of 17beta-HSD type 2 messenger RNA. No significant correlations were detected between 17beta-HSD type 2 and estrogen receptor LI, Ki67 LI, amount of aromatase messenger RNA or histological grade. These data indicated that the expression of 17beta-HSD type 2 in hyperplastic and/or neoplastic endometrium may represent altered cellular features through hyperplastic and neoplastic transformation. However, 17beta-HSD type 2 may also play some protective and/or suppressive roles toward unopposed estrogenic effects through inactivating E2 in situ, especially in premenopausal patients.
The chemistry of indoles. CIII. Simple syntheses of serotonin, N-methylserotonin, bufotenine, 5-methoxy-N-methyltryptamine, bufobutanoic acid, N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine, and lespedamine based on 1-hydroxyindole chemistry.
Application of regioselective nucleophilic substitution reactions of 1-hydroxytryptamines to novel and simple syntheses of serotonin (1a), N-methylserotonin (1b), bufotenine (1c), 5-methoxy-N-methyltryptamine (2a), bufobutanoic acid (3a), N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine (4), and lespedamine (5) are described. Effective syntheses of 5-benzyloxytryptamine and 1-methoxy-2-oxindoles are also reported.
Application of the cell block method, utilizing mount quick mounting medium.
Our objective was to determine the applicability of cell transfer and cell block methods using Mount Quick (Daido Sangyo, Saitama, Japan) mounting medium (MQ) for hematoxylin-eosin (H&E) and immunohistochemical staining of several limited amounts of biological materials in slide preparations. The materials investigated were histopathologically confirmed malignant mesotheliomas (pleural effusions) and malignant lymphomas, a malignant melanoma, and an amelanotic melanoma in sealed slides. Monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cancer antigen 125 (CA-125), vimentin, thrombomodulin (TM), cytokeratin, UCHL-1, L-26, melanoma-specific antigen (HMB45), and S-100 protein (S-100) were applied in the investigation. The malignant mesotheliomas were found to be positive for EMA, cytokeratin, vimentin, TM, and CA-125, and negative for CEA, with no differences being observed in findings from direct contact preparations. Using T-cell-type malignant lymphomas for immunohistochemistry, UCHL-1 positivity and L-26 negativity were clearly demonstrated. The malignant melanoma and amelanotic melanoma materials stained strongly for HMB45 and S-100. Cell transfer employing MQ is a suitable approach for immunohistochemical investigations of limited materials. In addition, cell blocks derived from MQ-embedded smears can be used for both H&E and immunohistochemical staining. Diagn. Cytopathol. 2000;22:117-119.
Papillary renal-cell carcinoma demonstrating prominent foamy macrophages by cytobrush scrapings: a case report.
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Developmental changes in steroidogenic enzymes in human postnatal adrenal cortex: immunohistochemical studies.
Adrenarche is considered to occur as a result of intra-adrenal changes in steroidogenic enzymes involved in C19 steroid production. The present study was conducted because developmental changes in steroidogenic enzymes have not been examined well in human postnatal adrenal. Twenty-four specimens of nonpathological human adrenals from 7 months to 62 years retrieved from autopsy files. Immunohistochemistry for P450 side-chain cleavage (P450scc), 17alpha hydroxylase (P450c17), dehydroepiandrosterone sulfotransferase (DHEA-ST), P450 oxidoreductase, cytochrome b5, and 3beta-hydroxysteroid dehydrogenase (3betaHSD) was per-formed in these specimens, and the immuno-intensity was evaluated using CAS 200 computed image analysis system. Immunoreactivity of P450scc was marked in the zona glomerulosa, fasciculata and reticularis in the adrenal glands of all the cases examined. P450c17 and DHEA-ST immunoreactivity was weak in the zona fasciculata and reticularis in the adrenals of age 7 months to 5 years, but thereafter became prominent in the zona reticularis. Immunoreactivity of P450 oxidoreductase and cytochrome b5, components of the electron transfer system hypothesized to regulate the 17-20 lyase activity of P450c17, was weak in all three zones of adrenal cortex from 7 months to 5 years, and became more marked in the zona reticularis after age 5 years. 3betaHSD immunoreactivity was marked in all three zones of the adrenal cortex from 7 months to 8 years but thereafter decreased in the zona reticularis. These data suggest that the human adrenal zona reticularis markedly begins to develop morphologically and functionally at around 5 years of age. The increased level of P450c17, DHEA-ST, P450 oxidoreductase, and cytochrome b5, and the decreased level of 3betaHSD in the reticularis is likely to contribute to increased C19 steroid production during adrenarche.
17Beta-hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma: a correlation to clinicopathological parameters.
The expression of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1 and type 2 was examined immunohistochemically in 111 invasive ductal carcinomas, and correlated with various clinicopathological parameters. This study investigates local regulatory mechanisms of oestrogens in human breast carcinoma. 17Beta-HSD type 1 was immunolocalized in carcinoma cells of 68 out of 111 invasive ductal carcinoma cases (61.3%). 17Beta-HSD type 2 immunoreactivity was not detected in all cases examined. A significant inverse correlation was observed between the immunohistochemical expression of 17beta-HSD type 1 and histological grade of the carcinoma (P < 0.02). There was a significant correlation between 17beta-HSD type 1 and oestrogen receptor (ER) labelling index (LI) (P < 0.05). In addition, carcinoma cells expressing immunoreactive 17beta-HSD type 1 were frequently positive for ER. 17Beta-HSD type 1 was also correlated with progesterone receptor (PR) LI (P < 0.05). There was a significant inverse correlation between 17beta-HSD type 1 and Ki-67 LI (P < 0.0001). No significant correlations were detected between 17beta-HSD type 1 and other clinicopathological parameters, including patient age, menopausal status, stage, tumour size, lymph node status and prognosis. This study suggests that 17beta-HSD type 1 plays an important role in the regulation of in situ oestradiol production in hormone-dependent breast carcinomas.
11Beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human placenta.
In mineralocorticoid target organs, 11beta-hydroxysteroid dehydrogenase type II (11beta-HSD2) confers specificity on the mineralocorticoid receptor (MR) by converting biologically active glucocorticoids to inactive metabolites. Placental 11beta-HSD2 is also thought to protect the fetus from high levels of circulating maternal glucocorticoid. In this study, we examined the immunoreactivity of 11beta-HSD2 and MR in human placenta from 5 weeks gestation to full term using immunohistochemistry, 11beta-HSD2 messenger RNA (mRNA) expression using Northern blot analysis, and MR mRNA expression using RT-PCR analysis. Marked 11beta-HSD2 immunoreactivity was detected in placental syncytiotrophoblasts at all gestational stages. MR immunoreactivity was moderately detected in syncytiotrophoblasts, some cytotrophoblasts, and interstitial cells of the villous core. Marked mRNA expression of 11beta-HSD2 was detected in placenta by Northern analysis. RT-PCR analysis of MR in placental tissues showed an amplified product consistent in length with the primers selected. These results suggest that placental 11beta-HSD2 is involved in not only regulating the passage of maternal active glucocorticoids into the fetal circulation but also in regulation of maternal-fetal electrolyte and water transport in the placenta, as in other mineralocorticoid target organs.
[New theory predicting molecular shapes (deviation of framework and orbital from those of norm)].
The aim of this paper is to understand why the molecule has its own structure (optimized geometry) which differs from the standard one (norm). Basic strategy to obtain the optimized geometry is to start from the norm. The emphases are 1) a theory predicting polarization exemplified by norbornene HOMO distortion and 2) when we apply any theory of 1), what framework should we use? The latter is very important due to the fact that the optimized geometries of cations and anions differ greatly from the norms. For polarization, we have elaborated "in-bond orbital method." The method is based on the well-known correlation between separated atoms and united atom and able to represent polarization within minimum basis set only by the first-order perturbation theory. For cationic and anionic hydrocarbons, a new method consisting of an assumption and a few recipes is developed. Although the assumption that the framework distortion surpasses the orbital distortion (polarization) is based solely on organic chemist's intuition, this method correctly suggests the structure (framework) to which the in-bond orbital method should be applied. All of the optimized geometries used in this study are obtained by HF/6-31 + G*.
Huge hamartoma with inverted papilloma in the nasal cavity.
We report clinical experience in managing a 46-year-old Japanese man with long-standing nasal obstruction resulting from a huge left nasal mass. Computed tomography, magnetic resonance imaging and biopsy were used to make a provisional diagnosis of inverted papilloma. The mass was resected via a frontal approach combined with rhinotomy. Histopathologic examination of the resected specimen was consistent with a hamartoma that included an inverted papilloma on a portion of its surface. In addition to being rare tumors in the nasal cavity, we believe that our patient's tumor the largest nasal hamartoma ever reported.
Relationship between Ca-dependent change of serum PTH and extracellular Ca2+-sensing receptor expression in parathyroid adenoma.
Abnormal PTH secretion and cell growth in hyperparathyroid tissues are accompanied with reduced expression of Ca2+-sensing receptor (CaR) which plays a key role in Ca-regulated PTH release. In this study, we examined the receptor expression in parathyroid adenomas using specific anti-CaR antibody and investigated relationship between CaR expression in adenomatous tissues and parameters of Ca-dependent change of serum PTH. The results show a considerable variation in the number of CaR positive cells among the adenomatous tissues. Expression of the receptor protein was not related to set-point error but was more reduced in the patients with more elevated minimum or baseline levels of serum PTH. CaR expression was severely reduced in the patients with highly elevated maximum serum PTH, while the receptor expression was also decreased in some patients with normal maximum serum PTH. Baseline level / maximum level ratio of serum PTH was increased in these patients. In conclusion, reduced CaR expression is related to abnormality in three parameters of PTH secretion (minimum serum PTH, maximum serum PTH, and baseline level / maximum level ratio of serum PTH) and may contribute to hypersecretion from parathyroid adenomas.
Presence of nuclear grooves in endometrial cytology.
Although the presence of nuclear grooving in papillary carcinomas of the thyroid has been well-described, so far the attention paid to similar structures in endometrial cell samples has been limited. In order to investigate the occurrence of nuclear grooves in endometrial specimens from patients with various pathologic conditions of the endometrium, we compared their appearance with papillary thyroid cancers. A total of 10 cases was studied (age range, 40-72 yr), all cases demonstrating nuclear grooves. In each case, 10 random high-power fields (HPFs) were investigated, and the numbers of fields in which nuclear grooving could be seen were recorded. Nuclear grooves were observed in 3-36 of each HPFs and were more often observed in atypical endometrial cells than in their normal-appearing counterparts; however, these nuclear alterations were thought to be nonspecific findings.