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Biomedical subjects

M Hiroi

Publications and source records attributed to M Hiroi.

At least 55 records · Page 3Linked to original sources

Adenoid basal carcinoma of the uterine cervix: a case report with ultrastructural findings.

Adenoid basal carcinoma of the uterine cervix is a rare tumor with a favorable prognosis. A case of adenoid basal carcinoma (ABC) of the uterine cervix was studied using light and electron microscopy. The patient was a 74-year-old Japanese woman who had undergone hysterectomy due to cervical intraepithelial neoplasia 3. Incidentally, ABC was found in the resected uterus. The tumor cells made small nests and infiltrated the cervical portion of the uterus. In the nests, glands, cribriform patterns with glandlike structures, and squamous differentiation were seen. Immunohistochemically, the glandlike structures were positive for laminin and type IV collagen. Ultrastructurally, the tumor cells had irregular nuclei, scanty cytoplasm, and cribriform patterns in which glandlike structures were covered with basal lamina. No myoepithelial differentiation of the tumor cells was seen. These findings suggest a similarity between adenoid basal carcinomas and adenoid cystic carcinomas. Furthermore, both tumors are considered to originate in the reserve cells of the uterine cervix. Because their outcomes are different, they should be distinguished from each other.

Aged↗

Mesangial myofibroblastic transformation in steroid-dependent minimal change nephrotic syndrome.

Patients with minimal change nephrotic syndrome (MCNS) occasionally show frequent relapses with proteinuria after cessation of steroid treatment, even though no significant pathological abnormalities are found in the glomeruli, compared with those in nonrelapsed and good-prognosis cases of MCNS. To resolve this contradiction, we immunohistochemically and ultrastructurally examined a biopsied renal tissue of a patient who showed glomerular features of MCNS and frequent clinical relapses. Immunohistochemistry demonstrated the overexpression of alpha-smooth muscle actin (ASMA) and vimentin in glomerular mesangial cells despite no mesangial cell proliferation, compared with nine nonrelapsed cases of MCNS. These facts may be an important clue to the investigation of the pathogenesis of steroid-dependent MCNS with frequent relapses. Furthermore, the immunohistochemical examination of ASMA and vimentin may be useful to detect mesangial myofibroblastic transformation that is not demonstrated in conventional light microscopy and immunofluorescence study.

Actins↗

Hyaluronan in follicular fluids and fertilization of oocytes.

OBJECTIVE: To determine the concentrations of hyaluronan, E(2), and progesterone in follicular fluids (FFs) and the incidence of apoptotic granulosa cells. Also, to examine the relationship between the concentration of hyaluronan and follicular steroids, the incidence of apoptotic cells, and the fertilizability of the oocyte in the same follicle. DESIGN: Samples of 130 follicles were retrospectively analyzed for hyaluronan and steroids and the incidence of apoptotic cells. SETTING: The reproductive center in Yamagata University Hospital. PATIENT(S): Forty women infertile because of tubal damage or unknown causes undergoing IVF treatment were selected. INTERVENTION(S): The samples were collected from follicle aspirations. MAIN OUTCOME MEASUREMENT(S): The concentrations of hyaluronan and steroids in FFs, the incidence of apoptotic granulosa cells, and oocyte fertilizability. RESULT(S): The levels of hyaluronan in FF were found to correlate positively with P (r=0.444, P<0.0001) and the incidence of apoptotic cumulus granulosa cells (r=0.387, P=0.002) and inversely with E(2) (r = -0.601, P<0.0001) and free T (r = -0.344, P=0.001). The concentration of hyaluronan in FFs containing a subsequently fertilized oocyte after insemination was significantly lower than that in FFs containing a subsequently unfertilized oocyte (P=0.0005) (fertilized, 50.0 +/- 2.6 ng/mL; triploidy, 59.1 +/- 6.8; and unfertilized, 66.9 +/- 5.9). CONCLUSION(S): The concentration of hyaluronan in FF is an indicator for estimation of oocyte viability for fertilization.

Apoptosis↗

Moderate and severe endometriosis is associated with alterations in the cell cycle of granulosa cells in patients undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: To determine whether folliculogenesis is impaired in patients with endometriosis. DESIGN: Prospective study. SETTING: Yamagata University School of Medicine, Yamagata, Japan. PATIENT(S): Thirty women participating in an IVF program. INTERVENTION(S): The patients were divided into four groups according to the cause of their infertility: tubal factor (T), n = 7; male factor (M), n = 7; idiopathic (I), n = 7; and endometriosis (E), n = 9. Granulosa cells were obtained from the follicular fluid of each patient and analyzed by flow cytometry. MAIN OUTCOME MEASURE(S): The percentage of granulosa cells in each cell-cycle stage. RESULT(S): The mean (+/- SD) rate of apoptosis in the granulosa cells obtained from the patients with endometriosis was the highest among the four groups (T = 11.7% +/- 3.3%; M = 5.6% +/- 3.8%; I = 9.6% +/- 5.1%; and E = 18.6% +/- 9.6%). The percentage of S-phase granulosa cells was significantly higher in the patients with endometriosis than in all the other patients combined (E = 12.5% +/- 6%; T + M + I = 9.3% +/- 2.9%). The percentage of G2/M-phase granulosa cells was significantly lower in the endometriosis group than in the other three groups combined (E = 2.3% +/- 2.5%; T + M + I = 4.6% +/- 2.1%). CONCLUSION(S): Endometriosis impairs the cell cycle in granulosa cells. This phenomenon may have a detrimental effect on folliculogenesis.

Adult↗

Relatively poor oocyte quality is an indication for intracytoplasmic sperm injection.

OBJECTIVE: To determine the relation between the insemination method used and the quality of oocytes and embryos. DESIGN: Prospective study. SETTING: Assisted reproductive centers at Yamagata University Hospital and Kuramoto Women's Clinic in Yamagata, Japan. PATIENT(S): Forty patients undergoing IVF and 40 patients undergoing intracytoplasmic sperm injection (ICSI). INTERVENTION(S): To estimate oocyte quality, the granulosa cells surrounding the oocyte were fixed and stained with a commercial dye in both groups of patients. One thousand granulosa cells were examined under a fluorescence microscope. MAIN OUTCOME MEASURE(S): The incidence of apoptotic granulosa cells surrounding each oocyte. RESULT(S): The incidence of apoptosis in the granulosa cells enclosing the oocytes that were fertilized by IVF was significantly lower than that in the oocytes that were fertilized by ICSI. Moreover, the incidence of apoptosis in the granulosa cells enclosing the oocytes that grew into good-quality or fair-quality embryos was significantly lower after conventional IVF than after ICSI. With ICSI, the incidence of apoptosis was not significantly different among the granulosa cells surrounding the oocytes that were inseminated, were fertilized, or developed into good-quality or fair-quality embryos. With IVF, the incidence of apoptosis was highest in the granulosa cells surrounding the oocytes that were inseminated and lowest in the granulosa cells surrounding the oocytes that developed into good-quality and fair-quality embryos. CONCLUSION(S): A good-quality oocyte is necessary for the development of a good-quality embryo with IVF but not with ICSI. Thus, relatively poor oocyte quality is a good indication for the use of ICSI.

Apoptosis↗

Effects of aging on ovarian fecundity in terms of the incidence of apoptotic granulosa cells.

PURPOSE: The objective was to determine the effects of women's age on the ovarian fecundity as assessed by the incidence of apoptotic granulosa cells. METHODS: Twenty-eight normo-ovulatory women underwent ovulation induction for standard IVF. The husbands of these women showed severe male infertility factors. The women were divided into four groups according to their ages. Women underwent follicle aspiration after the administration of human menopausal gonadotropin plus human chorionic gonadotropin. The nuclei of granulosa cells were examined by using fluorescence microscopy, and the incidence of apoptotic granulosa cells was tabulated. RESULTS: Granulosa cells in the older women revealed a significant increase in the number of apoptotic cells. The number of total oocytes and the number of mature oocytes obtained significantly decreased with age. However, endometrial thickness and follicular estradiol, progesterone, and free testosterone levels were not significantly different among four different age groups. CONCLUSIONS: Age increases apoptotic changes in granulosa cells and consequently decreases the ovarian fecundity.

Adult↗

Hyaluronic acid inhibits apoptosis in granulosa cells via CD44.

PURPOSE: This study was designed to examine whether hyaluronic acid (HA) inhibits apoptosis in cumulus and mural granulosa cells and to examine whether this effect of HA was mediated through CD44. METHODS: Mural and cumulus granulosa cells were obtained from in vitro fertilization patients. The cells were cultured with various concentrations of HA or HA plus various concentrations of anti-CD44 antibody without serum supplement. After 24 hr of culture, the cells were fixed and stained with Hoechst 33258. One thousand granulosa cells of each conditions were observed by fluorescence microscopy. RESULTS: HA inhibited apoptosis in both kinds of granulosa cells, and anti-CD44 antibody prevented this effect of HA. CONCLUSIONS: The incidence of apoptotic granulosa cells with fragmented condensed nuclei was reduced by HA via CD44.

Apoptosis↗

Effects of controlled ovarian hyperstimulation on oocyte quality in terms of the incidence of apoptotic granulosa cells.

PURPOSE: The aim was to investigate which ovarian hyperstimulation protocol performed in the same patients causes development of oocytes of good quality. METHODS: Twenty normo-ovulatory women underwent three different controlled ovarian hyperstimulation protocols for in vitro fertilization-embryo transfer. Patients underwent follicle aspiration after administration of human chorionic gonadotropin (hCG). The total number of retrieved oocytes, the number of mature oocytes, and the rate of mature oocytes were examined. Recovered granulosa cells were stained with Hoechst 33258 and examined by fluorescence microscopy to estimate the incidence of apoptotic cells. RESULTS: The total number of oocytes and the number of mature oocytes in gonadotropin-releasing hormone agonist (GnRHa) + human menopausal gonadotropin (hMG) + hCG and hMG + hCG cycles were higher than those in the natural cycle (P < 0.0001). The rate of mature oocytes in hMG + hCG cycle was the highest among the three protocols (P < 0.04). In the mural granulosa cells, the incidence of apoptotic cells in the GnRHa + hMG + hCG cycle was significantly higher than those of the natural (P < 0.002) and hMG + hCG cycles (P = 0.0002). The incidence of apoptotic cumulus granulosa cells in the GnRHa + hMG + hCG cycle was significantly higher than those of natural and hMG + hCG cycles (P < 0.002). Moreover, the incidence of apoptotic cumulus granulosa cells in the hMG + hCG cycle was significantly lower than that in the natural cycle (P < 0.01). CONCLUSIONS: These results indicated that hMG + hCG is the most appropriate controlled ovarian hyperstimulation protocol among the three examined with regard to oocyte quality.

Adult↗

Vinculin: its possible use as a marker of normal collecting ducts and renal neoplasms with collecting duct system phenotype.

Vinculin is a cytoskeletal protein associated with membrane actin-filament-attachment sites of cell-cell and cell-matrix adherens-type junctions. In this article, we examine the expression of vinculin to elucidate its role in human renal neoplasms. We reviewed surgically resected specimens and selected available tissue from 79 renal tumors in 78 patients. There were 55 men and 23 women. Their mean age was 61 years and the mean size of the renal tumors was 6.1 cm. All renal tumors were examined by immunohistochemistry using a monoclonal antibody against vinculin. Overall, 17 (21.5%) renal tumor samples reacted with vinculin. The positive ratio in various types of renal tumors was as follows: conventional-type (clear cell), 0/54; papillary-type, 5/12; chromophobe-type, 5/5; sarcomatoid-type, 3/4; collecting duct carcinoma, 3/3; and oncocytoma, 1/1. The positive rate of conventional-type renal cell carcinomas (RCCs) is significantly different from that of other renal tumors (P < .01). Normal kidney, conventional, and papillary-type RCCs exhibited positive signals in Western blot analysis. These results suggest that vinculin may serve as a useful marker of renal neoplasms with collecting duct system phenotype such as chromophobe-type RCC.

Biomarkers, Tumor↗

Anaplastic carcinoma of the pancreas with rhabdoid features.

The malignant rhabdoid tumor (MRT) is histologically characterized by the invasive proliferation of polygonal to ovoid cells with abundant eosinophilic cytoplasm and eccentric vesicular nuclei with a prominent nucleolus. MRT frequently occurs in the kidney, but may also arise in other organs. However, MRT should be strictly distinguished from carcinomas with rhabdoid features. A post-mortem examination of a 68-year-old woman found an anaplastic carcinoma of the pancreas with rhabdoid features displaying extensive invasion into the neighboring tissues. To the best of our knowledge, this is the first case of a pancreatic tumor with rhabdoid features. Pathologists should consider that carcinomas showing rhabdoid features may also appear in the pancreas. As pancreatic tumors with rhabdoid features have characteristic histopathological features and poor prognosis compared to other pancreatic tumors, careful histopathological differential diagnosis is important.

Aged↗

Adult-onset giant juxtaglomerular cell tumor of the kidney.

The juxtaglomerular cell tumor (JGCT) of the kidney is a rare neoplasm which commonly secretes renin. This tumor often occurs in teenagers. This paper documents the 14th adult-onset (over 30-years-old) case with a giant JGCT which measured 9.0 x 8.0 x 7.5 cm. Histologically, this tumor was composed of both vascular and tubular components. Immunohistochemically, the vascular component reacted with renin, cytokeratin 7, ulex europaeus agglutinin-1, vascular endothelial growth factor (VEGF) and Flk-1 (VEGF-R2), whereas the tubular component was positive for renin, epithelial membrane antigen (EMA), cytokeratin 7, alpha-1-antitrypsin, VEGF and Flk-1. This finding suggests that both vascular and tubular components of JGCT may promote neoplastic proliferation via an autocrine mechanism through the action of VEGF.

Female↗

Bronchial granular cell tumor with osteopontin and osteonectin expression: a case report.

The case of a 52-year-old Japanese man with bronchial granular cell tumors with osteopontin and osteonectin expression is reported here because there have been few investigations of their expression in benign tumors. He was admitted because of sudden hematemesis. A bronchoscopic examination revealed a lobulated polypoid tumor located in the left and right bronchi. Histologically, most tumor cells had abundant granular eosinophilic cytoplasm and were immunoreactive for S-100, neuron-specific enolase (NSE), CD68 and vimentin. Moreover, osteopontin-positive tumor cells were randomly distributed in the tumor tissue, but few stromal cells were positive. In contrast, osteonectin was mainly expressed in the peripheral tumor cells and was also distributed in the stromal cells. Blood vessels at the tumor border in which osteonectin-positive tumor cells were distributed, proliferated moderately. These results suggest that osteopontin and osteonectin may play a role in the progression of granular cell tumors and in the interaction between the tumor and host or angiogenesis around the tumor, respectively.

Biomarkers, Tumor↗

Elimination of atretic follicles from the mouse ovary: a TEM and immunohistochemical study in mice.

We examined numerous ovarian follicles from 32-35 d virgin mice by transmission electron microscopy and light microscopic immunohistochemistry. No macrophages were seen, but various stages of apoptotic granulosa cells were encountered. Presumably a granulosa cell or its debris in an advanced stage of apoptosis was destined to be phagocytosed by adjacent normal-looking granulosa cells. Other granulosa cells of normal appearance were seen in the region of the zona pellucida in contact with and apparently phagocytosing atrophic oocytes. Such granulosa cells were characterised by the presence of gap junctions with other cells and frequently contained annular gap junctions in the cytoplasm. To confirm the lack of involvement of macrophages in the process of follicular atresia and elimination, specially prepared ovarian sections were incubated with antimouse macrophage monoclonal antibodies (F4/80, Mac-1, Mac-2). None of the follicles examined showed positive immunoreactivity with these antibodies. Atretic follicles may shrink and eventually disappear from the ovary as a result of repeated apoptosis and phagocytosis by granulosa cells. There is no evidence for the presence or involvement of macrophages in the atretic follicles, at least in prereproductive mice as examined.

Animals↗

An immunohistochemical study of developing glomeruli in human fetal kidneys.

BACKGROUND: In the glomerulonephritis, mesenchymal cells frequently repeat the expression of fetal immunohistochemical phenotypes. However, in human glomerulogenesis the phenotypic alteration of mesangial and other types of glomerular cells has not been clearly defined. Our aim was to clarify the characteristics of fetal mesangial cells and glomerular capillary endothelial cells, as well as their changes during glomerulogenesis using immunohistochemistry. METHODS: We examined the renal tissues of 34 autopsied fetuses and neonates, 5 children, and 5 adults using immunohistochemistry and immunoelectron microscopy, using antibodies for cytoskeletons, contraction-associated proteins, and endothelial cell markers. RESULTS: In the V and S stages, there were no cells showing mesangial and endothelial features within the vesicles and the S-shaped bodies. In the S stage, small blood vessels, consisting of endothelial cells (CD31+, CD34+) and primitive perivascular mesenchymal cells (alpha-smooth muscle actin+, low molecular caldesmon+, vimentin+), were branched from developing interlobular arteries and appeared to extend to the lower clefts of the S-shaped bodies. In the C stage, the perivascular mesenchymal cells aggregated at the root of the immature glomeruli. In the M stage, they migrated toward the periphery of immature glomeruli and gradually lost their fetal immunohistochemical features. Similarly, with further maturation, the fetal glomerular capillary endothelial cells gradually lost the immunostaining for CD34, while the strong staining intensity of CD31 remained unchanged, just as that in the adult glomerular capillary endothelial cells. CONCLUSIONS: In human glomerulogenesis, we demonstrate that fetal mesangial and capillary endothelial cells change their immunohistochemical phenotypes with maturation. They gradually lose fetal immunohistochemical phenotypes. Already before birth, the mesangial cells in almost all glomeruli at the late M stage acquire the adult phenotype.

Adolescent↗

The role of anti-epithelial cell antibodies in the pathogenesis of bilateral radiation pneumonitis caused by unilateral thoracic irradiation.

Two cases of bilateral radiation pneumonitis associated with unilateral thoracic irradiation against lung cancer are described. Both patients died of respiratory failure and autopsy was performed. Histologically, bilateral diffuse alveolar damage was demonstrated in both cases, associated with marked organization of hyaline membrane in one case (case 1). In addition, numerous hyperplastic type II pneumocytes which strongly expressed cytokeratins 8, 18 and 19 were observed. In both patients' sera, antibodies against cytokeratin 8, 18 and 19 were demonstrated by a Western immunoblot. The possible association between autoantibodies to cytokeratins and diffuse alveolar damage observed in patients with bilateral radiation pneumonitis are discussed.

Adenocarcinoma↗

KL-6, a mucinous glycoprotein, as an indicator of chronic lung disease of the newborn.

KL-6 is a mucinous glycoprotein that is preferentially expressed by alveolar type 2 cells. Plasma KL-6 was higher in infants with chronic lung disease (n = 12) than in infants without chronic lung disease (n = 14) on day 0-1, 10, and 30 (P =.04). KL-6 correlated with the alveolar-arterial oxygen tension difference on day 10 and day 30. Plasma KL-6 may be useful as an early marker of chronic lung disease and an indicator of severity.

Antigens↗

Mouse oviduct-specific glycoprotein gene: genomic organization and structure of the 5'-flanking regulatory region.

A member of the chitinase protein family, oviduct-specific glycoprotein (OGP), can directly associate with gametes or with the early embryo in the oviduct. Although the glycoprotein is widely distributed among mammalian species and there is indirect evidence concerning the involvement of the molecule in the fertilization process, its physiological functions are far from completely understood. To understand the fundamental mechanisms that direct gene expression as well as to know the physiological significance of OGP, we have isolated and characterized a mouse OGP gene (mogp-1). The gene was found to span 13.4 kilobases (kb) including 11 exons and 10 introns. The genomic organization of mogp-1 is well conserved compared to the other members of the chitinase family. Two transcription initiation sites were found at positions 18 and 14 upstream from the first ATG codon. Fluorescence in situ hybridization analysis demonstrated that the mogp-1 was located on the R-positive F3 band of mouse chromosome 3. Although the putative promoter region of mogp-1 lacked typical TATA, CAAT, or GC box sequences, the region contained several motif sequences of transcription factor binding sites including 10 half-palindromic estrogen responsive elements (ERE) and an imperfect ERE. Transient transfection experiments demonstrated that promoter activity could be modulated by various sequences within the 2.2 kb of the 5'-flanking region, and that the mogp-1 promoter was transactivated in an estrogen receptor-positive cell line, MCF-7, by the addition of estradiol-17beta (E(2)). In addition, relevant promoter activity for E(2) responsiveness resides within the first 270 base pairs upstream of the mogp-1. These findings should facilitate our understanding of the regulation of OGP gene expression, and they may be helpful for designing experiments to unravel the role of OGP in the process of mammalian fertilization.

Amino Acid Sequence↗