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Biomedical subjects

N Hayashi

Publications and source records attributed to N Hayashi.

At least 217 records · Page 12Linked to original sources

[A case of female paraurethral cyst diagnosed as epithelial inclusion cyst].

The patient was a 36-year-old woman with a chief complaint of pain of the urethral meatus. A cyst existed just below the urethral meatus. The paraurethral cyst was removed completely. Histologically, the cyst was lined by stratified squamous epithelium. According to the criteria proposed by Das, paraurethral cysts are classified into 4 groups: epithelial inclusion cysts, Müllarian cysts, Gärtner duct cysts, Skene duct cysts. In this case, the cyst seemed to be an epithelial inclusion cyst. In the Japanese literature, paraurethral cysts have been incompletely classified from an etiological perspective. Differential diagnoses based on the histological findings of the cysts may be important to determine the etiology.

Adult↗

Histologic correlation of human neural retinal transplantation.

PURPOSE: To describe the histologic findings of the transplanted eye of a 94-year-old man with neovascular age-related macular degeneration, who 3 years earlier underwent subretinal transplantation of both a fetal neural retinal sheet and a retinal microaggregrate suspension. METHODS: Serial sections of the posterior segment of the eye and the transplanted areas were processed and studied by routine histologic techniques, including both light and transmission electron microscopy (TEM). Transplanted areas were also examined for the presence of glial, neuronal, and photoreceptor cell markers by standard immunohistochemical methods. RESULTS: After transplantation in this patient, there was no visual improvement. Light microscopic examination disclosed survival of the transplanted cells in the subretinal space with no evidence of inflammation or rejection. The neural retinal sheet transplant developed a layered configuration. The retinal pigment epithelium (RPE) was absent over much of the posterior pole, including the area of transplantation. TEM examination and immunohistochemical analysis disclosed the presence of neuronal and glial cells within the transplant. A few transplant neuronal cell processes overlying a focus of residual RPE cells were positive for S-antigen, but well-developed photoreceptor outer segments were not present. CONCLUSIONS: Long-term survival of transplanted neural retinal tissue can be achieved in human patients without immunosuppression. The lack of photoreceptor development in this patient may be the result of absent or dysfunctional RPE. Nonetheless, the long-term survival of grafted tissue in the human subretinal space in the absence of immunosuppressive treatment is promising for future efforts in the field of neural retinal transplantation.

Aged↗

Predominant T helper 1 cells in patients with idiopathic portal hypertension.

BACKGROUND: The pathologic mechanism of idiopathic portal hypertension (IPH) is unknown. Because cytokines and the balance of T helper (h) 1 and Th2 CD4+ T cells have been reported to be important for regulating the immune response, in the present study we investigated the role of cytokines and the distribution of cytokine-producing cells in IPH patients. METHODS: Serum levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor-I, -II, interferon (IFN)-gamma and interleukin (IL)-4 were measured in IPH patients, fatty liver patients, chronic hepatitis patients and control subjects. The percentages of Th0, Th1 and Th2 CD4+ T cells were examined in peripheral and spleen lymphocytes in IPH patients by intracellular staining. RESULTS: Serum levels of TNF-alpha, soluble TNF receptor-I, interferon-gamma and IL-4 of IPH patients were not increased in comparison with control subjects. Only the mean value of soluble TNF receptor-II was significantly higher than that of control subjects and fatty liver patients. The ratios of Th1 and Th2 in both peripheral and spleen lymphocytes of IPH patients were significantly increased compared with the ratios found in peripheral lymphocytes of control subjects. The increase in the ratios was due to a decrease in the percentage of Th2 CD4+ T cells. CONCLUSIONS: These results suggest that the imbalance of Th1 and Th2 CD4+ T cells and TNF may be associated with the pathogenesis of IPH.

Adult↗

[Radiation exposure to patient and radiologist during transcatheter arterial embolization for hepatocellular carcinoma].

PURPOSE: To evaluate radiation exposure to patients and radiologists during transcatheter arterial embolization(TAE) for hepatocellular carcinoma. MATERIALS AND METHODS: In 39 TAE procedures performed at eight institutes, skin doses were evaluated with thermoluminescence dosimeters at the patient's back(entrance surface) and lower abdomen, and at the radiologist's forehead and abdomen. Real-time dosimeters were also used to evaluate patient skin dose. RESULTS: The patients' mean entrance surface dose was 973 +/- 681 mGy(range, 185 to 3543 mGy) with the mean fluoroscopic time of 21 minutes and 6 digital subtraction angiography(DSA) acquisitions. The dose at the patients' lower abdomen was 0.98 +/- 0.77 mGy. Doses for the radiologists were 0.04 +/- 0.04 mGy at the forehead and 0.15 +/- 0.19 mGy and 0.005 +/- 0.01 mGy at the abdomen over and under the apron, respectively. Fifty-six percent of the patients' skin dose was from DSA and 44% from fluoroscopy. CONCLUSIONS: Patient skin dose may occasionally exceed the dose for transient erythema. Because a patient may have repeated TAEs, skin doses or X-ray conditions should be recorded. The exposed doses of radiologists were considered to be acceptable with proper techniques. Further efforts to reduce radiation should be directed toward both DSA and fluoroscopy.

Aged↗

[Clinical study of prostate cancer: statistical analysis of 107 cases in the past 12 years].

One hundred and seven patients with prostate cancer were treated at Mie University Hospital during the past 12 years between 1988 and 1999. They were between 53 and 83 years old, with an average age of 70.8 years old. The clinical stage was defined as A, B, C and D in 3 (2.8%), 19 (17.8%), 50 (46.7%) and 35 (32.7%) patients, respectively. At initial diagnosis, the tumor was well, moderately and poorly differentiated adenocarcinoma in 26 (24.3%), 47 (43.9%) and 34 (31.8%) patients, respectively. The median follow-up period was 52.3 months. The overall 1, 3 and 5-year survival rates were 98.0%, 86.8% and 75.2%, respectively. The 5-year survival rates for stage A, B, C and D were 100%, 93.8%, 82.1% and 56.9%, respectively. A significant difference (p = 0.017) in 5-year survival rate was noted between stage C and D. The 5-year survival rate was 100% for well differentiated, 78.0% for moderately differentiated, and 53.2% for poorly differentiated adenocarcinoma. A significant difference (p = 0.0016) in the 5-year survival rate was noted between well differentiated and poorly differentiated adenocarcinoma. According to the therapy, the 5-year survival rate in stage C was 86.2% for the radical prostatectomy group and 84.0% for the endocrine therapy group. There was no significant difference between these 2 treatment groups. Endocrine therapies, classified into maximum androgen blockade (MAB) and endocrine therapy other than MAB were performed for stage D as an initial therapy. Although the prognosis in the patients treated with MAB was better than that with other endocrine therapies, there was no significant difference between these 2 endocrine treatment groups.

Adenocarcinoma↗

[The current status of personality disorders in psychiatry].

A growing body of research has elucidated the bio-psycho-social backgrounds and clinical facts of personality disorders defined in DSM-III-IV Axis II, and has endorsed the clinical value of the diagnoses. However, the concept of personality disorder still remains diaphanous, and requires further clarification. One complication is that personality disorder can be seen from either the perspective that is a milder variant of other Axis I disorders, or that it is an abnormally exaggerated form of normal personality traits. That the disorders can be grouped according to these viewpoints indicates that there may be heterogeneity within them, while they have common characteristics: a long duration, extended areas of affected functioning, subtle and marginal severity of symptoms, and "person-near" nature. These features may also account for the difficulty in defining and assessing the disorder. Treatment is another important focus for discussion. Patient-therapist cooperation is essential and of itself is a difficult goal. Most failures of the therapeutic relationship lead to a variety of problems, including legal or ethical ones. Prerequisites for involuntary treatment, remedies for the risk of treatment disruption by violent acting-out and preventing malpractice are issues to be discussed. Inexorably we must return to the principle that our task is to help our patients take ultimate responsibility for decisions about their personality.

Humans↗

A new approach to develop a biohybrid artificial liver using a tightly regulated human hepatocyte cell line.

Currently patients with liver failure have been treated with a various liver support systems including a whole liver perfusion, a non-biological artificial liver, and a biohybrid artificial liver. In a hepatocyte-based bioreactor, porcine hepatocytes or transformed human liver tumor cells have been utilized because of the ease of preparation. According to the clinical data reported as of now, satisfactory results have not been obtained from the use of currently available liver support devices. One of the problems is limited availability of primary human liver cells for developing live support systems because of the shortage of human liver. To resolve this issue, human hepatocytes were immortalized with a retroviral vector SSR#69 which contained the genes of simian virus 40 large T antigen (SV40Tag) and herpes simplex virus-thymidine kinase (HSV-TK). One of the immortal cell lines, NKNT-3, showed the gene expression of differentiated liver functions, grew steadily in chemically defined serum-free CS-C medium, and doubled in number in about 48 hours. Essentially unlimited availability of NKNT-3 cells supports their clinical use for liver support devices. To realize the high density culture of NKNT-3 cells in a bioartificial liver device, we have developed cellulose microspheres (CMS) which contain cell adhesive GRGDS (Gly-Arg-Gly-Asp-Ser) peptides. Within 24 hours after starting a stirring suspension culture, GRGDS-CMS efficiently immobilized NKNT-3 cells. An electron microscopic examination demonstrated that NKNT-3 cells attached on GRGDS-CMS had well-developed mitochondria, rough reticulums, and villous extensions. In this article, we review the history of extracorporeal liver support systems and describe an attractive strategy for developing a novel extracorporeal liver assist device using NKNT-3 cells and GRGDS-coated cellulose microspheres.

Animals↗

Kupffer cells from Schistosoma mansoni-infected mice participate in the prompt type 2 differentiation of hepatic T cells in response to worm antigens.

Infection with Schistosoma mansoni, a portal vein-residing helminth, is well known to generate life cycle-dependent, systemic immune responses in the host, type 1 deviation during the prepatent period, and type 2 polarization after oviposition. Here we investigated local immunological changes in the liver after infection. Unlike splenocytes, hepatic lymphocytes from infected mice during the prepatent period already produced a higher amount of IL-4 and a lesser amount of IFN-gamma than those from uninfected mice. Hepatic lymphocytes, particularly conventional T cells, but not NK1.1+ T cells, promptly produced IL-4 in response to worm products, soluble worm Ag preparation (SWAP), whenever presented by Kupffer cells from infected mice. The hepatic lymphocytes that had been stimulated with SWAP presented by infected mice-derived Kupffer cells produced a huge amount of IL-4, IL-13, and IL-5 as well as little IFN-gamma in response to immobilized anti-CD3 mAb. Kupffer cells from uninfected mice produced IL-6 and IL-10, but not IL-12 or IL-18, in response to SWAP stimulation and gained the potential to additionally produce IL-4 and IL-13 after the infection. These results suggested that prompt type 2 deviation in the liver after the infection might be due to the alteration of Kupffer cells that induces SWAP-mediated type 2-development of hepatic T cells.

Animals↗

A new matrix protein family related to the nacreous layer formation of Pinctada fucata.

We have isolated a new matrix protein family (N16) which is specific to the nacreous layer of the Japanese pearl oyster, Pinctada fucata, and have cloned and characterized the cDNAs coding for the components. Analysis of the deduced amino acid sequence revealed that N16 showed no definitive homology with other proteins. The in vitro studies of the crystallization clarified that N16 induced aragonite crystals when fixed on the substrate but inhibited crystal formation without it. The aragonite crystals showed platy morphology different from those formed inorganically, and long intervals of incubation resulted in crystalline layers highly similar to the nacreous layer.

Amino Acid Sequence↗

Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload.

Erythroid 5-aminolevulinate synthase (ALAS-E) catalyzes the first step of heme biosynthesis in erythroid cells. Mutation of human ALAS-E causes the disorder X-linked sideroblastic anemia. To examine the roles of heme during hematopoiesis, we disrupted the mouse ALAS-E gene. ALAS-E-null embryos showed no hemoglobinized cells and died by embryonic day 11.5, indicating that ALAS-E is the principal isozyme contributing to erythroid heme biosynthesis. In the ALAS-E-null mutant embryos, erythroid differentiation was arrested, and an abnormal hematopoietic cell fraction emerged that accumulated a large amount of iron diffusely in the cytoplasm. In contrast, we found typical ring sideroblasts that accumulated iron mostly in mitochondria in adult mice chimeric for ALAS-E-null mutant cells, indicating that the mode of iron accumulation caused by the lack of ALAS-E is different in primitive and definitive erythroid cells. These results demonstrate that ALAS-E, and hence heme supply, is necessary for differentiation and iron metabolism of erythroid cells.

5-Aminolevulinate Synthetase↗

Double-stranded RNA and virus-like particles in the edible basidiomycete Flammulina velutipes (Enokitake).

One of the commercial strains of Flammulina velutipes was analyzed for the presence of double-stranded RNA (dsRNA) elements to examine the underlying mechanism of strain degeneration. As a result, two dsRNA elements sized 1.9 and 1.8 kb were detected in mycelium derived from spontaneously brown-colored fruit body. They were not detected in the normal strains or in fruiting-impaired degenerative isolates. The dsRNAs were not in the nuclear or mitochondrial fractions, but were located in the cytoplasmic fraction. The presence of virus-like particles of ca. 50 nm diameter associated with the dsRNAs was confirmed by electron microscopic observation.

Agaricales↗

Dose optimization and indication of Linac radiosurgery for brain metastases.

PURPOSE: The authors have examined treatment effects of linear accelerator based radiosurgery for brain metastases. Optimal doses and indications were determined in an attempt to improve the quality of life for terminal cancer patients. METHODS AND MATERIALS: Ninety-two patients with 162 lesions were treated with Linac radiosurgery for brain metastases between April 1993 and September 1998. To determine prognostic factors, risk factors for recurrence, and appearance of new lesions, univariate and multivariate analyses were performed. To compare the local control between the high-dose (minimum dose > or =25 Gy: prescribed to the 50-80% isodose line) and low-dose (minimum dose <25 Gy) irradiated groups, matched-pairs analysis was performed. RESULTS: Median survival time was 11 months. In univariate analysis, extracranial tumor activity (p<0.001) and Karnofsky Performance Status (KPS) (p = 0.036) were two significant predictors of survival. In multivariate analysis, the status of an extracranial tumor was the single significant predictor of survival (p = 0.005). Minimum dose was the single most significant predictor of local recurrence in univariate, multivariate, and matched-pairs analyses (p<0.05). As to the appearance of new lesions, activity of extracranial tumors was a significant predictor (p<0.05). Side effects due to radiosurgery were experienced in 4 of 92 cases (4.3%). CONCLUSIONS: We concluded that brain metastases patients should be irradiated with > or =25 Gy, when extracranial lesions are stable and longer survival is expected. Combined surgery and conventional radiation may have little advantage over radiosurgery alone when metastatic brain tumors are small and extracranial tumors are well controlled. When extracranial tumors are progressive, the rate of appearance of new lesions in other nonirradiated locations becomes higher. In such cases, careful follow-up is required and a combination with whole brain irradiation should be considered.

Adult↗

The mouse GATA-2 gene is expressed in the para-aortic splanchnopleura and aorta-gonads and mesonephros region.

We previously reported that the mouse GATA-2 gene is regulated by two alternative promoters (Minegishi et al, J Biol Chem, 273:3625, 1998). Although the more proximal IG (general) promoter is active in almost all GATA-2-expressing cells, the distal IS (specific) promoter activity was selectively detected in hematopoietic tissues but not in other mesodermal tissues. We report here in vivo analysis of the GATA-2 locus and its regulatory characteristics in hematopoietic tissues of transgenic mice. Transgenes containing 6 or 7 kbp of sequence flanking the 5' end of the IS first exon direct expression of beta-galactosidase or green fluorescent protein (GFP) reporter genes specifically to the para-aortic splanchnopleura, aorta-gonads, and mesonephros (AGM) region, and in the neural tissues. In situ hybridization analysis showed that reporter gene expression specifically recapitulates the endogenous expression profile of GATA-2 in these tissues. The flk-1, CD34, c-kit, and CD45 antigens were identified in the GFP-positive cells from the AGM region and fetal liver, indicating that GATA-2 is expressed in immature hematopoietic cells. Deletion of 3.5 kbp from the 5' end of the 6.0 kbp IS promoter construct, including one of the DNase I hypersensitive sites, completely abolished hematopoietic expression. These experiments describe an early developmental GATA-2 hematopoietic enhancer located between 6.0 and 2.5 kbp 5' to the IS exon.

Animals↗

Effects of basic fibroblast growth factor on spontaneous resorption of herniated intervertebral discs. An experimental study in the rabbit.

STUDY DESIGN: Histologic examination was performed on the autologous intervertebral disc material that was removed from the intervertebral space at L1-L2 and then relocated to the L4 posterior epidural space after the addition of basic fibroblast growth factor (bFGF) in a rabbit. OBJECTIVES: To evaluate whether basic fibroblast growth factor influences the resorption process of the herniated intervertebral disc through the promotion of angiogenesis and chemotaxis. SUMMARY OF BACKGROUND DATA: It has been reported that newly formed vessels, inflammatory cells, and their products may play an important role in the spontaneous resorption process of herniated intervertebral discs. In a rabbit model that mimics the sequestration type of intervertebral disc herniation, it has been reported that the autologous intervertebral disc material that relocated into the epidural space was penetrated by newly formed vessels originating from the epidural fat tissue. Therefore, it is possible that promotion of angiogenesis may influence the resorption of herniated intervertebral discs. Basic fibroblast growth factor is well known as an angiogenesis stimulation factor in vivo. METHODS: Thirty-six adult rabbits were divided into three groups. The L1-L2 intervertebral disc was partially incised through a retroperitoneal approach in each rabbit. The harvested disc material, which contained nucleus pulposus and anulus fibrosus, was immersed in one of three kinds of solution before relocation into the posterior epidural space at L4. In the control group, the harvested intervertebral disc was immersed in physiologic saline for 2 hours before relocation. In the group receiving 5 micrograms bFGF, the disc was immersed in 5 micrograms/mL bFGF for 2 hours before the relocation. In the group receiving 20 micrograms bFGF, the disc was immersed in 20 micrograms/mL bFGF for 2 hours before the relocation. Rabbits of each group were killed for histologic examination 1, 2, 4, and 8 weeks after surgery. RESULTS: In the bFGF-treated groups, newly formed vessels were observed to be in more numerous than those in the control group, 1 and 2 weeks after surgery. The number of inflammatory cells, including macrophages, lymphocytes, and fibroblasts, also increased in the bFGF-treated groups. The period from the surgery to the degradation of the intervertebral disc in the bFGF-treated groups was shorter than that in the control group, although the resorption process of the relocated discs was also observed in the control group. The size of relocated intervertebral discs in the bFGF-treated groups decreased at a higher rate than in the control group as time progressed. The rate of decrease in the size of discs in the group treated with 20 micrograms bFGF was more than that in the group treated with 5 micrograms. CONCLUSIONS: Epidural injection of bFGF facilitated the resorption of the intervertebral disc relocated to the epidural space.

Animals↗

Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals.

In hepatitis C virus (HCV) infection, Th responses are implicated in the pathogenesis of liver disease. The dendritic cell (DC) is the most potent activator of CD4 T cells for supporting Th1 differentiation. To clarify the roles of DC of HCV-infected individuals in the development of CD4 T cell responses, we generated peripheral DC with GM-CSF and IL-4 from 24 chronic hepatitis C patients and 14 healthy donors. We then compared their potentials for stimulating allogeneic CD4 T cells, autologous CD4 T cells against influenza A or HCV core Ags, and cytokine production. The DC from the patients (HCV-DC) expressed lower degrees of CD86 than DC from the donors (N-DC), whereas no difference was found in the HLA molecules and other costimulators. HCV-DC stimulated allogeneic T cells less than N-DC; however, influenza A- or core-pulsed HCV-DC retained the potentials for autologous T cell proliferation. In allogeneic DC/T cell cultures, the IFN-gamma levels with HCV-DC were lower than those with N-DC, which may be related to the low expressions of IL-12 p35 and p40 transcripts in HCV-DC. The stimulation with LPS disclosed that HCV-DC is less potent in IL-12 p70 production than N-DC. In the autologous cultures, the pulsing of the Ags to HCV-DC increased the IL-12 p40 and IFN-gamma production and up-regulated the transcription of both IL-12 subunits. Exogenous IL-2 or IL-12 restored the low allogeneic T cell proliferation with HCV-DC in a dose-dependent manner. Therefore, low expression of CD86 and/or IL-12 is crucially involved in the low allostimulatory capacity of HCV-DC. Low IL-12 and low IFN-gamma milieu with HCV-DC on encounters with alloantigens may impede Th1 polarization.

Adult↗

Overexpression of alpha1-6 fucosyltransferase in hepatoma cells suppresses intrahepatic metastasis after splenic injection in athymic mice.

Changes in oligosaccharide structures alter the biological functions of cancer cells. Alpha1-6 fucosyltransferase (alpha1-6FucT) catalyzes the transfer of fucose to the innermost GlcNAc in N-glycans. Although alpha1-6FucT is barely detected in normal liver, it is enhanced during rat hepatocarcinogenesis and in human hepatoma. To understand the biological meaning of the alpha1-6FucT in hepatoma, especially in terms of metastasis, we established human hepatoma cell lines, which express high levels of alpha1-6FucT by transfection of the alpha1-6FucT gene and investigated intrahepatic metastasis after splenic injection to athymic mice. Tumor formation in the liver was dramatically suppressed in the alpha1-6FucT transfectants (1 of 9 and 1 of 10 in alpha1-6FucT transfectants versus 6 of 9 and 6 of 9 in controls). Although there were no differences in terms of cell invasiveness to a Matrigel or in terms of cytotoxicity to interleukin 2-treated lymphocytes between alpha1-6FucT transfectants and control cells, cell adhesion to mice hepatocytes and nonparenchymal liver cells in culture was significantly inhibited in alpha1-6FucT transfectants, compared to the controls. Attachment of alpha1-6FucT transfectants to a fibronectin-coated dish was decreased compared to controls because alpha5beta1 integrin was more strongly alpha1-6 fucosylated in the alpha1-6FucT transfectants. Two-dimensional electrophoresis followed by lectin blot showed that certain glycoproteins (Mr 50,000-150,000, pI 4.8-5.5) were alpha1-6 fucosylated and might be linked to suppression of intrahepatic metastasis. This is the first demonstration of the biological significance of alpha1-6 fucosylation on N-glycans in hepatoma cells under in vivo conditions.

Animals↗