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Biomedical subjects

N Nagai

Publications and source records attributed to N Nagai.

At least 145 records · Page 8Linked to original sources

Cytological analysis for human papillomavirus DNAs in cervical intraepithelial neoplasia by in situ hybridization.

Human papillomavirus (HPV) type 16 and 18 DNAs are reported to be associated with uterine cervical cancer. In order to investigate the relationship between the presence of HPV DNA and cervical intraepithelial neoplasia (CIN), we attempted the cytological detection of HPV DNAs in uterine cervical smear samples. The samples included those of severe dysplasia and carcinoma in situ (CIS). They were analysed by DNA-DNA in situ hybridization using biotinylated HPV DNA probes. The results of in situ hybridization analysis revealed that HPV sequences were present in the nuclei of cells with koilocytotic atypia. When probed for HPV type 6, 11, 16 and 18, the nuclei of dysplastic cells and cancer cells were positive for HPV type 16 and 18 DNA. Out of 26 CIN cases, 17 contained HPV type 16 DNA and 5 contained HPV type 18 DNA. We suggest that cytological analysis for HPV sequences by the in situ hybridization technique might provide a molecular diagnosis for assessment in uterine cervical intraepithelial neoplasia.

DNA, Viral↗

[Gene diagnosis of uterine cervical cancer].

Molecular biologic studies have shown that human papillomavirus (HPV), some oncogenes and tumor suppressor genes are associated with uterine cervical carcinogenesis. We examined HPV DNA typing and its gene expression, oncogenes (c-myc, EGF-R, c-erb B2) and p53 in cervical dysplasia and cancer with molecular biologic, immunohistochemical technique and binding assay to establish a gene diagnosis of uterine cervical cancer. The HPV study revealed that HPV DNA was detected at a high frequency at a higher grade of dysplasia and in the early stage of cervical cancer; especially HPV type 16 was associated with cervical carcinogenesis. In the oncogene study, c-myc gene overexpression was recognized in the advanced stage of cervical cancer. The other oncogene and p53 were found in a low frequency and were non-specific genes in cervical cancer. These findings indicated that HPV DNA diagnosis is a useful tool for screening the high risk group of cervical precancerous lesions and that oncogene detection might be useful in determining the biological behavior of a malignant tumor.

Base Sequence↗

Precise diagnosis by gene analysis and successful management of delivery in three patients with type IIB von Willebrand disease.

Type IIB is a rare variant of von Willebrand disease (vWD). An affected individual's bleeding tendency and thrombocytopenia are exacerbated with pregnancy, and the proper management of these patients during delivery has not been well established. Since it is important to distinguish this disease from the platelet type vWD in order to administer the appropriate therapy, gene analysis is necessary to make the precise diagnosis. We now report the successful management of delivery in three patients, who were diagnosed as having type IIB vWD by the detection of missense mutations in the von Willebrand factor (vWF) gene (C3916-->T and C3922-->T). These changes cause Arg543-->Trp and Arg545-->Cys substitutions in the A1 domain of vWF. We were able to manage the bleeding tendency of these patients at delivery mainly with vWF concentrates to supply normal vWF.

Adult↗

[Interleukin-4 (IL-4)].

Helper T cells can be divided into Th1 type cell which produces IL-2 and IFN-gamma and Th2 type cell which produces IL-4, IL-5, and IL-6. In general, cytokine has a pleiotropic action. Furthermore cytokines have redundancy in their action. IL-4 is a major product of Th 2 type cell and is an essential cytokine for IgE production, which is also induced by recently found IL-13. Additionally IL-4 is a key factor for the development of Th2 cell, which produces cytokines responsible for inducing allergic reaction. In this paper, we described the gene regulation, molecular structure and biological action including the anti-tumor activity of IL-4.

Animals↗

[Distribution of platinum in the female genital tract after intraarterial carboplatin infusion during the operation of uterine cervical cancer].

We investigated the platinum concentration in the female genital tract, the regional lymph nodes and serum after intraarterial carboplatin 150mg infusion during the operation of uterine cervical cancer. The following results were obtained. 1. The mean platinum concentration in the region of cervical cancer was highest (1.77 micrograms/g wet tissue of the female genital tract). However the other genital tract including the endometrium, ovary and fallopian tube showed the same platinum concentration. 2. The level of the serum total platinum concentration became maximum at 30 min and gradually decreased thereafter. From these results, intraarterial CBDCA infusion seemed to show the therapeutic effect against the primary region of uterine cancer and the other genital tract.

Adenocarcinoma↗

Reduced increase in plasma renin activity on water-deprivation in blind hereditary microphthalmic rats.

We compared the plasma renin activity (PRA) before and after 24-h water-deprivation in blind hereditary microphthalmic rats and Donryu rats. In the congenitally blind rats with a morphologically abnormal suprachiasmatic nucleus (SCN), hypovolemia induced significantly less elevation of the PRA and significantly more increase in the hematocrit value than in normal rats. The changes after water-deprivation in the blind rats were quite similar to those reported in rats with SCN lesions. However, the free-running circadian rhythms persisted in these blind rats, whereas those in rats with SCN lesions were completely eliminated. Thus, it is likely that SCN cells are involved in regulation of the PRA, and that if this is the case these cells are different from those containing the circadian pacemaker.

Animals↗

Primary scirrhous carcinoma of the nipple with symptoms simulating Paget's disease: report of a case.

We report herein an extremely rare case of primary scirrhous carcinoma of the nipple, being of particular interest in that the patient presented with symptoms very similar to those of Paget's disease. The carcinoma cells were detected by aspiration biopsy cytology rather than by touch smear, although both were performed to differentiate this lesion from Paget's disease and other diseases of the nipple. Thus, we recommend that both touch smear and aspiration biopsy cytology should be performed for all patients presenting with symptoms such as those observed in this case to rule out the possibility of scirrhous carcinoma of the nipple or Paget's disease.

Adenocarcinoma, Scirrhous↗

Effects of light stimulation on the activity of the autonomic nerves in anesthetized rats.

The existence of the retino-hypothalamic pathway suggests that light stimulation may influence the activity of the autonomic outflows. Efferent activities of the pancreatic, hepatic, and gastric branches of the vagus nerve and those of pancreatic, hepatic, splenic, adrenal, and renal branch of the splanchnic nerve were recorded. Light stimulation with 2000 1x for 10 min to the left eye increased the splanchnic (sympathetic) outflows and suppressed the vagal outflows. The effects lasted for several hours. The minimal effective stimulation was 20 1x for 1 min or 200 1x for 0.1 min. These responses were observed in the light period as well as dark period. However, in the suprachiasmatic nucleus (SCN) lesioned rat, the changes in autonomic outflows following light stimulation were absent. The observations suggest that light stimulation modulates visceral functions through changes in the autonomic nervous system activities via the SCN.

Animals↗

Investigation of clinical characteristics of ventricular extrasystole in children--using two dimensional RR interval plotting method.

Eighty-three children were monitored by Holter electrocardiography for ventricular premature contraction (VPC), and the relationship between the preceding RR interval and the coupling interval was plotted using a two-dimensional RR interval plotting method. With this method, the slope (a) and standard deviation (SD) of the linear regression (Y = aX+b) were determined. These parameters were used to classify the patients into one of two types: a fixed type (SD < 40 msec, a < 0.2) and an unfixed type. The unfixed type was further divided into four subtypes, based on the plotted morphology: scattered, dependent, biphasic, and intermediate. The relationships between the VPC origin, organic heart disease, ventricular tachycardia (VT) and parasystole were investigated in the five types. The fixed and dependent types comprised significantly greater proportions of the subjects with VPC of right ventricular origin than of subjects with VPC of left ventricular origin (fixed: 31/59 right VPC vs 4/24 left VPC, p < 0.005; dependent: 13/59 vs 1/24, p < 0.05). On the other hand, comparatively very few subjects of the scattered type showed right VPC (4/59 vs 18/24, p < 0.005). Finally, the biphasic and intermediate types were distributed fairly equally among the subjects with VPCs of right and left ventricular origin (biphasic: 5/59 vs 0/24, p = 0.31, intermediate: 6/59 vs 1/24, p = 0.67). Organic heart disease was present in 13 subjects (15.7% of total subjects), seven of whom were of the fixed type with right ventricular origin (22.6% of subjects of this type). VT was observed in 34 subjects, but was rare in the scattered type (2/22 subject, 9.1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Production of alpha-fetoprotein by human submandibular gland.

Alpha-fetoprotein (AFP) is a 590 amino acid polypeptide that was initially defined as an embryonal serum globulin. The yolk sac endoderm, fetal liver and fetal gut were shown to be the main sites of AFP synthesis in the embryo (Gitlin and Boesman, J. Clin. Invest. 46: 1010-1016, 1967). AFP synthesis is still continued in human adults (Ruoslahti and Seppala, Int. J. Cancer 8: 374-383, 1971) although the physiological level of serum AFP is lower than 10 ng/ml. AFP was also demonstrated in certain tumors and in various diseases or conditions such as yolk sac tumor, hepatoma, hepatoblastoma, acute and chronic liver cirrhosis, pregnancy and so on (Abelev, Adv. Cancer Res. 14: 295-358, 1971; Ruoslahti and Seppala, Cancer Res. 29: 275-346, 1979). Salivary glands have not been implicated in AFP synthesis. We investigated the expression of AFP in normal human salivary glands by immunohistochemistry with a monoclonal antibody against AFP, and documented immunoreactivity in intercalated and striated ducts of adult human submandibular glands.

Adult↗

[Study of proliferating cell nuclear antigen (PCNA), nucleolar organizer regions (NORs) and mitotic activity in epithelial ovarian tumors].

We investigated the proliferating cell activity of 121 epithelial ovarian tumors with formalin-fixed, paraffin-embedded tissue sections by means of the proliferating cell nuclear antigen (PCNA) labeling index, the mean number of nucleolar organizer regions (NORs) and mitotic activity. In the order of the malignant group (82 cases), the borderline-malignant group (19 cases) and the benign group (20 cases), the mean PCNA labeling index was 32.9, 12.8, 3.4(%), the mean number of NORs was 11.1, 5.8, 2.9 (/nucleus) and the mitotic index was 30.8, 8.0, 0.5 (/10HPF) and there was a significant difference (p < 0.001) between groups. There was a positive correlation (p < 0.001) among the PCNA labeling index, the mean number of NORs and the mitotic index. In 11 cases in the malignant group, the PCNA labeling index, the mean number of NORs and mitotic index in postchemotherapy were significantly lower than those in the prechemotherapy. It was suggested that the evaluation of proliferating cell activity in malignant cases was useful in investigating the malignant potential as well as the effect of chemotherapy.

Cell Count↗

[Comparative study of HPV infection and proliferating cell nuclear antigen of uterine cervix].

We investigated the proliferating activity of human papillomavirus (HPV) infection in cervical neoplasia obtained from 37 mild dysplasia, 26 moderate dysplasia, 34 severe dysplasia and 26 carcinoma in situ (CIS) and 10 normal cervical epithelium by in situ hybridization (ISH) with biotinylated HPV 6, 11, 16 and 18 DNA probes and by immunohistochemical staining with monoclonal antibody (PC10) to proliferating cell nuclear antigen (PCNA). The results were as follows: 1) The immunohistochemical study of PCNA was useful as a marker to detect proliferating activity in formalin-fixed, paraffin-embedded tissue sections. The PCNA labelling index was significantly increased as the grade of cervical neoplasia become higher (normal cervical epithelium: 3.5%, mild dysplasia: 10.3%, moderate dysplasia: 16.9%, severe dysplasia: 23.7%, CIS: 36.3%) (p < 0.01). 2) The PCNA labelling index of the HPV type 6, 11, 16, 18 positive group was not significantly different from that of the no HPV detected group in each grade of cervical lesions. 3) The PCNA labelling index group positive for HPV 16, 18 DNA was significantly higher than the HPV 6, 11 positive group and the no HPV detected group at every grade of dysplasia (p < 0.05). The precancerous lesions positive for HPV type 16 or 18 were thought to be a high risk group judging from the proliferating activity. These results suggest that PCNA can be used as one of the growth factors in cervical neoplasia and that HPV type 16 and 18 infection had a significant proliferating cell activity in every grade of cervical dysplasia.

Antigens, Neoplasm↗

Localization of bone morphogenetic protein-induced bone and cartilage formation on a new carrier: fibrous collagen membrane.

A fibrous collagen membrane (FCM) made of crosslinked reconstituted collagen fibers was applied as a carrier of BMP. The effectiveness of FCM as a BMP carrier was compared with conventionally used insoluble bone matrix (IBM). Partially purified BMP was obtained from a guanidine HCl extract of bovine bone after a three-step chromatographic procedure. The BMP fraction was combined with FCM or IBM and implanted subcutaneously in the back of rats. Bone and cartilage formation were determined by radiographic, histologic, and biochemical analyses after removal at 1, 2, 3 and 4 weeks. After 2 weeks, bone and cartilage formation were evident histologically in IBM-BMP and FCM-BMP. In IBM-BMP, cartilage was formed in the area of presumptive bone. On the other hand, in FCM-BMP, cartilage formation occurred in the space between the fibers of fiber-bundles, while on the surface of the fibers bone formation started independently. Biochemically, the most noteworthy difference between FCM-BMP and IBM-BMP was the marked increase in type II collagen content in FCM-BMP, which contrasted with its decrease in IBM-BMP at 3 weeks. This study demonstrated that FCM definitely functioned as a BMP carrier that led to bone and cartilage formation at distinct sites. Therefore, we conclude that BMP could induce differentiation of immature cells preferentially into either osteogenic cells or chondrocytes depending upon the nature of the carrier which provides the environment for cell differentiation.

Alkaline Phosphatase↗

Effect of orbital enucleation on glucose homeostasis and morphology of the suprachiasmatic nucleus.

In rats there is a direct neural connection called the retinohypothalamic tract (RHT) from retinal ganglion cells to the ventrolateral part of the suprachiasmatic nucleus (SCN), which has neurons containing vasoactive intestinal polypeptide (VIP)-like substance. Previously, we observed that bilateral orbital enucleation (blinding) caused temporary suppression of the hyperglycemic response to intracranial injection of 2-deoxy-D-glucose (2DG) from week 4 to 6 after blinding. Moreover, bilateral lesions of the SCN had a similar effect. From these findings, we supposed that the neurons responsible for the hyperglycemic response to 2DG were present in the SCN, that after blinding these neurons temporarily lost their activity, and that this functional change was reflected in the morphology of the SCN. To investigate this possibility, we examined the morphological changes of the SCN by Nissl staining and immunohistochemical studies with anti-VIP and anti-peptide histidine isoleucine (PHI) antibodies in blinded rats, and the relationship between these morphological changes and the hyperglycemic response to 2DG. After surgical blinding, we observed following changes. (1) The optic chiasm became thinner. (2) The SCN became displaced rostrally. (3) The density of neurons in the middle to caudal part of the SCN, where the retinal ganglion cells projected, decreased markedly without change in cell number during the period when the hyperglycemic response to intracranial injection of 2DG was temporarily suppressed after blinding. The first and second changes seemed to reflect reduction of fibers and axon terminals of retinal ganglion cells and their innervation, respectively. As the third change was parallel with suppression of the hyperglycemic response to 2DG injection, it may reflect functional change of the neurons in the SCN that are responsible for the hyperglycemia due to 2DG.

Animals↗