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Biomedical subjects

M Kako

Publications and source records attributed to M Kako.

At least 55 records · Page 3Linked to original sources

Transmission of hepatitis C virus from mothers to infants. The Vertical Transmission of Hepatitis C Virus Collaborative Study Group.

BACKGROUND: Although there are case reports of vertical transmission of hepatitis C virus (HCV), it remains uncertain to what extent infected mothers transmit this virus to their infants. METHODS: We investigated the transmission of HCV from infected mothers to their babies by analyzing HCV RNA in the blood. Three independent studies were performed. First, 7698 parturient women were tested for anti-HCV antibodies; 53 were positive. Their 54 infants (including one set of twins) were followed prospectively for at least six months and tested for HCV disease were prospectively studied. Third, the families of three HCV-infected infants were examined retrospectively. RESULTS: Of the 53 antibody-positive mothers, 31 were also positive for serum HCV RNA: Three of the 54 babies born to these mothers (5.6 percent) became positive for HCV RNA during the follow-up period. None of the babies of the 22 women who were antibody-positive but HCV RNA-negative became positive for HCV RNA: In the second study, HCV RNA was detected in one of the six infants of infected mothers. In the third study, HCV RNA was detected in the mothers of the three HCV-infected infants. In each of the seven infected infants we studied, the genomic sequence of HCV was almost identical to that from the mother. These seven mothers had significantly higher titers of HCV RNA than did the mothers of infants with no evidence of infection (mean [+/- SD], 10(6.4 +/- 0.5) vs. 10(4.4 +/- 1.5) per milliliter; P < 0.001). CONCLUSIONS: HCV is vertically transmitted from mother to infant, and the risk of transmission is correlated with the titer of HCV RNA in the mother.

Adult↗

[HCV-serotype and IFN response].

The relation between HCV-serotypes and response to interferon (IFN) in 114 cases with chronic hepatitis C treated with IFN-alpha were studied. HCV-serotypes; two distinct subgroups (serotype 1 and 2) of hepatitis C virus defined by antibodies directed to the putative core protein, were examined by ELISA developed by Machida et al. 1) Of 33 cases with serotype 2, 20 were responders, whereas, only 5 of 35 cases with serotype 1 responded to IFN therapy. 2) Of 23 cases with HCV-genotype III, 18 (78.3%) responded to IFN. Moreover, 12 (85.7%) of 14 cases who had serotype 2 were responders. On the other hand, only 17 (21.0%) cases with genotype II and 4 (12.1%) cases with serotype 1 responded to IFN. HCV-serotyping as well as HCV-genotyping in cases with chronic hepatitis C seems to be important in predicting the response to IFN therapy.

Adult↗

Production and secretion of endothelin by hepatocellular carcinoma.

To clarify whether hepatocellular carcinoma (HCC) may produce and secrete endothelin (ET), we measured plasma levels of ET-1 and big ET-1, a precursor form of ET-1, in 30 patients with HCC. When compared to normal subjects, a substantial number of patients had elevated plasma ET-1 and big ET-1 levels, determined by specific enzyme immunoassays. The mean (+/- SD) plasma concentrations of ET-1 (1.7 +/- 0.9 pmol/L) and big ET-1 (6.1 +/- 4.8 pmol/L) in patients' group were significantly (P < 0.01) higher than those (1.0 +/- 0.3 and 2.0 +/- 0.8 pmol/L, respectively) in control group. There was a significant positive correlation between plasma big ET-1 and alpha-fetoprotein (r = 0.77, P < 0.01). Some of the 29 patients with liver cirrhosis also had modestly elevated plasma big ET-1 levels. The mean (+/- SD) plasma big ET-1 concentration (3.1 +/- 0.9 pmol/L) in patients with liver cirrhosis was significantly (P < 0.01) higher than that in control group, although there was no significant difference between the mean plasma ET-1 levels of both groups. Raised plasma big ET-1 and, less markedly, ET-1 levels in patients with HCC decreased after successful transcatheter arterial embolization concomitantly with a reduction in tumor sizes and a decrease in plasma alpha-fetoprotein levels. In six patients, an arteriovenous difference in ET-1 and big ET-1 levels across the tumor bed with a higher concentration in the venous circulation was found. Reverse-phase high performance liquid chromatography revealed that major portions of immunoreactive ET-1 and big ET-1 in hepatic venous plasma coeluted with synthetic ET-1 and big ET-1, respectively. Immunohistochemistry of HCC tissues from two patients demonstrated HCC cells positive for ET-1 and big ET-1, whereas no ET immunoreactivity was found in adjacent nontumorous hepatocytes. We conclude from these results that ET is produced by and released from a substantial number of HCC, which may stimulate proliferation of carcinoma cells as an autocrine or paracrine growth factor.

Adult↗

[The point mutation of pre-C region HBV-DNA in sera from chronic hepatitis B].

To clarify the relationship between a point mutation of HBV-DNA Pre-C region and the serological feature of chronic hepatitis B, we determined the Pre-C region sequence of HBV-DNA obtained sera of 39 patients with chronic hepatitis B. The screening of the gene arrangement of Pre-C region of HBV-DNA was performed by a direct sequence method amplifying HBV-DNA by polymerase chain reaction methods. In 22 of HBeAg positive cases, a mutant type (the 28th codon changed from TGA to TAG: stop codon) was found in only one case. The other hand, In 17 of HBeAg negative cases, it was found in 6 cases with fluctuating ALT and DNA-polymerase levels. We concluded that mutant viral infections could be the main cause of HBeAg negative cases with fluctuating ALT and DNA-polymerase levels.

Adult↗

Adrenal myelolipoma associated with congenital adrenal 21-hydroxylase deficiency.

The occurrence of adrenal myelolipomas is reported in an untreated patient with congenital adrenal 21-hydroxylase deficiency. Laparotomy demonstrated the presence of two lesions, a large tumor which arose from an ectopic adrenal cortex and a smaller tumor in the left adrenal gland. Six cases of adrenal myelolipomas and congenital adrenal hyperplasia have been reported in the literature. All patients were associated with excessive ACTH secretion for a long period of time. The relative frequency of this association, coupled with the observation by Selye and Stone (Am J Pathol 26:211, 1950) that anterior pituitary extracts cause myelolipomatous changes in rats, may indicate a possible role for ACTH in the development of myelolipomas.

Adrenal Gland Neoplasms↗

[Hepatic cancer].

Several problems in the evaluation of the antitumor effects of chemotherapy for hepatic cancer were discussed: tumor biopsy, complicating of liver cirrhosis, measuring errors of tumor size, evaluation of inner change of tumors after chemotherapy, AFP and evaluation of unchanged tumor size after chemotherapy.

Antineoplastic Agents↗

Expression of a hepatocyte membrane antigen during hepatocarcinogenesis and in the developing liver of the rat.

Changes in the expression of a cell membrane antigen during hepatocarcinogenesis and in the developing liver were analyzed by HAM.4, a monoclonal antibody (MAb) against a membrane glycoprotein of normal rat hepatocyte. Of the precancerous lesions observed during hepatocarcinogenesis induced by diethylnitrosamine, 2-acetylaminofluorene and partial hepatectomy, early neoplastic foci were uniformly stained by HAM.4. In contrast, some cells in the neoplastic nodules at the late stage did not express HAM.4 antigen on the cell surface. Of the cancer tissues, well-differentiated hepatocellular carcinomas were stained by HAM.4 whereas poorly differentiated carcinomas did not bind HAM.4 In developing rat liver, HAM.4 antigen was first expressed on fetal hepatocytes at the 18th day of gestation. It gradually increased until 4 weeks after birth when the intensity of the stain was almost the same as in adult rat liver. These results suggest that the expression of a membrane antigen defined by HAM.4 is closely associated with the differentiation of bile canalicular face and that HAM.4 might be useful in characterizing differentiation of cells during malignant transformation of hepatocytes.

Animals↗

[Interferon production in vitro].

Interferon production in vitro was induced by poly I: C and PHA in leukocytes obtained from patients with cancer, benign diseases and control subjects. The interferon response per lymphocyte was relatively constant in all groups. However, interferon production was slightly inhibited in patients receiving cancer chemotherapy. The peak response of interferon occurred at 48 hours after the initiation of the combined culture in each specimen. From our observations, it was suggested that interferon production in vitro seems to be useful marker for evaluation of effect of chemotherapy and or immunotherapy, and, furthermore, in the treatment of cancer patients with interferon inducers, there seems to be optimum BRM dose and optimum timing of administration.

Cell Wall Skeleton↗

[Host factors in cancer chemotherapy].

Cancer grows in interaction with the host, that is, a host-tumor relationship exists. Investigations of host factors in patients receiving cancer chemotherapy are important, as they reveal the conditions in which a tumor response can develop. Furthermore, reliable host factors, if present, will be useful for quantitative evaluation of the effects of treatment. We have investigated the following three categories of host factors in relation to the effects of cancer chemotherapy and/or immunotherapy. CBC, and blood chemistries (44 parameters). Tumor markers; sialic acid, RNase, lysozyme, ferritin, IAP (immunosuppressive acidic protein), elastase I, AFP, CEA, POA, CA 19-9, CA 125, etc. Immunological parameters; lymphocyte, active T cell, T cell, B cell, IgG Fc receptor-positive T cell, lymphocyte blastogenesis stimulated by PHA, or concanavalin-A, ADCC activity, interferon production in vitro induced by poly I: C, or PHA, PPD skin test, immune complex, immunoglobulin G, A, and M, OKT series 3, 4, 8, 11, 4/8 ratio, antihuman HLA-DR, Leu 11, NK cell activity, etc. From our clinical observations, there were no significant differences in the pretreatment levels of these parameters between responders and non-responders. In responders, there was a tendency for the host factors to show greater degrees of improvement following treatment than in non-responders, but none proved to be reasonably reliable parameters for evaluating therapeutic effects. On the other hand, from our clinical observations on the advanced gastric cancer cases, life span showed a close correlation with tumor regression induced by cancer chemotherapy. Because of these facts, it is only natural that the clinical effects of chemotherapy are currently determined by definite tumor regression.

Humans↗