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Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 433 records · Page 24Linked to original sources

[A case with hepatocellular carcinoma with complete remission due to gamma-IFN therapy].

A 65-year-old male was admitted to our hospital with the aim of closer examination of SOL in cirrhotic liver. By abdominal echography, CT and angiography etc., he was diagnosed as LC with multiple HCC, one in S5 about 2.0 cm, another in S1 about 5.0 cm in diameter, and other four small nodules in right lobe. We treated him with recombinant gamma-IFN at dose of 1.6 X 10(7) units/day for 5 consecutive days biweekly. Although until two months the tumours were gradually enlarged in size, then they became smaller, and at five months later after the beginning of gamma-IFN therapy the tumor stains in angiogram disappeared. Then we performed the surgical treatment. Both macro and microscopical findings of tumor specimens in S5, 2. 2 X 2.0 X 1.9 cm in size, showed complete necrotic tissue. Additionally the yellowish small tumor was found on surface of S8, and it was adenomatous hyperplasia histologically.

Carcinoma, Hepatocellular↗

Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix.

Loss of genes at specific chromosomal loci is a common genetic alteration in human tumors and is thought to be critical for unmasking the recessive genetic changes for tumorigenesis. To learn whether such recessive mutations are involved in the development of carcinoma of the uterine cervix, 18 fresh tumors were analyzed by Southern blot hybridization using 34 polymorphic DNA markers covering 19 different chromosomes. We found loss of heterozygosity at the D3S2 locus on chromosome 3p in all nine patients who could be evaluated. Human papillomavirus type 16 and type 18 were present in seven and three of 18 tumors, respectively, while no amplification of 13 oncogenes, including c-myc and H-ras, was detected in these tumors. These results suggest that recessive genetic changes on chromosome 3p are one of the important genetic alterations for the development of carcinoma of the uterine cervix. Since this locus is also lost commonly in lung cancer and in renal cell carcinoma, it is possible that these three different types of adult tumors result from mutations of the same recessive gene on chromosome 3p.

Blotting, Southern↗

[OK 432-induced production of IFN-gamma in peripheral mononuclear cells from healthy subjects and patients with cancer].

OK 432, a well-established immunopotentiator, has been recently noticed as one of biological response modifiers (BRM). IFN-gamma, also called immune interferon, is regarded as an important immunoregulator secreted by T-lymphocytes. In the present study, we measured the in vitro production of IFN-gamma in human peripheral mononuclear cells (PMC) induced by OK 432. PMC were isolated from the peripheral blood with the Ficoll-Conray centrifugation technique. The number of cells for culture was adjusted to 1 x 10(6) cells/ml in RPMI-1640 medium supplemented with 10% fetal calf serum. Incubation was performed over 7 days at 37 degrees C in the presence of OK 432 at 0.17KE/ml in microculture plates. IFN-gamma secreted in the supernatants was measured consecutively during the observation period with radioimmunoassay. IFN-gamma production in PMC from healthy subjects was already detectable at 24 hours of culture and elevated gradually with incubation, reaching as much as 94.3 +/- 44.6 u/ml (mean +/- SD) after 7 days of culture. In contrast, the production of IFN-gamma in patients with cancer was severely suppressed as 21.9 +/- 25.4 u/ml after 7 days of culture (p less than 0.01). Furthermore, both surgical and radiation treatments inhibited the production of IFN-gamma in PMC from patients with cancer.

Biological Products↗

Loss of heterozygosity on chromosomes 1p and 11p in sporadic pheochromocytoma.

We used 29 polymorphic DNA markers to analyze tumor DNA samples from six patients with sporadic pheochromocytoma for possible loss of chromosomal heterozygosity; four had benign disease and two had malignant disease. Loss of heterozygosity was observed on four chromosomes: 1p (three of four patients), 2p (one of one), 5q (two of six), and 11p (three of five). Chromosomes 1p and 11p frequently had allelic deletions in these tumors, and these deletions may play an important role in the development of pheochromocytoma.

Adrenal Gland Neoplasms↗

Frequent loss of heterozygosity on chromosome 14q in neuroblastoma.

Using 29 polymorphic DNA markers which detect allelic deletion of genes at specific loci on 19 different chromosomes, we analyzed 14 neuroblastomas for possible loss of chromosomal heterozygosity. The incidence of loss of heterozygosity was high at the D14S1 locus on chromosome 14q, being detected in six of 12 patients (50%). In spite of the cytogenetic finding suggesting high frequency of chromosome 1p deletion, loss of heterozygosity at the MYCL locus on 1p32 was detected only in two of nine patients (22%). It was also found in two of 11 patients (18%) on 13q, but not on chromosomes 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17, 18, 19, and 20. The present results indicate that recessive genetic changes involving sequences on chromosome 14q may play an important role in the development of neuroblastoma.

Chromosome Deletion↗

Electrophysiological changes in the fasciculus gracilis of the cat following chronic clioquinol administration.

Clioquinol was administered to cats for more than 200 days, in order to investigate the neural mechanisms underlying the sensory disturbances of subacute myelo-opticoneuropathy (SMON). Electrophysiological examination, carried out under urethane-chloralose anesthesia, revealed that there were 3 major abnormalities in the surface potentials of the nucleus gracilis evoked by sural nerve stimulation, i.e., a reduction in the peak-to-peak amplitude, prolongation of the N wave, and a reduction in P wave amplitude. The reduction in P-wave amplitude suggested suppression of presynaptic inhibition. This was confirmed by excitability tests of the presynaptic terminals of sural nerve fibers within the nucleus gracilis. Recordings of orthodromic volleys in the fasciculus gracilis, elicited by sural nerve stimulation, showed an increase in temporal dispersion. Increased temporal dispersion was also evident from recordings of antidromic volleys in the sural nerve. Peripheral axons of primary sensory neurons in the sural nerve and their terminals within the spinal cord showed no significant functional abnormalities in the chronic clioquinol cat. It is suggested that primary axons in the fasciculus gracilis near the nucleus gracilis are affected by chronic clioquinol administration.

Action Potentials↗

Molecular cloning of a human Ca2+-dependent cell-cell adhesion molecule homologous to mouse placental cadherin: its low expression in human placental tissues.

P-cadherin is a subclass of Ca2+-dependent cell-cell adhesion molecules present in mouse placenta, where its localization suggests a function of connecting the embryo to the uterus (Nose, A., and M. Takeichi. 1986. J. Cell Biol. 103:2649-2658). We recently identified a human cadherin detected by an mAb capable of disrupting cell-cell adhesion of A-431 cells, and found that it was closely related immunochemically to mouse P-cadherin. Curiously, this cadherin was undetectable in human placenta by immunohistochemical examination (Shimoyama, Y., S. Hirohashi, S. Hirano, M. Noguchi, Y. Shimosato, M. Takeichi, and O. Abe. 1989. Cancer Res. 49:2128-2133). We here report the cloning and sequencing of cDNA clone encoding the human homologue of mouse P-cadherin. The deduced amino acid sequence of the human P-cadherin consists of 829 amino acid and shows striking homology with mouse P-cadherin. On Northern blot analysis, human P-cadherin was scarcely expressed in human placenta in contrast to mouse P-cadherin, which was abundantly expressed in mouse placenta throughout pregnancy, and it was shown that E-cadherin, but not P-cadherin, was the major cadherin molecule in human placenta. Moreover, NIH3T3 cells transfected with human P-cadherin cDNA expressed the functional cadherin molecule, which was identical to the cadherin we had previously identified using the mAb, showing that this molecule really does mediate cell-cell adhesion and that the cadherin we detected immunochemically is undoubtedly human P-cadherin. The results obtained in this study support the idea that P-cadherin plays little role, if any, in Ca2+-dependent cell-cell binding in human placental tissue at least after several weeks of pregnancy.

Amino Acid Sequence↗

Low incidence of point mutation of c-Ki-ras and N-ras oncogenes in human hepatocellular carcinoma.

We examined the incidence of point mutation in codons 12, 13 and 61 of c-Ki-ras and N-ras genes in human hepatocellular carcinoma (HCC) using the polymerase chain reaction and oligonucleotide hybridization techniques. Among 34 tissues specimens surgically resected from 30 patients and 5 cell lines of human HCC, only two had ras point mutations; in one case, codon 12 of c-Ki-ras was altered from GGT, coding glycine, to GTT, coding valine; in the other case, codon 61 of N-ras was altered from CAA, coding glutamine, to AAA, coding lysine. Thus, point-mutational activation of ras oncogenes is an uncommon event in human HCC.

Carcinoma, Hepatocellular↗

Manners of arginine vasopressin secretion in schizophrenic patients--with reference to the mechanism of water intoxication.

Water intoxication occurs almost exclusively in many patients with chronic psychiatric disorder. To elucidate the mechanism of this syndrome, we undertook the following animal experiments and clinical study. Twelve rabbits were given neuroleptics for eight weeks. From measurement of arginine vasopressin (AVP) secretion response to osmotic stimuli (fluid deprivation, partaking ad lib. and water loading), we found that chronic neuroleptic administration might raise the sensitivity of AVP escretion response. Then we investigated the manners of AVP secretion during ad lib. drinking in seventeen schizophrenic patients with hyponatremia and sixteen schizophrenic patients without hyponatremia. Normal range of plasma AVP was obtained from healthy volunteers by water loading. Only in both schizophrenic groups was plasma AVP detected below 270 mOsm/kg osmolality. We observed that sensitivity of AVP secretion response to osmolality was decreased in schizophrenic patients, regardless of the presence of hyponatremia. We hypothesize that the primary low sensitivity of AVP secretion response to osmo-receptor and the secondary renal hypersensitivity of AVP receptor may play the major role in the occurrence of water intoxication, linked to SIADH, in schizophrenic patients.

Adult↗

A unique verrucous anogenital tumor associated with type 6b-related human papillomavirus.

Multiple dark brown papillomatous tumors, showing some histological features of verrucous carcinoma or giant condyloma, developed mainly in the anogenital region of a Japanese woman. The tumors first appeared when she was 51 years old and annoyed her for over 20 years with several recurrences without any frank malignant transformation, after surgery. Immunohistochemically, papillomavirus genus-specific antigen was demonstrated only in small foci of the lesions resected at first operation. Southern blot analysis revealed human papillomavirus type 6b-related DNA in a surgically resected specimen. The possible role of the human papillomavirus in the genesis of this unique tumor is discussed.

Aged↗

In situ hybridization and immunohistochemical study of human papillomavirus infection in adult laryngeal papillomas.

Routinely processed paraffin sections from 20 patients with adult laryngeal papillomas were examined for the presence of human papillomavirus type 11 (HPV-11) DNA and its specific mRNA by in situ hybridization methods using 35S-labeled RNA probes. Immunohistochemical techniques were also used to identify papillomavirus genus-specific common antigen (pgs-antigen). HPV-11 DNA signals and/or papillomavirus genus-specific common antigen were detected in all eight samples of multiple laryngeal papilloma. On the other hand, in 12 samples of single laryngeal papilloma, neither papillomavirus genus-specific common antigen nor HPV-11 DNA were detected. Four patients were positive for both HPV-11 DNA and pgs-antigen. In three of these four patients, HPV-11 mRNA signals were also detected. These results provided direct evidence of the association of HPV and adult multiple laryngeal papilloma.

Adult↗

Effect of prostaglandin E1 analogue TFC 612 on diabetic neuropathy in streptozocin-induced diabetic rats. Comparison with aldose reductase inhibitor ONO 2235.

The effect of a newly developed oral agent, prostaglandin E1 (PGE1) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE1 analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.

Adenosine Triphosphate↗

[Study of in vitro OK432-induced IFN-gamma production in patients with gastric and esophageal cancers: comparison with in vitro skin tests].

In the present study, we measured in vitro production of IFN-gamma induced by OK432 in peripheral mononuclear cells (PMC) and investigated the relationship between the skin reaction to Su-Ps, an extract of Streptococcus Pyogenes, and purified protein derivative (PPD) and the productibility of IFN-gamma in patients with gastric and esophageal cancers. PMC isolated with the Ficoll-conray centrifugation technique were adjusted to 10(6) cells/ml in RPMI-1640 medium supplemented with 10% fetal calf serum and incubated over 7 days at 37 degrees C in the presence of OK432 at 0.17 KE/ml in microculture plates. IFN-gamma secreted in the supernatants was measured consecutively during the observation period with radioimmunoassay. The results are summarized as follows. 1. The production of IFN-gamma in PMC from patients with negative skin reaction to Su-Ps and PPD was significantly decreased as compared with the value obtained from patients who were positive in these skin tests (p less than 0.001). 2. In vitro production of IFN-gamma induced by OK432 was significantly correlated with the degree of skin tests to Su-Ps and PPD as well (r = 0.48, r = 0.41, p less than 0.01, respectively). Thus, it is concluded that the assay of IFN-gamma produced in PMC cultures is useful to evaluate the immunological status of patients with cancer.

Bacterial Proteins↗

Biological significance of the hst-1 gene.

hst-1, or HSTF1 in human gene nomenclature, was originally identified as a transforming gene in DNA samples from human stomach cancer by NIH3T3 transfection assay. Many reports have followed to show the presence of a transforming hst-1 gene in various types of cancerous and noncancerous tissues, suggesting that the hst-1 gene is the most common non-ras transforming gene. We cloned the hst-1 genomic fragments from DNAs of a normal individual and a patient with leukemia and also from NIH3T3 cells themselves. All of these clones transformed NIH3T3 cells upon transfection. Sequence analysis of the cDNA and genomic hst-1 led us to conclude that the normal hst-1 protein transforms NIH3T3 cells when its expression is deregulated. The hst-1 protein has 40-50% homology to basic and acidic fibroblast growth factors (FGFs) and to the int-2 protein. The purified hst-1 protein synthesized in a baculovirus system was a potent heparin-binding growth factor for a variety of cells, including human endothelial cells. The hst-1 protein, when it was added to the culture medium, induced morphological transformation of NIH3T3 cells and anchorage-independent growth of NRK cells. The hst-1 gene is located 35 kbp downstream of one of its homologous genes, int-2, on human chromosome 11 at band q13.3. As in the case with the int-2 gene, the hst-1 transcripts were not detected in adult mice but found in mouse embryos. A relatively large amount of the hst-1 message was present in a mouse teratocarcinoma cell line, F9, while the int-2 mRNA was barely detected. Upon induction of differentiation in vitro, the hst-1 transcription was depressed to almost nil, and the int-2 message increased dramatically. The hst-1 and int-2 genes were coamplified in a variety of cancer cells, most notably in more than 50% of esophageal cancers.

Animals↗

Multiple genetic alterations in small-cell lung carcinoma.

By restriction fragment length polymorphism (RFLP) analysis, it was found that loss of heterozygosity (LOH) at three different chromosomal loci, 3p, 13q, and 17p, occurs simultaneously in nearly 100% of small-cell lung carcinomas (SCLC). This was observed even in stage I tumors and an untreated tumor, and it occurred prior to NMYC amplification. The common region of LOH on chromosome 3p was 3p14-24.1, and this region was also frequently lost in carcinoma of the uterine cervix (100% at D3S2 on 3p14-21) as well as renal cell carcinoma (56% at ERBA beta on 3p22-24.1), suggesting the presence of tumor suppressor gene(s) for these cancers in this region. On chromosome 13, LOH was observed commonly in the region between 13q12 and 13q22, including the RB locus on 13q14, and normal RB protein was not detected in any of 9 SCLC cell lines by immunoprecipitation analysis. The common region of LOH on chromosome 17 was 17p13 and is the same as that in colon carcinoma and osteogenic sarcoma. Since LOH is supposed to unmask the recessive mutation of tumor suppressor gene in the remaining allele, these results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC. RFLP analysis was performed on several other types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, and stomach cancer to determine the chromosomal loci of putative tumor suppressor genes in each tumor. Chromosomal loci showing frequent LOH were different among these tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Small Cell↗