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Biomedical subjects

H Yano

Publications and source records attributed to H Yano.

At least 289 records · Page 16Linked to original sources

Expression of CD44 in human hepatocellular carcinoma cell lines.

CD44 is a glycosylated cell surface adhesion molecule expressed on a diverse range of cells and has several variant forms, some of which are involved in metastasis of cancer cells. Because little is known about CD44 in human hepatocellular carcinoma (HCC), we investigated its expression in tissue specimens from primary lesions (12 cases), in smear specimens from peritoneal effusions (2 cases), and in cell lines (HCC cell lines, KIM-1, KYN-1, KYN-2, KYN-3, HAK-1A, and HAK-1B; combined hepatocholangiocarcinoma cell lines, KMCH-1 and KMCH-2; and bile duct carcinoma cell lines, KMC-1 and KMBC). Immunohistochemical studies using monoclonal antibody recognizing epitope Group 1 of human CD44 molecule showed that HCC cells in all tissue specimens, including the original tumors of one smear specimen and HAK-1A, were negative for CD44; whereas, HCC cells in two-smear specimens, KIM-1, KYN-2, KYN-3, HAK-1A, HAK-1B, KMCH-1, KMC-1, and KMBC, showed positive reactions on the cell membrane. Immunostain-positive cell lines showed a positive cell rate of 51.9% to 99.8% by flow cytometric analysis. Western blotting detected CD44 protein of hemopoietic type in KIM-1, KYN-3, HAK-1A, and HAK-B and epithelial type in KMC-1 and KMBC. Southern blotting of complementary DNA amplified after reverse transcriptase-polymerase chain reaction (RT-PCR) detected hemopoietic type and some variant forms with longer insertion in all cell lines but KMCH-2, whereas hemopoietic type and variants with minor insertion were only detectable in tissue specimens. These findings suggest that HCC cells in ascites and in culture often express CD44, but those in tissue do not at protein level.

Base Sequence↗

[Microorganisms cultured from sputum and blood in association with episodes of fever during anti-cancer therapy in patients with lung cancer].

We examined the clinical features and significance of pathogenic microbes isolated from sputum and blood of patients with lung cancer during anti-cancer therapy. Pathogenic bacteria were more likely to be isolated from patients with episodes of fever than from afebrile patients. The major species of bacteria isolated from sputum were Staphylococcus aureus, including methicillin-resistant strains, and Gram-negative bacilli, which are known to be frequently involved in hospital-acquired infections. The presence of an indwelling central venous catheter for intravenous hyperalimentation was an important risk factor for the development of a febrile episode, which indicates that bacteremia was a major cause of fever. In one quarter of the blood cultures from the patients with persistent fever, various species of pathogenic microbes were recovered, one-third of which were fungi. Bacteriological examinations done before and after the introduction of granulocyte-colony stimulating factor (G-CSF) revealed that strains of Klebsiella spp. decreased and those of methicillin-resistant S. aureus increased. There was no firm evidence that G-CSF decreased the incidence of episodes of fever. However, remains G-CSF may a allow the dose intensity of anti-cancer agents to be increased, which would lead to severe leukocytopenia. However, more detailed investigation is needed to clarify the role of G-CSF against bacterial infection during anti-cancer therapy.

Aged↗

Poor outcome in patients with advanced stage neuroblastoma and coincident opsomyoclonus syndrome.

BACKGROUND: Most patients with neuroblastoma who present with opsomyoclonus have a good prognosis. Neuroblastomas from such patients have been reported to contain a single copy of the N-myc gene. The authors describe three cases of patients with advanced neuroblastoma with opsomyoclonus, which had poor outcomes despite multimodal therapy. METHODS: Amplification and expression of the N-myc gene were examined in these three primary tumors using Southern and Northern blot analyses. Then, flow cytometric analysis of the cellular DNA contents of these tumors was performed. RESULTS: N-myc amplification was observed in two tumors and N-myc RNA overexpression was observed in all three. Analysis of the cellular DNA contents of the tissue specimens revealed hyperdiploidy in all three tumors; one had a triploid index and the other two had hypotetraploid indexes. CONCLUSIONS: These findings suggest that a poor outcome for patients with opsomyoclonus may be associated with N-myc gene activation (amplification and/or overexpression) and that a hyperdiploid tumor is not always associated with a good prognosis.

Adrenal Gland Neoplasms↗

Agonists and antagonists bind to different domains of the cloned kappa opioid receptor.

Opium and its derivatives are potent analgesics that can also induce severe side effects, including respiratory depression and addiction. Opioids exert their diverse physiological effects through specific membrane-bound receptors. Three major types of opioid receptors have been described, termed delta, kappa, and mu. The recent molecular cloning of these receptor types opens up the possibility to identify the ligand-binding domains of these receptors. To identify the ligand-binding domains of the kappa and delta receptors, we have expressed in COS-7 cells the cloned mouse delta and kappa receptors and chimeric delta/kappa and kappa/delta receptors in which the NH2 termini have been exchanged. The opioid antagonist naloxone binds potently to wild-type kappa receptor but not to wild-type delta receptor. The kappa/delta chimera bound [3H]naloxone with high affinity. In contrast, the kappa-specific agonist [3H]U-69,593 did not bind to the kappa/delta chimera. These findings indicate that selective agonists and antagonists interact with different recognition sites in the kappa receptor and localize the antagonist-binding domain to the NH2 terminus. Consistent with the results of radioligand-binding studies, the kappa/delta chimera did not mediate kappa-agonist inhibition of cAMP formation. In contrast, the delta/kappa chimera did mediate kappa-agonist inhibition of cAMP formation, but this effect was not blocked by naloxone. Furthermore, a truncated kappa receptor lacking its NH2 terminus was able to mediate agonist inhibition of cAMP accumulation in a naloxone-insensitive manner. This result further indicates that the NH2 terminus of the kappa receptor contains the selective antagonist-binding domain. The ability to dissociate agonist- and antagonist-binding sites will facilitate the development of more specific kappa agonists, which could have analgesic properties devoid of side effects.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Clinical importance of extraordinary integration patterns of human T-cell lymphotropic virus type I proviral DNA in adult T-cell leukemia/lymphoma.

The proviral DNA of human T-cell lymphotrophic virus type I (HTLV-I) is known to be integrated monoclonally in the malignant cells of adult T-cell leukemia/lymphoma (ATL), which is a peripheral T-cell malignancy caused by this virus. We studied the relationship between the integration patterns of HTLV-I and clinical characteristics in 89 patients with ATL. The proviral DNA of HTLV-I was examined by the standard Southern blot analysis using the endonucleases EcoRI and Pst I. One clear band of greater than 9 kb was detected in most of the patients (83 case) when cellular DNA was digested with EcoRI. On the other hand, extraordinary integration patterns of HTLV-I proviral DNA were detected in 6 patients; 3 of them showed two bands, while the other 3 showed one band smaller than 9 kb. When cellular DNA was digested with PstI, the band patterns of these patients were quite different from those of typical patients. The patients with the extraordinary integration patterns had clinical characteristics dissimilar to those of the other 83 patients with the ordinary integration pattern. The patients with two bands by EcoRI digestion always had severe hypoxemia with extremely high levels of serum lactate dehydrogenase at first presentation and showed peculiar organ infiltrations, such as retina and muscle, which were less frequent in the other ordinary 83 patients. They all died within 8 months after the onset. In contrast, the patients with one smaller band by EcoRI digestion always had small and mature T lymphocytes with bilobulated nuclei without lymphadenopathy and showed a favorable clinical course, which was uncommon in the ordinary cases. They were alive 20 to 38 months after diagnosis. Rearranged bands of the T-cell receptor gene were detected in all patients with unusual integration. These findings indicate that the integration patterns of HTLV-I proviral DNA have a clinical implication and may be one of the explanations for heterogeneity in the behavior of this disease.

DNA, Viral↗

Identification of two distinct promoters in the chicken caldesmon gene.

Caldesmon (CaD) is a suitable molecular marker for phenotypic modulation of smooth muscle cells. Chicken CaD gene is composed of 17 exons with a whole length of 100-150 kilobases (kb). Exons 1a-1, 1a-2, and 1a-3 encode the 5'-terminal sequence specific to mRNA for gizzard type CaD, and exon 1b encodes the sequence specific to brain type CaD mRNA. Here, we have characterized the 5'-upstream regions of chicken CaD gene. Primer extension analysis revealed that the transcriptional starting sites of gizzard and brain CaD mRNAs were 218 and 279 nucleotides upstream from each translational initiation codon, respectively. We have identified two distinct promoters (gizzard type and brain type promoters) in the CaD gene by bacterial chloramphenicol acetyltransferase (CAT) assay using chick embryo fibroblasts (CEFs). The 5'-upstream region of exon 1a-1 showed remarkable promoter activity, but the activity of the 5'-upstream region of exon 1b was low (10% of the former). These results indicate that CaD subtypes are generated by differential RNA transcriptions.

Animals↗

The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase.

Water-soluble ingredients of the herbal medicine sho-saiko-to dose-dependently inhibited the proliferation of a human hepatocellular carcinoma cell line (KIM-1) and a cholangiocarcinoma cell line (KMC-1). Fifty % effective doses on day 3 of exposure to sho-saiko-to were 353.5 +/- 32.4 micrograms/ml for KIM-1 and 236.3 +/- 26.5 micrograms/ml for KMC-1. However, almost no suppressive effects were detected in normal human peripheral blood lymphocytes or normal rat hepatocytes. Sho-saiko-to suppressed the proliferation of the carcinoma cell lines significantly more strongly than did each of its major ingredients, i.e., saikosaponin a, c, and d, ginsenoside Rb1 and Rg1, glycyrrhizin, baicalin, baicalein, and wogonin, or another herbal medicine, juzen-taiho-to (P < 0.05 or 0.005). Because such ingredients are barely soluble in water, there could be synergistic or additive effects of the ingredients in sho-saiko-to. Morphological, DNA, and cell cycle analyses revealed two possible modes of action of sho-saiko-to to suppress the proliferation of carcinoma cells; (a) it induces apoptosis in the early period of exposure and (b) it induces arrest at the G0/G1 phase in the late period of exposure.

Bile Duct Neoplasms↗

Effects of the amplification of the genes coding for the L-threonine biosynthetic enzymes on the L-threonine production from methanol by a gram-negative obligate methylotroph, Methylobacillus glycogenes.

We constructed recombinant plasmids carrying the genes coding for the L-threonine biosynthetic enzymes, the hom gene, the hom-thrC genes, and the thrB genes, of a gram-negative obligate methylotroph, Methylobacillus glycogenes, and examined the effects of them on the production of L-threonine from methanol. The hom gene, which encodes the homoserine dehydrogenase, and the hom-thrC genes, containing the gene coding for threonine synthase together with the hom gene, were cloned from a wild-type strain, and the thrB gene encoding the desensitized homoserine kinase was cloned from an L-threonine-producing mutant, ATR80. The recombinant plasmids were transferred into ATR80 and its L-isoleucine auxotroph, A513, by conjugation. Amplification of the genes coding for the L-threonine biosynthetic enzymes elevated the activities of the L-threonine biosynthetic enzymes of the transconjugants 10- to 30-fold over those of the strains containing only vectors. The L-threonine production from methanol in test-tube cultivation was increased about 30% and 40% by the amplification of the hom gene and the hom-thrC gene respectively, and it was slightly increased by that of the thrB gene. The effects of gene amplification were confirmed by the cultivation in 5-1 jar fermentors. The best producer, an A513 transconjugant containing the plasmid carrying the hom-thrC genes, produced 16.3 g/l L-threonine for 72 h.

Biotechnology↗

Pediatric spigelian hernia: reports of three cases.

We herein report three pediatric cases of spigelian hernia involving a 6-month-old girl, an 8-month-old girl, and a 3-year-old boy. This is a rare condition with only 20 children (12 boys and 8 girls) younger than 15 years of age previously reported in the literature. Their ages ranged from 6 days to 15 years. The hernia was situated on the right side in six cases, on the left side in nine, and was bilateral in four (with one case unreported). Among these, four cases were caused by trauma and one case by a postoperative complication. Our first and third cases were spontaneous, while the second case was a postoperative lateral ventral hernia. The first and second cases were associated with ipsilateral mediastinal neuroblastoma. No previous report of spigelian hernia has been associated with mediastinal neuroblastoma. We suspected that muscle atrophy caused by the neuropathy of the ninth to twelfth intercostal nerves may have been the cause of the hernia. These two cases are thus believed to be the first such cases to be reported.

Abdominal Injuries↗

The microcirculation during enflurane and isoflurane anaesthesia in dogs.

The effects of enflurane and isoflurane of 0.75 and 1.5 MAC on capillary blood flow were studied by the microsphere (9 +/- 1 microns in diameter) method in two groups of seven dogs. Simultaneously, changes in the arteriolo-venular shunt were studied by collection of venous blood at a rate of 4.8 ml.min-1 for two minutes. Enflurane anaesthesia at 0.75 MAC decreased capillary blood flow in the thyroid glands (35% of control), left and right ventricular wall (59% and 50%), adrenal gland (59%), liver (63%), spleen (56%), pancreas (35%), omentum (20%), and small intestine (60%) and at 1.5 MAC it decreased further in the thyroid glands (15%), left and right ventricular wall (31% and 32%), adrenal gland (42%), liver (47%), spleen (31%), pancreas (23%), omentum (20%), stomach (45%), and small intestine (54%). No marked changes were noted in the brain, kidney, large intestine or skeletal muscle. The arteriolo-venular shunt was decreased in the kidney from an initial rate of 12.1 to 3.8% at 0.75 MAC and to 2.5% at 1.5 MAC enflurane. In contrast, during isoflurane anaesthesia, capillary blood flow remained unchanged, except for a decrease to the thyroid glands (43%) and right ventricular wall (74%) during 1.5 MAC anaesthesia. However, the arteriolo-venular shunt was increased in the brain from 12.0 to 29.7% and 33.0% during 0.75 and 1.5 MAC isoflurane anaesthesia, respectively. It also increased from 25.0 to 41.0% and 46.3% in the skeletal muscle, and from 8.9 to 19.9% and 17.4% in the whole systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

How to deal with advanced cases of neuroblastoma detected by mass screening: a report from the Pediatric Oncology Study Group of the Kyushu area of Japan.

Since 1985, a nationwide program of mass screening (MS) for neuroblastoma has been underway for 6-month-old infants throughout Japan. As a result, the number of patients with stage I or II disease has obviously increased, and this has resulted in overall improvement of the prognosis for neuroblastoma. Some cases detected by MS were already in an advanced stage and have also had a good prognosis. In such cases, no definitive treatment protocol has been developed. Therefore, the authors investigated (1) the clinical and biological features of the advanced neuroblastoma cases detected by MS and (2) the best way to deal with such cases. The authors analyzed 94 cases of advanced-stage neuroblastoma registered in the Kyushu area (population, 15 million) between 1985 and 1990. Eighteen cases (16 stage III, 2 stage IV) were found by MS, and the others (23 stage III, 53 stage IV) were diagnosed clinically. The following results were obtained: (1) No N-myc amplifications were observed in cases detected by MS, whereas 16 of the 45 examined patients in the non-MS group had high amplifications of N-myc. (2) With regard to Shimada's classification, DNA content, and S-100 protein positivity, most of the advanced tumors found by MS showed characteristics indicating a good prognosis. (3) The 5-year survival rate for the non-MS group is less than 25%, whereas all of the patients whose tumors were detected by MS are alive, even after undergoing mild chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

The motility of lung lymphocytes in hypersensitivity pneumonitis and sarcoidosis.

Lymphocytes obtained by bronchoalveolar lavage (BAL) in hypersensitivity pneumonitis (HP) and pulmonary sarcoidosis (PS) are believed to be derived from interstitial inflammatory lesions of the lung in which lymphocytes have migrated from the blood. Because cellular motility is one of the important factors in lymphocyte migration, we investigated the motility of BAL lymphocytes from 12 patients with HP and 12 with PS, as well as their responsiveness to chemoattractants in vitro by modified Boyden chamber method. Motility was evaluated by the number of migrated cells and the migration distance. The numbers of migrated BAL lymphocytes from patients with HP and PS in albumin-containing medium were 318.3 +/- 93.0 (mean +/- SD) and 207.6 +/- 35.5, respectively, and were greater than those of BAL lymphocytes from normal control subjects (133.3 +/- 40.9) and blood lymphocytes, and comparable with those of mitogen-activated blood lymphocytes. The motility of BAL lymphocytes in these diseases compared with blood lymphocytes was also increased in protein-free medium. In addition, the culture supernatants of alveolar macrophages (AM) enhanced the motility of BAL, mitogen-activated, and blood lymphocytes. These results suggest that BAL lymphocytes in these diseases are functionally motile, and their enhanced motility, as well as mediators from AM, may facilitate the accumulation of lymphocytes at the epithelial surface.

Alveolitis, Extrinsic Allergic↗

Successful pregnancy after curative therapy for advanced lung cancer.

We report a single case in which two successful pregnancies occurred in a young woman following curative management of an advanced adenocarcinoma of the lung with resectional surgery and high-dose postoperative radiotherapy. This is the first case of advanced lung cancer with a favorable outcome.

Adenocarcinoma, Papillary↗

Suppressive effects of polygonati rhizoma on hepatic glucose output, GLUT2 mRNA expression and its protein content in rat liver.

The intraperitoneal administration of the methanol extract of Polygonati Rhizoma (OM) into normal rats caused a significant decrease in the blood glucose level at 4 h after its administration of 800 mg/kg (P < 0.01), but not the serum insulin level. Using the perfused rat liver in vitro, a significant decrease of the hepatic glucose output was observed by the infusion of OM (P < 0.05 at 250 micrograms/ml OM). In addition, the hepatic content of facilitative glucose transporter isoform 2 (GLUT2) mRNA and its protein content in the total membrane fraction from rat liver significantly decreased in the intraperitoneally OM-treated rats when compared to that in the controls (mRNA P < 0.01, protein P < 0.001). On the other hand, OM (500 micrograms/ml) exhibited no apparent stimulatory effect on the insulin secretion from the isolated rat pancreatic islets. These results suggest that the hypoglycemic effect of OM is derived, at least in part, from the decrease in hepatic glucose output, due presumably to the reduction of GLUT2 mRNA expression and its protein content in total membrane of the liver, and that because of its unique therapeutic mechanism, OM could be a new category of therapeutic agent for non-insulin-dependent diabetes mellitus.

Animals↗