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Biomedical subjects

H Hamada

Publications and source records attributed to H Hamada.

At least 325 records · Page 18Linked to original sources
PubMed1996

[KL-6 in patients with interstitial pneumonitis].

Levels of KL-6 are high in serum and in bronchoalveolar lavage fluid (BALF) from patients with interstitial pneumonitis. To examine the usefulness of the KL-6 level as a marker of disease activity in interstitial pneumonitis, KL-6 was measured in serum and in BALF from patients with this disease. Correlations between KL-6 levels and the number of cells in BALF and between KL-6 levels and pulmonary function were computed. Serum KL-6 levels were abnormally high and correlated with the number of lymphocytes in BALF in patients with interstitial pneumonitis. Furthermore, changes in serum KL-levels reflected clinical coursed in these patients. KL-6 levels in BALF were very high and correlated with the total number of cells, and with the numbers of lymphocytes, neutrophils, and eosinophils in BALF. KL-6 levels in serum and in BALF correlated significantly with %VC, %DLco, and %DLco/VA. These results suggest that KL-6 levels in serum and in BALF reflect the degree of alveolitis and of deterioration of pulmonary function in these patients, and that KL-6 is a useful indicator of disease activity in interstitial pneumonitis.

Antigens↗
PubMed1995

The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse.

We generated mice carrying a loss-of-function mutation in Brn-2, a gene encoding a nervous system specific POU transcription factor, by gene targeting in embryonic stem cells. In homozygous mutant embryos, migratory precursor cells for neurons of the paraventricular nuclei (PVN) and the supraoptic nuclei (SO) of the hypothalamus die at approximately E12.5. All homozygous mutants suffered mortality within 10 days after birth, possibly because of a complete deficiency of these neurons in the hypothalamus. Although neither developmental nor histological abnormalities were observed in heterozygous mice, the levels of expression of vasopressin and oxytocin in the hypothalamus of these animals were half these of wild-type mice. These results strongly suggest that Brn-2 plays an essential role in the determination and development of the PVN and SO neuronal lineages in the hypothalamus.

Animals↗
PubMed1995

The epidermal growth factor-like domain of recombinant human thrombomodulin exhibits mitogenic activity for Swiss 3T3 cells.

Thrombomodulin (TM) is an anticoagulant endothelial cell surface glycoprotein containing six tandem epidermal growth factor (EGF)-like structures. We prepared a recombinant TM peptide (rTME1-6, from R214GHWA to DSGK466 of native TM) composed of these six EGF-like structures and investigated the effect of rTME1-6 peptide on the growth of the Swiss 3T3 fibroblast cell line. It was found that rTME1-6 induced proliferation of Swiss 3T3 cells and accelerated [3H]thymidine uptake into their DNA. [3H]Thymidine uptake increased in a dose-dependent manner, plateauing at 50 ng/mL rTME1-6, which was 1.8 times the control level. rTME1-6 peptide (50 ng/mL) also accelerated the DNA synthesis of human dermal fibroblasts (HDFs), A549 (a human lung cancer cell line), HepG2 (a human hepatocarcinoma cell line), and U937 cells (a human monocytic cell line) to 1.5, 1.6, 1.4, and 1.2 times the control level, respectively. The magnitude of the acceleration of DNA synthesis in Swiss 3T3 induced by rTME1-6 was approximately 20% of that of EGF on a molar basis. The uptake of [3H]thymidine was accelerated synergistically by coculture of the cells with rTME1-6 and insulin, similar to the coculture with EGF and insulin. The effects of rTME1-6 were abolished by addition of polyclonal antihuman TM IgG, whereas the actions of insulin and EGF were not influenced. Glucose uptake in Swiss 3T3 cells also increased 1.6 times over control levels by culture with 50 ng/mL rTME1-6 (1.25 nmol/L), compared with 2.7 times by 10 ng/mL EGF (1.66 nmol/L). Binding of [125I]EGF (0.5 ng/mL, 0.083 nmol/L) by the cells was inhibited by about 60% by addition of an eight-fold molar excess of nonlabeled EGF (0.664 nmol/L), whereas no inhibition of [125I]EGF binding was observed, even in the presence of a 1,000-fold molar excess (83 nmol/L) of rTME1-6. Specific binding of [125I]rTME1-6 on the cells showed a saturation curve, and the apparent concentration of rTME1-6 required for half maximum binding of the peptide on the cells was calculated to be 31.5 ng/mL. Thus, the overall results indicated that the rTME1-6 peptide had mitogenic activity for Swiss 3T3 cells, accelerated DNA synthesis and glucose uptake, and that the mitogenic activity might be mediated by binding of the peptide to a specific site different from the EGF receptor.

3T3 Cells↗
PubMed1995

Mid-trimester fetal sex determination from maternal peripheral blood by fluorescence in situ hybridization without enrichment of fetal cells.

To determine the fetal sex on 30 women who were 16-20 weeks pregnant, about 100,000 maternal blood nucleated cells were analysed by means of fluorescence in situ hybridization (FISH) with a Y-chromosome-specific DNA probe. Cells with the hybridization signal were detected in 12 of the 30 women. All the 12 mothers gave birth to a male child. Of the other 18 women who had no Y-positive cells in the peripheral blood, 14 gave birth to a female child and four gave birth to a male child. These false-negative results probably occurred because the number of cells examined was inadequate. The data obtained in this study suggest that fetal sex determination using maternal peripheral blood with FISH is possible and that this diagnostic method will be clinically useful when more cells are analysed.

Blood Cells↗
PubMed1995

Lysinuric protein intolerance in pregnancy: case report with successful outcome.

We present a 28-year-old pregnant woman who exhibited intolerance to lysinuric protein. However, she gave birth to a normal child without serious maternal complications. Since four of seven similar patients reported previously developed serious complications such as hemorrhage and eclampsia, patients with lysinuric protein intolerance are considered to be at high risk during pregnancy. A successful outcome can be achieved, provided that the anemia, thrombocytopenia, toxemia and hyperammonemia are well controlled.

Adult↗
PubMed1995

Antitumor effect induced by granulocyte/macrophage-colony-stimulating factor gene-modified tumor vaccination: comparison of adenovirus- and retrovirus-mediated genetic transduction.

Irradiated tumor cells genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine) are potent stimulators of systemic antitumor immunity. For the preparation of a GM-CSF gene-modified tumor vaccine, it is important to achieve efficient genetic transduction of tumor cells, leading to an appropriate expression of the induced gene. In this report, with a view to developing a protocol for an effective cancer vaccination therapy, we examined the vaccination efficacies of tumor cells secreting GM-CSF by either adenovirus- or retrovirus-mediated genetic transduction. By using an adenoviral vector, Adex1CAmGMCSF, a highly efficient gene delivery and a high-level expression of the GM-CSF gene were achieved. Unexpectedly, animal vaccination studies showed that the GM-CSF tumor vaccine transduced with the Adex1CAmGMCSF recombinant adenovirus (adenoviral GM-CSF tumor vaccine) was less efficacious than that transduced with the MFGmGMCSF recombinant retrovirus (retroviral GM-CSF tumor vaccine). The GM-CSF serum concentration attained by the adenoviral GM-CSF tumor vaccine was much higher than that obtained by the retroviral GM-CSF tumor vaccine. Our findings indicate that an optimal level of GM-CSF production is important for the tumor vaccine to elicit an adequate response in the host antitumor immunity.

Adenoviridae↗
PubMed1995

Cytokine-gene-modified tumor vaccination intensified by a streptococcal preparation OK-432.

Vaccinations with tumor cells engineered to express certain cytokines have been demonstrated to induce potent and specific antitumor immunity. In our previous report, we carried out a comparative study on the ability of cytokine-gene-modified tumor vaccines to induce host immune responses, and found that irradiated tumor cells, genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine), were the most potent stimulators of systemic antitumor immunity. In this report, using the experimental tumor models in which the GM-CSF tumor vaccine was less effective in immunopotentiation, we found that the combined use of a biological response modifier (BRM) OK-432 remarkably enhanced the antitumor activity induced by the GM-CSF tumor vaccine. These data indicate the possible role of a BRM such as OK-432 to intensify further the specific tumor vaccination therapy.

Animals↗
PubMed1995

Liver retransplantation in children.

Between January 1988 and December 1993, 132 children received 154 orthotopic liver transplantation (OLT) at Bicêtre Hospital (France). Among them, 18 children underwent two and 2 children underwent three transplants (retransplant rate; 15.2%). Retransplantations were classified into three groups according to the interval between both OLTs: 1 (< 7 days, n = 8), 2 (8 days to 6 months, n = 10) and 3 (> 6 months, n = 4). Each group was compared with a control group whose grafts survived more than 1 week. There were no significant differences regarding age (35 +/- 49, 23 +/- 13, and 33 +/- 15 versus 49 +/- 41 months), cold ischemic time (566 +/- 105, 470 +/- 144, and 476 +/- 58 versus 455 +/- 110 minutes) and reduced size graft ratio (62.5%, 60%, and 75%, versus 58.3%). The causes of graft failure included primary nonfunctioning liver (PNF, n = 8) all in group 1 cases, biliary complications associated with hepatic artery thrombosis (HAT, n = 10; group 2, 6; group 3, 4), chronic rejection (n = 3; group 2, 1; group 3, 2) and three others (uncontrollable acute rejection, fulminant hepatitis, and secondary dysfunction, all in the group 2). The authors were unable to detect the cause of PNF. The overall survival rate after retransplantation was 62.5%, 60.0% and 75%, respectively. To reduce the rate of retransplants and improve the prognosis after OLT, further investigation into the cause of PNF, refinements in the anastomotic technique of the hepatic artery, and also early treatment of HAT are some of the goals to be achieved.

Adolescent↗
PubMed1995

Fetal nucleated cells in maternal peripheral blood after delivery in cases of fetomaternal hemorrhage.

OBJECTIVE: To determine how long fetal nucleated cells can be detected in maternal peripheral blood after delivery in cases of fetomaternal hemorrhage, using fluorescence in situ hybridization or polymerase chain reaction. METHODS: Nucleated cells with Y chromosomes were analyzed in 90 blood samples using fluorescence in situ hybridization with a Y-chromosome-specific DNA probe. The samples were obtained from 15 mothers (gravida 1), who were delivered of normal male neonates at University of Tsukuba Hospital, Japan, with fetomaternal hemorrhage 1 and 7 days, and 1, 3, 6, and 12 months after delivery. The 15 mothers were selected if fetal cells were detected above the ratio of one fetal cell per 3000 mothers' cells at 1 day after delivery. Polymerase chain reaction amplifying two different Y-specific fragments (a 102 base-pair fragment in the pHY10 vector, which was a highly repetitive sequence, and a single-copy, Y-specific 198 base-pair fragment) was also carried out for the analysis of genomic DNA from the same samples. RESULTS: Seven days and 1 month after delivery, Y-positive cells were detected in nine and four of 15 samples, respectively. No cells with the hybridization signal were detected in any of the 45 samples obtained 3 months or more after delivery. When we performed the polymerase chain reaction experiment amplifying the single-copy Y-specific fragment, none of the 45 samples after 3 months or more showed the expected band. However, from the same 45 samples, four obtained from different mothers showed positive results by amplification of the fragment in the pHY10 vector. Because multiple samples taken from these mothers before the collection of the positive samples showed negative results in the three experiments, these findings strongly suggest that the observed positive results were false-positives. CONCLUSION: Fetal nucleated cells in maternal peripheral blood become undetectable 3 months after delivery in most, if not all, cases of fetomaternal hemorrhage.

False Positive Reactions↗
PubMed1995

Evaluation of serum KL-6 levels in patients with pulmonary tuberculosis.

SETTING: KL-6, a human MUC-1 mucin preferentially expressed on type II pneumocytes, is a sensitive serum marker for evaluating alveolar damage of interstitial pneumonia and pulmonary fibrosis. Some patients with pulmonary tuberculosis develop severe respiratory dysfunction caused by extensive pulmonary fibrosis, compensatory emphysema and fibrous pleural thickening. OBJECTIVE: To evaluate the clinico-pathological significance of KL-6 in pulmonary tuberculosis. DESIGN: Serum KL-6 levels were measured in sera from 57 patients with active pulmonary tuberculosis and 38 healthy controls by a sandwich-type enzyme-linked immunosorbent assay. Immunohistochemistry was performed by an avidin-biotin-peroxidase complex method. RESULTS: KL-6 levels were significantly higher in the patients than in the healthy controls (518 +/- 693 [SD] vs 227 +/- 91 U/ml, P < 0.001) and increased significantly according to the extent of pulmonary lesions evaluated by chest X-ray (P < 0.001). There was a significant negative correlation between serum KL-6 levels and % vital capacity (VC) (r = 0.642, P < 0.05). KL-6 was strongly expressed on proliferated type II pneumocytes and cuboidal epithelial cells adjacent to thickened intralobular septa and pleura. CONCLUSIONS: In pulmonary tuberculosis, serum KL-6 originates from proliferated type II pneumocytes and cuboidal epithelial cells, and is a useful marker presenting the degree and extent of pulmonary fibroproductive lesions.

Aged↗
PubMed1995

Circulating interleukin-6 levels in patients with bronchial asthma.

Circulating interleukin-6 (IL-6) levels were determined using a sensitive enzyme immunoassay in adults with asthma in stable condition during naturally occurring attacks and before and after allergen inhalation tests. IL-6 was significantly elevated even in asymptomatic asthmatic subjects (n = 17) compared with normal control subjects (n = 17). During naturally occurring asthmatic attacks, serum IL-6 levels were significantly elevated in comparison with those in a symptom-free condition (4 wk interval; n = 8, p < 0.01). No significant difference was observed in serum IL-6 levels obtained from control asymptomatic asthmatic subjects during the period (n = 10). There was a significant elevation in circulating IL-6 levels in eight asthmatic patients following inhalation of allergen but not methacholine. These results suggest that IL-6 is involved in the pathophysiology of bronchial asthma.

Adult↗
PubMed1995

[3H]naloxone binding sites in porcine ovarian follicles and corpora lutea during the ovarian cycle.

We demonstrated the presence of opioid receptors in the porcine ovary using [3H]naloxone. We also examined the change in the number of opioid receptors during follicular maturation. In addition, we found specific binding of [3H]naloxone in the porcine ovary using naloxone, beta-endorphin, methionine-enkephalin and dynorphin. The binding of [3H]naloxone to porcine granulosa cells and the 2000-g subcellular fraction of corpora lutea was examined to demonstrate the presence of specific [3H]naloxone binding in the porcine ovary. Binding of [3H]naloxone to porcine granulosa cells was displaced by cold naloxone and beta-endorphin but not by dynorphin and methionine-enkephalin. A similar phenomenon was also demonstrated in the 2000 g subcellular fraction of porcine corpora lutea. However, Scatchard analyses revealed a single class of high-affinity (Kd = 28.5 x 10(-9) mol/l) and low-capacity binding sites (Bmax = 30.5 fmol/5 x 10(6) cells) in porcine granulosa cells. Similar binding parameters were obtained in the 2000-g subcellular fraction of porcine luteal tissue (Kd = 28.3 x 10(-9) mol/l, Bmax = 59.3 nmol/kg protein). [3H]Naloxone binding sites in the porcine ovary showed binding characteristics similar to those of opioid receptors in other organs like brain, uterus and placenta. Furthermore, we demonstrated that the specific binding sites of [3H]naloxone in porcine granulosa cells decreased during follicular maturation. Opioid receptors have been detected in the uterus, placenta and Sertoli cell cultures in some species. However, there is no detailed study on opioid receptors in granulosa cells and luteal tissues in any species. Our data suggest a relationship between folliculogenesis and ovarian opioid peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[A case of chylothorax caused by mesenteric panniculitis].

A 76-year-old female was referred to our hospital for examination of milky pleural effusion. We diagnosed her illness as chylothorax because of the high concentration of triglyceride in the effusion. There was neither obstruction nor damage of the thoracic duct. Systemic evaluation disclosed an abdominal mass in the umbilical region. Fasting with intravenous hyperalimentation followed by pleurodesis with minocycline successfully eliminated the effusion. On the other hand, the abdominal mass was diagnosed as mesenteric panniculitis by open biopsy. Since she also had chylous ascites, the tumor could have obstructed the intestinal lymphatics. Chylothorax was probably caused by damage to collateral lymph circulation.

Aged↗
PubMed1995

[Small cell lung cancer that appeared as a strange shape on chest X-ray films].

A 70-year-old man was admitted for diagnosis of an abnormal shadow on chest X-ray film. Chest X-ray films and chest tomograms showed a club-like shadow close to the pulmonary artery. The tumor was diagnosed as a small cell lung cancer, after transbronchial biopsy. The patient underwent chemotherapy and radiation therapy. This patient had small cell lung cancer that appeared on chest X-ray films to have a strange shape.

Aged↗
PubMed1995

Nitric oxide mediated metallothionein induction by lipopolysaccharide.

The roles of calcium and/or of the other cellular transduction pathways, and of nitric oxide (NO) on the induction of metallothionein (MT) mRNA by lipopolysaccharide (LPS) has been studied in rat primary cell culture, using inhibitors of protein kinase pathways (H-7, W-7 and TMB-8) and NO production inhibitors (L-NAME, PTIO). LPS exposure led to a rapid increase of MT-mRNA and a peak level revealed 2.5-fold induction as compared to control for 6h incubation at a dose of 3.0 mg/L. A dose of 5.0 and 10.0 mg/L of LPS also provided the same level of MT-mRNA induction. The inhibition of MT induction by LPS was observed with L-NAME, PTIO, but not H-7, W-7. These findings indicate that the alteration of cellular calcium concentration and distribution does not relate to the induction of MT-mRNA by LPS in hepatocytes and that protein kinase C and calmodulin dependent protein kinase pathways have not contributed to MT-mRNA induction by LPS. Finally, the present results show that NO plays an important role in MT induction by LPS.

Animals↗