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Biomedical subjects

N Kawamura

Publications and source records attributed to N Kawamura.

At least 127 records · Page 7Linked to original sources

Intermittent cisplatin therapy for stage-III ovarian cancer patients following clinical remission.

Intermittent cisplatin (CDDP) administration as consolidation therapy for stage-III ovarian cancer was studied. No patients with residual disease at surgery or at second-look operation or patients with <8 U/ml of CA125 after remission induction chemotherapy were enrolled in this study. Fifteen subjects received intermittent chemotherapy, and 10 control patients did not. CDDP of 20 mg/m2 for 5 days was administered every 3-4 months for 5 years. A significant increase in 5-year survival rate was found in the intermittent chemotherapy group when compared with the control group. Side effects from the intermittent chemotherapy were controllable. Intermittent CDDP therapy seems to be an effective consolidation therapy for stage-III ovarian cancer patients.

Antineoplastic Agents↗

Increased natural killer cell activities in patients treated with gonadotropin releasing hormone agonist.

Natural killer (NK) cell activity in patients treated with gonadotropin-releasing hormone agonists (GnRH-a) was studied. The subjects were 8 patients with endometriosis (6 with ovarian endometrial cyst, 2 with adenomyosis) and 3 patients with uterine leiomyoma. Changes in serum estradiol (E2) concentration and NK cell activity in peripheral blood were analyzed before and after GnRH-a treatment (buserelin 900 microg/day for 4-5 months). NK cell activity was determined by 51Cr release assay and E2 by radioimmunoassay. NK cell activity before GnRH-a treatment was 37.7 +/- 19.0%, and after therapy activity increased significantly to 50. 8 +/- 18.2%. However, no significant correlation between the increase in NK cell activity and the decrease in E2 concentration was found. Results indicate that the standard GnRH-a treatment for endometriosis and uterine leiomyoma might increase NK cell activity. The etiology of the increase of NK activity with GnRH-a treatment is likely related to factors other than E2 concentration.

Adult↗

Leiomyomas in uterine remnants associated with vaginal agenesis.

A premenopausal woman with vaginal agenesis underwent surgery for leiomyomas in rudimentary uterine horns. Immunohistochemical study of surgical specimens revealed that progesterone receptors are distributed in the nuclei of a majority of the leiomyoma cells and in the nuclei of a minority of the myometrial cells. Estrogen receptors are not detected in the surgical specimens.

Cell Nucleus↗

Morphometric comparison of the human optic nerve fiber with various other human nerve fibers.

The morphometric characteristics of nerve fibers of the human optic nerve in the chiasmatic region were measured with the combination of an image analyzer and a computer, using the Luxol fast blue-periodic acid-Schiff-hematoxylin discriminative staining method. The mean axonal transverse area of the human optic nerve fibers was 0.644 +/- 0.361 micron 2. Comparison of the size of the axon of the human optic nerve fiber with that of various other human nerves showed optic nerve fibers were definitely thinner than the other nerve fibers, and were surrounded by a thinner myelin sheath. Optic nerves may be more liable to mechanical damage at surgery that previously believed.

Aged↗

Stresgenin B, an inhibitor of heat-induced heat shock protein gene expression, produced by Streptomyces sp. AS-9.

Stresgenin B was isolated as an inhibitor of heat-induced heat shock protein (HSP) gene expression from a culture broth of Streptomyces sp. AS-9 by silica gel chromatography and HPLC. The molecular formula of the novel compound was determined as C11H13NO5 by high resolution FAB-MS analysis, and the structure was determined by UV, 1H NMR, 13C NMR, HMQC, HMBC, and NOESY spectra. Stresgenin B inhibited heat-induced luciferase reporter-gene expression directed by the human hsp70B promoter in Chinese hamster ovary (CHO) cells at concentrations lower than the concentrations for inhibition of dexamethasone-induced luciferase reporter-gene expression directed by the mouse mammary tumor virus (MMTV)-LTR promoter. The inhibition of heat-induced reporter gene expression was evident even when cells were exposed to stresgenin B only during heat stress treatment. Moreover, the compound inhibited heat-induced syntheses of hsp72/73, hsp90, and hsp110 and thereby suppressed the induction of thermotolerance. Stresgenin B showed moderate cytotoxic activities against several neoplastic cell lines and also showed antibacterial activities against Micrococcus luteus, Bacillus subtilis and Staphylococcus aureus strains.

Animals↗

[A comparative study; one week treatment versus two weeks treatment with lansoprazol, amoxycillin and clarythromycin for the eradication of Helicobacter pylori in patient with gastric and duodenal ulcer].

The combination therapy of lansoprazol (LPZ), amoxycillin (AMPC), and clarythromycin (CAM) (LAC regimen) is one of the most effective eradication regimen of Helicobacter pylori (HP) positive ulcer patients, but the optimal treatment period of this therapy is still pending. The aim of this study was to assess the optimal treatment period of this regimen. One hundred and six patients who diagnosed as HP positive gastric and duodenal ulcer since August 1996 were randomized to one-week treatment group (group 1) or to two-weeks treatment group (group 2): LPZ 30 mg once daily, AMPC 1500 mg twice daily, CAM 800 mg twice daily. Both group received four weeks LPZ treatment (30 mg once daily) following the each combination therapy. The eradication rate of HP was 82.1% (43/56) in group 1 and 85.7% (36/42) in group 2. There was no statistical significant difference between two groups (p = 0.636). Although both treatment regimen was very useful for eradicating HP in the HP positive ulcer patients, one week LAC regimen would be better choice judging from the cost benefit.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Erythrocyte P1 group antigen expression in VTEC-associated hemolytic uremic syndrome.

BACKGROUND: The P1 blood group antigen has been postulated as a protective host factor against the development of the verotoxin-associated with hemolytic uremic syndrome (HUS). PATIENTS AND METHODS: In this study the P1 blood group antigen in 59 Japanese children with a past history of hemorrhagic colitis (HC) was scored with a direct agglutination method using a commercial anti P1 antibody. RESULTS: The P1 antigen was positive in 4 (21.1%) of 19 patients with a history of postdiarrheal HUS and in 11 (28.0%) of 40 patients with no history. There were no significant differences in the frequency of the P1 phenotype between the 2 groups (p = 0.629). CONCLUSION: We concluded that the P1 blood group antigen is not a protective factor against the development of HUS from verotoxin-producing Escherichia coli(VTEC)-infected hemorrhagic colitis in Japanese individuals.

Bacterial Toxins↗

Identification of a 1-cM region of common deletion on 4q35 associated with progression of hepatocellular carcinoma.

To identify the location of one or more of the putative tumor suppressor genes (TSG) on chromosome arm 4q that may be involved in hepatocellular carcinoma (HCC), we examined 96 primary HCCs for their patterns of allelic loss at 39 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 71 (74%) HCCs. Detailed deletion mapping identified two distinct commonly deleted regions; one was located within a 1-cM interval flanked by D4S1534 and D4S2929 at 4q21-22, the other in the 1-cM interval flanked by D4S2921 and D4S2930 at 4q35. Of the tumors for which clinical data were available, allelic loss at 4q35 was more frequent in poorly or moderately differentiated tumors than in well-differentiated tumors (3/15, 20%, vs. 14/21, 67%, P = 0.008); in tumors larger than 2 cm in size (2/11, 18%, vs. 34/62, 55%, P = 0.046); and in tumors that arose from liver cirrhosis as opposed to HCCs arising from chronic hepatitis (25/42, 60%, vs. 9/27, 33%, P = 0.048). The association of allelic losses on 4q35 with larger tumor size and aggressive histological type implies that loss or inactivation of TSG located within the 1-cM interval of 4q35 identified here contribute to progression of HCCs.

Carcinoma, Hepatocellular↗

Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome.

The present study analyzed peripheral blood B cell populations separated by IgD and CD27 expression in six males with X-linked hyper-IgM syndrome (XHIM). Costimulation of mononuclear cells from most of the patients induced no to low levels of class switching from IgM to IgG and IgA with Staphylococcus aureus Cowan strain (SAC) plus IL-2 or anti-CD40 mAb (anti-CD40) plus IL-10. Measurable levels of IgE were secreted in some of the patients after stimulation with anti-CD40 plus IL-4. Costimulation with SAC plus IL-2 plus anti-CD40 plus IL-10 yielded secretion of significant levels of IgG in addition to IgM, but not IgA. The most striking finding was that peripheral blood B cells from all of the six patients were composed of only IgD+ CD27(-) and IgD+ CD27(+) B cells; IgD- CD27(+) memory B cells were greatly decreased. IgD+ CD27(+) B cells from an XHIM patient produced IgM predominantly. Our data indicate that the low response of IgG production in XHIM patients is due to reduced numbers of IgD- CD27(+) memory B cells. However, the IgG production can be induced by stimulation of immunoglobulin receptors and CD40 in cooperation with such cytokines as IL-2 and IL-10 in vitro.

Adolescent↗

Visible integration of the adenosine deaminase (ADA) gene into the recipient genome after gene therapy.

Gene therapy for patients with adenosine deaminase (ADA) deficiency has become practical in the 1990s, and the exogenous gene has been reported to survive for several years in the recipient genome. To evaluate the integration efficiency of the ADA gene (ADA) into peripheral blood lymphocytes (PBL) of a patient with ADA deficiency who is receiving gene therapy, we performed two-color interphase fluorescence in situ hybridization (FISH) analysis by using digoxigenin-labeled ADA-cDNA and the biotin-labeled lambda-genomic ADA clone as probes. After each of 9 sequential series of gene therapy, interphase nuclei of 100 mononuclear cells from the patient were analyzed, and those of a LASN-producing cell line were used as a control. FISH signals were detected with rhodamine and FITC for the cDNA and the genomic DNA, respectively. The number of PBL giving a transgene signal grew after the sequential gene therapies, and the proportion of signal-positive cells reached about 10%. Our results indicate that the two-color FISH system can be used as a potential aid to monitor the efficiency of the ADA gene therapy.

3T3 Cells↗

Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency.

Ten patients with adenosine deaminase deficiency (ADA-) have been enrolled in gene therapy clinical trials since the first patient was treated in September 1990. We describe a Japanese ADA- severe combined immune deficiency (SCID) patient who has received periodic infusions of genetically modified autologous T lymphocytes transduced with the human ADA cDNA containing retroviral vector LASN. The percentage of peripheral blood lymphocytes carrying the transduced ADA gene has remained stable at 10% to 20% during the 12 months since the fourth infusion. ADA enzyme activity in the patient's circulating T cells, which was only marginally detected before gene transfer, increased to levels comparable to those of a heterozygous carrier individual and was associated with increased T-lymphocyte counts and improvement of the patient's immune function. The results obtained in this trial are in agreement with previously published observations and support the usefulness of T lymphocyte-directed gene transfer in the treatment of ADA-SCID.

Adenosine Deaminase↗

Hepatic cirrhosis: magnetisation transfer contrast in the globus pallidus.

The magnetisation transfer ratio (MTR), a quantitative tissue characteristic, and the pallidal index were measured in the globus pallidus of 37 patients with hepatic cirrhosis and 37 control subjects. The MTR decreased with severity of the disease, as indicated by the serum total bililubin, indocyanine green 15-min retention rate, and plasma ammonia. The pallidal index correlated significantly with haematological parameters, although the correlation coefficients tended to be lower than those between MTR and haematological parameters. This change in MTR corresponded to the results of the manganese chloride experiments. T1 shortening in the pallidum of patients with cirrhosis is presumably caused by paramagnetic effects, and possibly attributed to manganese deposition.

Case-Control Studies↗

Hepatocellular carcinoma with obstructive jaundice successfully treated with a self-expandable metallic stent.

We report on a 71-year old man with hepatocellular carcinoma (HCC) whose obstructive jaundice was successfully treated with external irradiation and a self-expandable metallic stent (EMS); Wallstent; Schneider (Europe) AG, Bülach, Switzerland. He was admitted to our hospital because of jaundice. HCC was found in S8; the tumor had invaded the bile duct with growth in the common hepatic duct. Endoscopic nasobiliary drainage was performed with difficulty. Radiation therapy to the stenosis enabled us to place a Wallstent endoscopically. He survived without icterus for 1 year.

Aged↗

Correlation between the growth of uterine leiomyomata and estrogen and progesterone receptor content in needle biopsy specimens.

OBJECTIVE: To examine the relationship between estrogen receptor (ER) and progesterone receptor (PR) content in needle biopsy specimens and the growth of uterine leiomyomata after biopsy. DESIGN: Prospective clinical study. SETTING: University teaching hospital. PATIENT(S): Thirty-one women with uterine leiomyomata and a normal menstrual cycle. INTERVENTION(S): Transcervical needle biopsy of uterine leiomyomata. MAIN OUTCOME MEASURE(S): The relationships between histologic features (smooth muscle content, immunohistochemical expression of ER and PR) and the percent increase over a 12-month observation period in the volume of the largest myoma nodule measured by magnetic resonance imaging were analyzed. RESULT(S): Both the density and intensity of immunohistochemical staining of PRs in uterine leiomyoma tissue showed significant positive correlation with leiomyoma growth. CONCLUSION(S): The growth of uterine leiomyomata can be determined by histologic and immunohistochemical analysis of needle biopsy specimens from uterine leiomyomata.

Adult↗

Elevation of serum IgE level and peripheral eosinophil count during T lymphocyte-directed gene therapy for ADA deficiency: implication of Tc2-like cells after gene transduction procedure.

We have successfully carried out T-cell-directed gene therapy for a boy with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA SCID) and unexpectedly found an elevation of serum IgE level and peripheral eosinophil count during the course. More than 90% of transduced cells cultured for 7-11 days before infusion into the patient were positive for CD8 and expressed Th2-type cytokine genes such as IL-4, IL-5 and IL-13. Furthermore, CD4(+) T-depleted PBMC (peripheral blood mononuclear cells) from the patient synthesized IgE in vitro by stimulation with IL-4. Collectively, these results suggested that Tc2-like cells in the transduced cells have distinct immunological functions to help IgE synthesis and activate eosinophils.

Adenosine Deaminase↗

Polyethylene glycol-modified bilirubin oxidase improves hepatic energy charge and urinary prostaglandin levels in rats with obstructive jaundice.

BACKGROUNDS/AIMS: No study has so far been conducted to clarify whether the presence of hyperbilirubinemia is detrimental to liver and renal functions. In the present study, the effects of polyethylene glycol-modified bilirubin oxidase (PEG-BOX) therapy on liver and renal function tests, hepatic energy charge and urinary prostaglandin levels were evaluated in a rat model of obstructive jaundice. METHODS: Sprague-Dawley rats were used in the experimental model of obstructive jaundice. PEG-BOX or an equivalent amount of PEG alone was intravenously injected into the animals and sampling of blood and urine, and liver harvesting were done sequentially after bile duct ligation. RESULTS: Conventional liver function tests showed no difference between PEG-BOX and control groups. However, bilirubin concentrations in the peripheral blood and liver tissue specimens markedly decreased, and the hepatic energy charge significantly increased in the PEG-BOX group as compared to controls. The blood concentration of bile acid was lower, but its urinary excretion was higher in the PEG-BOX group than in the control group. In vitro incubation of PEG-BOX with serum from rats with obstructive jaundice decreased the concentration of bilirubin but not that of bile acid. The urinary levels of prostaglandin E2 and the thromboxane B2/6-keto-prostaglandin Fla ratio were significantly lower in the PEG-BOX group than in the control group. CONCLUSIONS: The systemic reduction of bilirubin concentration may contribute to normalization of the urinary levels of prostaglandins and thromboxane B2, to decrease in serum bile acid levels, and to improvement of the hepatic energy charge in obstructive jaundice. These findings suggest that preoperative improvement of jaundice may be beneficial to patients with obstructive jaundice.

Animals↗

Behavior of centrioles during meiosis in the male silkworm, Bombyx mori (Lepidoptera).

The behavior of centrioles during eupyrene and apyrene meiosis was examined in the silkworm, Bombyx mori, by transmission electron microscopy and indirect immunofluorescence for tubulin. In eupyrene spermatocytes the centrioles, accompanied by axonemes, attached temporarily to the nucleus at diplotene, then detached from the nucleus in diakinesis. After the separation, a beret-shaped structure consisting of a double membrane covered the proximal region of the pair of centrioles. The structure disappeared after breakdown of the nuclear membrane. The centriole, with the axoneme, reattached to the nucleus at telophase I. The process was repeated during meiosis II until the centrioles maintained their nuclear attachment in newly developed spermatids. In stark contrast to their eupyrene counterparts, apyrene spermatocytes were conspicuously devoid of any attachment of the centrioles to the nucleus. These eupyrene-specific and apyrene-specific relationships were consistently and repeatedly found between the nuclear membrane and centrioles, giving rise to suspicion that the behavioral phenomena may be related to differentiation of the dimorphic sperm types.

Animals↗