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Biomedical subjects

K Kasahara

Publications and source records attributed to K Kasahara.

At least 37 records · Page 2Linked to original sources

Fatal acute hepatic failure induced by danazol in a patient with endometriosis and aplastic anemia.

We describe a 47-year-old woman with severe aplastic anemia with genital bleeding who developed acute severe hepatitis after the administration of danazol while she was receiving cyclosporin. She had been diagnosed with severe aplastic anemia 1 year previously and, while hospitalized, had received methyl prednisolone pulse therapy, which was not successful. She was then referred to our hospital. She was treated with antithymocyte globulin, cyclosporin, granulocyte colony-stimulating factor, and methyl prednisolone; a good response was achieved after 3 months of this therapy. Subsequently, oral administration of cyclosporin was continued, but she was readmitted to our hospital when pancytopenia gradually developed and the genital bleeding recurred. Danazol was administered for pancytopenia and endometriosis. Four days after the first administration of danazol, epigastric pain occurred, and the danazol was stopped. Eighteen days after the first danazol administration, very severe hepatic injury occurred abruptly. The patient died of hepatic failure. Postmortem examination revealed centrilobular massive necrosis of the liver. Danazol was implicated as the agent responsible for causing the hepatic failure. Drug interactions between danazol and cyclosporin may cause adverse effects.

Anemia, Aplastic↗

Follicle-stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome.

OBJECTIVE: To determine whether the known inactivating FSH receptor gene mutations are present in Japanese women with secondary amenorrhea because of premature ovarian failure (POF) and polycystic ovary syndrome (PCOS). DESIGN: Clinical and molecular studies. SETTING: An outpatient clinic in a university hospital. PATIENT(S): Fifteen women with idiopathic POF, 38 women with PCOS, and three normal controls. INTERVENTION(S): Extraction of DNA from blood samples for subsequent polymerase chain reaction (PCR). MAIN OUTCOME MEASURE(S): PCR fragments digested with MunI, BsmI, and HhaI were compared in patients and controls. PCR fragments were also analyzed by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. RESULT(S): No inactivating mutations reported thus far in exons 6, 7, 9, and 10 of the FSH receptor gene were identified in Japanese women with POF and PCOS. DGGE analysis of PCR fragments of exon 10 also revealed no FSH receptor gene mutations in this region. CONCLUSION(S): Although we cannot exclude the presence of point mutations in other regions of the FSH receptor gene, the described FSH receptor mutations may be uncommon in Japanese patients with POF and PCOS.

Adult↗

Characterization of increased cough sensitivity after antigen challenge in guinea pigs.

Increased sensitivity of cough reflex is a fundamental feature of bronchodilator resistant non-productive cough associated with eosinophilic tracheobronchitis. Our hypothesis is that cough sensitivity is increased by airway allergic reaction characterized by airway eosinophilic inflammation. The aim of this study was to elucidate the hypothesis and clarify the characteristics of the increased cough sensitivity. Number of coughs elicited by inhalation of increasing concentrations of capsaicin (10-8, 10-6 and 10-4 M) was counted 24 h after an aerosolized antigen or saline in actively sensitized or non-sensitized (naive) conscious guinea pigs and then bronchoalveolar lavage was performed. The cough response was also measured 1 day before and 1, 2, 3, 5 and 7 days after an aerosolized antigen challenge in sensitized or naive animals. In addition, effect of procaterol (0.1 mg/kg), atropine (1 or 10 mg/kg), phosphoramidon (2.5 mg/kg) given intraperitoneally 30 min before the capsaicin challenge or capsaicin desensitization on the cough response was examined. Furthermore, the thromboxane A2 (TXA2) receptor antagonist S-1452 in a dose of 0.01 or 0.1 mg/kg or vehicle (saline) was given intraperitoneally at 24 and 1 h before the measurement of cough response. Number of coughs caused by capsaicin was extremely increased 24 h after an antigen challenge in sensitized guinea pigs compared with a saline or an antigen challenge in naive animals or a saline challenge in sensitized animals. The increased cough response disappeared at 3-7 days after the antigen challenge. Eosinophils in bronchoalveolar lavage fluid obtained after the measurement of capsaicin-induced coughs, which was performed 24 h after the antigen challenge, were significantly increased in sensitized guinea pigs. The eosinophil count was significantly correlated to the number of capsaicin-induced coughs. Procaterol or atropine did not alter the antigen-induced increase of cough sensitivity, whereas atropine did reduce the cough response in naive animals. Phosphoramidon increased the number of capsaicin-induced coughs in naive guinea pigs but not in sensitized and antigen-challenged animals. Capsaicin desensitization decreased the cough response in both antigen-challenged sensitized guinea pigs and naive animals. S-1452 reduced the antigen-induced increase of cough response in sensitized guinea pigs, but not in naive animals. Airway allergy accompanied with airway eosinophilia induces transient increase in cough sensitivity, which is not mediated by bronchoconstriction. The increased cough sensitivity may result in part from inactivation of neutral endopeptidase and TXA2, one of the inflammatory mediators.

Allergens↗

IFN-gamma production in response to IL-18 or IL-12 stimulation by peripheral blood mononuclear cells of atopic patients.

BACKGROUND: Several studies have shown that interleukin (IL)-4 and interferon-gamma (IFN-gamma) are important for the regulation of immunoglobulin E (IgE) production and that IL-18 and IL-12 induce IFN-gamma. OBJECTIVE: IFN-gamma production in response to IL-18 or IL-12 stimulation was investigated in peripheral blood mononuclear cells (PBMCs) of atopic patients with various levels of serum IgE. METHODS: Cytokine production from PBMCs was measured following stimulation with a non-specific stimulator (phytohemagglutinin: PHA), IL-18 or IL-12 in 12 healthy controls and 26 atopic patients with various serum IgE levels. RESULTS: IFN-gamma production by IL-18-stimulated PBMCs was positively correlated with IFN-gamma production by IL-12-stimulated PBMCs (P < 0.05). However some atopic patients showed discrepancy between the levels of IFN-gamma production stimulated by IL-12 and by IL-18. CONCLUSIONS: The results shown here suggest the presence of abnormalities in the IL-12 and/or IL-18 signalling pathways, such as genetic defects in the atopic patients.

Adolescent↗

Advanced adenocarcinoma of the urinary bladder successfully treated by the combination of cisplatinum, mitomycin-C, etoposide and tegafur-uracil chemotherapy.

Primary adenocarcinoma of the urinary bladder has shown an extremely poor response to radiation or chemotherapy. Therefore, radical surgery is the only therapeutic treatment for it. A case report is presented of a primary advanced adenocarcinoma of the urinary bladder invaded into the uterus with distant metastases which responded completely to systemic combination chemotherapy including tegafur-uracil. The patient was a 53-year-old woman with a history of asymptomatic macrohematuria. She was treated with the combination of cisplatinum, mitomycin-C, etoposide and tegafur-uracil chemotherapy. After four courses of the chemotherapy, computed tomography showed marked regression of the primary tumor of the urinary bladder and the complete disappearance of the distant metastases in the liver, lung and para-aortic lymph node. Subsequently, she underwent radical cystectomy and cutaneous ureterostomy. Pathologically, no viable cancer cells were detected. Three years after the operation, she has no evidence of disease recurrence. Treatment of advanced adenocarcinoma of the urinary bladder by this combination chemotherapy is of benefit.

Adenocarcinoma↗

Analysis of Ig subclass deficiency: First reported case of IgG2, IgG4, and IgA deficiency caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon in a Mongoloid patient.

BACKGROUND: The cause of Ig class or subclass deficiencies has been unclear except for IgH gene deletions and a homozygous 1-base insertion (1793insG) in C gamma 2 exon 4 of IgG2 deficiency. In addition, there are no reports that IgH gene deletions are found in patients who are Mongoloid (a category that includes most of the people of Asia, such as the Japanese, Chinese, Indonesians and Malaysians). OBJECTIVE: To investigate the cause of Ig subclass deficiency, we extensively investigated 4 Japanese patients with low serum IgG2 levels. Patient 1 was a 23-month-old girl whose serum IgG2, IgG4, and IgA levels were under the detection limits; she also had idiopathic thrombocytopenic purpura. Patient 2 was a 5-year-old boy whose serum IgG2 level was under the detection limit. Patient 3 was a 14-month-old boy whose serum IgG2 and IgG4 levels were under the detection limits. Patient 4 was 3-year-old girl whose IgG2 level was low and whose IgA level was under the detection limit. METHODS: DNA was extracted from neutrophils, and Southern blot analysis was performed. RESULTS: Southern blot analysis revealed that patient 1 had lost the C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon genes and was a homozygous carrier of the deletion described above. Her mother was of the heterozygous genotype. DNA from patients 2, 3, and 4 revealed no deletions in comparison with control DNA. CONCLUSION: This is a report of the first case of a Mongoloid in whom IgG2, IgG4, and IgA deficiency was caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon. Our finding contributes to investigations of Ig subclass deficiency.

Asian People↗

Messenger ribonucleic acid for the mouse decidual prolactin is present and induced during in vitro decidualization of endometrial stromal cells.

Although decidualization of endometrial stromal cells is crucial for blastocyst implantation and maintenance of pregnancy, its complex mechanism still remains largely unknown. To explore the mechanisms of decidualization, we have established an in vitro decidualization model in mice. Through extraction of mRNA from endometrial stromal cells for subsequent reverse transcriptase polymerase chain reaction analysis, we found that two ovarian hormones, 17 beta-estradiol and progesterone, induced morphological changes and expression of mRNA for prolactin (PRL) and the decidual/trophoblastic PRL-related protein (d/tPRP) in cultured mouse endometrial stromal cells. The expression of mRNA for the decidual PRL was also detected in the mouse decidua in vitro. In conclusion, mouse mRNA for decidual PRL is present and induced by estradiol and progesterone through in vitro decidualization of endometrial stromal cells.

Animals↗

Involvement of lipid peroxidation in spontaneous pancreatitis in WBN/Kob rats.

To cast light on the mechanisms underlying development of spontaneous pancreatitis lesions, tissues from WBN/Kob rats at various ages were histopathologically and immunohistochemically investigated with special reference to the existence of the lipid peroxidation products 4-hydroxy-2-nonenal (HNE), 4-hydroxy-2-hexenal (HHE), and malondialdehyde (MDA). Male 4-20-week-old WBN/Kob rats were killed to allow sampling of pancreatic tissues, which were fixed in cold acetone and 10% neutral-buffered formalin. and then processed for routine histopathology as well as immunohistochemistry for proteins modified by HNE, HHE, and MDA. Although no remarkable histologic changes were noted in younger animals, edema, hemorrhage, inflammatory cell infiltration, fibrosis, vacuolation of acinar cells, and ductular proliferation were observed in exocrine pancreatic tissue from animals at 10-15 weeks of age. In animals aged 20 weeks, the lesions had progressed remarkably and deposits of hemosiderin were apparent with fibrosis. Immunohistochemical examination for lipid peroxidation product-modified proteins showed HNE and MDA to be negative in all pancreatic tissues, but HHE was positive in the areas involving atrophy of acinar cells and fibrosis in the islets. The results of the present study thus provide support for the conclusion that lipid peroxidation during spontaneous pancreatitis in WBN/Kob rats may possibly be involved in the development of diabetes in this model.

Aging↗

[Pathogenetic study on bronchopulmonary infections in 1,416 patients by transtracheal aspiration method].

We have performed transtracheal aspiration (TTA) in 1,416 patients, who were suspected to have bronchopulmonary infection, in order to collect non-contaminated specimens directly from the lower airway. The overall isolation rates in 1,416 TTA were 68.7% for any microorganisms. Aerobes had a high incidence but many kinds of microorganisms were associated with bronchopulmonary infections. Haemophilus influenzae was the major pathogen in patients with acute bronchitis. Streptococcus pneumoniae was the most important pathogen and mycoplasma was often isolated in patients with community-acquired pneumonia. Major pathogens of nosocomial pneumonia consisted of alpha-streptococcus spp., anaerobes and Pseudomonas aeruginosa. Anaerobes were isolated from transtracheal aspirates in 20 of 33 episodes of lung abscesses. H. influenzae and P. aeruginosa were the main persistent pathogens and H. influenzae, S. pneumoniae and anaerobes were important exacerbated pathogens in patients with chronic lower respiratory tract infection. S. pneumoniae was isolated more from TTA than expectorated sputa. Oropharyngeal flora bacteria were easily isolated in the culture of expectorated sputa. We assessed the final diagnosis or causative factor in 443 patients whom no microorganism was isolated from transtracheal aspirates. The final diagnosis was infectious diseases in 52 patients (11.7%) and non-infectious diseases in 80 patients (18.1%), respectively. The causative factor was unsuited TTA sample in 81 patients (18.3%), preceding antimicrobial chemotherapy in 95 patients (21.4%) and unknown in 135 patients (30.5%), respectively. The pathogenesis of bronchopulmonary infections is complex and various microorganisms are associated with pathogens of bronchopulmonary infections. Therefore, we should accurately diagnose the pathogens in patients with bronchopulmonary infections. TTA is one of the useful methods that we can accurately detect the respiratory pathogens.

Adolescent↗

The role of human chorionic gonadotropin on decidualization of endometrial stromal cells in vitro.

Although decidualization of endometrial stromal cells (ESC) is crucial for blastocyst implantation and maintenance of pregnancy, its complex mechanism still remains largely unknown. It has long been believed that hCG can directly induce in vitro decidualization of ESC via cAMP signaling. Recently, however, it has been reported that the LH/CG receptor is not present in human endometrium, and the direct effect of hCG on decidualization has become controversial. To reevaluate the exact effect of hCG on decidualization, human ESC were isolated and cultured with hCG and/or ovarian steroids. ESC treated with 17beta-estradiol plus progesterone (E(2)/P) transformed morphologically and produced significant PRL, whereas ESC treated with hCG alone showed no significant increase in PRL in culture medium and exhibited no morphological changes. Moreover, hCG did not promote E(2)/P-induced PRL production or intracellular cAMP accumulation, and protein kinase A inhibitor failed to block E(2)/P-induced PRL production. These results suggest that hCG does not directly affect in vitro decidualization of human ESC and that the process of E(2)/P-induced in vitro decidualization might consist of several pathways, including the intracellular cAMP signaling cascade.

Adult↗

Radicicol binding to Swo1/Hsp90 and inhibition of growth of specific temperature-sensitive cell cycle mutants of fission yeast.

A panel screening using cdc mutants of Schizosaccharomyces pombe identified radicicol as a potent growth inhibitor of certain mutants at the permissive temperature. The strains sensitive to radicicol were cdc7, cdc11, and cdc14, all of which are defective in early septum formation. Cytokinesis but not nuclear division of these mutants was inhibited by radicicol, but that of cells with the wild-type background was not. A biologically active derivative of radicicol with a biotin moiety at the C-11 position bound Swo1, an Hsp90 homologue in S. pombe. Increased Swo1 expression partially suppressed radicicol sensitivity of cdc14 and almost completely rescued morphological abnormalities in cdc14 and cdc7 cells induced by radicicol at the permissive temperature. On the other hand, the increased Swo1 expression did not restore septum formation at the nonpermissive temperature. These results suggest that Swo1, as a molecular chaperone, plays a role in stabilizing these temperature-sensitive proteins at the permissive temperature or in activating the cytokinesis signaling cascade.

Antifungal Agents↗

Telomerase activity in cell lines and lymphoma originating from Bloom syndrome.

Bloom syndrome (BS) is characterized by premature aging and high predisposition to various types of cancer. BLM is the causative gene for BS. BLM functions as a DNA helicase in the direction of 3' to 5' and small subsets of telomeres colocalize with BLM protein. We investigated telomerase activity and telomere repeat length in the cells from BS patients. In Epstein-Barr-virus (EBV) transformed lymphoblastoid cell lines and lymphoma cells from BS patients, telomerase activity was detected as in the control and compared. The metastatic tumor from BS patient, which had a 9-bp deletion of p53 DNA showed the strongest telomerase activity. Telomere repeat length in BS cells showed that there is no large difference compared with normal cells. Collectively, the results show that the BLM gene is not a major structural and regulatory factor in maintaining telomere repeat length and telomerase activity.

Adenosine Triphosphatases↗

Early reduction in the aneuploidy at chromosomes 7 and 8 are significantly correlated with clinical effect in high-dose rate brachytherapy with external beam radiotherapy in localized prostate cancer.

Although reduction in the serum prostate specific antigen (PSA) correlates with clinical outcome for high dose rate Iridium-192 (HDR Ir-192) brachytherapy, it takes a long latency period. We investigated numerical chromosome changes of prostatic cancer during the pre- and post-treatment periods of HDR Ir-192 brachytherapy (and external beam radiotherapy), using fluorescence in situ hybridization (FISH) to clear the effect of treatment in early phase. Transitional changes in the frequency of aneuploidy for chromosomes 7, 8, 10, 12, 16, X, and Y in prostate cancer during the pre- and post-treatment periods were observed. Gains of chromosomes 7, 8 and 12 were noted in the pre-treatment samples (4 out of 12 cases in chromosomes 7 and 8; 1 out of 12 cases in chromosome 12), while a notable reduction in the number of cells with extra copies of these chromosomes was observed in post-treatment specimens. This change appears earlier than the reduction in the value of prostate specific antigen (PSA) and strongly reflects the effect of HDR brachytherapy with external beam radiotherapy in localized prostate cancer. Decrease in the number of cells with high ploidies of chromosomes 7, 8 and 12 at 12 weeks after treatment may predict clinical effects of radiation therapy, which may explain the radiation dependency of localized prostate cancer cells.

Aged↗

Fluorescence in situ hybridization to assess transitional changes of aneuploidy for chromosomes 7, 8, 10, 12, 16, X and Y in metastatic prostate cancer following anti-androgen therapy.

There have been few detailed studies conducted on the cell population in relation to cytogenetic changes between the pre- and post-treatment periods in patients with prostate cancer. We investigated numerical chromosome changes associated with anti-androgen therapy, using fluorescence in situ hybridization (FISH). FISH using chromosome-specific centromeric probes was used to assess transitional changes in the frequency of aneuploidy for chromosomes 7, 8, 10, 12, 16, X, and Y in prostate cancer during the pre- and post-treatment periods. Gains of chromosomes 7, 8 and 12 were notable in the pre-treatment samples (8 out of 9 cases in chromosome 7; 8 out of 9 cases in chromosome 8; 7 out of 9 cases in chromosome 12), while a notable reduction in the number of cells with extra copies of these chromosomes was observed in post-treatment specimens. Other chromosomes did not show noticeable change in their FISH signals at each phase of clinical treatment in all 9 cases. Changes in cell number with high ploidies of chromosome 7, 8 and 12 reflect the clinical effects of anti-androgen therapy at the early phase, which might explain the androgen dependency of metastatic prostate cancer cells.

Adenocarcinoma↗

[High-dose rate Iridium-192 brachytherapy with flexible applicator--a trial toward decrease of stress during treatment and improvement of quality of life].

PURPOSE: We tried to improve the materials and methods of high-dose rate Iridium-192 brachytherapy for localized prostate cancer and evaluated the stress during the treatment in 20 patients with whom the therapy was performed. MATERIALS AND METHODS: Rigid applicators made of stainless steel of 1.6 mm in diameter were indwelt with a template as usual for 30 hours in 14 patients (group A). Flexible applicators made of polyoxymethylene rosin (POM) of 2.0 mm in diameter were indwelt without a template for 30 hours after the applicator insertion in 6 patients (group B). We made inquiries about lumbago, inconvenience and necessity of assistant help and sleep in the course of therapy, and urinary incontinence and erectile function after the course of therapy as the QOL. RESULTS: The stress during the course of therapy in the patients of group B was obviously less than that of group A. There were no significant differences in urinary incontinence and erectile function after the course of therapy between group A and B. CONCLUSION: In this study, our trial successfully reduced the stress during the course of therapy in the patients with localized prostate cancer in the course of high-dose rate Iridium-192 brachytherapy.

Aged↗

[High-dose rate iridium-192 brachytherapy combined with external beam radiotherapy for localized prostate cancer].

PURPOSE: We report our technique and also preliminary results in the cases with localized prostate cancer treated by the combination of high-dose rate Iridium-192 (HDR-Ir192) brachytherapy and external irradiation. MATERIALS AND METHODS: From June 1999 to August 2000, 17 patients were treated by the combination of HDR-Ir 192 and external beam. The mean age of patients was 72 years (range, 48-81 years). The clinical stage was B1 in 5, B2 in 7 and C (no cancer with seminal vesicle) in 5 cases. Of 10 patients without neoadjuvant hormonal therapy, the median initial pretreatment PSA was 15.3 ng/ml (6.93-222.32 ng/ml). The treatment was given by HDR-Ir 192 brachytherapy (6 Gy x 3 times/2 days) and external beam irradiation (40 or 45 Gy). The brachytherapy was given using TRUS guided percutaneously inserted temporary needles with a high dose rate remote afterloading control. Local control was evaluated by digital rectal examination. TRUS-guided biopsies and serum PSA evaluations. Follow-up ranged from 2 to 14 months, with a median of 8 months. RESULTS: In 4 (40.0%) of 10 patients without neoadjuvant hormonal therapy the level of serum PSA was decreased to less than 4.0 ng/ml within 3 months after the therapy. The effective grade in the biopsy specimens of 8 patients without neoadjuvant hormonal therapy was Grade Ob in 4, Grade 1 in 1, Grade 3 in 3 cases at 3 months after the therapy. No severe intra- or peri-operative complications occurred. CONCLUSION: The combined radiotherapy treatment is safe and effective for use in the patients with localized prostate cancer. However, more comprehensive studies involving long-term follow-up and great numbers of the cases with localized prostate cancer treated by the combination of HDR-Ir 192 brachytherapy and external irradiation will be necessary to determine whether this therapy contributes to better prognosis.

Aged↗