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Biomedical subjects

Y Okubo

Publications and source records attributed to Y Okubo.

At least 127 records · Page 7Linked to original sources
PubMed1999

Phase I study of a combination of irinotecan and ifosfamide in advanced primary lung cancer.

We sought to investigate cisplatin-free chemotherapy for patients with primary lung cancer. We therefore conducted a Phase II study to identify; a) the maximum tolerated dose (MTD) of irinotecan (CPT-11) given with a fixed dose of ifosfamide (IFM), and b) the principal toxic effects associated with this regimen in a Phase I study. A total of 27 patients with previously treated or untreated primary lung cancer received CPT-11 on days 1, 8 and 15 in combination with a fixed dose of IFM, 1.5 g/m2/day, on days 1 through 3, given every 4 weeks. The starting dose of CPT-11 was 30 mg/m2, which was increased by amounts of 10 mg/m2. Four patients were assigned to different dosage levels, and drug toxicity was evaluated for the first 2 cycles. The MTD of CPT-11 was 90 mg/m2, with leukopenia being the dose-limiting effect. The response rate was 43% (6/14; 1 complete response) in non-small cell lung cancer, and 78% (7/9; no complete response) in small cell lung cancer. The recommended dose of CPT-11 for a Phase II study is thus 80 mg/m2 on days 1, 8 and 15 with IFM 1.5 g/m2 given on days 1 through 3. This regimen appears particularly encouraging, because of its low toxicity. Phase II trials of the combination are indicated.

Adult↗
PubMed1999

[A case of submucosal endosalpingiosis in the urinary bladder].

A 47-year-old woman was admitted when a mass in the urinary bladder was pointed out on ultrasound follow-up after hysterectomy for uterine myoma. Cystoscopy, ultrasonography, CT scan and MRI suggested a tumor in the muscle layers of the urinary bladder. Since the possibility of malignancy could not be ruled out, partial cystectomy was performed. The tumor was diagnosed as endosalpingiosis, a subclassification of mullerianosis histologically. The concept of endosalpingiosis has appeared recently and only 3 cases have been reported none of who had severe symptoms. Our case is the forth in the world. One of these cases had been treated with hormonal therapy as endometriosis, with no effect. Therefore, surgery is recommended as the first treatment of choice.

Choristoma↗
PubMed1999

[RT-PCR assay for detecting PSA mRNA in peripheral blood of prostate cancer patients].

A sensitive technique using reverse transcription and polymerase chain reaction (RT-PCR) has been used to detect circulating tumor cells in the peripheral blood of men with prostate cancer. We evaluated the clinical utility of this method for staging and monitoring for prostate cancer. Peripheral blood from 39 patients with prostate cancer and 7 non-prostate cancer controls was analyzed for prostate specific antigen (PSA) messenger RNA (mRNA) using RT-PCR. In 8 among 22 patients (36.4%) with clinically localized prostate cancer (T2 or T3), PSA mRNA was detected by RT-PCR (RT-PCR positive). Five out of 8 patients (62.5%) with regional lymph node and/or bone metastases were RT-PCR positive. The number of patients with RT-PCR positive was more frequent in a higher clinical stage. In 22 patients with clinically localized prostate cancer, 2 of the 9 patients who underwent radical prostatectomy had positive surgical margins and both patients were RT-PCR positive. Six of the 7 patients with negative surgical margin were RT-PCR negative. In the 9 cases that had been treated by combined antiandrogen blockade for metastatic prostate cancer, 4 patients whose serum PSA level were less than 4 ng/ml were all RT-PCR negative. More over 4 of 5 patients with more than 4 ng/ml of serum PSA level were RT-PCR positive. All control samples were RT-PCR negative. This study suggested that this technique using RT-PCR may provide useful information in treating patients with prostate cancer, especially for candidates for radical prostatectomy. The value of this modality as a prognostic factor awaits for further follow-up.

Biomarkers, Tumor↗
PubMed1999

[Amyopathic dermatomyositis with interstitial pneumonia: effective treatment with cyclophosphamide pulse therapy].

A 42-year-old man was admitted to our hospital because of dyspnea on exertion, skin eruptions on the face and extremities, and interstitial shadows mainly in the lower fields of both lungs. Characteristic skin lesions and skin biopsy findings without muscle symptoms or elevated CPK resulted in a diagnosis of amyopathic dermatomyositis (ADM). Thoracoscopic lung biopsy specimens disclosed BOOP-type interstitial pneumonia. Oral prednisolone (PSL) was initiated at 60 mg/day and gradually tapered. However, because his respiratory symptoms and laboratory findings deteriorated, the patient underwent 5 courses of cyclophosphamide (CPA) pulse therapy. Following improvement of his subjective symptoms, arterial blood gas data, and respiratory functions, the patient was discharged and placed on oral PSL and CPA. CPA was discontinued 18 months later. The patient has continued to receive PSL (5 mg/day) and has been in good condition for 3 years. Though the prognosis for interstitial pneumonia associated with ADM is reported to be poor, our patient represented a rare case of BOOP-type interstitial pneumonia brought into remission by CPA pulse therapy.

Adult↗
PubMed1998

Association between polymorphisms in the type 1 sigma receptor gene and schizophrenia.

Several antipsychotic agents such as haloperidol and rimcazole are known to bind to sigma receptors with high affinity, and evidence for a potential link between sigma receptors and the etiology of schizophrenia has been reported. The present study was conducted to systematically search for nucleotide variants of the type 1 sigma receptor gene in 48 schizophrenics. Two polymorphisms were found: GC-241-240TT in the 5' flanking region and Gln2Pro. These two polymorphisms were in nearly complete linkage disequilibrium with each other. The Pro2 variant of the Gln2Pro polymorphism changes the endoplasmic reticulum retention signal motif. These polymorphisms were examined in an extended sample of schizophrenics (n = 308) and controls (n = 433) and a significant association between the presence of the TT/Pro2 haplotype and schizophrenia was observed (odds ratio = 1.27, P = 0.04).

Adolescent↗
PubMed1998

Insulin-like growth factor-I inhibits the stress-activated protein kinase/c-Jun N-terminal kinase.

The pathways involved in the cellular responses to the insulin-like growth factors (IGFs) are numerous and vary according to cell type. Following activation of the IGF-I receptor, the mitogen-activated protein kinase and phosphatidylinositide 3'-kinase (PI3'K) pathways are activated and result in cellular proliferation and inhibition of apoptosis. In this study, we analyzed the IGF-I effect on the stress-activated protein kinase/c-Jun N-terminal kinase (JNK) activity using human embryonic kidney 293 cells, 293 cells transiently expressing hemagglutinin-JNK, and 293 cells stably expressing a hemagglutinin-JNK transgene. In all cell types, endogenous or transfected JNK activity was strongly stimulated by anisomycin or tumor necrosis factor-alpha, and 10 nM IGF-I pretreatment suppressed the induced JNK activity. To determine whether the effect of IGF-I on JNK activity involves the mitogen-activated protein kinase or PI3'K pathway, we used the specific MEK1 inhibitor PD098059 and the PI3'K inhibitor LY 294002. PD098059 did not alter the IGF-I suppressive effect on stressor-induced JNK activity, but LY 294002 suppressed the IGF-I effect. Moreover, in transiently transfected parental 293 cells expressing dominant-negative Akt, anisomycin-increased JNK activity was not suppressed by pretreatment with IGF-I. Our results demonstrate that the action of IGF-I on JNK in these cells is via PI3'K and Akt.

Anisomycin↗
PubMed1998

Evidence supporting an association between the DRB1 gene and schizophrenia in Japanese.

The authors attempted a replication of earlier studies that detected an association of HLA-DR4 and DR1 with schizophrenia. Japanese patients with schizophrenia (n = 266, DSM-III-R criteria) and Japanese controls (n = 283) were genotyped for DR1 and DR4 alleles using a combination of group-specific polymerase chain reaction (PCR) amplification and PCR-restriction fragment length polymorphism. Significant positive association with HLA-DR1 [odds ratio (OR) = 1.87, corrected p = 0.04] and a negative association with HLA-DR4 (OR = 0.63, corrected p = 0.02) was noted. DR1 and DR4 were independently associated with schizophrenia. The association of the DR1-positive/DR4-negative genotype with schizophrenia was modest (OR = 2.60, 95% confidence intervals = 1.38-4.89, corrected p = 0.008). Thus, these findings support an association of the HLA DRB1 gene locus with schizophrenia in the Japanese population. Since both DR4 and DR1 are positively associated with rheumatoid arthritis, our findings are not simply consistent with the known negative association between schizophrenia and rheumatoid arthritis.

Female↗
PubMed1998

Lung as reservoir for antidepressants in pharmacokinetic drug interactions.

BACKGROUND: Although high-affinity imipramine binding sites have been reported in both rat and human lung, the role of the lungs in the pharmacokinetics of antidepressants has not received much attention. Substantial accumulation of selective serotonin-reuptake inhibitors (SSRIs) in the lungs has been reported. We have investigated the role of the lungs in pharmacokinetic drug interactions between tricyclic antidepressants and SSRIs. METHODS: We used a carbon-11-labelled form of the imipramine derivative cyanoimipramine to measure uptake in the lungs and brain of healthy volunteers by positron emission tomography. Clomipramine (50 mg) was administered to measure the effect of antidepressants with high affinity for the serotonin transporter on lung and brain uptake. FINDINGS: A large proportion of the injected 11C-cyanoimipramine (68-86% in the four volunteers) was extracted by the lungs. Clomipramine decreased the lung uptake from 68% to 35% and from 81% to 54% in the two volunteers studied. By contrast, whole-brain uptake was low in control studies (1.7-2.0% in three volunteers) and increased after clomipramine administration (to 4.5-4.9%). Plasma radioactivity was also higher after clomipramine than in control studies. INTERPRETATION: The lungs may function as a reservoir for antidepressants with high affinity to the serotonin transporter. The accumulated antidepressants may be displaced by other antidepressants, and this displacement would substantially increase plasma concentrations and thus cause toxic effects.

Adult↗
PubMed1998

Sensitive diagnosis of cardiac allograft rejection by detection of cytokine transcription in situ.

OBJECTIVE: In situ transcription of cytokines which are important in the development of cardiac rejection has not been evaluated for diagnosing rejection. The objective was to evaluate the usefulness of in situ reverse transcriptase polymerase chain reaction (RT-PCR) for sensitive detection of acute cardiac rejection. METHODS: We studied interferon (IFN)-gamma and interleukin (IL)-2 expression using immunohistochemistry and in situ RT-PCR in murine cardiac transplant models. Hearts were heterotopically transplanted (BALB/c to C3H/He) and some mice were not treated (n = 23); others were treated with anti-intercellular adhesion molecule (ICAM)-1 and anti-lymphocyte function associated antigen (LFA)-1 monoclonal antibodies (mAbs) (n = 23). Allografts were removed at days 1 to 7. For control, isografts were harvested at day 7 (n = 2). RESULTS: Mice without treatment rejected allografts within 7 days, while all mAb-treated recipients accepted allografts for the same period. At day 1, allografts of both groups showed scattered myocardial cell infiltration which increased in non-treated allografts, but remained stable in mAb-treated grafts thereafter. In situ RT-PCR showed that IL-2 and IFN-gamma mRNA positive cells were present in non-treated allografts, while few mRNA positive cells were expressed in infiltrating cells in the mAb-treated allografts (IL-2, day 3: 88.8 +/- 28.3 vs. 7.2 +/- 6.4, p < 0.05, positive cells within 10 fields per section). However, immunohistochemistry could not reveal the difference at day 3. CONCLUSION: In situ RT-PCR is a sensitive method for diagnosing acute rejection, and it reveals the characteristics of myocardial infiltrate cells to determine their role in the process of rejection.

Animals↗
PubMed1998

Fosfomycin (FOM: 1 R-2S-epoxypropylphosphonic acid) suppress the production of IL-8 from monocytes via the suppression of neutrophil function.

We investigated the influence of fosfomycin (FOM) on the production and the mRNA expression of interleukin-8 (IL-8) by monocytes. In the incubation of whole blood stimulated by N-Formyl-Met-Leu-Phe (FMLP), FOM significantly suppressed the production and the mRNA expression of IL-8 by monocytes and its inhibitory action was concentration-dependent (FOM: 50-200 microg/ml). However, FOM did not influence the production and the mRNA expression of IL-8 in the incubation of fractionated mononuclear cell stimulated by FMLP. The supernatant of FMLP-stimulated polymorphonuclear leukocyte (PMNL) could induce the mRNA expression of IL-8 by monocyte. The supernatant of FMLP-stimulated PMNL which was pre-treated with FOM significantly (P < 0.05) inhibited the expression of IL-8 mRNA by monocyte. Moreover, FOM suppressed the production of leukotriene B4 (LTB4) from neutrophil in a concentration-dependent manner. When LTB4 was added to the fractionated mononuclear cells directory, the expression of IL-8 mRNA was enhanced (P < 0.05). The present study indicated that FOM suppress the production of LTB4 from neutrophils and suppress the expression of IL-8 mRNA by LTB4 from monocytes. It was also demonstrated that LTB4 produced by neutrophil is one of the factor which promotes the expression of IL-8 mRNA in monocytes.

Anti-Bacterial Agents↗
PubMed1998

Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology.

The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of IGF-I and IGF-II. The IGFs play a critical role in promoting development, stimulating growth and organogenesis via mitogenic, antiapoptotic and chemotactic activity. Recent research has focused on the events that occur intracellularly upon receptor activation. Several pathways have been shown to be important. The insulin-receptor substrate (IRS), SHC, GRB2, CRKII and CRKL adaptor proteins have all been implicated in transmitting signals to the nucleus of the cell. This review outlines some of the signalling pathways believed to be important in converting IGF-IR activation into changes in cell behavior and metabolism.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Peripheral blood monocytes in psoriatic patients overproduce cytokines.

Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) production by peripheral monocytes in 15 patients with psoriasis vulgaris and 13 healthy controls were investigated using an enzyme-linked immunosorbent assay. Polymorphonuclear leukocytes, mononuclear leukocytes, monocytes, lymphocytes and serum were isolated and cultured for 1, 12, 24 and 48 h in RPMI 1640 medium without fetal calf serum to release the cytokines. All cytokine levels in serum were very low in both psoriatic patients and the controls. However, a significant increase in the IL-1 alpha levels in the monocyte culture supernatants was observed in the psoriatic patients compared with that of the controls. IL-1 beta and IL-8 levels in the monocyte supernatants were also significantly increased in the psoriatic patients compared with the controls. TNF-alpha levels in the 12-h supernatants of the monocytes increased in some samples from psoriatic patients but not in the 48-h supernatants. Our study confirmed the overproduction of cytokines in the peripheral monocytes of the psoriatic patients and suggest the activation of monocytes in the patients with psoriasis.

Adult↗
PubMed1998

Effectiveness of kampo medicine (sai-boku-to) in treatment of patients with glossodynia.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of a Kampo medicine (Sai-boku-to) for treatment of patients with glossodynia. STUDY DESIGN: Sai-boku-to or an antianxiety drug (diazepam) with vitamin B complex was administered orally for 3 months to each of 200 patients with glossodynia. Clinical examination evaluated the following subjective symptoms: pain, burning sensation, and discomfort. Effectiveness was evaluated as follows: "markedly effective," all 3 symptoms disappeared; "effective," pain improved; "ineffective," no improvement in pain. RESULTS: The effective rates were 70% after 1 month, 85% after 2 months, and 92% after 3 months of administration of Sai-boku-to (the Kampo group) and 74% after 1 month, 71% after 2 months, and 69% after 3 months of administration of the antianxiety drug with vitamin B complex (the control group). No significant side effect was noted in the Kampo group, but sleepiness was recorded in 33 cases in the control group. CONCLUSIONS: The results indicate that Sai-boku-to may be a clinically useful medicine for the long-term treatment of patients with glossodynia.

Adult↗
PubMed1998

A case of pathophysiologic study in Kimura's disease: measurement of cytokines and surface analysis of eosinophils.

BACKGROUND: Kimura's disease is a rare but distinctive eosinophilic inflammatory disorder of unknown etiology; few reported case studies have focused on the immunopathologic background of this unique disease. OBJECTIVE: To define better the immunopathogenetic features of Kimura's disease, we attempted to quantitatively analyze values of cytokines and soluble interleukin-2 receptor (sIL-2R) in peripheral blood (PB), as well as perform surface immunophenotypic analysis of eosinophils from a Japanese patient with chronic relapsing Kimura's disease. RESULTS: Granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and sIL-2R were elevated, and newly expressed antigens on eosinophils CD4, CD25, and HLA-DR were found to be involved in the pathophysiology of this disorder. CONCLUSIONS: Kimura's disease may be a disease in which activated lymphocytes release cytokines, and these released cytokines, such as GM-CSF and TNF-alpha cause eosinophil activation. These processes may be related to the pathogenesis of this disorder.

Aged↗
PubMed1998

Changes in serum insulin-like growth factor binding protein-2, -3, and -6 levels in patients with chronic renal failure following renal transplantation.

The pathophysiological roles of insulin-like growth factor binding protein (IGFBP)-6 have not been elucidated. Recently, we measured serum IGFBP-6 by Western immunoblot (WIB) and have found that serum IGFBP-6 levels increased in patients with chronic renal failure (CRF). In the present study, serum IGFBP-6 levels were measured in 10 patients with CRF before and 1, 7 and 14 days after renal transplantation to investigate further clinical significance and regulation of serum IGFBP-6. IGFBP-2 and -3 levels, usually elevated in patients with CRF, were also measured after renal transplantation. Serum IGFBP-2 and -6 levels from patients with CRF by Western immunoblot increased to 230+/-90% (mean +/- SD), and 400+/-110% of the reference serum, respectively, and these levels did not change after hemodialysis. Serum IGFBP-6 levels decreased to 47+/-20% of the basal level 1 day after renal transplantation, and the IGFBP-6 levels in two patients whose renal function worsened again due to rejection increased to more than 60% of the basal levels on the 14th day. In contrast to IGFBP-6, serum IGFBP-2 levels did not decrease during the 14 days after renal transplantation in all patients. Serum IGFBP-3 levels were significantly higher in CRF than normal sera (5.5+/-1.2 vs 3.7+/-0.5 microg/ml, P < 0.01), and the levels decreased to the normal range (2.7+/-1.0 microg/ml) within 1 day after the transplantation, whereas the levels increased again in one of two patients with poorly-functioning graft. In addition, we demonstrated IGFBP-6 in urine from normal adults. These results indicate that IGFBP-6 might be excreted by the kidneys and serum IGFBP-3 and -6 levels might be related with renal function, and that the regulation of serum IGFBP-2 levels differs from those of IGFBP-3 and -6.

Adult↗