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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 289 records · Page 16Linked to original sources
PubMed2001

Tissue-engineered pancreatic islets: culturing rat islets in the chitosan sponge.

Subcutaneous islet transplantation has become an attractive modality. With development of tissue-engineering techniques, it is possible to rectify the disadvantage of poor blood supply in the subcutaneous site by reconstruction of the capillary network. According to reports, the Chitosan sponge (CS) could be used for reconstruction of in vitro capillary-like network and could be used in artificial skin equivalent. In this study, we cultured the islets in CS for future application. CSs, having 200-500 microm pore size, were prepared by freeze-drying method. Rat islets were isolated from the pancreas of Lewis rats (10 weeks old, 280-300 g, male) by collagenase digestion followed by discontinuous dextran gradient centrifugation method. Each 20 islets were seeded equally into the CSs and were cultured for 62 days with various culture media such as RPMI-1640, Dulbecco's modified Eagle's medium (DMEM), and Eagle's MEM. They contained 10% fetal bovine serum (FBS) and 5 ml/L antibiotic-antimycotic mixed stock solution in the culture dishes. Insulin concentration both inside and outside of the islet-seeded CS was measured during culture. Changes in the morphology of islets were also observed in this study. Freshly isolated islets had a loose appearance with an irregular border, and most were seen as a single islet. Occasionally a cluster, consisting of 2-4 islets ranging mainly from 150 to 250 microm in diameter, was observed. Islets cultured in the CSs in different culture media retained initial morphology, which had well-delineated smooth borders for at least 53 days. The insulin release behavior of islets cultured in the CS showed constant secretory capacities for 49 days. After that they exhibited a rapid and definitive decline from the initial insulin release. Until this stage, insulin concentration in the CS was well maintained. The properties were dependent on culture medium used and insulin diffusion released from islets. This experiment is a new study model for establishment of islet culture in a three-dimensional matrix. Also extension of this observation will provide new insights for islet transplantation at the subcutaneous site by a tissue-engineering approach.

Animals↗
PubMed2001

Treatment with low-dose interferon-alpha restores the balance between matrix metalloproteinase-9 and E-cadherin expression in human transitional cell carcinoma of the bladder.

Tumor invasion and metastasis are regulated by the expression of genes such as E-cadherin, which regulates cell adhesion, and matrix metalloproteinase-9 (MMP-9), which alters the integrity of the extracellular matrix. Both up-regulation of MMP-9 and down-regulation of E-cadherin correlate with bladder cancer metastasis. The purpose of this study was first to determine whether an imbalance between MMP-9 and E-cadherin expression correlates with metastasis from human transitional cell carcinoma (TCC) of the bladder after therapy with neoadjuvant chemotherapy and radical cystectomy and then to determine whether treatment of human TCC xenografts growing in nude mice with interferon (IFN)-alpha would restore this balance, thereby limiting tumor invasion and metastasis. We used in situ hybridization to evaluate the expression of several metastasis-related genes, including MMP-9 and E-cadherin, in paraffin-embedded biopsy specimens from 55 patients with muscle-invasive TCC treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy and radical cystectomy. By multivariate analysis, an MMP-9:E-cadherin ratio of >1.8 was an independent prognostic factor for disease progression. In vitro incubation of an IFN-resistant, highly metastatic human TCC cell line, 253J B-V(R) with noncytostatic concentrations of IFN-alpha down-regulated the activity of MMP-9, up-regulated E-cadherin, and inhibited in vitro invasion. 253J B-V(R) cells were implanted into the bladders of athymic nude mice. Systemic therapy with IFN-alpha (10,000 units s.c. daily) decreased the expression of MMP-9, increased expression of E-cadherin, reduced tumor volume, and inhibited metastasis. The MMP-9:E-cadherin ratio was 4.5 in untreated controls and 1.1 after IFN-alpha treatment. Moreover, systemic low-dose daily IFN-alpha potentiated the efficacy of paclitaxel. These studies indicate that in addition to its antiproliferative and antiangiogenic effects, IFN-alpha limits tumor invasion by restoring the normal balance between MMP-9 and E-cadherin and enhances the activity of systemic chemotherapy.

Adult↗
PubMed2001

[Overview of hepatitis C virus from its discovery to now].

Hepatitis C was first recognized as a form of viral hepatitis that was distinct from disease caused by hepatitis A virus and hepatitis B virus. The etiologic agent of hepatitis C was proposed to be a small, enveloped virus based on demonstrations of its transmissibility to chimpanzees, electron microscopic studies, and sensitive to chloroform. Successful molecular cloning of viral genome in the late 1980's led to the development of assay for serological diagnosis of HCV and it is currently estimated that at least 170 million people are chronically infected with the hepatitis C virus. HCV evades host antiviral defenses by mechanisms that remain to be identified and establishes a persistent infection in a majority of patients. Persistent infection of HCV is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Therefore development of antiviral treatment for HCV is an urgent worldwide health problem. Although much has been learned about HCV genome organization, polyprotein processing, protein function and structure, many key questions remain to be answered. Major efforts of Japanese investigators should now be directed at establishing cellular system and animal models appropriate for dissecting the various steps in HCV replication cycle and strategies for blocking them.

Animals↗
PubMed2001

Counterattack of re-emerging tuberculosis after 38 years.

The recent tuberculosis prevalence rates in Japan have been among the highest in industrialised countries. In 1997 the number of newly identified tuberculosis patients in Japan increased for the first time in 38 years. There are many underlying reasons for this resurgence, including public ignorance of the threat, epidemiological factors, insufficient medical countermeasures, and inadequate public health measures against tuberculosis. Improving the situation will require urgent scientific and political action.

Adolescent↗
PubMed2001

[Elderly-onset anticentromere antibody-positive pulmonary-renal syndrome: report of an autopsy case].

We report an autopsy case of elderly-onset anticentromere antibody-positive pulmonary-renal syndrome. An 84-year-old woman was admitted to our hospital with complaints of leg edema and general malaise. Neither skin rush nor arthritis was seen. Because of hematuria, proteinuria with various casts, renal dysfunction and anemia, a clinically diagnosis of rapidly progressive glomerulonephritis was made. Slight pulmonary hypertension was observed in ultrasonic cardiography. Hypocomplementemia was not seen. Tests for MPO- and PR 3-anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibody were negative, but a high titer of antinuclear antibody with a discrete speckled pattern on immunofluorescent staining was disclosed. Results for anticentromere antibody and anti-Ki antibody were positive, but for anti-Sm antibody and anti-double stranded DNA antibody were both negative. She did not present any clinical features of systemic sclerosis or CREST syndrome. Subsequently, prednisolone was administered, but pulmonary alveolar hemorrhage occurred and the patient died of acute respiratory failure caused by massive pulmonary hemorrhage. Autopsy revealed crescentic glomerulonephritis including glomerular capillaritis and pulmonary capillaritis with positive granular deposits of immunoglobulins and compliment on the glomerular and pulmonary capillary walls. Immunologically mediated crescentic glomerulonephritis and pulmonary capillaritis was then diagnosed histopathologically. The main pathological feature of the case was small-vessel vasculitis with immune-complex deposition. Although this case did not fulfill the clinical criteria for systemic lupus erythematosus (SLE), its histological features resembled those of lupus nephritis and acute lupus pneumonitis. We speculated that anticentromere antibody-positive pulmonary-renal syndrome without any other symptoms or signs of connective tissue disease, such as our case, is a clinical entity distinct from typical SLE or CREST syndrome.

Aged↗
PubMed2001

[Intermittent androgen deprivation treatment of prostate cancer restarted at low level of serum prostate specific antigen: a pilot study].

We report a pilot study on a novel protocol of intermittent androgen deprivation (IAD) treatment of prostate cancer (PC), in which androgen deprivation is restarted when serum prostatic specific antigen (PSA) level reached more than 2 ng/ml and is stopped when PSA level decreased below 0.3 ng/ml. Thirty-two patients (aged 60 to 86 years, median 74 years) with prostate cancer (Stage A in 4 patients, B in 20, C in 1, D in 5, and relapse after radical prostatectomy in 2) were treated with IAD. Median serum PSA prior to the start of endocrine therapy was 15.65 (range 2.67 to 306.3) ng/ml. Eleven patients were treated with lutenizing-hormone-releasing hormone (LHRH) agonist alone and 21 were treated with LHRH agonist plus an antiandrogen. Median duration of first endocrine therapy was 572 (range 100 to 1,543) days. Median serum PSA at the start of first off-phase was 0.038 (range 0.003 to 0.489) ng/ml. After a median of 207 days (range 140 to 843) of follow-up, 19 patients were in the first cycle, 9 in the second cycle, 3 in the third cycle, 1 in the fourth cycle. Two patients developed androgen-independent PC. The median duration of first off-phase of IAD was 287 days. There was a significant inverse relation between the duration of the first on-phase and testosterone level measured 4 months after the cessation of first on-phase therapy (R = -0.518). These results suggest that our protocol provides a reasonable length of off-phase duration and that the long term-androgen deprivation phase might delay the recovery of the testicular endocrine function which should be maintained during the off-phase of IAD.

Aged↗
PubMed2001

[Current condition of early peripheral lung cancer and related problems].

Early peripheral lung cancer is defined as a tumor whose diameter is within 20 mm and that has not metastasized to lymph nodes. We developed thoracoscopic surgery (two windows method) in 1993. We have been conducting this thoracoscopic surgery in early peripheral lung cancers to identify possible indications as well as to clarify problems related to early peripheral lung cancer. The subjects of this study were 176 tumors, with diameters within 30 mm, including 97 lung cancers with diameters within 20 mm. Of the 97 tumors 20 mm or less in diameter, 18 were N 1 or more severe (N 1, 8 cases: N 2, 10 cases). One patient (N 2) died of bone metastasis and two patients died due to diseases other than lung cancer. Nearly 20% of the patients with tumors 20 mm or less were in the advanced stage, suggesting that mediastinal lymph node resection is necessary. Based on these results, it is advisable to define tumors with a diameter of no more than 10 mm as early peripheral lung cancer.

Adenocarcinoma↗
PubMed2001

[A case of cholinergic urticaria with epileptic seizure and abnormalities on electroencephalogram].

We report a 10-year-old boy with cholinergic urticaria associated with epileptic seizure and abnormalities on electroencephalogram. In March 1999, many red wheals developed over the entire body during exercise and at increased body temperature. In April, systemic red wheals developed during exercise. Simultaneously, loss of consciousness was noted for 2 to 3 minutes. After the patient's body was cooled, consciousness improved, and these exanthemas disappeared. In the Department of Dermatology, his illness was diagnosed as cholinergic urticaria. Neurologically, a heat tolerance and mental strain induced cholinergic urticaria, followed by generalized epilepsy(clonic seizure). In addition, electroencephalography revealed high voltage polyspikes and 14 Hz positive spikes. The mechanism involved in cholinergic urticaria associated with epileptic seizure was assumed as follows: sweat-promoting stimuli, such as heat, exercise and tension, stimulate the autonomic center in the diencephalon or brain stem, and excitation in the autonomic center is transmitted to the efferent sympathetic nerve, causing cholinergic urticaria; when the intensity of stimulation is high, the autonomic center exhibits abnormal activities and causes epileptic seizure.

Autonomic Nervous System↗
PubMed2001

[The usefulness of autologous blood transfusion for urologic surgery].

To avoid potential risks associated with homologous blood transfusion including viral infection and graft versus host disease (GVHD), autologous blood donations have been promoted in urologic surgery. We assessed its necessity in the patients undergoing radical retropubic prostatectomy and total cystectomy. A total of 27 patients ranging from 54 to 78 years old donated 400 to 1,200 ml of blood prior to radical prostatectomy (17 patients) and total cystectomy (10 patients). Recombinant erythropoietin was administered in 26 out of 27 patients. The mean hemoglobin concentration was 14.1 g/dl before donation and 12.8 g/dl before operation. The mean volume of surgical blood loss was 1,659 ml ranging from 529 to 2,990 ml in total cystectomy, and 1,438 ml ranging from 553 to 2,841 ml in radical prostatectomy. Overall, 22 out of 27 patients (82%) did not require an additional homologous blood transfusion. In conclusion, autologous blood donation is a safe and useful method to avoid homologous transfusion in radical prostatectomy and total cystectomy. Eight hundred ml of blood donation is suggested to be appropriate prior to these surgeries.

Aged↗
PubMed2001

[Early phase II clinical trial of amrubicin hydrochloride in patients with malignant lymphoma].

An early phase II multi-center collaborative study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, was conducted for malignant lymphoma at 12 institutions nationwide. A total of 41 patients were enrolled in this study between January 1988 and October 1990. Of these, 36 patients, six patients with Hodgkin's disease (HD) and 30 patients with non-Hodgkin's lymphoma (NHL), were eligible for the study. The starting dose of amrubicin hydrochloride was 100 mg/m2 (body surface area) and it was administered once every three weeks, in principle. The efficacy was assessed for 34 patients, excluding two patients: one who has not been followed up adequately and the other violated the dosing schedule (once per week). The overall response rates (CR + PR) were 50.0% (3/6) for HD and 42.9% (12/28) for NHL. Furthermore, a relatively high response rate was noted in 8 (36.4%) of 22 NHL patients who had been treated with other anthracycline derivatives prior to the trial. The safety of amrubicin hydrochloride was assessed for 36 eligible patients. Leukopenia (grade 3 or higher) and thrombocytopenia were noted in 21 patients (58.3%) and 10 patients (27.8%), respectively. Anorexia, nausea/vomiting, fever, alopecia, decrease in hemoglobin and elevations of GOT and GPT levels were observed with a relatively high frequency. Other than myelosuppression, the following adverse reactions (grade 3 or higher) occurred during the course of the trial: diarrhea (two patients), alopecia (two patients), stomatitis (one patient), anorexia (one patient), nausea/vomiting (one patient) and fever (one patient). In conclusion, these results indicate that amrubicin hydrochloride is effective in the treatment of patients with malignant lymphoma.

Aged↗
PubMed2001

Fertilization without spermatozoa.

Mammalian spermatozoa first acquire the ability to fertilize oocytes as they pass through the epididymis to mature. Due to recent advances in microinsemination techniques, not only mature spermatozoa, but also immature sperm cells at certain stages in the testis, have been used to construct diploid zygotes, some of which subsequently develop to normal offspring. Using round spermatids, the most youngest haploid male germ cells, normal births have been reported in the mouse, rabbit, and human. Furthermore, in the mouse, secondary and primary spermatocytes also support full term development after incorporation into immature or mature homologous oocytes. Spermatogenic cells of several species can be cryopreserved easily in simple cryoprotectant solutions. Thus, the microinsemination techniques using spermatogenic cells give us a way to treat infertility, and provide valuable information on gametogenesis, including spermatogenesis, meiosis, and genomic imprinting.

Animals↗
PubMed2001

[Extracorporeal shock wave lithotripsy for upper urinary tract stones using piezoelectric shock wave lithotripsy].

Between August 1999 and July 2000, 123 cases of renal stones and 52 cases of ureteral stones in 116 males and 59 females were treated with the New Piezolith 2500. The average number of sessions required for renal and ureteral stones was 2.50 and 1.48, respectively. At 3 months postoperatively, stone-free rates for renal and ureteral stones were 64.2% and 72.7%, respectively. Assessing residual stones less than 4 mm in diameter as an effective treatment outcome, the efficacy rates for renal and ureteral stones were 94.3% and 86.4%, respectively. Side effects were encountered in 5 cases (2.9%) of high fever and one case (0.57%) of renal subcapsular hematoma. New Piezolith 2500 is effective and safe for the treatment of upper urinary stones.

Adult↗
PubMed2001

Inhibitory effect of T-614 on tumor necrosis factor-alpha induced cytokine production and nuclear factor-kappaB activation in cultured human synovial cells.

OBJECTIVE: To investigate the mechanism of the immunosuppressive effect of T-614 [N-(3-formylamino-4-oxo-6-phenoxy-4H-chromen-7-yl)methanesulfonamide], a new antirheumatic drug whose clinical efficacy has been determined for the treatment of patients with rheumatoid arthritis (RA). METHODS: RA synovial fibroblast-like cells were cultured with tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml) in the presence or absence of T-614. After incubation, cytokine production was measured by ELISA. Expression of interleukin 6 (IL-6) and IL-8 mRNA was examined by real-time quantitative reverse transcriptase-polymerase chain reaction analysis and TNF-alpha induced nuclear factor-kappaB (NF-kappaB) activation was observed using immunostaining with an antibody against NF-kappaB p65. RESULTS: T-614 suppressed TNF-alpha induced production of IL-6, IL-8, and monocyte chemoattractant protein 1, and also reduced the accumulation of IL-6 and IL-8 mRNA in a concentration dependent manner. T-614 interfered with the TNF-alpha induced translocation of NF-kappaB to the nucleus from the cytoplasm. CONCLUSION: Inhibition of NF-kappaB activation and transcription of proinflammatory cytokines by T-614 contributes to its clinical antirheumatic effect.

Antirheumatic Agents↗
PubMed2001

[Relation between autonomic dysfunction and progression of Parkinson's disease].

It has been claimed that cardiovascular dysfunction in patients with Parkinson's disease is less severe than multiple system atrophy. Autonomic dysfunction, however, increases with progression of Parkinson's disease. We studied the relation between autonomic dysfunction and disease severity by cardiovascular function testing with the Valsalva maneuver. The study group comprised 20 healthy controls (age, 52.7 +/- 13.6 years) and 31 patients with Parkinson's disease (59.0 +/- 7.2 years), including 13 who were previously untreated (55.0 +/- 6.2 years) and 18 who were receiving levodopa (61.8 +/- 7.1 years). The Valsalva maneuver was done having the subject exhale into a mouthpiece with an expiratory pressure of 40 mmHg for 15 seconds. Blood pressure and RR interval were measured during the Valsalva maneuver by tonometry, using a non-invasive blood pressure monitoring system (ANS 508, Nihon Colin Co., Ltd). Baroreceptor reflex sensitivities (BRS) of the second phase (BRS II) and fourth phase (BRS IV) of the Valsalva maneuver were calculated, and blood pressure elevations during the late second phase (IIp) and fourth phase (IVp) were measured. BRS II, BRS IV, and IVp in the patients of Parkinson's disease were significantly lower than those of healthy controls. BRS II, BRS IV, and IIp, however, did not significantly differ between the previously untreated patients and healthy controls. IVp of the previously untreated patients was significant lower than that of healthy controls. BRS II and BRS IV of patients with Parkinson's disease who were receiving levodopa for less than 5 years were significantly lower than those of the healthy controls. BRS II, BRS IV, and IIp decreased as disease duration increased, while IVp was unrelated to disease duration. These results suggest that patients with early Parkinson's disease have cardiac sympathetic autonomic dysfunction with maintained baroreceptor reflex sensitivity. Reduced baroreceptor reflex sensitivity was associated with levodopa treatment in patients with Parkinson's disease. Baroreceptor reflex sensitivity decreased and vasomotor sympathetic autonomic dysfunction developed as duration of disease increased.

Adult↗
PubMed2001

[A study on contamination from Legionella spp. at a home for the elderly in Toyohashi City].

OBJECTIVE: Legionnaires disease has been attributed to Legionella spp. in the water distribution systems of buildings. However, recently cases due to contamination of thermal-bath water have been reported in Japan. In this investigation, we examined the supervision of baths and the presence of Legionella spp. in thermal-bath water of homes for the elderly in Toyohashi city. METHODS: The research was conducted through questionnaires on bathing facilities at 50 sites. Thermal baths were found to be installed at 14 of the sites. We then tested 22 samples from the 14 sites for Legionella spp. and other materials. RESULTS: From the genus Legionella, only Legionella pneumophila was detected, in 8 samples from 4 sites. Coliforms were also detected. Moreover, disinfectant was not detected in any of the Legionella positive samples of bath water. Legionella positive sites had, however, been replacing their water once a day. CONCLUSIONS: These findings indicate that the use of disinfectant and the proper supervision of bathing facilities are important in controlling Legionella spp. Legionnaires disease can be averted in homes for the elderly through appropriate measures.

Aged↗
PubMed2001

[A case with left mesial temporal lobe epilepsy characterized by abnormal massive salivation].

A 26-year-old woman was admitted because of a 12-year history of intractable epileptic seizures. Every seizure began with an upper abdominal discomfort, and often followed by massive salivation. Whenever the epileptic salivation happened, the patient lost consciousness, and sometimes she developed generalized convulsions. In terictal sphenoidal EEG recordings revealed abnormal discharges in the left mesial temporal region. MRI demonstrated left hippocampal atrophy. Since her seizures were medically intractable, left temporal lobectomy was performed. Neuropathologic examination revealed hippocampal sclerosis. After the operation, she became completely seizure-free with no episode of massive salivation. From the literature, epileptic salivation can originates from the rolandic area; fronto-orbital cortex & cingulate gyrus; insula & operculum; and mesial temporal structures. The abnormal massive salivation in our patient might be attributable to the activation of frontal limbic system triggered by hippocampal abnormal firing during the ictal period of TLE.

Adult↗