Search PubMed⌕ Search

Biomedical subjects

N Ishikawa

Publications and source records attributed to N Ishikawa.

At least 163 records · Page 9Linked to original sources
PubMed1999

Molecular epidemiological study of Haemophilus influenzae serotype b strains obtained from children with meningitis in Japan.

We report an epidemiological study of 30 Haemophilus influenzae serotype b (Hib) strains derived from the cerebrospinal fluid of children with meningitis. The Hib strains were biotyped, tested for beta-lactamase production, and genotyped by long PCR-ribotyping, random amplified polymorphic DNA (RAPD) analysis, and genomic DNA restriction fragment length polymorphism (RFLP) analysis by pulsed-field gel electrophoresis (PFGE). The phenotypic study characterized 22 of the strains (73%) as biotype I. A genotypic study using long PCR-ribotyping with HaeIII restriction digestion showed no polymorphisms among these 30 Hib strains, but RAPD analysis with two sets of primers demonstrated two distinctive subtypes: one typical of the strains of biotype group II and the second characteristic of the strains of biotype groups I and IV. Each RAPD group was subtyped into several genotypic groups by PFGE-RFLP with SmaI digestion. The genotyping of clinically isolated Hib strains may help to elucidate transmission routes in community infections, endemicity, and the reasons for vaccine failure.

Child, Preschool↗
PubMed1999

Thyrotropin regulates c-Jun N-terminal kinase (JNK) activity through two distinct signal pathways in human thyroid cells.

c-Jun N-terminal kinases (JNK) participate in cellular responses to mitogenic stimuli and environmental stresses. We investigated whether and how TSH, which promotes the proliferation and differentiation of thyroid cells, regulates JNK activity in primary cultured human thyroid cells. TSH stimulated JNK activity in cytosolic fractions of thyroid cells measured by in vitro kinase assay. A low concentration of TSH (10(-11) M) stimulated JNK activity but at a higher dose (10(-8)-10(-7) M), TSH suppressed JNK activity without any change of JNK protein level. Activation of JNK by TSH was also observed in CHO cells stably transfected with TSH receptor complementary DNA (cDNA), suggesting a ligand-receptor specific interaction. TSH stimulated JNK activity through a pertussis toxin-sensitive pathway. We next elucidated the signal transduction pathways in TSH-induced JNK activation by examining the involvement of four distinct intracellular signal molecules; protein kinase C (PKC), cAMP, Ca2+, and PI3-kinase. The stimulation of JNK by TSH was blocked by two PKC inhibitors and suppressed by 8-bromo-cAMP or forskolin. These findings demonstrate that TSH regulates JNK activity biphasically in human thyroid cells through an interaction between Gi-PKC and cAMP-PKA pathways.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

[Participation of neuropeptide Y Y3-receptor subtype in the increase in lung vascular permeability--for therapy of respiratory failure].

In order to find some treatments for respiratory failure caused by pulmonary edema, we investigated the mechanism of neurogenic pulmonary edema. Previously, stimulation of sympathetic nerves caused an increase in pulmonary vascular permeability, possibly due to neuropeptide Y. Neuropeptide Y injected into the trachea increased lung vascular permeability dose-dependently, the ED50 of which was 0.3-1 nM. Such an effect remained even after treatment with reserpine, as well as in the presence of alpha- and beta-blockers. And norepinephrine enhanced the effect of neuropeptide Y on lung vascular permeability. These responses were almost similar to those obtained by stimulation of sympathetic nerves. Furthermore, neuropeptide Y, in fibrin-induced pulmonary edema, was localized in alveolar macrophages and alveolar spaces, amounting to approximately 200 nM in edema fluid. The value was significantly greater than that obtained in hydrostatic pulmonary edema by 10-30 times. Peptide YY, an analogue of neuropeptide Y, had no action on lung vascular permeability, whereas the effect of neuropeptide Y was inhibited by pretreatment with neuropeptide Y- 13-36, an antagonist for Y3-recetor subtype. These results suggested that neuropeptide Y enhances the lung vascular permeability via Y3-recetor subtype. Neuropeptide Y- 13-36, in fibrin-induced pulmonary edema, decreased a ratio of protein concentration in edema fluid to that in serum, indicating that neuropeptide Y actually acts a role in the development of neurogenic pulmonary edema, via an increase in lung vascular permeability.

Adrenergic Uptake Inhibitors↗
PubMed1999

Ethanol injection therapy of the prostate for benign prostatic hyperplasia: preliminary report on application of a new technique.

PURPOSE: We evaluate the efficacy of a new technique of minimally invasive treatment for benign prostatic hyperplasia involving direct injection of dehydrated ethanol. MATERIALS AND METHODS: Dehydrated ethanol was injected transurethrally with lumbar or sacral and urethral anesthesia in 10 patients with prostatic hyperplasia. Endoscopic injection was performed at 4 to 8 sites in the prostate and 3.5 to 12.0 ml. ethanol were used. RESULTS: There were no intraoperative complications but postoperative urinary retention occurred transiently in all patients which required catheterization for a mean of 8.8 days. Mean symptom score plus or minus standard deviation was 12.2+/-5.8 at 3 months postoperatively, which was significantly improved from 23.1+/-7.0 preoperatively (p<0.01). Mean quality of life score also improved significantly from 5.1+/-0.6 preoperatively to 3.2+/-1.5 at 3 months postoperatively (p<0.01), mean peak urinary flow rate increased from 8.0+/-2.2 (9 patients) to 13.1+/-3.6 ml. per second (p<0.05) and mean residual urine volume decreased from 129.1+/-55.3 (9 patients) to 49.3+/-34.7 ml. (p<0.05). There was no significant change in prostate volume. Acute epididymitis and chronic prostatitis occurred in 1 patient each. CONCLUSIONS: This technique can be performed as an outpatient procedure and appears to be safe and cost-effective. Retrograde ejaculation can be avoided.

Aged↗
PubMed1999

[Current epidemiological trend of tuberculosis among foreigners in Japan].

In Japan, the proportion of foreign patients among the total tuberculosis patients is still very small, but their problems in tuberculosis case finding and treatment require intensive control activities as in other low prevalence countries with higher proportion of foreign-born cases. The latest national survey for the foreign tuberculosis patients conducted in 1996 shows the epidemiological status between 1990 and 1993. The number of foreign tuberculosis patients in 1993 was 484, consisting of 1.0% of the total new patients in Japan. The new case rate among foreigners was estimated to be 53 per 100,000 against 38 for whole Japan in 1993. Compared with the figure in the 1993 survey, the number of foreign patients declined from 585 in 1992 to 484 in 1993. However, the number of bacillary positive tuberculosis patients in 1992 was 230 and almost the same as in 1992. The decline or stagnation of total number of tuberculosis patients can be due either to the decrease in the foreign population inflow into Japan (real decline), or partially to the reduction of overdiagnosis in X ray examination and the possible loss of some cases in the 1996 survey method. A manual sorting method from the registration cards was used at each public health center, since there is no item of country of origin in the routine tuberculosis surveillance system, and some cards might have already been displaced by the time of the survey for patients who were excluded from the registry, either cured, died or defaulted. The average treatment completion rate (1991-93) among foreign patients was 51%, which was much lower than the national figure of 81% for the same years. Moreover the rate showed deteriorating trend by year. For more accurate information, the foreigner's data must be taken in the national tuberculosis surveillance system and control activities for foreigners need to be strengthened.

Adolescent↗
PubMed1999

[Serial cerebral computed tomography and magnetic resonance imaging in a case of hemolytic uremic syndrome with the complication of the central nervous system due to Escherichia coli O157:H7].

We report serial cerebral computed tomography (CT) and magnetic resonance imaging (MRI) in a case of hemolytic uremic syndrome (HUS) with the complication of the central nervous system due to Escherichia coli O157:H7. Although initial brain CT was normal, follow-up CT and MRI revealed lesions in the white matter and bilateral basal ganglia, representing brain edema and infarcts, respectively. Especially, lesions in the bilateral basal ganglia were very unique. Serial CT and MRI findings are useful to understand the mechanism of the complications of the central nervous system associated with HUS.

Brain↗
PubMed1999

Overexpression of nm23-H2/NDP kinase B in a human oral squamous cell carcinoma cell line results in reduced metastasis, differentiated phenotype in the metastatic site, and growth factor-independent proliferative activity in culture.

The metastasis suppressor activity of nm23/nucleoside diphosphate (NDP) kinase was assessed using human oral squamous cell carcinoma (SCC) cell lines. When the expression of nm23/NDP kinase was compared among several SCC cell lines, nm23-H2/NDP kinase B gene product, but not nm23-HI/NDP kinase A gene product, was reduced in the metastatic cells. Transfection of nm23-H2 into the metastatic SCC cell line LMF4 caused reduction in the lung metastasis in an experimental metastasis assay. A histological analysis of the pulmonary metastatic foci revealed that although foci of the control clones were composed of anaplastic squamous cells, those of the nm23-H2-transfected clones consisted of mostly well-differentiated cells mimicking normal stratified epithelial constitution. The transfected cells were morphologically indistinguishable from the control ones in culture, but they differed from each other in that the former cells proliferated faster than the latter, became less serum dependent, and lost responsiveness to growth factors such as platelet-derived growth factor, insulin-like growth factor I, and insulin, although both clones retained sensitivity to transferrin. These results demonstrate that nm23-H2 protein does have metastasis suppressor activity for human SCC cells and suggest that this activity may be elicited by modulating growth and/or differentiation potential in response to environmental factors.

Animals↗
PubMed1999

Clinical and histological analysis of acute tacrolimus (TAC) nephrotoxicity in renal allografts.

UNLABELLED: Tacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Acute nephrotoxicity due to TAC in kidney transplant patients is either similar to, or significantly more frequent than that of cyclosporin A (CsA). In this study we describe the clinico-morphologic characteristics of acute TAC nephrotoxicity in kidney transplant recipients. PATIENTS AND METHODS: We studied retrospectively the clinical courses of 67 patients who underwent kidney transplantation under TAC immunosuppression at Tokyo Women's Medical University between July 1990 and January 1997. We compared the recipient's characteristics with and without acute TAC nephrotoxicity. We also studied retrospectively the clinico-morphologic profiles of the acute TAC nephrotoxicity with 16 kidney transplant recipients under TAC immunosuppression, who were diagnosed with acute TAC nephrotoxicity by allograft biopsies between January 1996 and January 1997. RESULTS: There were no significant differences between acute TAC nephrotoxicity and non-nephrotoxicity groups about age, sex, donor source, age of donor, the proportion of ABO incompatible and the number of human leukocyte antigen (HLA) mismatches. Of 27 acute TAC nephrotoxicity recipients, 7 patients (26%) had moderate-to-severe grade arteriosclerosis in their allograft arteries. The onset of TAC nephrotoxicity occurred 8-69 days post-operatively. The baseline creatinine level was 1.92 mg/dL (range 0.4-5.1 mg/dL) and rose by 38.4% (range 0-84.6) during episodes of nephrotoxicity. The mean peak of the whole blood TAC trough level during the toxic episodes was 32.5 ng/mL (range 21.2-58.5 ng/mL). The rise in creatinine level preceded the highest TAC level in 10 cases. A mean reduction in TAC dosage of 18.9% (range 0-50% led to a fall of 17.2% (range 0-43%) in serum creatinine levels. The moderate-to-severe arteriosclerosis in allograft arteries was seen in 5 (31%) patients. CONCLUSION: The high trough level of the whole blood TAC and the existence of moderate-to-severe arteriosclerosis in allograft arteries have the potential of causing TAC nephrotoxicities. A reduction of TAC dosage may be effective in improving allograft functions.

Adult↗
PubMed1999

A case of bronchial squamous cell carcinoma in situ detected by sputum cytology.

A 64-year-old man underwent a medical checkup in May 1996 and was evaluated as class V using sputum cytology. Chest X-ray examination, bronchoscopy and chest computed tomography (CT) demonstrated no abnormalities. Thereafter, the patient was followed up with chest X-ray, bronchoscopy and chest CT at 3-month intervals. In December 1996, chest CT showed an increased density at the mediastinal side of the left upper bronchus, B1+2. There were no findings on bronchoscopy, but subsequent exfoliative cytology demonstrated keratinized malignant cells in samples obtained from left upper bronchus, B1+2. Although, it was difficult to identify localization of the tumor, left upper lobectomy was performed and the diagnosis of squamous cell carcinoma in situ was finally made. Here, we report on the course of this patient and discuss the diagnostic usefulness of sputum cytology as well as the pathogenesis of lung squamous cell carcinoma.

Bronchial Neoplasms↗
PubMed1998

Long-term renal function in on-heart-beating donor kidney transplantation: a single-center experience.

BACKGROUND: One of the most serious problems facing major transplant programs is the severe shortage of organs. Expansion of the donor pool to include nontraditional donors, such as non-heart-beating donors (NHBDs), would considerably expand the availability of organs. METHODS: Between 1983 and 1996, we performed a total of 125 non-heart-beating cadaveric renal transplantations under cyclosporine-based or tacrolimus-based immunosuppression. Thirty-nine recipients were females and 86 were males. Total ischemic time (TIT) and warm ischemic time (WIT) were an average of 761+/-347 min (322-2027 min) and 7.4+/-13.1 min (0-45 min), respectively. RESULTS: Of the 125 transplanted kidneys from NHBDs, 98 (78.4%) developed delayed graft function (DGF), which lasted a mean of 16+/-21 days (range 3-37 days). One hundred and eight patients (86.4%) were off dialysis by the time of discharge. Of the 125 grafts, 11 (8.8%) were primary nonfunction. The average of the nadir of serum creatinine levels, which was evaluated using 108 patients who were off dialysis by the time of discharge, was 1.4+/-0.5 mg/dl. The lowest creatinine levels (nadir) were under 2.0 mg/dl in 98 (78.4%) of the 125 patients. Acute rejection occurred in 64 (51.2%) of the 125 recipients. Patient survival rates were 90% at 5 years and 88% at 10 years. Graft survival rates were 65% at 5 years and 46% at 10 years. We tried to find the risk factors that affected graft survival. We examined the various possible risk factors, including harvesting condition (controlled versus uncontrolled), HLA-AB mismatches, HLA-DR mismatches, graft weight, donor age and sex, recipient age and sex, posttransplant DGF, acute rejection, WIT, and TIT. However, no significant risk factor was identified except acute rejection. We tried to discover the risk factors that caused primary nonfunction. Possible risk factors, including donor age, TIT, WIT, graft weight, and harvesting condition were compared, but no significant risk factor was identified. Long-term renal function was evaluated by serum creatinine levels. Serum creatinine levels at 1, 5, and 10 years were 1.76+/-0.7 mg/dl, 1.7+/-0.96 mg/dl, and 1.53-/+0.6 mg/dl, respectively. CONCLUSIONS: In conclusion, our data demonstrated that the procurement of kidneys from NHBDs leads to acceptable long-term graft survival and renal function, despite a high incidence of DGF.

Adult↗
PubMed1998

Escherichia coli MutY protein has a guanine-DNA glycosylase that acts on 7,8-dihydro-8-oxoguanine:guanine mispair to prevent spontaneous G:C-->C:G transversions.

Low rates of spontaneous G:C-->C:G transversions would be achieved not only by the correction of base mismatches during DNA replication but also by the prevention and removal of oxidative base damage in DNA. Escherichia coli must have several pathways to repair such mismatches and DNA modifications. In this study, we attempted to identify mutator loci leading to G:C-->C:G transversions in E.coli. The strain CC103 carrying a specific mutation in lacZ was mutagenized by random miniTn 10 insertion mutagenesis. In this strain, only the G:C-->C:G change can revert the glutamic acid at codon 461, which is essential for sufficient beta-galactosidase activity to allow growth on lactose. Mutator strains were detected as colonies with significantly increased rates of papillae formation on glucose minimal plates containing P-Gal and X-Gal. We screened approximately 40 000 colonies and selected several mutator strains. The strain GC39 showed the highest mutation rate to Lac+. The gene responsible for the mutator phenotypes, mut39 , was mapped at around 67 min on the E.coli chromosome. The sequencing of the miniTn 10 -flanking DNA region revealed that the mut39 was identical to the mutY gene of E.coli. The plasmid carrying the mutY + gene reduced spontaneous G:C-->T:A and G:C-->C:G mutations in both mutY and mut39 strains. Purified MutY protein bound to the oligonucleotides containing 7,8-dihydro-8-oxo-guanine (8-oxoG):G and 8-oxoG:A. Furthermore, we found that the MutY protein had a DNA glycosylase activity which removes unmodified guanine from the 8-oxoG:G mispair. These results demonstrate that the MutY protein prevents the generation of G:C-->C:G transversions by removing guanine from the 8-oxoG:G mispair in E.coli.

Base Pair Mismatch↗
PubMed1998

Ionizing radiation activates c-Jun NH2-terminal kinase (JNK/SAPK) via a PKC-dependent pathway in human thyroid cells.

Thyroid gland is known to be higher sensitive to carcinogenic effects of external ionizing radiation (IR) than other tissues. To clarify the cell-specific response following irradiation, activations of c-Jun NH2-terminal kinases (JNKs), which is one of mitogen-activated protein kinases (MAPKs) family members, and extracellular signal-regulated kinase (ERK) were examined in primary cultured human thyroid cells in comparison with human diploid fibroblast cells, WI-38. Although UV exposure strikingly induced JNK activity in both cells, the dose-response increase following IR exposure was observed in thyroid cells with the maximal JNK activity (3.5 fold induction) obtained at 10 Gy exposure, but no increase in WI-38 cells. The JNK activity was reached a maximum of 2.2 fold induction at 30 min after 5 Gy exposure and then sustained for at least 12 hr. On the other hand, ERK activity was not stimulated in thyroid cells following irradiation. The effects of 12-O-tetradecanoylphorbol beta-acetate (TPA) mimicked those of radiation on JNK cascade and 1-(5-isoquinolinesulphonyl)-2,5-dimethylpiperazine 2HCl (H7) and pretreatment with TPA blocked JNK activation following irradiation. Our results demonstrate that IR stimulates JNK activity in cultured human thyroid cells but not in fibroblasts indicating distinct activation and regulation mechanisms of JNK cascade. The JNK activation following IR exposure is mediated at least partially through a PKC-dependent pathway.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Long-term results of ABO-incompatible living kidney transplantation: a single-center experience.

BACKGROUND: Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT. METHODS: Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases. RESULTS: Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa

ABO Blood-Group System↗
PubMed1998

Development of a non-invasive treatment system for urinary incontinence using a functional continuous magnetic stimulator (FCMS).

A system composed of a functional continuous magnetic stimulator (FCMS) and a saddle-type coil has been developed for non-invasive treatment of urinary incontinence, especially stress incontinence and urge incontinence. The FCMS conditions were as follows: 2 kW maximum electrical power consumption, 800 V maximum capacitor voltage, 720 microseconds pulsewidth (180 microseconds rise time), and 5-30 Hz frequency. A frequency between 5 and 10 Hz is used to treat urge incontinence and a frequency between 25 Hz and 30 Hz is used to treat stress incontinence. The coil (120 mm long, 90 mm wide and 50 mm thick) fits the most suitable region for this treatment, the region from the anus to the perineum. The coil is cooled to maintain a coil temperature between 20 and 25 degrees C so that it can be used efficiently and safely. In experiments with anaesthetised dogs, it was confirmed that the urethral pressure increased when the circumference of the perineum received continuous magnetic stimulation of 720 microseconds pulsewidth (180 microseconds rise time), 10 Hz frequency and about 520 V capacitor voltage. This result suggests that magnetic stimulation can be effective as a urinary incontinence therapy.

Animals↗