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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 505 records · Page 28Linked to original sources

Apoptosis of intestinal intraepithelial lymphocytes induced by exogenous and endogenous glucocorticoids.

To investigate the effect of glucocorticoids on apoptosis in intestinal intraepithelial lymphocytes (i-IEL), we examined the changes of i-IEL followed by in vivo treatment with dexamethasone. The fragmented DNA of i-IEL were significantly increased at 15 hr after dexamethasone treatment and, subsequently, the number of total i-IEL were decreased by day 4 after treatment. Although all subsets of i-IEL including CD8 alpha/alpha(+), CD8 alpha/beta(+), CD4+ and CD4+CD8+ i-IEL were decreased after dexamethasone treatment, CD8 alpha/alpha(+) i-IEL appeared to be relatively resistant to dexamethasone-induced apoptosis. Consistent with the in vivo findings, CD8 alpha/alpha(+) i-IEL exhibited less susceptibility to dexamethasone-induced cell death in vitro than other subsets. To investigate whether this process occurs under physiological conditions, we examined the kinetics of i-IEL after treatment with 15-hr water immersion stress. In mice subjected to water immersion stress, plasma glucocorticoids were remarkably elevated soon after the 15-hr stress. The increase in the fragmented DNA of i-IEL and subsequent decrease in the number of i-IEL were observed in the stressed mice in the same kinetics as seen in the dexamethasone-treated mice. Similar to dexamethasone-induced ell death, CD8 alpha/alpha(+) i-IEL appeared to be relatively resistant to stress-induced apoptosis compared with other i-IEL subsets. The expression level of Bcl-2 was significantly higher in CD8 alpha/alpha(+) i-IEL than in CD8 alpha/beta(+) i-IEL. Our results indicate that i-IEL are subjected to cell death via apoptosis by exogenous and endogenous glucocorticoids and that different sensitivity to steroid-induced apoptosis may exist among i-IEL subsets in relation to their Bcl-2 expression.

Animals↗

Retroviral introduction of the p16 gene into murine cell lines to elicit marked antiproliferative effects.

The p16 gene is a candidate tumor suppressor, because mutation of the gene has been reported in many transformed cell lines and some primary tumor tissues. We have examined this possibility in murine cell lines (NIH3T3 and RSV-M) which lack p16 gene expression. Full-length human p16 cDNA was obtained from a HeLa cell line using polymerase chain reaction amplification. We constructed two separate retrovirus vectors carrying this p16 cDNA. First, we transduced the p16 cDNA into the murine cell lines using a retrovirus vector harboring the neomycin-resistance gene. The p16 gene-transduced cells formed no colonies after selection with G418, in contrast to the vector-transduced cells. Next, we used another retrovirus vector that expresses both the p16 cDNA and the Lac Z gene, which enabled us to distinguish affected cells from unaffected ones. Proliferation of the p16 gene-transduced cells was markedly inhibited and morphological change in the cells was also observed. Thus, we concluded that the p16 gene has an antiproliferative effect on the cell cycle and that the loss of its function may play a major role in dysregulated proliferation of the cells.

3T3 Cells↗

Large cell carcinoma of the lung metastatic to nuchal muscle.

Clinically apparent hematogenous skeletal muscle metastases from lung cancer are extremely rare. We present a 72-year-old man with a large cell lung carcinoma metastatic to nuchal muscle. Cervical computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a well-defined mass in the left splenius capitis muscle. A percutaneous needle biopsy was performed to establish a diagnosis. Localized skeletal muscle swelling may rarely prove to be metastases in patients with lung cancer, but should be investigated in the case of muscle swelling.

Aged↗

[Usefulness of 7 day therapy with cefluprenam in the management of respiratory tract infections].

Efficacy and safety of a newer injectable cephalosporin, cefluprenam (CFLP) on cases with bacterial pneumonia and chronic respiratory tract infections were evaluated at a dose of 1g (potency), d.i.d for 7 days. 1. Of 130 cases in total, 116 cases were enrolled for the clinical efficacy evaluation. The efficacy rate (excellent and good responses) was 94.8% (110/116). The efficacy rate was 93.8% (60/64) for cases with bacterial pneumonia, and 96.2% (50/52) for cases with chronic respiratory tract infections. The recurrence was noted in 1.2% (1/82). The bacteriological response rate was 100.0% (32/32) for gram positive cocci, 93.8% (15/16) for gram negative rods and 97.9% (47/48) in total. 2. Adverse drug reactions were noted in 3.9% (5/129), consisting of 2 cases with skin rash, 1 case with drug fever, 1 case with skin rash and skin itching and 1 case with drug fever and headache. The abnormal laboratory changes were noted in 23.6% (30/127), mainly containing the elevation in GPT and GOT, and eosinophylia. The safety rate (no problem evaluation) was 74.8% (95/127). 3. The usefulness rate (very useful and useful evaluations) was 93.1% (108/116). As suggested by the evaluation on the secondary endpoint in the phase III comparative studies with both bacterial pneumonia and chronic respiratory tract infections, it was confirmed that the 7 day therapy of CFLP was promising for treatment of moderate bacterial pneumonia and chronic respiratory tract infections, because the high clinical efficacy was obtained and also the incidence of allergic reactions with CFLP was almost the same as that of ceftazidime (CAZ) evaluated highly safe. Based on these results, it was concluded that CFLP was useful in the management of moderate respiratory tract infections and also the recommended therapeutic period with CFLP was within 7 days.

Adult↗

[A clinical study of skin flora in patients with MRSA colonization after introduction of preventive measures of hospital infection in a geriatric ward].

In early 1980's methicillin-resistant Staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in the geriatric hospital MRSA infection was prevalent. To decrease nosocomial infections some active preventive measures against hospital infection were taken since Oct. 1991. After introduction of preventive measures of hospital infection in the geriatric ward (190 beds) nosocomial bacteremia and pneumonia were markedly decreased in comparison of episode number before introduction of prevention. However several patients with MRSA colonization were observed every month. The aim of this clinical study was to clear how frequent MRSA was isolated from skin. Consequently 3 strains (3.4%) of MRSA were observed in 86 cultured skin. In conclusion we considered frequency of MRSA colonization frequency of MRSA colonization on skin was not so high but rather very low under the preventive measures.

Aged↗

Fis is required for illegitimate recombination during formation of lambda bio transducing phage.

Specialized transducing particles of phage lambda are formed by illegitimate recombination during prophage induction. We examined the effects of an Esherichia coli int, xis, himA, himD, or fis mutation on illegitimate recombination during formation of lambda Spi- phage, a class of lambda bio transducing phage. This type of phage is distinguishable from the docL and docR particles, which contain one cohesive end and are formed by cutting of the cos site, by plaque formation of lambda bio on Escherichia coli P2 lysogens. The yields of lambda Spi- phage in the int, xis, int-xis deletion, and b2 deletion mutants were about 50- to 200-fold higher than that of the wild-type prophage when bacteria were irradiated with UV light. This result indicates that Int and Xis functions, and the att site, are not required for illegitimate recombination. The yield of lambda Spi- phage in the himA, himD, or fis mutant carrying lambda delta int-xis prophage was 2.6-, 3.3-, or 17-fold lower, respectively, than that in the wild-type bacteria under UV irradiation. Analysis of the nucleotide sequences of the junctions of the transducing phages indicates that recombination at the hotspots, as well as at non-hotspots, takes place between short homologous sequences. Because the growth of infecting phages was not suppressed by the himA, himD, or fis mutation, we conclude that Fis is required, but IHF is only partially required, for short-homology-dependent illegitimate recombination during the formation of lambda bio transducing phage.

Bacterial Proteins↗

Sinus pericranii: neuroradiologic findings and clinical management.

We report an 11-year-old boy with a sinus pericranii. Magnetic resonance images demonstrated a small hole in the cranium underneath the subcutaneous mass. Magnetic resonance angiography (MRA) with sequential two-dimensional time-of-flight (2D-TOF) method demonstrated that the venous flow via the sinus pericranii was directed from the intra- to the extracranial venous system (the drainer type). This was confirmed by a combination of conventional cerebral angiography and percutaneous sinography. We advocate that both the correct diagnosis and classification of sinus pericranii can be established with a combination of current noninvasive neuroradiologic studies, especially for the pediatric age group. MRA with the 2D-TOF method is useful in the assessment of this venous anomaly.

Cerebral Veins↗

Capsaicin-sensitive A delta fibers in cat tooth pulp.

How close a correlation there is between the conduction velocity and receptive properties of pulpal nerve fibers is still unclear. Our specific aims were to confirm whether: (1) capsaicin affects not only polymodal C fibers but A delta fibers as well, and (2) A alpha polymodal nociceptors exist in the tooth pulp. A total of 139 functional single cat tooth pulp nerve fibers was isolated for analysis, of which 21 were A beta, 37 C, and 81 A delta fibers. The A delta fibers were divided into two groups: One (n = 38) consisted of those fibers whose conduction velocities were more than 2.0 m/s both inside and outside the tooth pulp, and the other (n = 43) consisted of those fibers whose intrapulpal conduction velocities were less than 2.0 m/s, with extrapulpal conduction velocities greater than 2.0 m/s. We used 82 fibers to record the neural response following the topical application of capsaicin for 60 min at increasing concentrations (1 nM, 100 nM, 10 muM) through thin dentin. Six of 25 slow A delta, 10/20 C, and no A beta (0/11) or fast A delta (0/26) fibers responded to 1 nM or 100 nM of capsaicin. When the three concentrations of capsaicin solution were applied in turn, the electrical threshold and latency of A beta and fast A delta fibers did not change, whereas those of slow A delta and C fibers gradually increased. In 0/11 A beta, 0/26 fast A delta, 13/25 slow A delta, and 18/20 C fibers, the conduction was blocked reversibly or irreversibly following the application of 10 muM of capsaicin. The amplitude of the late component of antidromic action potential of fast A delta fibers decreased after the capsaicin application. No neural discharge could be recorded from 19 (3 A beta, 5 fast A delta, 6 slow A delta, and 5C) fibers following the application of a single high concentration of capsaicin (10 muM). A single low concentration of capsaicin (100 nM) activated only some slow-conducting fibers (0/4 A beta, 0/4 FA delta, 3/6 SA delta and 4/6 C). Response properties recorded from the remaining 18 fibers (3 A beta, 3 fast A delta, 6 slow A delta, and 6 C) were not changed following the application of the control vehicle. These results confirm that a low concentration of capsaicin has an excitatory effect on the response of slow pulpal A delta as well as C fibers, and that a high concentration of capsaicin blocks the conduction of slow A delta and C fibers as well as the terminals of fast A delta fibers in the pulp.

Animals↗

Effect of an insulin sensitizer, pioglitazone, on hypertension in fructose-drinking rats.

To determine whether insulin resistance is responsible for the development of hypertension, we examined whether blood pressure changes in an insulin-resistant animal that was given a fructose solution as their drinking water. Wistar Kyoto rats that drank a 10% fructose solution for 10 weeks showed significant increases not only in plasma triglyceride and insulin levels but also in systolic blood pressure. The decrease in blood glucose in response to the intraperitoneal injection of insulin (0.2-1.0 U/kg) was slight in these fructose-drinking rats. To confirm whether insulin resistance contributes to the observed hypertension, we examined the effect of pioglitazone, an insulin sensitizer, on blood pressure in rats given a 10% fructose solution. When pioglitazone was administered to the rats at a dose of 10 mg/kg/day for 4 weeks from 12 weeks of age, plasma triglyceride and insulin levels and systolic blood pressure decreased, and blood glucose reduction in response to insulin was normalized. These results suggest that insulin resistance is responsible for the development of hypertension in fructose-drinking rats.

Animals↗

MRI findings in the liver in biliary atresia patients after the Kasai operation.

To evaluate liver function in biliary atresia (BA) patients after the Kasai operation, magnetic resonance imaging (MRI) was carried out 28 times in 19 BA patients. Sixteen of these were divided into three groups on the basis of the serum level of total bilirubin (t-bil), glutamic pyruvic transaminase (GPT) and gamma-glutamyltransferase (gamma-GTP) in the postoperative follow-up period (2-11 years). In group 1 (n = 7) the t-bil was continuously kept under 1 mg/100 ml. In group 2 (n = 4) the t-bil was continuously kept under 1 mg/100 ml, but GPT and gamma-GTP remained high (GPT > 100 IU/liter, gamma-GTP > 200 IU/ liter) for more than 2 years. In group 3 (n = 5) an increase in the t-bil level reappeared (1-2 mg/100 ml; n = 4, > 2 mg/100 ml; n = 1). The differences between MRI finding in the 3 groups, and the correlation between MRI findings and laboratory data (t-bil, cholinesterase; ChE, GPT and gamma-GTP), which were taken around the time of MRI examinations, were studied. The results were as follows: (1) All 19 patients had normal or high signal areas of various sizes on T1 weighted images (WI). (2) Eighteen of 19 patients had high signal areas of various sizes on T2 WI in the portal system areas and/or liver parenchyma, and these areas were enhanced by gadolinium-DTPA in about half of the patients. (3) Ten of 16 patients had atrophic change over one liver lobe. (4) MRI findings for group 1 and the other groups were significantly different, and MRI findings, except for atrophic change, were correlated with the increase or decrease in laboratory data taken around the time of MRI examinations (p < 0.05). These results indicate that a normal or high signal area on T1 WI shows functional tissue, and that a high signal area on T2 WI shows tissue damaged by inflammation and/or progressive fibrosis. MRI is useful for evaluating liver function, especially in terms of morphological features, in BA patients after the Kasai operation, and will be one method for establishing their prognosis.

Alanine Transaminase↗

[A 26-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in rats followed by a 9-week recovery test].

A 26-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in Sprague-Dawley rats. Male and female rats were given the drug orally for 26 weeks at doses of 0 (control), 5, 50 and 500 mg/kg. After discontinuation of the treatment, a 9-week recovery test was also conducted. Two cases of death occurred in the 500 mg/kg group. Mydriasis, salivation and lacrimation were seen in the 50 and 500 mg/kg groups. Alopecia, a suppression of body weight gain and an increase in water consumption were seen in the 500 mg/kg group. Food consumption measurement showed no abnormalities attributable to the treatment. Ophthalmologic examination confirmed mydriasis in the 50 and 500 mg/kg groups. Urinalysis showed an increase in urine volume in the 50 and 500 mg/kg groups, and an increase in urinary protein and decreases in Na+, K+ and Cl- excretions in the 500 mg/kg group. Hematological examination showed decreases in hemoglobin, hematocrit, MCV, MCH, MCHC and lymphocytes in the 500 mg/kg group. Blood chemical examination showed increases in total cholesterol, phospholipid and total protein and decreases in glucose, triglyceride, free T3 and T4 in the 500 mg/kg group. Measurements of liver drug-metabolizing enzymes showed an increase in T4UDP-GT activity in the 50 and 500 mg/kg groups, and an increase in cytochrome P-450 in the 500 mg/kg group. Pathological examination disclosed hepatocellular hypertrophy caused by hyperplasia of smooth-ER in the 50 and 500 mg/kg groups, and a decrease in number of glycogen granules in the 500 mg/kg group. Stimulated thyroid follicles were seen in the 50 and 500 mg/kg groups. Increases in incidence and severity of chronic progressive nephropathy were also observed in the 500 mg/kg group. In this dose group, adrenocortical hypertrophy was also observed. The recovery test showed that the above-mentioned changes were satisfactorily reversible. The serum concentrations of NS-21 and its active metabolite, RCC-36, in the treated groups were increased in a dose-dependent manner. No treatment-related effects were seen in the 5 mg/kg group. These results show that the NOAEL (no observed adverse effect level) of NS-21 is 5 mg/kg for 26-week oral toxicity in rats.

Administration, Oral↗

Staged transsphenoidal surgery for fibrous nonfunctioning pituitary adenomas with suprasellar extension.

Staged transsphenoidal surgery was performed in seven patients with nonfunctioning pituitary adenomas with suprasellar extension. Remnant adenomas were present in a supersellar position after complete removal of the intrasellar tumor, and did not descend into the sella because of the fibrous nature in five patients or fibrous nature and dumbbell shape in two. Magnetic resonance images were obtained every 2 weeks following initial surgery. The suprasellar residual adenomas descended into the sella within 2 months in six patients and 1.5 months in one patient. A second transsphenoidal operation was performed 2 months following the initial procedure in four patients, 3 months in one, and 5 months in two. In six of the seven patients, extensive tumor removal was achieved safely and easily by the staged approach. Patients were followed up over 6 to 58 months (mean +/- SD 24.7 +/- 18.9 months). There were no major surgical complications or recurrence of tumor on follow-up images. Our postoperative imaging studies and surgical results demonstrated that staged transsphenoidal surgery is an effective and safe treatment for fibrous nonfunctioning pituitary adenomas with suprasellar extension.

Adenoma↗

Histamine-induced calcium released from cultured human mucosal microvascular endothelial cells from nasal inferior turbinate.

Changes in cytosolic Ca2+ concentration ([Ca2+]i) in cultured human mucosal microvascular endothelial cells (HMMECs) from nasal inferior turbinate were measured using a fluorescent Ca(2+)-sensitive dye, fura-2, and photometric fluorescence microscopy. Histamine caused a transient increase in intracellular free Ca2+ in cell populations and in individual cells, followed by a decrease to a sustained elevation. Histamine (100 microM) elevated [Ca2+]i in HMMECs up to 563 +/- 20 nM from a resting level of 60 +/- 45 nM (means +/- SD, n = 31). Promethazine (a histamine H1 receptor antagonist) inhibited [Ca2+]i increase during histamine stimulation, whereas cimetidine (a H2 receptor antagonist) and thioperamide (a H3 receptor antagonist) showed no inhibition. These results suggest that the histamine increase [Ca2+]i in HMMECs induces both a Ca2+ release from stores and a Ca2+ influx through activation of the H1 receptor.

Calcium↗

Chloropeptins, new anti-HIV antibiotics inhibiting gp120-CD4 binding from Streptomyces sp. I. Taxonomy, fermentation, isolation, and physico-chemical properties and biological activities.

Chloropeptins I and II, which are gp120-CD4 binding inhibitors, were isolated as pale yellow-brown powders from the mycelia of a soil actinomycete, Streptomyces sp, WK-3419. Their physico-chemical properties showed that they are chlorinated peptides. Chloropeptin I (C61H45N7O15Cl6) is a novel compound, but chloropeptin II was identified as complestatin. Both compounds inhibited gp120-CD4 binding (IC50: 1.3 and 2.0 microM, respectively), the cytopathic effect of HIV in MT-4 cells (EC50: 1.6 and 1.7 microM, respectively) and syncytium formation in co-cultured HIV-1-infected and uninfected MOLT-4 cells (IC50. 0.5 and 1.1 microM, respectively). Chloropeptin I was synergistic in the inhibition of the cytopathic effect when combined with other anti-HIV drugs such as zidovudine (AZT), didanosine (ddI), zalcitabine (ddC) and nevirapine.

Anti-Bacterial Agents↗

[Radiotherapy for non-small cell lung cancer].

Standard therapy for unresectable localized non-small cell lung cancer has been radiotherapy alone, but the treatment results were not satisfactory in terms of high incidence of distant metastasis and poor local control. Various kinds of prospective randomized clinical trials (RCT) were undertaken to solve the problems of encompassing the treatment field, total treatment dose, alteration of fractionation and combination of the chemotherapy drugs since 1970's. Radiation field which includes the primary site, ipsilateral hilar and mediastinal lymph nodes, and the total radiation dose of 60Gy in 6 to 7 weeks has been assumed as standard. However, with the advent of 3-dimensional treatment planning including the inverse planning method, particle radiotherapy and intraluminal brachytherapy, some trials are on-going to increase the total dose up to 70Gy or more in relation to the more confinement of the treatment field to the primary site only. Fractionation has also been studied to reduce the late normal tissue damage or to increase the total tumor dose, and is at present in favor of the accelerated hyperfractionation. Meta-analysis of the results of 11 RCT's revealed that the results with combination chemoradiotherapy including cisplatin yields longer MST, and higher 2-year survival rate.

Carcinoma, Non-Small-Cell Lung↗

[Primary malignant lymphoma of the bladder: a case report].

An 86-year-old woman was admitted to our hospital with genitourinary bleeding. Abdominal computerized tomography demonstrated a low density mass on the posterior wall of the bladder. Cystoscopy revealed a nonpapillary bladder tumor. A transurethral cold cup biopsy showed lymphocytic infiltration with no malignant cells. She died 2 years after the initial presentation and autopsy revealed malignant lymphoma, diffuse B cell type, small cell type. A cold cup biopsy of the bladder mucosa sometimes fails to detect primary malignant lymphoma of the bladder because of its submucosal location.

Adenocarcinoma↗

[Improvement in function-preservation in radiotherapy for pediatric malignancies].

In radiotherapeutic management for pediatric tumors, we have to pay more attention to confinement of higher dose to the target volume than for adult tumors, in order that the risk of untoward normal tissue complications dose not increase, such as growth retardation. Two current approaches performing in our department to match this purpose are presented, namely, perioperative brachytherapy and fractionated stereotactic radiotherapy (F-SRT). In perioperative brachytherapy for bone and soft tissue sarcoma, plastic guide tubes for introducing radioactive sources are placed in the residual tumor bed or at the margins during the surgery, and patients are treated by high-dose-rate brachytherapy after surgery. Patients are not restricted in radioprotective area, and the overall treatment period is short enough. F-SRT is used either as the boost of conventional brain radiotherapy in primary brain neoplasms, or as hypofractionated F-SRT for control of metastatic brain tumors, with nearly perfect local control and maintenance of good quality of life. F-SRT is planned in 3-dimensional fashion from computed tomography images. Easily detachable, relocatable cast made for F-SRT is useful in pediatric patients.

Brachytherapy↗