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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 235 records · Page 13Linked to original sources
PubMed2000

An analysis of serum interleukin-6 levels to predict benefits of medroxyprogesterone acetate in advanced or recurrent breast cancer.

Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.

Adult↗
PubMed2000

Neuropsychological outcome following pallidotomy and thalamotomy for Parkinson's disease.

Cognitive and emotional outcomes were assessed after unilateral posteroventral pallidotomy (PVP) and ventral intermediate nucleus thalamotomy (Vim-Th) in patients suffering from idiopathic Parkinson's disease (PD). PVP was performed on 12 PD patients (8 men and 4 women, mean age 56.4 years, 6 left lesions and 6 right lesions) and Vim-Th was performed on 13 PD patients (5 men and 8 women, mean age 63.2 years, 6 left lesions and 7 right lesions). In both the PVP group and the Vim-Th group, the Hoehn and Yahr staging scores (p < 0.01) and the Unified Parkinson's Disease Rating Scale activities of daily living and motor scores (p < 0.001) improved significantly. No significant changes in cognitive function were observed 4 weeks after unilateral PVP or Vim-Th. PVP produced a significant decline in Hasegawa's Dementia Scale-Revised scores in immediate postoperative assessments (p < 0.05), which resolved 4 weeks after surgery. While the Minnesota Multiphasic Personality Inventory depression and social introversion scores improved significantly in the Vim-Th group (p < 0.01 and p < 0.05, respectively), the hypochondriasis and hypomania scores improved significantly in the PVP group (p < 0.01 and p < 0.05, respectively). We conclude that PVP and Vim-Th influence postoperative emotional status rather than postoperative cognitive status.

Adult↗
PubMed2000

Alteration of hemoglobin oxygenation in the frontal region in elderly depressed patients as measured by near-infrared spectroscopy.

In an attempt to elucidate the neurobiological basis of hypofrontality in depression, alterations of oxyhemoglobin and deoxyhemoglobin were examined by using near-infrared spectroscopy of the left frontal region in 9 elderly patients with depressive disorders and 10 control subjects. Verbal repetition task, verbal fluency test, hyperventilation, and paper-bag breathing were performed. During the verbal fluency test, oxyhemoglobin significantly increased and deoxyhemoglobin significantly decreased in control subjects, whereas no significant change was observed in patients. During hyperventilation, oxyhemoglobin significantly decreased and deoxyhemoglobin significantly increased in both groups. These findings suggest that functional hypofrontality in elderly depression is not due to altered vasodilator response.

Aged↗
PubMed2000

Identification and characterization of Caenorhabditis elegans gamma-tubulin in dividing cells and differentiated tissues.

gamma-Tubulin is an essential component of the microtubule-nucleation machinery and therefore plays a crucial role during mitosis. To gain further insights into the function of this protein in the events that take place during embryogenesis and differentiation, we carried out detailed studies on gamma-tubulin during all the developmental stages of Caenorhabditis elegans. We identified the gamma-tubulin gene from this organism and analyzed the localization of the protein by both immunofluorescence and GFP reporter construct. We show that gamma-tubulin association with the centrosome is highly dynamic in mitotic cells, being massively recruited at prophase and released at anatelophase. This accumulation in mitotic centrosomes is dramatic during the first embryonic divisions. We provide the first description of the morphological changes at the centrosome level during the orientation of the mitotic spindle and the flattening of the posterior aster. Loss of function of the gamma-tubulin gene by RNAi induces a strong polyploidization of mitotic germ cells and embryos, but does not affect meiosis and pronuclear migration. In addition, we demonstrate the prominent redistribution of gamma-tubulin in adults at basal bodies of amphid and phasmid neurons, and at the apical membrane of polarized intestinal cells.

Amino Acid Sequence↗
PubMed2000

Association of polymorphism in the promoter region of the apolipoprotein E gene with diastolic blood pressure in normotensive Japanese.

The epsilon4 allele of apolipoprotein E (APOE) is reported to be a genetic risk factor of atherosclerosis through hyperlipidemia and late-onset Alzheimer's dementia. A recent report showed that a genetic variant (A -491T) in the promoter region of the APOE gene increases the risk of Alzheimer's disease. In the present study, we examined whether these APOE polymorphisms were genetically involved in essential hypertension. Japanese hypertensives (n=180) with a family history of hypertension and normotensive controls (n=195, sex and age matched with hypertensives) were recruited from the outpatients of Osaka University Hospital, and an informed consent to participate in the study was obtained from each person. APOE polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the A -491 allele in hypertensives and normotensives were 0.98 and 0.97, respectively, and the TT/-491 genotype was not found in either group. No significant differences between hypertensives and normotensives were observed in allele frequencies in either APOE polymorphism; however, the mean diastolic blood pressure in normotensive subjects with AA/-491 was significantly higher than in the subjects with AT/-491 (p < 0.01). These results suggest that the presence of the APOE promoter polymorphism is not a major risk factor for hypertension but that it does have some minor effect on basal blood pressure variation.

Adult↗
PubMed2000

Multiple brain metastases from a diffuse sclerosing variant of papillary carcinoma of the thyroid.

We report a 53-yr-old man who presented with multiple brain metastases from a diffuse sclerosing papillary carcinoma of the thyroid. The presenting clinical features were those of an intracranial space-occupying lesion. Three brain tumors, confirmed pathologically to be metastatic thyroid papillary carcinomas, were removed. Two weeks after craniotomy, total thyroidectomy with cervical lymph node dissection was performed. Both lobes of the thyroid were diffusely enlarged and firm with a dominant mass. Histologically, the tumor was characterized by a combination of bilateral diffuse involvement of the gland, marked fibrosis, squamous metaplasia, abundant psammoma bodies, lymphocytic infiltration, frequent lymphatic and blood vessel permeation of the tumor, and typical elements of a conventional papillary carcinoma. In addition to these histologic findings, elements of other papillary carcinoma variants such as follicular and tall cell variants were also found focally. Twenty-three of twenty-four resected bilateral lymph nodes showed metastases of papillary carcinoma. Although the diffuse sclerosing variant of papillary carcinoma of the thyroid seems to be recognized as an aggressive variant of papillary carcinoma, there is no previous report of brain metastasis from this variant.

Journal Article↗
PubMed2000

Activation of transepithelial ion transport by secretin in human intestinal Caco-2 cells.

Secretin stimulates bicarbonate secretion from pancreatic duct cells, but what influence secretin exerts on intestinal tissues remains to be clarified. The aim of this study is to examine effects of secretin on ion transport in intestinal epithelial Caco-2 cells. We mounted monolayers of Caco-2 cells grown on permeable supports for 21-28 d in a Ussing chamber and measured short-circuit currents (I(sc)). Addition of secretin (5-100 nM) to the basolateral solution dose-dependently induced biphasic increases of I(sc) (transient and sustained phase). Dibutyryl cyclic AMP (200 microM), forskolin (10 microM), and 3-isobutyl-1-methylxanthine (IBMX, 1 mM) also induced I(sc) responses similar to the administration of secretin. Addition of 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB, 100 microM) or benzamil (100 microM) to the apical solution markedly reduced the secretin-induced I(sc) increase in the transient phase. A selective antagonist of cAMP-dependent protein kinase (PKA), N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89, 1 microM), and a membrane permeable Ca(2+) chelator, 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM, 10 microM) reduced the secretin-induced I(sc). Basolateral addition of 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 1 mM) suppressed the sustained phase I(sc) increase. Secretin also induced alkalinization of the apical solution (DeltapH, 0.053 +/- 0.013). The alkalinization did not occur when DIDS (1 mM) was added to the basolateral solution or Na(+) was removed from the solutions. Taken together, our observations suggest: (1) secretin stimulates a benzamil-sensitive Na(+) influx and an NPPB-sensitive Cl(-) efflux across the apical membrane through PKA-dependent and Ca(2+)-sensitive pathways; and (2) secretin also induces alkalinization of the apical solution through the activation of a DIDS-sensitive Na(+)-HCO(3)(-) cotransport in the basolateral membrane of Caco-2 cells.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Serum itraconazole and hydroxyitraconazole concentrations and interaction with digoxin in a case of chronic hypertrophic pachymenigitis caused by Aspergillus flavus.

A patient treated with itraconazole (ITCZ) under the diagnosis of Aspergillus flavus-induced chronic hypertrophic pachymeningitis is presented. The reason for the successful cure of this patient was investigated by the pharmacokinetic analysis of serum levels of ITCZ. Concurrently administered digoxin was also investigated for its drug-drug interaction. The patient (a 75-year-old male) developed ophthalmopathy, and was diagnosed as having A. flavus hypertrophic pachymeningitis by pachymeninx biopsy. After admission, he was treated with FLCZ, AMPH, 5-FC and MCZ. The infection tended to subside with the AMPH administration. Since renal insufficiency was induced by AMPH and the other antifungal drugs were ineffective, daily administration of 200 mg of ITCZ was initiated, and the inflammatory signs and symptoms gradually subsided. The symptoms did not recur during the 36 months of itraconazole treatment after discharge, and it was concluded that ITCZ was effective for A. flavus hypertrophic pachymeningitis. Pharmacokinetic parameters of ITCZ and OH-ITCZ as follows: ITCZ: Cmax 93.2 ng/ml, T1/2 beta 11 hours, AUC0-24 999 ng.h/ml, OH-ITCZ: Cmax 159.4 ng/ml, T1/2 beta 16. 2 hours, AUC0-24 of 1391 ng.h/ml. Both ITCZ and OH-ITCZ reached steady states seven days after administration began. The ITCZ and OH-ITCZ levels in serum collected 36 months after the initiation of administration were 452.9 ng/ml and 1233.6 ng/ml, respectively. Cmax and AUC0-24 of ITCZ and OH-ITCZ on the second day were markedly lower than those in healthy adults reported by Oguchi et al., and hypoalbuminemia observed at administration on that day was considered the most probable cause. It was assumed that the most plausible reason for a successful cure even at a low dose of ITCZ was the increase of distribution to tissue by the increase of the unbound form. Digoxin was concurrently given to this patient at 0. 125 mg/day, but the blood digoxin level was not elevated. Consideration of the blood level of albumin is believed to be important for evaluating the blood concentration of ITCZ.

Aged↗
PubMed2000

Induction of NADPH:quinone oxidoreductase in murine hepatoma cells by methylsulfinyl isothiocyanates: methyl chain length-activity study.

Methylsulfinyl isothiocyanates (MITC) are a class of isothiocyanates occurring in a variety of cruciferous vegetables showing anticarcinogenic activity. To develop analogues of methylsulfinyl isothiocyanate with less toxicity and better biological activity, four types of methyl chain length (designated as 2-, 4-, 6- and 8-MITC) were synthesized. The murine hepatoma cells (Hepa 1c1c7) were treated with various concentrations of MITC, and then assessed for cell growth, enzyme activity and mRNA expression of the detoxifying enzyme NADPH:quinone oxidoreductase (QR). All of four MITC augmented the induction of QR activity and the expression of QR mRNA in a dose-dependent manner. In the non-toxic concentration range, an increase in the methyl chain length resulted in a higher QR induction in both activity and mRNA expression. However, increasing cytotoxicity was also observed by an increase in the methyl chain length. Our results suggested that 4- and 6-MITC as QR inducers appeared to be less toxic and even more potent.

Animals↗
PubMed2000

Expression levels of thymidine phosphorylase and dihydropyrimidine dehydrogenase in various human tumor tissues.

Thymidine phosphorylase (dThdPase) is the rate-limiting enzyme that metabolizes 5'-deoxy-5-fluorouridine (5'-dFUrd, doxifluridine), an intermediate metabolite of capecitabine, to the active drug 5-fluorouracil (5-FUra), while dihydropyrimidine dehydrogenase (DPD) catabolizes 5-FUra to an inactive molecule. The susceptibility of tumors to fluoropyrimidines is reported to correlate with tumor levels of these enzymes. To obtain some insight into the tumor types susceptible to fluoropyrimidine therapy, we measured expression levels of these two enzymes in various types of human cancer tissues (241 tissue samples) by the ELISA methods. DPD exists in all the cancer types studied, such as bladder, breast, cervical, colorectal, esophageal, gastric, hepatic, pancreatic, prostate, and renal cancers. Among them, the cervical, hepatic, pancreatic, esophageal, and breast cancer tissues expressed high levels of DPD (median >70 U/mg protein), while high concentrations of the dThdPase were expressed in esophageal, cervical, breast, and pancreatic cancers and hepatoma (median >150 U/mg protein). The dThdPase/DPD ratio, which was reported to correlate with the susceptibility of human cancer xenografts to capecitabine, was high in esophageal, renal, breast, colorectal, and gastric cancers (median ratio of >1.5). In any of these three parameters, the inter-patient DPD variability for each cancer type was much larger than the DPD variability among cancer types; highest/lowest ratios for dThdPase, DPD, and dThdPase/DPD were 10-321, 7-513, and 2-293, respectively. These results indicate that measurements of the three parameters, DPD, dThdPase and dThdPase/DPD, would be useful criteria for selecting cancer patients suitable for fluoropyrimidine therapy rather than for selecting cancer types.

Animals↗
PubMed2000

Computerized tomographic ureteroscopy for diagnosing ureteral tumors.

PURPOSE: Helical computerized tomography (CT) image acquisition has led to the availability of improved data sets for CT endoscopic imaging that represent virtual endoscopy using CT. We assessed the usefulness of CT ureteroscopic imaging for diagnosing ureteral tumors. MATERIALS AND METHODS: A total of 16 patients with ureteral stenosis underwent surface rendering CT ureteroscopy after the intravenous administration of contrast material and furosemide. To distinguish ureteral tumors from ureteral strictures 2 observers blinded to other patient history and evaluation data independently and prospectively evaluated CT ureteroscopy with reformatted CT ureterograms in these 16 patients. CT ureteroscopic images were then correlated with surgical and pathological findings, which served as the gold standard. RESULTS: Surgical and pathological findings in the 16 patients revealed 16 ureteral tumors, including carcinoma in 10 (carcinoma in situ in 1, fibroepithelial polyps in 2 and hyperplastic polypoids in 4), inflammatory intrinsic stricture in 2 and extrinsic stricture in 4 caused by retroperitoneal fibrosis in 2 and lymph node metastasis in 2. CT ureteroscopy correctly detected all lesions except 1 carcinoma in situ, 1 polypoid carcinoma and 1 hyperplastic polypoid. The sensitivity and specificity of CT ureteroscopy for detecting ureteral tumors and carcinoma were 81% and 100%, and 80% and 75%, respectively, when tumors without stalks were considered carcinoma. CONCLUSIONS: CT ureteroscopy is useful for visualizing the complex morphology of ureteral tumors and distinguishing tumor from ureteral stricture.

Adult↗
PubMed2000

[Epilepsy surgery for focal cortical dysplasia and dysembryoplastic neuroepithelial tumor].

We studied six patients with focal cortical dysplasia (CD) and four patients with dysembryoplastic neuroepithelial tumor (DNT) who had surgical resection for medically intractable epilepsy. In all CD patients, ictal single photon emission computed tomography (SPECT) using 99mTc-ECD revealed hyperperfusion in the regions where magnetic resonance (MR) imaging showed CD abnormalities. Interictal epileptiform activity and ictal seizure onset on electrocorticography using subdural strip or grid electrodes were demonstrated in the CD itself. In contrast, in all DNT patients, interictal SPECT disclosed hypoperfusion in the area of the lesions. Ictal SPECT in one DNT patient disclosed hyperperfusion in the superior area of the region where MR imaging showed cystic abnormalities. Interictal spiking in all DNT patients and ictal seizure onset in two DNT patients were demonstrated not in the lesions themselves but in the distinct zone from the region of the tumor-involved brain. All CD patients who underwent lesionectomy became seizure-free with a mean follow-up period of 33.5 months. All DNT patients who underwent lesionectomy and resection of the epileptogenic cortex became seizure-free or had their seizure significantly reduced a mean follow-up period of 41.5 months. We conclude that CDs have intrinsic epileptogenicity, while DNTs have epileptogenicity not intrinsically but in encompassed cortical surface areas.

Adolescent↗
PubMed2000

[Therapeutic effect and clinical findings in patients with MPO-ANCA associated vasculitis syndrome].

We investigated to clarify the clinical findings, course and therapeutic effect in the patients with MPO (myeloperoxidase)-ANCA (anti-neutrophil cytoplasmic antibody) associated vasculitis syndrome. We analyzed clinical findings and data of 19 cases of MPO-ANCA associated vasculitis. These patients were diagnosed with clinical symptoms (fever, arthralgia, body weight loss, etc.), laboratory data (high titer of CRP, leukocytosis, thrombocytosis, and high titer of MPO-ANCA) and pathologic findings of necrotizing vasculitis. They were 14 male and 5 female aged 18 to 84 years (mean 65 years) and were treated with prednisolone and immunosuppressive agents, and additional therapy included pulse therapy and plasma exchange. Seven cases were dead within 3 months. Post-mortum examination showed that these cases died of pneumonitis, cerebral events and gastric bleeding. There was no mortal case induced by over-immunosuppression. In survival cases, the MPO-ANCA levels decreased rapidly after these therapies and these antibodies were maintained low levels (360 to 25 EU/l). Comparison of fatal cases and survival cases, there were difference in the initial dose of prednisolone (27 mg/day vs. 56 mg/day), the ratio of double filtration plasmapheresis (14% vs. 42%), and the ratio of immunosuppressive therapy (14% vs. 83%). The measurement of MPO-ANCA is useful makers of the diagnosis and effectiveness of the therapy in patients with MPO-ANCA associated vasculitis. We recommend the aggressive therapy, including prednisolone, immunosuppressive agents and plasma exchange for MPO-ANCA associated vasculitis. We believe that the aggressive therapy improve the survival rate of the patients with MPO-ANCA associated vasculitis.

Adolescent↗
PubMed2000

Glutathione depletion enhances the formation of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge.

BACKGROUND: We examined the effects of glutathione depletion on the level of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge. METHODS: Rats were given 1 mg/kg of maleic acid diethyl ester to deplete glutathione in vivo and then 0.5 mg/kg body weight of lipopolysaccharide. RESULTS: This treatment significantly depleted serum reduced glutathione (32.7 +/- 1.7 vs. 23.0 +/- 3.2 mM, p = 0.002). However, it did not affect the serum oxidized glutathione concentration (2.88 +/- 0.56 vs. 3.10 +/- 0.78 mM, not significant). The lipopolysaccharide challenge caused significant superoxide anion formation as compared with controls (0.12 +/- 0.04 vs. 0.22 +/- 0.05 o.d., p < 0.001), and it was enhanced significantly by glutathione depletion (0.28 +/- 0.04 o.d., p < 0.05). There were no significant differences in levels of lipopolysaccharide (2142 +/- 452 vs. 2503 +/- 612 pg/ml) and tumor necrosis factor alpha (277 +/- 186 vs. 252 +/- 88 pg/ml) after the lipopolysaccharide challenge between the glutathione-depleted and nondepleted rats. Moreover, the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in liver perfusates, a marker of damage to endothelial cells in hepatic sinusoids, was significantly higher in the glutathione-depleted rats than in the nondepleted rats. CONCLUSIONS: The reduced form of glutathione can decrease levels of the superoxide anion released into hepatic sinusoids and can decrease subsequent damage to endothelial cells in these sinusoids caused by lipopolysaccharide; that is, it can reduce lipopolysaccharide-induced liver injury.

Animals↗
PubMed2000

[Clinical effects of trandolapril in chronic glomerulonephritis patients with renal insufficiency].

Trandolapril is a newly developed angiotensin converting enzyme inhibitor (ACEI) whose characteristic is that it undergoes hepatic excretion. ACEI appears to have a specific reno-protective and antiproteinuric role in patients with chronic glomerulonephritis(CGN). Although renally excreted ACEI tend to accumulate and cause side-effects in patients with renal dysfunction, the pharmacokinetics of trandolapril were not affected by renal dysfunction. We compared the effect of other renally excreted ACEI with those of trandolapril on serum creatinine (s-Cr), creatinine clearance(Ccr), proteinuria and total protein(TP) in CGN patients who switched from another ACEI to trandolapril. Twelve hypertensive patients with chronic renal failure(nine males and three females, ranging from 30 to 72 years of age) who were treated by other renally excreted ACEIs for long periods(2 to 8 years) with some effects on proteinuria and renal function, were enrolled in the present study. After ACEI therapy, s-Cr had decreased(2.09 to 1.80 mg/dl, p < 0.01) as well as proteinuria(1.65 to 0.71 g/day, p < 0.01). A single daily oral dose of 1 mg of trandolapril was administered to these patients regardless of their blood pressure status and renal functions. After change to trandolapril therapy, s-Cr(2.25 to 2.06 mg/dl, p < 0.01) and urinary protein(1.82 to 1.34 g/day, p < 0.05) significantly decreased. On the contrary, both Ccr and TP significantly increased at the level of 39.4 to 44.4 ml/min(p < 0.05) and 6.80 to 7.02 g/dl (p < 0.01), respectively. No apparent side effects, such as hyperkalemia, hyponatremia, anemia or worsening of the existing renal dysfunction except for coughing, were observed in these patients. Furthermore, none of the 12 patients treated with trandolapril required discontinuation of the compound. In conclusion, it was shown from this study that trandolapril is effective for the treatment of hypertensive patients with renal insufficiency irrespective of the original diseases. Thus, it can be envisaged that trandolapril is one of the most appropriate agents compared to other renally excreted ACEI for these patients with renal insufficiency. We recommend the change from other ACEIs to trandolapril, when renal dysfunction might be due to ACEI accumulation.

Adult↗