Biomedical subjects

M Kubota

Publications and source records attributed to M Kubota.

At least 91 records · Page 5Linked to original sources

PubMed2000

Cancer chemotherapy and somatic cell mutation.

The occurrence of a second neoplasm is one of the major obstacles in cancer chemotherapy. The elucidation of the genotoxic effects induced by anti-cancer drugs is considered to be helpful in identifying the degree of cancer risk. Numerous investigations on cancer patients after chemotherapy have demonstrated: (i) an increase in the in vivo somatic cell mutant frequency (Mf) at three genetic loci, including hypoxanthine-guanine phosphoribosyl-transferase (hprt), glycophorin A (GPA), and the T-cell receptor (TCR), and (ii) alterations in the mutational spectra of hprt mutants. However, the time required for and the degree of such changes are quite variable among patients even if they have received the same chemotherapy, suggesting the existence of underlying genetic factor(s). Accordingly, some cancer patients prior to chemotherapy as well as patients with cancer-prone syndrome have been found to show an elevated Mf. Based on the information obtained from somatic cell mutation assays, an individualized chemotherapy should be considered in order to minimize the risk of a second neoplasm.

Antineoplastic Agents↗

PubMed2000

Prevention of etoposide-induced apoptosis by proteasome inhibitors in a human leukemic cell line but not in fresh acute leukemia blasts. A differential role of NF-kappab activation.

Recent research indicates that the proteasome is one of the non-caspase proteases involved in apoptotic signaling pathways. Nuclear factor-kappaB (NF-kappaB) activation, one of the key factors in apoptosis, can be prevented through abrogation of IkappaBalpha degradation by proteasome inhibition. We have investigated the effects of the proteasome inhibitors carbobenzoxyl-L-leucyl-L-leucyl-L-leucinal (MG132) and N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal (LLnL) on apoptosis and NF-kappaB activation induced by etoposide, using a human leukemia cell line (U937) and leukemia blasts freshly isolated from patients with acute leukemia. Pretreatment of U937 cells with MG132 or LLnL inhibited etoposide-induced morphological apoptosis and caspase-3 activation. Furthermore, MG132 or LLnL prevented NF-kappaB activation and IkappaBalpha degradation, but not IkappaBalpha phosphorylation at Ser32. Other inhibitors of NF-kappaB activation, including pyrrrolidine dithiocarbamate (an antioxidant) and the peptide SN50 (an inhibitor of translocation of activated NF-kappaB into the nucleus), also attenuated etoposide-induced apoptosis. In leukemia blasts, although proteasome inhibitors suppressed NF-kappaB activation induced by etoposide, they were unable to prevent morphological apoptosis. Moreover, proteasome inhibitors by themselves caused apoptosis in leukemia blasts at the concentrations employed in this study. These results suggest that the role that NF-kappaB plays in apoptosis induced by etoposide in a human leukemia cell line may be different from the role it plays in freshly isolated leukemia blasts.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Effect of a 5-HT(1A) receptor agonist, flesinoxan, on the extracellular noradrenaline level in the hippocampus and on the locomotor activity of rats.

We have studied effects of 5-hydroxytryptamine 1A (5-HT(1A)) receptor-selective compounds on the extracellular noradrenaline (NA) level in the hippocampus of rats using microdialysis and on their locomotor activity. A selective 5-HT(1A) receptor agonist, flesinoxan (5 mg/kg, i.p.) increased the extracellular NA level in the hippocampus, and increased the locomotor activity. Both responses were blocked by pretreatment with a 5-HT(1A) receptor antagonist, WAY100635 (1 mg/kg, i.p.) and an alpha(2) adrenoceptor agonist, clonidine (50 microg/kg, i.p.). Bilateral intrahippocampal injection of flesinoxan (200 nmol in 2 microl, respectively) increased the locomotor activity of rats and the intrahippocampal perfusion of flesinoxan (1 mM, 2 microl/min) increased the extracellular NA level in the hippocampus. Bilateral intrahippocampal injections of a small amount of WAY100635 (0.1 nmol in 2 microl, respectively) blocked the flesinoxan (5 mg/kg, i.p.)-induced hyperactivity. Flesinoxan (5 mg/kg, i.p.) did not significantly influence the level of serotonin or its major metabolite in the hippocampus, or dopamine or its metabolites in the striatum. In conclusion, these behavioral as well as pharmacological results indicate that postsynaptic 5-HT(1A) receptor activation by flesinoxan increase the extracellular NA level in the hippocampus, which may be the cause of the increase of the locomotor activity.

Animals↗

PubMed2000

Cloning and nucleotide sequence of a gene encoding a glycogen debranching enzyme in the trehalose operon from Arthrobacter sp. Q36.

A gene located just upstream of the treYZ operon was isolated from Arthrobacter sp. strain Q36. The gene, designated treX, encoded an 823-amino acid protein. The amino acid sequence of the protein had 50% identity with the TreX protein (isoamylase) from Sulfolobus acidocaldarius ATCC 33909 which has a treZXY operon on the genome. We suggest that Arthrobacter treX is an isoamylase gene, and that it is a component of a treXYZ operon.

Amino Acid Sequence↗

PubMed2000

Sphingolipid biosynthesis by L-PDMP after rat MCA occlusion.

L-PDMP (L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) exhibits stimulatory effects on glycosphingolipid biosynthesis and its neurotrophic actions in cultured neuron. The effects of intraperitoneal administration of L-PDMP on sphingolipid metabolism and behavioral changes in the rat following permanent occlusion of the left middle cerebral artery (MCA) were investigated. The L-PDMP treatment induced increases in glucosylceramide (ganglioside precursor) and sphingomyelin (SM) levels in the ischemic cerebral cortex, and improved acquisition of memory and learning in the Morris water maze task. The pharmacological effects of L-PDMP have been proposed to have a significant activity on promoting cell survival and improving neural functions.

Animals↗

PubMed2000

Comparative efficacy of positron emission tomography and ultrasonography in preoperative evaluation of axillary lymph node metastases in breast cancer.

PURPOSE: In primary breast cancer, axillary nodal status is the most powerful predictive factor of recurrence. However, axillary lymph node dissection may cause surgical complications. If preoperative evaluation of axillary lymph node metastases is possible, unnecessary axillary lymph node dissections can be avoided. The purpose of this study was to evaluate the efficacy of positron emission tomography (PET) on detection of axillary lymph node metastases in breast cancer. METHODS: PET scans of the axilla were obtained in 32 patients with primary breast cancer. All patients fasted for at least 4 hours before the examination. After transmission scans for attenuation correction were performed, emission scans after intravenous injection of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) were obtained. RESULTS: Overall accuracy of PET alone, ultrasonography alone, and in combination in the detection of axillary metastases were 82%, 79%, and 85% respectively. CONCLUSION: There were no significant differences between PET, ultrasonography, and PET in combination with ultrasonography regarding sensitivity, specificity and accuracy in the detection of axillary metastases.

Adult↗

PubMed2000

Radical esophagectomy and secondary anastomosis for high-risk patients with intrathoracic esophageal carcinoma.

OBJECTIVE: We have often conducted esophageal reconstruction via a thoracic subcutaneous route in high-risk patients to avoid major complications following anastomotic leakage. This type of reconstruction is nonphysiological, however, and presents a poor cosmetic appearance. In better risk patients, therefore, we usually conduct gastric-tube replacement via a posterior mediastinal route. We have recently begun gastric-tube replacement via the posterior mediastinal route with secondary anastomosis for high-risk patients to avoid anastomotic leakage. RESULTS: From 1996 to 1999, secondary anastomosis was conducted in 25 patients with different degrees of risk--10 with diabetes mellitus, 7 with liver dysfunction, 3 with simultaneous laryngeal and/or pharyngeal cancer, 2 each with induction chemoradiotherapy, cardiac failure, renal dysfunction, respiratory failure, and cardiorespiratory dysfunction, and 1 with cerebral infarction. 6 patients had with multiple combined diseases. Secondary anastomosis was conducted 3-12 weeks (mean: 5.5 weeks) after esophagectomy. Stomach-tube necrosis was not seen in any of the 25 patients undergoing this 2-step procedure. Anastomosis leakage was seen in 5 of the 25 patients (20%), but was slight, in all but 1. CONCLUSION: Our 2-step procedure has the following advantages: low risk of anastomotic leakage, radical surgery for esophageal cancer, the potential for early adjuvant therapy after esophagectomy, easy and early training in swallowing, and no cosmetic problem. Its disadvantages are prolonged hospitalization, multiple surgery, and esophageal stoma formation. Secondary anastomosis thus appears helpful in treating high-risk patients with advanced esophageal cancer.

Aged↗

PubMed2000

Important role of the hepatic vagus nerve in glucose uptake and production by the liver.

We examined the role of the hepatic vagus nerve in hepatic and peripheral glucose metabolism. To assess endogenous glucose production (EGP), hepatic uptake of first-pass glucose infused intraportally (HGU), and the metabolic clearance rate of glucose (MCR), rats were subjected to hepatic vagotomy (HV, n = 7) or sham operation (SH, n = 8), after 10 days, they were then subjected to a euglycemic-hyperinsulinemic clamp together with a portal glucose load in the 24-hour fasting state. Metabolic parameters were determined by the dual-tracer method using stable isotopes. During the experiment, [6,6-2H2]glucose was continuously infused into the peripheral vein. To maintain euglycemia (4.5 mmol/L), insulin (54 pmol x kg(-1) x min(-1)) and glucose were infused peripherally after the 90-minute tracer equilibration and 30-minute basal periods, and glucose containing 5% enriched [U-13C]glucose was infused intraportally (50 micromol x kg(-1) x min(-1)) for 120 minutes (clamp period). EGP was significantly higher in HV rats versus SH rats during the basal period (64.3 +/- 7.6 v 43.6 +/- 5.3 micromol x kg(-1) x min(-1), P < .005)) and was comparable to EGP in SH rats during the clamp period (9.3 +/- 21.5 v 1.1 +/- 11.7 micromol x kg(-1) x min(-1)). HGU was reduced in HV rats compared with SH rats during portal glucose infusion (5.9 +/- 2.4 v 10.1 +/- 3.2 micromol x kg(-1) x min(-1)). The MCR in HV rats was significantly higher than in SH rats in the basal period (11.0 +/- 2.0 v 7.9 +/- 0.8 mL x kg(-1) x min(-1), P < .01)) and was comparable to the MCR in SH rats during the clamp period (41.9 +/- 10.0 and 36.6 +/- 5.7 mL x kg(-1) x min(-1)). We conclude that innervation of the hepatic vagus nerve is important for the regulation of hepatic glucose production in the postabsorptive state and HGU in the postprandial state.

Animals↗

PubMed2000

Zonisamide - induced urinary lithiasis in patients with intractable epilepsy.

We report here three patients with intractable epilepsy who developed urinary lithiasis during zonisamide (ZNS) treatment. Abdominal pain due to left-sided hydronephrosis was the initial symptom in the first patient, and it was resolved after the excretion of a stone. The second patient, who had no specific symptoms, was found to have a thick sludge of calcium phosphate in the bladder when he suffered from aspiration pneumonia and dehydration. The third patient, who had a history of recurrent urinary obstruction, was also found to have a thick sludge of calcium oxalate in the bladder. The urinalysis of the three patients revealed alkaline urine and hypercalciuria. Although their urinary lithiasis was resolved by discontinuation of ZNS and supportive therapy, routine examination of urine parameters such as pH and sediments, and daily urine-output checks are thought to be necessary during treatment with ZNS, especially for patients who are bedridden for a long time and receive multiple antiepileptic drugs.

Adolescent↗

PubMed2000

The house musk shrew (Suncus murinus): a unique animal with extremely low level of expression of mRNAs for CYP3A and flavin-containing monooxygenase.

Expression of drug-metabolizing enzymes including cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in various tissues of Suncus murinus (Suncus) were examined. Northern blot analysis showed that mRNAs hybridizable with cDNAs for rat CYP1A2, human CYP2A6, rat CYP2B1, human CYP2C8, human CYP2D6, rat CYP2E1, human CYP3A4 and rat CYP4A1 were expressed in various tissues from Suncus. The mRNA level of CYP2A in the Suncus lung was very high. Furthermore, it was found that the level of CYP2A mRNA in the Suncus lung was higher compared to the Suncus liver. The expression level of mRNA hybridizable with cDNA for human CYP3A4 was very low. The presence of CYP3A gene in Suncus was proven by the induction of the CYP with dexamethasone. Very low expression levels of mRNAs hybridizable with cDNAs for rat FMO1, rat FMO2, rat FMO3 and rat FMO5 were also seen in Suncus liver. No apparent hybridization band appeared when human FMO4 cDNA was used as a probe. The hepatic expression of mRNAs hybridizable with cDNAs for UDP-glucuronosyltransferase 1*6, aryl sulfotransferase, glutathione S-transferase 1, carboxyesterase and microsomal epoxide hydrolase in the Suncus were observed. These results indicate that the Suncus is a unique animal species in that mRNAs for CYP3A and FMO are expressed at very low levels.

Animals↗

PubMed2000

New ocular movement detector system as a communication tool in ventilator-assisted Werdnig-Hoffmann disease.

A non-contact communication system was developed for a ventilator-assisted patient with Werdnig-Hoffmann disease who had lost all voluntary movements except for those of the eye. The system detects the extraocular movements and converts them to either a 'yes' signal (produced by one lateral eyeball movement) or a 'no' signal (produced by two successive lateral eyeball movements) using a video camera placed outside the patient's visual field. The patient is thus able to concentrate on performing a task without any intrusion from the detection system. Once the setting conditions of the device have been selected, there is no need for any resetting, as the patient is unable to move his body. In addition to playing television games, the child can use the device to select television channels, compose music, and learn written Japanese and Chinese characters. This seems to broaden the patient's daily world and promote mental development.

Activities of Daily Living↗

PubMed2000

Long-term ventilator support in patients with Werdnig-Hoffmann disease.

BACKGROUND: Withholding and withdrawing life-sustaining treatment for patients with Werdnig-Hoffmann disease (WHD) have been accepted as standard medical practice in most Western countries. However, a number of Japanese pediatricians are providing ventilator care for patients with this otherwise fatal disorder. We investigated the attitude of physicians in Japan who are providing ventilator care for patients with WHD. METHODS: A postal questionnaire was sent to 40 hospitals where pediatricians were taking care of 55 ventilator-assisted patients with WHD. Their views were sought on aspects of the care of these patients. RESULTS: Thirty-three pediatricians from 31 hospitals responded to the questionnaire. Mechanical ventilation was initiated as an emergency measure in one-third (12/32) of the patients before obtaining full informed consent from the parents. Two-thirds (19/32) of parents asked the physicians to start ventilator care for the patients, while only three parents asked for the life-sustaining treatment to be withheld. Although 80% (24/30) of the physicians thought that the quality of life of the ventilator-dependent patients with WHD was inadequate, about half (17/30) answered that they would start ventilator assistance if they had a new patient with WHD. DISCUSSION: Strong familial endorsement for the prolongation of a patient's life, the secure national insurance and general pro-life beliefs could have affected physicians' decisions in favor of providing life-sustaining treatments for patients with WHD.

Adult↗

PubMed2000

Histopathological analysis of non-malignant and malignant epithelium in achalasia of the esophagus.

We studied the premalignant nature of achalasia using anti-Ki-67 and anti-p53 monoclonal antibodies immunohistochemically. In this study, four patients with esophageal carcinoma and achalasia were investigated. Three tumors were pT4 (UICC pTNM) and one tumor was pT1. The majority of non-malignant esophageal epithelium showed esophagitis and/or dysplasia histologically. Esophageal epithelial cells in the lesions of esophagitis and/or dysplasia had a higher number of Ki-67-positive cells than normal epithelial cells. p53 protein was expressed in two tumors and it was not expressed in non-malignant epithelium. From these results, we found that esophageal epithelium in achalasia lesions is changed to varying degrees of esophagitis and/or dysplasia by stagnation of intake foods, and these abnormal epithelial cells showed a high proliferative state compared with the normal cells without the p53 gene mutation. We suggest that the distinct proliferative status is a cause of carcinogenesis.

Adult↗

PubMed2000

Control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit by unselective use of nasal mupirocin ointment.

In September 1996, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization occurred in the neonatal intensive care unit (NICU) of our hospital. After failing to control the outbreak by conventional methods we implemented an intranasal blanket use programme of mupirocin ointment from the beginning of November 1997. In the programme, patients who had been carrying MRSA received intranasal administration of the ointment three times daily for the first three days and consecutively three times weekly, while newly admitted patients and those who had not been colonized were prophylactically medicated three times weekly. This blanket administration was executed for one month. Methicillin-resistant Staphylococcus aureus colonization became undetectable in all but one intubated inpatient who had already been colonized before the start of the programme, and no new acquisitions occurred until the middle of January 1998, seven weeks after the termination of the blanket use programme. The rate of colonized patients in the unit also decreased. During and after the programme, neither an increase in minimum inhibitory concentration for the antibiotic nor apparent adverse reactions in any of the treated patients were observed. We concluded that this procedure is an effective method of controlling an MRSA outbreak in an NICU when the outbreak cannot be managed with conventional measures.

Administration, Intranasal↗

PubMed2000

Comparative performance of magnetic resonance angiography and conventional angiography in moyamoya disease.

Patients with moyamoya disease verified by conventional cerebral angiography (CCA) were evaluated by means of magnetic resonance angiography (MRA), in order to clarify its advantages and limitations in comparison with CCA. This retrospective study was carried out in 13 hemispheres of seven patients with moyamoya disease (including one atypical patient). In MRA, magnetisation transfer contrast (MTC) and maximal intensity projection (MIP) techniques were used. A good correspondence between MRA and CCA was noted in 11 hemispheres (86.4%) on evaluating stenotic lesions and overestimation in the remaining 2. Underestimation of moyamoya vessels in MRA was noted in 3 hemispheres, since well developed moyamoya vessels were detectable, while poorly developed ones were not. No difference between MRA and CCA findings was found in 10 hemispheres (76.9%). MRA tends to overestimate the stenosis and underestimate moyamoya vessels. These characteristics may lead to wrong classification in the angiographic grade of patients with early and advanced stages and should be taken into consideration in interpreting MRA images of moyamoya disease (compatible rate of grade between MRA and CCA; 84.6%). In conclusion MRA with MTC and MIP techniques offers an acceptable quality of assessment of stenotic lesions and moyamoya vessels. MRA is a useful follow up method at present and in the near future it may replace CCA as the initial diagnostic tool.

Adult↗

PubMed2000

Therapeutic time window in the penumbra during permanent focal ischemia in rats: changes of free fatty acids and glycerophospholipids.

To better define a therapeutic time window for reducing the extent of damage in ischemic penumbra, the time courses of changes in the glycerophospholipid and free fatty acid (FFA) levels were determined in the rat cerebral cortex following induction of the permanent focal ischemia. Focal ischemia induced a biphasic increase in FFA levels in the cerebral cortex, which had been recognized as the ischemic penumbra during the early stages after permanent occlusion of the middle cerebral artery (MCA). The first increase in FFA levels, in which the polyunsaturated fatty acid (PUFA) contained a large number of arachidonic acid (C20:4) molecules, began at 30 min and reached a peak at 1 h, followed by transient return to each sham level 2-6 h after the onset of MCA occlusion. Thereafter, the delayed increase in FFA levels, showing more increases of docosahexaenoic acid (C22:6) molecules than the C20:4 in PUFA compositions, occurred at 24 h. In contrast, the levels of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) decreased rapidly at 30 min of ischemia and returned transiently to each sham level at 1-6 h. The levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), including polyphosphoinositides (PIPs), began to decrease significantly during the late stages, i.e., 24 h after induction of ischemia. These results suggest that the time-dependent changes in FFA and PIPs levels during the early stages of ischemia (until 6 h after induction) might be an important determinant of the subsequent neuronal death in the ischemic penumbra and that the breakdown of glycerophospholipids in the later stages after the induction of focal ischemia was associated with the development of infarction in the cerebral cortex.

Animals↗

PubMed2000

Interleukin-6 gene expression in peripheral blood mononuclear cells from patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis.

To compare the interleukin-6 (IL-6) gene expression in the peripheral blood mononuclear cells (PBMCs) and plasma IL-6 levels in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with those in patients undergoing hemodialysis. Eleven hemodialysis patients, 10 CAPD patients, 15 non-dialyzed patients with end-stage kidney disease (ESKD), and 7 healthy controls were included in this study. PBMCs were collected by differential centrifugation. Plasma IL-6 concentration was measured by enzyme immunoassay. Plasma IL-6 levels were significantly increased in the hemodialysis and CAPD patients as compared with non-dialyzed ESKD patients and normal subjects (p < 0.01). Following hemodialysis, plasma IL-6 levels exceeded those before hemodialysis. No significant difference was found in plasma IL-6 levels in CAPD patients and in hemodialysis patients when blood was drawn before hemodialysis. Low but steady-state levels of IL-6 mRNA expression were observed in the non-dialyzed ESKD patients. The expression of IL-6 mRNA in PBMCs was significantly increased in the patients undergoing hemodialysis or CAPD as compared with the non-dialyzed ESKD patients. The PBMC IL-6 mRNA was significantly lower in CAPD patients than in hemodialysis patients (p < 0.01). A significant correlation was found between the plasma concentration of IL-6 and the expression of IL-6 mRNA in PBMCs from patients undergoing hemodialysis or CAPD (p < 0.01). The hemodialysis or CAPD procedure contributed to the increase in PBMC IL-6 mRNA expression and plasma IL-6 concentration. CAPD treatment stimulated the production of IL-6 to a lesser extent than hemodialysis treatment.

Adult↗

PubMed2000

An effective ultrasonic strain measurement-based shear modulus reconstruction technique for superficial tissues--demonstration on in vitro pork ribs and in vivo human breast tissues.

An effective shear modulus reconstruction technique is described which uses ultrasonic strain measurements for diagnosis of superficial tissues, i.e. our previously developed ultrasonic strain measurement and shear modulus reconstruction methods are combined and enhanced. The technique realizes very low computational load, yet yields fairly high quantitativeness, high stability and spatial resolution, and large dynamic range. The suitability of the method is demonstrated on in vitro pork ribs and in vivo human breast tissues (fibroadenoma and scirrhous carcinoma).

Adenocarcinoma, Scirrhous↗