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Biomedical subjects

M Kubota

Publications and source records attributed to M Kubota.

At least 109 records · Page 6Linked to original sources

Potent preventive action of curcumin on radiation-induced initiation of mammary tumorigenesis in rats.

This investigation evaluated the preventive effect of curcumin on radiation-induced tumor initiation in rat mammary glands. Fifty-four female rats were mated and then divided into two groups at day 11 of pregnancy. As the control group, 27 rats were fed a basal diet during the experimental period. As the experimental group, 27 rats were fed a diet containing 1% curcumin between day 11 of pregnancy and parturition (day 23 of pregnancy). All rats of both groups received whole body irradiation with 1.5 Gy gamma-rays from a (60)Co source at day 20 of pregnancy and were then implanted with a diethylstilbestrol pellet 1 month after weaning. A high incidence (70.3%) of mammary tumorigenesis was observed in the control group. The tumor incidence (18.5%) was significantly reduced in the rats fed curcumin during the initiation stage. The appearance of the first palpable tumor was delayed by 6 months in the curcumin-fed group and the average latent period until the appearance of mammary tumors was 2.5 months longer in the curcumin-fed group than in the control group. By histological examination, the proportion of adenocarcinoma (16.7%) in total tumors in the curcumin-fed rats was found to be decreased to half that (32.1%) in the control group. Compared with the control rats, the body weight of rats in the experimental group was decreased slightly by administration of the curcumin diet from day 11 of pregnancy, in spite of a similar intake of diet, but had recovered to the level of the control by the end of the experiment. At the time of irradiation, curcumin did not have any effect on organ weight or on the development and differentiation of mammary glands of pregnant rats. In addition, the serum concentrations of fatty acids, thiobarbituric acid-reactive substances and ovarian and pituitary hormones, except LH, remained at the control level. Also, no change in litter size and body weight of pups born from curcumin-fed rats indicated no toxicity of curcumin. These results suggest that curcumin does not have any side-effects and is an effective agent for chemoprevention acting at the radiation-induced initiation stage of mammary tumorigenesis.

Animals↗

Three cases of malignant lymphoma of the breast.

We report three cases of malignant lymphoma (ML) of the breast and discuss diagnosis and management. The first case is a 35-year-old woman who had a left breast tumor. Fine needle aspiration cytology (FNAC) showed ML. Mastectomy was performed without any adjuvant chemotherapy. Histology revealed diffuse large B-cell lymphoma of REAL classification. Seventy one months after surgery, lesions indicating relapse were detected in nodes of the right axilla, mediastinum and para-aorta. She underwent eight cycles of CHOP regimen, but 1 month after the chemotherapy a brain metastasis was detected. The patient then received a high-dose methotrexate regimen with whole-skull irradiation. The second case is a 47-year-old woman who had anterior neck swelling and bilateral breast tumors. Histology of the tumor revealed diffuse large B-cell lymphoma. The patient underwent eight cycles of CHOP regimen and high-dose chemotherapy (HDC) with peripheral blood stem cell transplantation (PBSCT). Forty eight months after the PBSCT, there is no evidence of disease. The third case is a 38-year-old woman who had a right breast tumor. FNAC of the breast tumor showed ML and a CT scan of the chest revealed lymphadenopathy at the crus of the diaphragm. Histology of the tumor revealed low-grade B-cell lymphoma of MALT type. The patient underwent six cycles of CHOP regimen and HDC supported by PBSCT. Eighteen months after the PBSCT, relapse lesions were detected in nodes of the neck, mediastinum and renal hilum. The patient received nine cycles of a THP-COP regimen.

Adult↗

Close association between pulmonary disease manifestation in Mycoplasma pneumoniae infection and enhanced local production of interleukin-18 in the lung, independent of gamma interferon.

To investigate pathophysiologies of Mycoplasma pneumoniae infection from an immunological point of view, we measured the levels of interleukin-18 (IL-18) (originally designated gamma interferon [IFN-gamma]-inducing factor) in 19 serum samples from 10 patients with pneumonia without pleural effusion (ages 1 to 16 years), 3 serum and 13 pleural fluid samples from 11 patients with pleural effusions (ages 11 months to 15 years), and 18 serum and 27 cerebrospinal fluid samples from 24 patients with central nervous system complications (ages 1 to 15 years). IL-18 was measured by a commercially available enzyme-linked immunosorbent assay kit (MBL, Nagoya, Japan). In addition, the levels of tumor necrosis factor alpha, IFN-gamma, IL-6, IL-12, and KL-6 (a mucin-like glycoprotein expressed on type 2 pneumocytes) were measured in selected samples. The results concerning pleural effusions showed that elevated levels of IL-18 in pleural fluid, but not in serum, were solely associated with a sustained fibrotic change of the lung on chest roentgenography which might represent a pathological feature of intraluminal organization. All the pleural fluid samples with elevated levels of IL-18 were positive by PCR for M. pneumoniae DNA. There was no association between IL-18 and IFN-gamma levels in serum or in the pleural fluid. On the other hand, elevated levels of IL-18 in serum, but not in cerebrospinal fluid samples, were observed in the cases complicated by central nervous system involvement, including profound brain dysfunction with seizures. Our study demonstrated that M. pneumoniae can induce IL-18 and that the enhanced local production of IL-18 in the lung is closely associated with pulmonary disease manifestation.

Adolescent↗

Magnetoencephalographic study of giant somatosensory evoked responses in patients with rolandic epilepsy.

We report five patients with rolandic epilepsy associated with giant somatosensory responses to median nerve stimulation, in whom we analyzed the pathophysiologic relationship between rolandic discharges and the somatosensory responses using magnetoencephalography. Four of the five patients showed giant P30m, the current source of which was localized in the primary somatosensory cortex, while the first cortical response, N20m, was not enhanced, except in one patient. The current source of the giant middle-latency component, N70m, was localized posterior to that of N20m, possibly in the posterior parietal cortex, in all patients. The initial positive peak and large negative peak of rolandic discharges were identical to P30m and N70m with respect to the current source localization, wave form, topographic pattern, and time relationship in the electroencephalogram and magnetoencephalogram, and somatosensory evoked magnetic field and somatosensory evoked potential records, respectively. In addition, the secondary sensory cortex was considered to be the generator of the middle-latency component in one patient. In one patient, the current intensity of the N70m was normalized along with clinical improvement and the disappearance of rolandic discharges, whereas those of other somatosensory evoked magnetic field components remained unchanged. Our data suggest that the rolandic discharge generator mechanism in these patients could be closely related to the developmental alteration of excitability in the primary somatosensory cortex, posterior parietal cortex, and secondary somatosensory cortex, which decreased with age, and it could share a common neuronal pathway, at least in part, with the giant P30m-N70m (N90m) in the somatosensory evoked magnetic field through the sequential and parallel processing of somatosensory information.

Case-Control Studies↗

Mechanisms of [2,3-butanedione bis(N4-dimethylthiosemicarbazone)]zinc (Zn-ATSM2)-induced protection of cultured hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.

Hyperexcitation of glutamatergic neurons may play a key role in ischemia-related neurodegeneration. Recent studies have suggested that the zinc ion (Zn2+), which is present in the central nervous system, has a modulatory role in glutamatergic neuron activity. Zinc ions block glutamate-induced depolarizing currents and neuronal damage by binding with zinc sites on the NMDA subtypes. Therefore, we examined the usefulness of zinc as a therapeutic agent for the prevention of ischemic neuronal damage in the brain. In our previous study, 2,3-butanedione bis(N4-dimethylthiosemicarbazonato) zinc complex (Zn-ATSM2), with high brain uptake, showed significant neuroprotective effects against cerebral ischemia in rats when administered systemically. In this study, to elucidate the mechanism of the neuroprotective effect of Zn-ATSM2, we first examined its in vitro protective effects against glutamate-, NMDA- and kainite-induced neurotoxicity in primary cultures of hippocampal neurons. Zn-ATSM2 elicited protective effects against this glutamate- and NMDA-induced neurotoxicity, but did not affect kainite-induced cytotoxicity. In addition, we studied the effects of Zn-ATSM2 on influx of Ca2+, which undergoes modification subsequent to NMDA activation. Zn-ATSM2 significantly decreased glutamate-induced 45Ca2+ uptake. Thus, Zn-ATSM2 protected against glutamate-induced neurotoxicity and its protective effect was, at least in part, due to the blockage of NMDA receptor-mediated Ca2+ influx.

Animals↗

Long-term outcome of endocrine function in patients with neurohypophyseal germinomas.

Since neurohypophyseal germinomas occur at the pituitary and hypothalamic axis in children and adolescents, the endocrinopathy is one of the common and critical QOL determinants. We carried out a retrospective study on the outcome of endocrine function in patients with neurohypophyseal germinoma, in order to improve or preserve pituitary function after treatment. Sixteen patients (7 men and 9 women), aged 6 to 26 years were admitted and followed up for 95.3 (14-197) months. DI was noted in 12 patients in pretreatment and 16 in posttreatment regardless of tumor size. We carried out the replacement of GH in all 8 patients, presenting the symptoms under 15 years of age. Gonadal or gonadotropic, thyroid and adrenal hormones were replaced in 9, 12 and 15 patients, respectively. Patients with large tumor compressing chiasm or hypothalamus needed hormonal replacement such as gonadal or gonadotropic and thyroid hormones more frequently (<0.01) than those with small one. In addition, two patients with a small tumor at the pituitary stalk and the 3rd ventricle floor showed the improvement of secretion pattern in gonadotropins and ACTH after chemotherapy, although they later needed radiation therapy to control the tumor. Based on our study and review of literature, the endocrinological studies before and after treatment demonstrated that pituitary dysfunction present before treatment persisted or worsened even after tumor remission, except for patients with small and localized ones. The poor endocrine results is considered to be largely radiation-related. Chemotherapy alone seems to be insufficient to obtain complete response (CR). To avoid radiation related pituitary injury, combination of 24 Gy or less dosage of radiation and appropriate chemotherapy is essential. The earlier diagnosis by repeatedly using neuroimaging and serum and CSF tumor markers and earlier initiation of treatment, before irreversible pituitary-hypothalamic damage occurs, contributes to improvement of the outcome of pituitary functions in patients with neurohypophyseal germinomas.

Adolescent↗

Women's anxiety in old age and long-term care provision for the elderly.

The purpose of this study was to verify the differences in women's anxiety in old age, the expected long-term care provision, and the expected final location for terminal care for the women themselves and for their parents. In addition, we examined factors that related to their anxiety and needs. The subjects were 1,000 women of the Seikatsu Club customer cooperative association in Chiba; 539 responded to our survey. The subjects were more anxious for their parents than for themselves. They more strongly expected long-term care for their parents to be provided by their family than they expected the same for themselves. Although no differences were observed in the expected location for terminal care, most subjects expected their home to be the terminal location. Analysis by the multiple logistic regression model indicated that the following factors were significantly related to the anxiety in old age: age odds ratio [OR = 1.81], employment [OR = 2.25] for women, and planning to live with parents [OR = 2.42], housing conditions [OR = 0.56] for parents. The following factors were significantly related to the expected long-term care provision: age [OR = 2.22] for women, and age [OR = 2.15], living with parents [OR = 3.58], and employment [OR = 2.33] for parents. Age [OR = 2.14] for women, and planning to live with parents [OR = 2.09] for parents were significantly related to the expected final location of terminal care. This survey showed that women expected long-term care for their parents to be provided by their family, while many expected public long-term care services for themselves. This is the biggest difference in women's outlook on long-term care for their parents and for themselves. Multivariate analysis suggested that women aged 40 years or over, who will need long-term care in the future, tended to expect public home care services for themselves. It is virtually certain that the demand for public home care services will increase in the future.

Adult↗

Detection of ornithine transcarbamylase deficiency heterozygotes by measuring of urinary uracil.

The importance of detecting heterozygosity for X-linked ornithine transcarbamylase deficiency is well known. Although the DNA analysis and the allopurinol loading tests are commonly used for this purpose, both methods require complicated procedures. In order to establish a simple test for detecting female heterozygotes, we examined the uracil and orotic acid in single-voided urine samples from 70 healthy women, and from 12 asymptomatic females with ornithine transcarbamylase deficiency. Based on the results of healthy women, we were able to determine a screening cut-off line of 11.9 micromol/mmol creatinine (mean +/- 1SD in logarithmic form) for uracil. Using this cut-off line, the sensitivity of OCT heterozygotes was 100%. We were also able to establish a second cut-off line of 28.9 micromol/mmol creatinine (mean +/- 3SD in logarithmic form) for diagnosis. Using this second cut-off line, the specificity of OCT heterozygotes was 100%. Our study has shown that the measurement of urinary uracil is a relatively simple and effective method for detecting female heterozygotes.

Female↗

Addition of antibacterial agents to MMA-TBB dentin bonding systems--influence on tensile bond strength and antibacterial effect.

To produce a bonding system which has both high bond strength and antibacterial properties, an antibacterial agent (vancomycin: VCM or metronidazol: MN) was added to the PMMA powder of 4-META/MMA-TBB resin (CB). The influence of the addition of an antibacterial agent on tensile bond strength to dentin and the antibacterial effect were investigated in this study. Forty-seven freshly extracted bovine first or second incisors were used to measure the tensile bond strength to dentin. The bond strengths to bovine dentin were not significantly decreased by addition of VCM (1%, 2%, 5%), or MN (1%) to CB (p < 0.05). The antibacterial effect of CB containing antibacterial agent on six strains of bacteria was investigated by the agar plate diffusion method, analyzing the appearance of the inhibition zone around a resin disk following anaerobic culturing. The resin disks containing VCM showed antibacterial effects on all of the strains examined; the widths of the inhibition zones were 4-15 mm. The resin disks containing MN showed antibacterial effects on three strains; the widths of the inhibition zones were 0-4 mm. It was thus possible to produce a bonding system with both antibacterial effect and high tensile bond strength by addition of VCM to PMMA powder.

Acrylic Resins↗

Analysis of the prognostic factors relating to better clinical outcome in ganglioneuroblastoma.

PURPOSE: To elucidate the precise reason for the better prognosis in ganglioneuroblastoma (GNB) than in neuroblastoma (NB), the prognostic factors (age at diagnosis, stage at diagnosis, primary site, N-myc amplification, Shimada classification, and ploidy) were analyzed. METHODS: A retrospective analysis of the 57 neuroblastoma cases (20 GNB cases and 37 NB cases), that had not been detected by mass screening over the past 19 years at the authors' institute, was carried out. RESULTS: A Kaplan-Meier analysis of the 5-year survival rates were 67.2% and 35.1% in cases of GNB and NB, respectively, and these rates were significantly higher in GNB (logrank test; P = .04631). No significant differences were seen between GNB and NB regarding the rate in patients 1 year of age or older (95.0% v 78.4%; P = .1005), the rate of advanced cases (60.0% v 78.4%, P = .1406), the rate of an unfavorable histology (Shimada classification, 54.5% v 68.4%, P = .4473), or the diploid pattern rate (75.0% v 76.9%, P = .9200). However, N-myc amplification was found exclusively in NB (amplified cases per examined cases; 15/31), and all cases with N-myc amplification died. When the 5-year survival rate was evaluated in the patient without N-myc amplification between GNB and NB, no significant difference was observed (logrank test; P = .8568). CONCLUSION: The better prognosis in patients with GNB was thus thought to be exclusively related to an absence of N-myc amplification.

Ganglioneuroblastoma↗

[Three pediatric cases of erythroleukemia: review of the literature on prognostic factors].

We encountered 3 patients with erythroleukemia who showed differing outcomes. The first patient was an 11-year-old girl who was treated with an ANLL 91 national protocol followed by bone marrow transplantation from an HLA-identical brother. She is still in complete remission after 6 years. The second patient was a 15-year-old girl. Treatment with low dose Ara-C was effective. She experienced a relapse once, but achieved her second remission with low dose-Ara-C plus vitamin D. Up to the present, she has maintained remission for 5 years. The third patient was a 1-month-old girl who initially presented with an increase of proerythroblasts with infiltration to the liver. Although her response to Ara-C and etoposide was favorable, she died of a generalized fungal infection in the leukopenic phase. Chromosomal analyses of bone marrow cells were normal for patients 1 and 2, but patient 3 had an abnormal complex karyotype. We think the prognosis for erythroleukemia in childhood is not necessarily poor in all cases. Appropriate treatment should be based on the patient's age, the proportion of proerythroblasts, and the presence of chromosomal abnormalities.

Adolescent↗

Detection of TT virus sequences in children with liver disease of unknown etiology.

DNA sequences of TT virus (TTV) in 55 serum samples taken from 20 children with liver disease of unknown etiology (16 with acute liver disease, 2 with fulminant hepatitis, and 2 with chronic liver disease) and from 35 healthy children as controls were examined by using the hemi-nested polymerase chain reaction (PCR). The PCR was carried out using the established primers (NG059, NG061, NG063) to amplify TTV DNA sequences. The sequences were detected in 6 of the 20 patients (30.0%) with liver disease and in 5 of the 35 healthy children (14.2%) by direct gel analysis. There was no significant difference between the prevalence of liver disease patients and controls. However, both patients with fulminant hepatitis and both patients with chronic hepatitis had TTV DNA sequences. Four of the six TTV isolates from liver disease patients were genotype 1a, whereas only one of the five TTV isolates from controls was genotype 1a. Although the study population was small, it is possible that genotype 1a of TTV might be more pathogenic than other genotypes in children.

Adolescent↗

[Clinical data obtained through coagulation testing suggests that hypothermia exerts influence on a patient's blood coagulation reaction].

It often takes longer to achieve hemostasis when performing an operation on a patient in cerebral hypothermia therapy than in a normal patient, despite the lack of abnormal clinical blood coagulation findings, and this study was conducted to investigate the cause of delays in coagulation in patients with hypothermia. In this study, 93 samples of plasma were collected at our center from 10 patients(7 men and 3 women; mean age, 33.7) who were in cerebral hypothermia therapy with a urinary bladder temperature maintained at 32-34 degrees C. Each sample was divided into two, and PT(prothrombin time) and APTT(activated partial thromboplastin time) were measured at the normal analysis temperature of 37 degrees C in one sample, and at the hypothermia temperature of 32-34 degrees C in the other sample. The results showed that PT and APTT tended to shorter at 37 degrees C, than those measured at 32-34 degrees C. Thus, we suggest that it is necessary to regulate the temperature of patients with accidental hypothermia or in whom hypothermia therapy is performed.

Adult↗

[Proteinkinase B/Akt].

Proteinkinase B/Akt, which was identified in 1991, is a serine/threonine kinase that becomes activated at two residues, Thr308 and Ser473. Activated proteinkinase B/Akt activates glycogen synthesis, protein synthesis, and most important, the survival and proliferation of cells. It was recently reported that mutant preseniline-1 downregulates proteinkinase B/Akt and that lithium treatment changes proteinkinase B/Akt activity. Proteinkinase B/Akt thus seems important from a psychiatric point of view.

Aging↗

Effect of temporary materials on bond strength of resin-modified glass-ionomer luting cements to teeth.

PURPOSE: To evaluate the effect of temporary materials on the bond strength of resin-modified glass-ionomer luting cements to teeth. MATERIALS AND METHODS: 240 freshly extracted bovine central incisors were ground to expose enamel and dentin surface. Fuji Lute and Vitremer Luting Cement were bonded to enamel and dentin surfaces after pretreatment for 1 week with (1) a eugenol-containing cement (Propac), (2) a eugenol-free cement (Freegenol Temporary Pack), (3) a polycarboxylate cement (HY-Bond Temporary Cement Hard), (4) a chemically cured temporary restorative resin (Plast Seal), and (5) a light-cured temporary restorative resin (Fermit). The flattened enamel and dentin surfaces were used as controls. After bonded specimens were stored in water at 37 degrees C for 24 hrs, the tensile bond strength was measured at a crosshead speed of 0.5 mm/min. The data were statistically analyzed by one-way ANOVA and Dunnett's Post-hoc Procedure (P < 0.05). RESULTS: Plast Seal had no adverse effect on the tensile bond strength of Fuji Lute on both enamel and dentin surfaces, while the other temporary materials revealed significant decrease in bond strength. In Vitremer Luting Cement, Propac, and Fermit, as well as Plast Seal demonstrated tensile bond strengths similar to the controls.

Analysis of Variance↗

Gene structure of mouse BIT/SHPS-1.

BIT/SHPS-1/SIRPalpha/P84 is a unique molecule with a high degree of homology with immune antigen recognition molecules (immunoglobulin, T-cell receptor and MHC), and is highly expressed in the brain. The extracellular region contains three immunoglobulin-like domains (V-type, C1-type and C1-type), and the intracellular region contains two signalling motifs that interact with SHP-2 protein tyrosine phosphatase. BIT-coated plates support cell-substrate adhesion and neurite extension of neurons, and BIT participates in neuronal signal transduction. Diversity of the V-type domain sequences of human BIT has been reported. In the present study we analysed the structure of the mouse BIT gene (Bit). The protein coding region consists of eight exons corresponding to a signal peptide, a V-type domain, a C1-type domain, a C1-type domain, a transmembrane region and three parts of one cytoplasmic region. The two signalling motifs are encoded in one exon. Four splicing forms of mouse BIT were revealed. We also found the sequence diversity in three mouse strains, namely BALB/c, 129/Sv and C57BL/6. The substitution patterns of amino acids and nucleotides indicate positive pressure to alter the amino acids in the V-type domain in evolution. Immunoblot analyses showed that mouse BIT and human BITalpha are predominantly expressed in the brain. On the bases of these findings we discuss the possibility that BIT contributes to the genetic individuality and diversity of the brain.

Alternative Splicing↗

Layer-specific horizontal propagation of excitation in the auditory cortex.

Optical imaging was conducted in rat auditory cortex slice preparations to study how horizontal excitation propagates in the cerebral cortex. When a horizontal cut was made between supragranular and infragranular layers, electrical stimulation of layer II/III elicited horizontally propagating excitation in supragranular layers with the same propagating velocities as those seen before a cut was made. Electrical stimulation of layer VI or the border between the white matter and layer VI also elicited horizontally propagating excitation in infragranular layers with the same propagating velocities as those seen before a cut was made. These results suggest that the horizontal propagation of excitation in supragranular and infragranular layers can occur independently in the auditory cortex.

Animals↗