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Biomedical subjects

H Kuwabara

Publications and source records attributed to H Kuwabara.

At least 19 recordsLinked to original sources

In vivo measurement of the serotonin transporter with (S)-([18F]fluoromethyl)-(+)-McN5652.

The radiolabeled serotonin transporter (SERT) ligand [(11)C](+)-McN5652 has recently been used in clinical positron emission tomography (PET) studies for SERT imaging. However, this radioligand offers disadvantages in routine clinical settings because of its short radioisotope half-life (eg PET facilities within hospitals without a cyclotron need to acquire such radioligands from distant cyclotron units for clinical use). S-([(18)F]fluoromethyl)-(+)-McN5652 ([(18)F](+)-FMe-McN5652) is an analogue which has been synthesized newly, and has a significantly longer radioisotope half-life. In the porcine brain, it demonstrates the same characteristic distribution pattern of serotonin-uptake sites like the (11)C-labeled congener with the highest binding in the midbrain and thalamus and the lowest in the cerebellum and occipital cortex. It shows a 30% higher blood-brain transfer and a slower peripheral metabolism than [(11)C](+)-McN5652. Rather uniform brain binding was observed after injection of the pharmacologically inactive radiolabeled enantiomer, or after pretreatment with the highly selective SERT inhibitor citalopram. The norepinephrine uptake inhibitor maprotiline did not show any inhibitory effect. Using a one-tissue compartment model (K(1), k"(2)) or a two-tissue compartment model (K(1) to k(4)) with or without constraints for calculation, the regional binding parameters of [(11)C](+)-McN5652 and [(18)F](+)-FMe-McN5652 are highly correlated among each other and with the SERT density, as determined by in vitro binding of [(3)H]citalopram. Using constraints to correct for the free fraction and nonspecific binding of the radiotracers, a considerable increase of the midbrain-occipital cortex ratios with higher values for [(18)F](+)-FMe-McN5652 compared to [(11)C](+)McN5652 was revealed. It is concluded that [(18)F](+)-FMe-McN5652 has better features than [(11)C](+)McN5652 for SERT imaging with PET.

Animals↗

Overexpression of granulocyte colony-stimulating factor induces severe osteopenia in developing mice that is partially prevented by a diet containing vitamin K2 (menatetrenone).

Mice transgenic for granulocyte colony-stimulating factor (G-CSF) exhibit severe osteopenia with an increase of osteoclast number and acceleration of bone resorption in adult mice. To examine the effect of G-CSF overexpression on developing bone, bone mineral density levels were examined from 4 weeks through 36 weeks after birth. Peak bone mass was observed at around 24 weeks of age irrespective of G-CSF expression. Apparent osteopenia was observed as early as 4 weeks of age without detectable developmental retardation in bone length and skeletal structure. Morphological examination confirmed a reduction of cancellous bone and cortical bone at this early stage of life, indicating that overexpression of G-CSF results in apparent osteopenia in developing mice, similar to that in adult animals. The effect of vitamin K2 (menatetrenone) (MK4) on bone phenotypes during development was then examined. Mice were fed chow containing either 0.05 mg MK-4 per 100 g or 20.0 mg MK-4 per 100 g for 12 weeks as the control and experimental diets, respectively. This treatment did not change bone length, irrespective of the type of mouse or diet. Peripheral quantitative computed tomography (pQCT) revealed an increase of in CT value bone of MK4-treated mice. Taken together, these results indicate that overexpression of G-CSF induces an apparent reduction of bone mass and results in osteopenia in developing mice. The bone reduction was partially restored by feeding the mice MK4, suggesting a choice for treatment on the osteopenia induced by G-CSF.

Animals↗

Double-injection FDG method to measure cerebral glucose metabolism twice in a single procedure.

UNLABELLED: [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be used to examine changes in cerebral glucose metabolism in two physiological conditions. We proposed and evaluated a double injection-single session FDG method with biological constraints for this purpose. METHODS: Simulated brain time-radioactivity curves (TACs) generated by using a plasma TAC from an actual study and physiological combinations of input values in a kinetic model were analyzed to evaluate the accuracy of the proposed method. The reproducibility of the estimated values obtained by this method was tested in five normal volunteers who were studied with a dynamic PET scan and two injections of FDG in a single session while fasting. RESULTS: The simulation study showed that the estimated values obtained by the proposed method agreed well with the input values. In the human study, plasma glucose levels were 5.3 +/- 0.2 and 5.0 +/- 0.2 mM in the first and second measurements, respectively. The difference between the plasma glucose measurements was small but statistically significant (p < 0.05). Although no systematic deviations were noted in K*1 or rCMRglc, there were small deviations in K* (less than 10%) and LC (less than 5%) with a statistical significance (p < 0.01). CONCLUSION: The deviation between the measurements in K* and LC seemed to relate to the difference in the plasma glucose level. The double-injection FDG method with biological constraints can be used to estimate rCMRglc and LC sequentially in a single PET scanning session.

Blood Glucose↗

Obsessional personality features in employed Japanese adults with a lifetime history of depression: assessment by the Munich Personality Test (MPT).

BACKGROUND: Although a number of studies have reported on the association between obsessional personality features as measured by the Munich Personality Test (MPT) "Rigidity" scale and depression, there has been no examination of these relationships in a non-clinical sample. METHODS: The dimensional scores on the MPT were compared between subjects with and without lifetime depression, using a sample of employed Japanese adults. The odds ratio for suffering from lifetime depression was estimated by multiple logistic regression analysis. To diagnose a lifetime history of depression, the Inventory to Diagnose Depression, Lifetime version (IDDL) was used. RESULTS: The subjects with lifetime depression scored significantly higher on the "Rigidity" scale than the subjects without lifetime depression. In our logistic regression analysis, three risk factors were identified as each independently increasing a person's risk for suffering from lifetime depression: higher levels of "Rigidity", being of the female gender, and suffering from current depressive symptoms. CONCLUSION: The MPT "Rigidity" scale is a sensitive measure of personality features that occur with depression.

Adolescent↗

Neural activation during frequency-memory performance.

Lesion studies have demonstrated that frequency memory, or memory for the frequency of occurrence, is associated with prefrontal and not temporal lobe lesions. This study examined neural activation during performance on a frequency-memory-judgment task and a recognition-memory task, both using words. Relative to a control task, the authors observed peaks of activation during frequency-memory performance in the left ventrolateral prefrontal cortex (BA 45) and other areas typically associated with working memory (dorsolateral prefrontal cortex, posterior parietal cortex). Recognition performance was associated with activation in the same left ventrolateral prefrontal location as was observed with frequency memory. When comparing activation during frequency memory with activation during recognition memory, the authors found a suppression of activation in the hippocampus bilaterally during frequency memory. This study supports a neuroanatomical distinction between frequency and recognition memory.

Adult↗

Overexpression of the granulocyte colony-stimulating factor gene impairs bone morphogenetic protein responsiveness in mice.

Granulocyte colony-stimulating factor (G-CSF) is the major hematopoietic growth factor regulating the production and differentiation of neutrophils. We previously demonstrated that permanent overexpression of G-CSF in transgenic mice produces a dramatic enlargement of the bone cavity and reduction of bone mass. This phenotype was shown to be associated with an increase of osteoclast-mediated bone resorption. As a way of determining the role of G-CSF in bone formation in vivo, an ectopic bone was induced subcutaneously into G-CSF transgenic mice by bone morphogenetic protein (BMP)-2, a potent initiator of bone and cartilage from undifferentiated mesenchymal cells. A BMP-2/atelocollagen pellet containing recombinant human BMP-2 was implanted into a dorsal subfascial pocket. At one week after implantation, proliferation of mesenchymal cells around the implant was significantly decreased in transgenic mice compared with control mice. At three weeks, an ectopic bone containing bone marrow was formed both in transgenic and control mice. However, the ectopic bones of the transgenic mice were smaller and less consistent than those of control mice, and the calcium contents were reduced to 56.2% of those of controls. The ectopic bone in the G-CSF mice showed poor development of both lamellar and trabecular bone. Semiquantitative reverse transcription-polymerase chain reaction analysis of the ectopic bone at 3 weeks disclosed no significant differences in the mRNA levels of type I collagen, osteopontin, and osteocalcin between G-CSF mice and control mice. Immunohistochemical study in G-CSF mice showed reduced staining of osteocalcin in the bone matrix surrounding the reduced number of osteoblasts. The half-life of BMP in the implants was prolonged to 7 to 9 days in the G-CSF mice, whereas it was 5 days in the control mice. Collectively, the permanent expression of G-CSF may retard the differentiation process of osteoblasts by impairing the initial induction of mesenchymal cells, resulting in reduction of bone mass, suggesting that G-CSF regulates the bone metabolism by modulating both osteoclast and osteoblast function. Furthermore, it is suggested that G-CSF is a potent modulator of the BMP-2 signal pathway in vivo.

Animals↗

Quantification of intrahepatic non-uniform distributions for assessing impaired function of liver using 99Tcm-DTPA-galactosyl serum albumin liver SPECT scintigraphy.

Quantitative evaluation of intrahepatic non-uniform distribution was attempted by functional volumetric analysis of liver single photon emission computed tomography (SPECT) scintigraphy using 99Tcm-diethylenetriaminepentaacetic acid galactosyl serum albumin (99Tcm-GSA) (185 MBq). A total of 148 patients were classified into three groups: diffuse liver disease, liver disease with space-occupying lesions, and non-hepatic disease. The volume obtained at the 10% cut-off threshold from reconstructed liver-specific SPECT images was assumed to be the functional total hepatic volume, and the functional volume rates were calculated every 10% threshold width from 10% to 100%. The hepatic distribution index (D index) was calculated from the sum of absolute differences from the control. The hepatic D index in liver cirrhosis was significantly higher than in hepatitis and other diffuse liver diseases, and the index in liver disease with primary malignant neoplasm was significantly higher than in liver disease with metastasis or a benign-space occupying lesion. Additionally, it was significantly negatively correlated with LHL15, and positively correlated with the clinical severity. However, in stages II and III, with which LHL15 did not significantly correlate, the hepatic D index matched the severity of hepatic impairment. The hepatic D index evaluates distribution of functional hepatocytes and may provide a new clinical method for quantitatively assessing hepatic impairment.

Hepatitis↗

Occludin regulates actin cytoskeleton in endothelial cells.

Occludin is a major membrane component of tight junctions of endothelial cells, though the role of this molecule is not fully understood. RLE cells, derived from rat lung endothelial cells, express a negligible level of occludin with clear expression of E-cadherin and ZO-1 at cell junctions. Introduction of occludin by transfection induced clear junctional expression of occludin with few or no changes of expression of E-cadherin and ZO-1. The paracellular barrier function, as determined by transelectrical resistance and flux of non-ionic small molecules, was not detectably upregulated. When cells expressing occludin were cocultured with RLE cells null for occludin, clear junctional expression of occludin was observed irrespective of the expression of occludin on the apposing cells. Cortical actin was developed at the site of these occludin positive cell junctions. Treatment of cells with an actin depolymerizing agent, mycalolide B, abolished junctional expression of occludin together with E-cadherin and circumferential actin. ZO-1 showed relative resistance to this actin depolymerizing treatment and was maintained at the cell junctions, though fragmentation of immunoreactivity was detectable. Collectively, junctional expression of occludin was not associated with paracellular barrier function in this cell line. There was, however, a close correlation of occludin with the actin cytoskeleton, indicating a role of occludin as an important molecule in the regulation of the actin cytoskeleton in endothelial cells.

Actins↗

Spectrophotometric analysis of 5-coordinate cobalt(II) species for ligand substitution of hexakis(acetonitrile)cobalt(II) with bulky 1,1,3,3-tetramethylurea in noncoordinating nitromethane.

The ligand substitution reaction of [Co(an)6]2+ (an = acetonitrile) with 1,1,3,3-tetramethylurea (TMU) in the noncoordinating solvent, nitromethane, was spectrophotometrically investigated by titration. The observed spectral changes were analyzed using a model with the four steps of ligand substitution. The component complexes involved in the substitution were found to be 6-coordinate [Co(an)6]2+ and [Co(an)5(tmu)]2+, 5-coordinate [Co(an)3(tmu)2]2+ and [Co(an)2(tmu)3]2+, and 4-coordinate [Co(tmu)4]2+. The logarithmic values of the stepwise equilibrium constant are 2.17 +/- 0.26, 1.06 +/- 0.15, 1.19 +/- 0.06, and -0.4 +/- 0.4 at 25 degrees C. The decrease in the coordination number of the Co(II) ion from 6 to 5 during the formation of [Co(an)3(tmu)2]2+ and from 5 to 4 during the formation of [Co(tmu)4]2+ is ascribed to the steric repulsion between the coordinating bulky TMU molecules.

Journal Article↗

[Successful second transplant from one-locus HLA-mismatched unrelated donor for graft rejection following initial transplant from another unrelated donor in a patient with chronic myelogenous leukemia].

We report a patient with chronic myelogenous leukemia who received a second transplant from a one-locus HLA-mismatched unrelated donor after rejection of an initial bone marrow graft. For the first transplant, HLAs were fully matched, conditioning with busulfan + cyclophosphamide (CY) was applied, and cyclosporin A + short-term methotrexate (sMTX) was used for prophylaxis against GVHD. A complete chimera was not obtained, and the graft was rejected on day 122. For the second transplant, there was a one-HLA locus (DR) mismatch, conditioning was done with total body irradiation + cytarabine + CY, and GVHD prophylaxis consisted of FK506 + sMTX. Engraftment was obtained on day 27, and no graft failure was occurred at the time of writing. This case suggests that strong immunosuppression may have prevented rejection of the second bone marrow graft.

Adult↗

Clinicopathological study of mucous pooling referred to as mucinous component (MUC) in colorectal submucosal invasive carcinomas.

We investigated the significance of a pool of mucin, individually termed mucinous component (MUC), at the leading invasion edge of colorectal submucosal invasive carcinoma (SIC). In particular, we studied the correlation between pathological adverse prognostic factors and stainability of the mucosubstances and tumor-associated glycoconjugates in MUC. We demonstrated that MUCs were present in 21% of SICs, and 20% of SICs with MUC were involved in metastasis or recurrence, while only 6% of SICs without MUC were positive for it (p=0.005). SICs with MUC showed strong staining of carcinoembryonic antigen and Ulex europaeus I in the MUCs as well as in the cancer cells with high-grade atypia. Moreover, the mucins in MUCs predominantly stained for sialomucin. This study was the first to investigate the importance of mucous nodules in colorectal SIC. We concluded that MUC in SIC would be an important adverse prognostic factor, and that we should at least consider employing a similar treatment strategy for it to advanced colorectal carcinoma.

Adenocarcinoma↗

Abdominosacral repair for a rectovaginal fistula with anastomotic stenosis after low anterior resection report of a case.

The management of a postoperative rectovaginal fistula after low anterior resection for rectal cancer is difficult and requires reconstruction of the anastomotic site and fistula. The results of reconstructive operation are often unsatisfactory. Herein, we describe our reconstruction technique using the posterior approach through the vaginal lumen for a high rectovaginal fistula repair. This reconstructive operation is useful for postoperative rectovaginal fistulas accompanied by severe stenosis of the anastomotic site following low anterior resection for rectal cancer.

Aged↗

Effect of partial volume correction on estimates of the influx and cerebral metabolism of 6-[(18)F]fluoro-L-dopa studied with PET in normal control and Parkinson's disease subjects.

The poor spatial resolution of positron emission tomography (PET) is a limiting factor in the accurate assay of physiological processes investigated by compartmental modeling of tracer uptake and metabolism in living human brain. The radioactivity concentration in a region-of-interest is consequently altered by loss of signal from that structure and contamination from adjacent brain regions, phenomena known as partial volume effects. We now apply an MRI-based algorithm to compensate for partial volume effects in the special case of compartmental modeling of the cerebral uptake of 6-[(18)F]fluoro-L-dopa (FDOPA), an exogenous substrate of dopa decarboxylase. High-resolution MRI scans were obtained from normal volunteers (n = 4) and patients with Parkinson's disease (n = 4) in order to segment specific brain regions and calculate the partial volume correction factors. Dynamic 2D PET scans were acquired during 90 min following intravenous infusion of FDOPA. After partial volume correction, the apparent net blood-brain clearance of FDOPA (K(i)) was greatly increased in caudate and putamen of normal subjects and in caudate of Parkinson's disease patients. The equilibrium distribution volume of FDOPA (V(D)(e)) in cerebral cortex increased by 35% in all subjects. Using a two-compartment model, the relative activity of dopa decarboxylase with respect to FDOPA (k(D)(3)) in the basal ganglia was increased 2-3 times in normal subjects, to the range obtained previously in brain of living rat. The partial volume correction also increased the magnitude of k(D)(3) in caudate of Parkinson's disease patients, but did not alter k(D)(3) in putamen. A three-compartment model correcting for elimination of decarboxylated metabolites also yielded higher estimates of k(D)(3), but with a penalty in precision of the estimates. Together, these observations suggest that the limited spatial resolution of PET results in substantial underestimation of the true rate of FDOPA uptake and metabolism in vivo, and may also tend to obscure regional heterogeneity in the neurochemical pathology of Parkinson's disease.

Adult↗

Induction of apoptosis and inhibition of DNA topoisomerase-I in K-562 cells by a marine microalgal polysaccharide.

We have previously purified an extracellular polysaccharide, D-galactan sulfate associated with L(+)-lactic acid, produced from a marine microalga Dinoflagellate Gymnodinium sp. A3 (GA3). The GA3 polysaccharide, irrespective of presence or absence of lactic acid, exhibited significant cytotoxicity, which is based on an induction of apoptotic cell death, toward human myeloid leukemia K562 cells. Furthermore, we found that the GA3 polysaccharide with or without lactic acid possesses an inhibitory effect on topoisomerase-I (topo-I). The potent cytotoxic effect of GA3 polysaccharide may result from its inhibitory effect on topo-I, because the topo-I inhibition is known to trigger apoptotic cell death.

Animals↗

The relationship between personality, dysfunctional parenting in childhood, and lifetime depression in a sample of employed Japanese adults.

BACKGROUND: Few studies have explored the relationship between personality, dysfunctional parenting in childhood, and adult depression. METHODS: Parental rearing styles and personality scores as measured by the Parental Bonding Instrument (PBI) and the Interpersonal Sensitivity Measure (IPSM) were compared in a group of employed Japanese adults with and without a lifetime history of depression. The diagnosis was provided by the Inventory to Diagnose Depression, Lifetime version (IDDL). To estimate the effects of the PBI and the IPSM scores on lifetime depression, a multiple logistic regression analysis was performed. RESULTS: Subjects with lifetime depression were seen to have significantly lower scores on the PBI 'care' and higher scores on the IPSM than the subjects without lifetime depression. Lower levels of maternal care and higher levels of 'interpersonal sensitivity' each independently increased the risk for lifetime depression. LIMITATIONS: The findings of the present study may not be conclusive since the data were retrospectively obtained. CONCLUSION: Dysfunctional parenting and personality seem to be correlated by lifetime depression, but it is uncertain whether they are independent risk factors

Adult↗

Synchronous four primary lung adenocarcinoma associated with multiple atypical adenomatous hyperplasia.

A 69-year-old woman with synchronous bilateral 4 primary lung adenocarcinoma accompanied by multiple atypical adenomatous hyperplasia (AAH) is described. The patient was found to have bilateral multiple tumors during a preoperative chest CT evaluation which was performed for the previously-diagnosed adenocarcinoma of the right middle lobe. Since intraoperative diagnosis of the left nodular lesion was adenocarcinoma and judged to be a pulmonary metastasis, a lobectomy of the right middle lobe only was performed. Postoperative pathological diagnosis including immunohistochemical findings demonstrated that the bilateral lesions were synchronous multiple primary adenocarcinoma, independent of each other and associated with multiple AAH. This case suggests the possibility of the AAH-adenocarcinoma sequence in the development of lung cancer. In addition, the strategy of treatment for synchronous multiple adenocarcinoma should be considered.

Adenocarcinoma↗

Verbal working memory and solvent exposure: a positron emission tomography study.

Neuropsychological studies have documented frontal dysfunction in patients with a history of exposure to organic solvents. The deficits typically observed in these patients appear to be related to working memory (WM). This study used [15O] water positron emission tomography (PET) to examine the pattern of neural activation during verbal working memory in patients with a history of exposure to solvents. Six individuals with solvent exposure were compared with 6 age- and education-matched controls. On the 2 WM tasks examined with PET, with equivalent task performance, participants with solvent exposure demonstrated frontal peaks that were atypical for the tasks, whereas the posterior peaks were typical for the tasks. The results support frontal dysfunction and compensatory use within anterior regions of the WM system in patients with solvent exposure.

Brain↗