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Biomedical subjects

R Goto

Publications and source records attributed to R Goto.

At least 37 records · Page 2Linked to original sources

[Left atrial pressure gradient and right heart failure secondary to compression of the left atrium by a huge ascending aortic aneurysm: a case report].

A 71-year-old man was admitted to our department with congestive heart failure on June 28, 1998. He previously had an aortic valve replacement because of aortic regurgitation probably due to annuloaortic ectasia in 1984. Thoracic aortic aneurysm was identified during the postoperative course. Magnetic resonance imaging showed a huge saccular ascending aortic aneurysm of 12 x 11.5 x 9.5 cm size, which had severely compressed the left atrium. Doppler echocardiography documented an accelerated flow (2.2 m/sec) in the left atrium in early diastole. The calculated pressure gradient was 19 mmHg. All pressures in the right heart system were elevated. This is the first case of pulmonary hypertension and right heart failure secondary to compression of the left atrium in a patient with thoracic aortic aneurysm.

Aged↗

Selective visual and auditory attention toward utterances-a PET study.

The purpose of this study was to reveal functional areas of the brain modulating processing of selective auditory or visual attention toward utterances. Regional cerebral blood flow was measured in six normal volunteers using positron emission tomography during two selective attention tasks and a control condition. The auditory task activated the auditory, inferior parietal, prefrontal, and anterior cingulate cortices. The visual task activated the visual association, inferior parietal, and prefrontal cortices. Both conditions activated the same area in the superior temporal sulcus. During the visual task, deactivation was observed in the auditory cortex. These results indicate that there exists a modality-dependent selective attention mechanism which activates or deactivates cortical areas in different ways.

Adolescent↗

Contribution of inflammatory cytokine release to activation of resident peritoneal macrophages after in vivo low-dose gamma-irradiation.

The activation mechanism of resident peritoneal macrophages by in vivo gamma-irradiation was investigated. The function of macrophages as accessory cells in concanavalin A-induced proliferation of spleno-lymphocytes (accessory function) was enhanced 4 h after a low-dose irradiation (4 cGy) in vivo, but not in vitro, indicating that low-dose irradiation acts indirectly on the activation of macrophages. Because we expected that macrophages were activated by the recognition of substances damaged by in vivo irradiation, we co-cultured macrophages with oxidized erythrocyte-ghosts. No change was found in their accessory function. The production of inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma), in the supernatant of cocultures of spleno-lymphocytes and macrophages was determined by an ELISA. Production of both increased in the presence of in vivo irradiated macrophages. Furthermore, IL-1 beta production from in vivo-irradiated macrophages treated with recombinant IFN-gamma also was enhanced. The mRNA expression of the cytokines released from macrophages and lymphocytes was determined by RT-PCR. Increases in IL-1 beta mRNA expression were found in both in vivo- and in vitro-irradiated macrophages. In vivo irradiation also enhanced the expression of IFN-gamma mRNA in lymphocytes, whereas there was no change after in vitro irradiation. On the basis of these observations, we propose that the activation of macrophages is caused by interaction with neighboring cells, such as lymphocytes, and by paracrine induction of certain cytokines which is initiated by the small amount of IL-1 beta released by irradiated macrophages.

Animals↗

The role of the left inferior temporal cortex for visual pattern discrimination--a PET study.

We measured regional cerebral blood flow using positron emission tomography in seven normal volunteers during discrimination tasks for visual patterns. For the 'attention to right or left' tasks, the subjects were instructed to press a key when sample and test stimuli presented in the right or left visual fields, respectively, were identical. In the control task, subjects were instructed to press a key on every second presentation of the test stimulus. Both discrimination tasks activated the same area in the inferior temporal sulcus of the left hemisphere. The results indicate that the left inferior temporal cortex plays a dominant role in the discrimination of visual pattern in right handed subjects.

Adult↗

A comparison of Tc-99m HMPAO brain SPECT images of young and aged normal individuals.

The purpose of this study was to examine the normal distribution patterns of 99mTc-HMPAO (HMPAO) in young and aged normal individuals and to clarify differences between the distribution patterns of the two groups by means of an anatomical standardization technique. The tracer distribution was measured with HMPAO and SPECT in 18 normal subjects; age range 20-81 yrs. SPECT images were globally normalized by averaging whole brain radioactivity counts to 100 counts/voxel. The SPECT images for each subject were transformed into the standard brain anatomy by means of a computerized brain atlas, together with each subject's CT images. Mean and SD images for young (28.8 +/- 6.4 yrs) and aged groups (62.3 +/- 10.2 yrs) were then calculated on a voxel-by-voxel basis. Statistically significant differences between young and aged groups were observed in the relative tracer distribution patterns. In the aged group, relative decreases were found in the cortical areas of the frontal and temporal lobes, limbic areas and basal ganglia regions. The results, as visualized changes in tracer distribution patterns with aging, may contribute to more accurate clinical diagnosis.

Adult↗

Distribution of 14 elements in tissues and organs of oceanic seabirds.

The concentrations of 14 trace elements (Li, V, Mn, Co, Cu, Zn, Se, Rb, Sr, Ag, Cd, Cs, Pb, and Hg) were determined in tissues and organs of three species and in the liver of 11 species of seabirds. Comparatively high concentrations of Li, Co, Sr, and V were found in the femur. Cd, Se, Cu, and Mn concentrations were relatively higher in the kidney than in other tissues and organs. Rb, Cs, and Pb concentrations were rather uniform among tissues. Concentrations of essential elements such as Mn, Cu, and Co were comparable among seabird species, except high Cu concentrations in northern giant petrel. Among nonessential elements, concentrations of Cd and Hg were variable according to seabird species. Pb levels were low in all the species. High Se levels (100 microg/g dry weight) were found in the liver of black-footed albatross and grey petrel. There were significant positive correlations between Se and Cd concentrations in three species and between Se and Hg in black-footed albatross, suggesting that Se has an antagonistic action on the toxic effects of Cd and Hg. Concentrations of Li, V, Ag, and Cs were usually low (less than 1 microg/g dry weight).

Animals↗

PET study of pointing with visual feedback of moving hands.

This study was conducted to determine where in the human brain visual feedback of hand movements is processed to allow accurate pointing. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H2 15O in nine normal volunteers while performing one control and two reaching tasks. In all tasks, visual stimuli were presented on a head mounted display (HMD). A target board was placed in front of the subjects bearing six red light-emitting diodes (LEDs) aligned on a circle with a green LED at its center. The center green LED and one of the six red LEDs, randomly selected, were repeatedly switched on and off, alternatively. In the control task, subjects were instructed to gaze at the lit LED. In the two reaching tasks, the reaching with visual feedback (RwithF) task and the reaching without visual feedback (RwithoutF) task, they had to point to the lit red LED with their right index fingers. In the RwithF task, their right hands were visible on the HMD before touching the target, whereas in the RwithoutF task, they were not visible. For each subject, subtraction images of each reaching task minus the control and the RwithF task minus the RwithoutF task were calculated after transformation of PET images into the standard brain shape with an adjustable computerized brain atlas. These subtraction rCBF images were then averaged among the subjects, and significant changes of rCBF were identified. Significant increases in rCBF not only in the RwithF task minus control image but also in the RwithF task minus the RwithoutF task image were observed in the supramarginal cortex, the premotor cortex and the posterior cingulate cortex of the left hemisphere, the caudate nucleus and the thalamus of the right hemisphere, and the right cerebellum and vermis. These results indicate that the supramarginal cortex, the premotor cortex, and the posterior cingulate cortex of the left hemisphere and the cerebellum are involved in integrating visual feedback of hand movements and execution of accurate pointing.

Adult↗

Low-dose irradiation induces expression of heat shock protein 70 mRNA and thermo- and radio-resistance in myeloid leukemia cell line.

We examined the effects of in vitro low-dose irradiation on myeloid leukemia cells (M1 cells) and found that it enhanced the colony-forming ability (CFA) of M1 cells in semi-solid agar. This enhancement was inhibited by treatment with a protein synthesis inhibitor, cycloheximide and with an RNA synthesis inhibitor, actinomycin D, after irradiation. These findings suggested that low-dose irradiation induced the synthesis of some proteins which were attributed to the enhancement of CFA. Since we expected that one species of these proteins were heat shock proteins (hsps), we attempted to detect the hsp70 family by the Western blotting method and inducible hsp70 mRNA by the RT-PCR method. Low-dose irradiation induced the expression of hsp70 mRNA, whereas the enhancement of hsp70 (an inducible isoform) and hsc70 (a constitutively expressed isoform) expression could not be found. Furthermore, the M1 cells showed thermoresistance 1 h after low-dose pre-irradiation, and also showed radioresistance 4 h after irradiation. This time difference after pre-irradiation might be attributed to the different species of proteins in showing resistance to lethal stress. Therefore, some proteins other than hsp70 were believed to be concerned with the augmentation of CFA and the induction of thermo- and radio-resistance.

Animals↗

[2-(omega-phenylalkyl)phenoxy]alkylamines: synthesis and dual dopamine2 (D2) and 5-hydroxytryptamine2 (5-HT2) receptor antagonistic activities.

A series of [2-(omega-phenylalkyl)phenoxy]alkylamines was synthesized and their 5-hydroxytryptamine2 (5-HT2) and/or dopamine2 (D2) receptor antagonistic activities were examined in vitro. [2-(4-Phenylbutyl)phenoxy]alkylamines showed strong inhibition of both 5-HT2 and D2 receptors. In particular, [2-(4-Phenylbutyl)phenoxy]-methylpiperidine derivatives, 10b, 10i and 10q, exhibited potent inhibition. The structure-activity relationships in this series of compounds are discussed.

Amines↗

Mean regional cerebral blood flow images of normal subjects using technetium-99m-HMPAO by automated image registration.

UNLABELLED: The purpose of this study was twofold: to calculate relative uptake values for 99mTc-HMPAO in various regions of the normal brain after alignment and registration to a standard shape and size, and to validate the automated image registration (AIR) program for SPECT-to-SPECT transformation. METHODS: Thirty subjects took part in this study. Technetium-99m-HMPAO brain SPECT and x-ray-CT scans were acquired. SPECT images were normalized to an average activity of 100 counts/pixel. Intersubject accuracy was evaluated on brain images of 17 normal subjects (mean age = 64.9 +/- 8.7 yr). These images were aligned and registered to a standard size and shape with the help of AIR. Realigned images were overlaid on reference images to determine the overlap areas. Intrasubject accuracy was evaluated by realigning 20 degree rotated brain images with an index calculated as: overlap area/(overlap area + nonoverlap area). Anatomical variability between realigned target and reference images was evaluated by measurements on corresponding x-ray-CT scans, realigned using transformations that were established by the SPECT images. Realigned brain SPECT images of 30 normal subjects (mean age = 50.7 +/- 18.7 yr), including those subjects examined in the accuracy validation study, were used to generate mean and s.d. images. Images based on the mean value of each voxel (n = 30) were compared with other mean images prepared by the human brain atlas (HBA) standardization technique on a voxel-by-voxel basis to generate T maps. RESULTS: Accuracy indices were 0.98 +/- 0.006 and 0.99 +/- 0.002 for the intersubject and intrasubject evaluations, respectively. The maximum anatomical variability was 4.7 mm after realignment. Paired Student's t-test comparisons of mean HBA and AIR images revealed statistically significant differences for the deep white matter, pons and occipito-temporal regions. These differences could be explained by variation in the population being studied and the protocol for data handling by AIR and HBA. CONCLUSION: AIR aligns and registers brain SPECT images with acceptable accuracy, without the necessity of MRI or x-ray-CT scans.

Brain↗

[A case of untreatable progressive bladder carcinoma effectively treated by single administration of tegafur and uracil].

Bloody urine was grossly observed and multinodular shadow confirmed in both lungs of an 81-year-old male, who had been referred to our department. The diagnosis was bladder cancer (TCC, G3, T4N3M1) from detailed examination. With his advanced age and lowered ADL, the family did not wish for aggressive treatment, so no combination multidrug chemotherapy was attempted. Instead he was given 300 mg/day UFT per os. After 4 weeks administration, the metastatic focus decreased and tended to contract; at the same time gross observation revealed no more bloody urine. Moreover, following 7 weeks of administration, the bladder tumor disappeared, the lung metastatic focus showed overall shrinkage of over 50%, the lymph node metastasis also was more than 50% less, and the case was considered to be PR. The literature reveals UFT was efficacious in only 2 other cases of progressive bladder carcinoma. Since UFT has fewer complications, such as myelosuppression, among antitumor agent, it is considered worth trying in cases where intensive treatment is not feasible.

Aged↗

Activity in the parietal area during visuomotor learning with optical rotation.

Regional cerebral blood flow (rCBF) was measured in six subjects to study changes of activity in the parietal cortex during learning of a visually guided pointing task with a discrepancy of visuomotor coordination and to determine whether reorganization affects the parietal activity after learning. During the early stage of learning, the right posterior parietal cortex showed a significant increase in rCBF. During the late stage, on the other hand, significant activation was noted in the postcentral gyrus of the right hemisphere. These results support a role for the posterior parietal cortex in remapping visuomotor coordinates and suggest the involvement of the human postcentral gyrus in retaining sensorimotor coordinates, considered to relate to the self image of the hand.

Adult↗

Different roles of the left and right parahippocampal regions in verbal recognition: a PET study.

We examined the role of the parahippocampal regions in humans during two types of verbal recognition process, i.e. delayed matching and non-matching, by measuring regional cerebral blood flow (rCBF) using PET. The results showed differential activation of each parahippocampal region during verbal memory tasks in which the side activated shifted depending on the nature of the task employed; an increase in rCBF in the left parahippocampal gyrus was associated with retrieval strategy of non-matching, and an increase in rCBF in the right parahippocampal gyrus was associated with retrieval strategy of matching. We conclude that lateralized parahippocampal activation may depend on the type of response required.

Adolescent↗

Altering substrate specificity of Bacillus sp. SAM1606 alpha-glucosidase by comparative site-specific mutagenesis.

The Bacillus sp. SAM1606 alpha-glucosidase with a broad substrate specificity is the only known alpha-glucosidase that can hydrolyze alpha,alpha'-trehalose efficiently. The enzyme exhibits a very high sequence similarity to the oligo-1,6-glucosidases (O16G) of Bacillus thermoglucosidasius and Bacillus cereus which cannot act on trehalose. These three enzymes share 80% identical residues within the conserved regions (CR), which have been suggested to be located near or at the active site of the alpha-amylase family enzymes. To identify by site-specific mutagenesis the critical residues that determine the broad substrate specificity of the SAM1606 enzyme we compared the CR sequences of these three glucosidases and selected five targets to be mutagenized in SAM1606 alpha-glucosidase, Met76, Arg81, Ala116, Gly273, and Thr342. These residues have been specifically replaced by in vitro mutagenesis with Asn, Ser, Val, Pro, and Asn, respectively, as in the Bacillus O16G. The 12 mutant enzymes with single and multiple substitutions were expressed and characterized kinetically. The results showed that the 5-fold mutation virtually abolished the affinity of the enzyme for alpha, alpha'-trehalose, whereas the specificity constant for the hydrolysis of isomaltose, a good substrate for both the SAM1606 enzyme and O16G, remained essentially unchanged upon the mutation. This loss in affinity for trehalose was critically governed by a Gly273 --> Pro substitution, whose effect was specifically enhanced by the Thr342 --> Asn substitution in the 5-fold and quadruple mutants. These results provide evidence for the differential roles of the amino acid residues in the CR in determining the substrate specificity of the alpha-glucosidase.

Amino Acid Sequence↗

A method for the quantification of benzodiazepine receptors by using 123I-iomazenil and SPECT with one scan and one blood sampling.

Iodine-123-iomazenil (Iomazenil) is a ligand of central type benzodiazepine receptors for single photon emission computed tomography (SPECT). Previously we reported a simple, table look-up method for quantification of its binding potential (BP) by using two SPECT scans and calibrated standard input function with one blood sampling. This method is based on a two-compartment model (K1: influx rate constant; k2: efflux rate constant; Vd (= K1/k2): the total distribution volume corresponding BP), and requires two SPECT scans for calculating both K1 and Vd values. If the K1 value in the two-compartment model can be assumed to be constant, the radioactivity of one SPECT scan at 180 min after injection can be considered to tabulate as a function of Vd for a given K1 value and a given input function, and a table look-up procedure provides the corresponding Vd value. The purpose of this study was to develop a simple, autoradiographic method for quantification of BP by using one SPECT scan and calibrated standard input function with one blood sampling. SPECT studies were performed on 14 patients. A dynamic SPECT scan was initiated following an intravenous bolus injection of Iomazenil. A static SPECT scan was performed at 180 min after the injection. Frequent blood sampling from the brachial artery was performed on all subjects to determine the arterial input function. Simulation studies revealed that errors in calculated Vd values were around +/-10-15% for varied K1 values. A good correlation was observed between total distribution volume values calculated by three-compartment model analysis and those calculated by the present method (r = 0.90), supporting the validity of this method. The present method is simple and applicable for clinical use, and will be able to provide images of BP.

Adult↗

Cranial computed tomography scans of premature babies predict their eventual learning disabilities.

It remains difficult to predict, early enough to intervene effectively, the risk of the development of learning disabilities among extremely low birth weight (ELBW) infants (birth weights less than 1,000 g). We prospectively studied the relationship between dilatations of lateral ventricles of the cranial computed tomography (CT) scan taken at the postconceptional age of 40 weeks and learning disabilities in their school age. Using a computer digitizer, we measured the areas of ventricles on cranial CT scans. The mean area of lateral ventricles of the learning disabilities-suspected group was significantly larger than that of the control group (392.9 and 277.4 mm2, respectively; P < .01). There were no significant differences between the two groups in gestation, birth weight, physical measurements, and developmental quotients at early school age. The dilatation of the lateral ventricles assessed by cranial CT at the corrected term may be one of the first predictors of learning disabilities recognizable at early school age.

Brain↗

Enhancement of NO production from resident peritoneal macrophages by in vitro gamma-irradiation and its relationship to reactive oxygen intermediates.

The functional changes in macrophages (Mphi) following exposure to a high dose (6 Gy) of gamma-rays in vitro were investigated. Resident peritoneal Mphi obtained from C57BL/6 mice were irradiated with gamma-rays (137Cs, 0.3 Gy/min). High-dose irradiation enhanced nitric oxide (NO) production from Mphi treated with interferon-gamma and their cytotoxic activity. The enhancement of NO production by irradiation was attributed to high levels of expression of the inducible nitric oxide synthase. Furthermore, the participation of reactive oxygen intermediates in NO production was examined. Nitric oxide production was not enhanced by treatment with the membrane-oxidizing agent tert-butyl hydroperoxide or the hypoxanthine/xanthine oxidase superoxide (O2.-)-generating system. On the other hand, NO production was enhanced by treatment with a low dose of hydrogen peroxide (H2O2), which can diffuse passively through the cell membrane and can be converted into hydroxyl radicals (HO.) that cause DNA breaks. In addition, treatment with low-dose actinomycin D, which induces DNA strand breaks, enhanced NO production, but hydroxyurea, which stops DNA replication without DNA strand breaks, had no such effect. These findings suggest that DNA strand breaks caused by hydroxyl radicals formed inside the cells by gamma-irradiation, or strand breaks caused directly by radiation, plays an important role in the enhancement of NO production, but peroxidation of cell membranes has little effect.

Animals↗