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Biomedical subjects

Takao Kodama

Publications and source records attributed to Takao Kodama.

12 recordsLinked to original sources

Alteration of regional cerebral blood flow in patients with chronic pain--evaluation before and after epidural spinal cord stimulation.

BACKGROUND: Chronic pain is defined as intractable pain caused by abnormal pain transmission or impairment of the pain control system per se. Alteration of regional cerebral blood flow (rCBF) is known to occur under the presence of pain stimulation. Epidural spinal cord stimulation (SCS) is occasionally effective in relieving the symptom. OBJECTIVE: The aim of the current study is to investigate the alteration of rCBF in baseline condition and to find the association between the rCBF change and the efficacy of SCS in chronic pain. METHODS: A total of 18 patients underwent Tc-99m-HMPAO SPECT before and after SCS. Analysis with three-dimensional stereo-tactic surface projections (3D-SSP) with stereo-tactic extraction estimation (SEE) software was adopted to evaluate the rCBF. We assessed the extent score of the abnormal region in each segment (rate of the coordinates with a Z-value that exceeds three kinds of threshold value 2.0, 2.5 and 3.0 in all coordinates within a segment). According to the therapeutic response defined by visual analogue scale, we categorized patients into two groups, the good responder (GR) group (n=12) and poor responder (PR) group (n=6). In the analysis, we compared the extent score in the following two conditions. (1) Comparison between the PR group and normal control group under both baseline condition and after SCS. (2) Comparison between the GR group and normal control group under both baseline condition and after SCS. RESULTS: (1) In the PR group, increased rCBF was observed in left thalamus, bilateral precuneus and bilateral cerebellum under the baseline condition. After SCS, the range of these increased rCBF areas localized but remained. Decrease of rCBF was noted in bilateral subcallosal gyrus, superior temporal gyrus (STG) and bilateral anterior cingulate gyrus (ACG). They localized after SCS, but remained. (2) In the GR group, increased rCBF areas were noted in bilateral precuneus and bilateral cerebellum under the baseline condition. After SCS, they localized in bilateral precuneus but those of bilateral cerebellum remained. Decreased rCBF area was noted in bilateral subcallosal gyrus, STG and bilateral ACG under the baseline. After SCS, they localized in bilateral subcallosal gyrus and bilateral STG. In contrast, they enlarged in bilateral ACG. CONCLUSION: Chronic pain patients demonstrated abnormal rCBF distribution on both baseline and post SCS conditions. Increased rCBF of thalamus and precuneus under both conditions in the PR group and decreased rCBF of ACG under post SCS conditions in the GR group were characteristic patterns. Tc-99m-HMPAO SPECT with 3D-SSP and SEE analysis is likely objective and effective in monitoring and evaluating therapeutic outcome by SCS in chronic pain. In addition, it provides information that is useful in the selection of SCS candidates.

Brain↗

Aggregation of partially unfolded Myosin subfragment-1 into spherical oligomers with amyloid-like dye-binding properties.

Proteolytic myosin subfragment 1 (S1) is known to be partially unfolded in its 50-kDa subdomain by mild heat treatment at 35 degrees C [Burke et al. (1987) Biochemistry 26, 1492-1496]. Here, we report that this partial unfolding is accompanied by aggregation of S1 protein. Characteristics of the aggregate thus formed were: (i) formation of transparent sediment under centrifugation at 183,000 x g; (ii) amyloid-like, dye-binding properties such as Congo red-binding and Thioflavin T fluorescence enhancement; (iii) a uniformly sized spherical appearance in electron micrographs; and (iv) sensitivity to tryptic digestion. Gel filtration analysis of the aggregation process indicates that the spheroid was formed through an intermediate oligomeric stage. The aggregate inhibited spontaneous aggregation of an isolated 50 kDa fragment into a large amorphous mass. The remaining native regions in the partially unfolded S1 were probably responsible for this effect. These results show that, unlike the 50-kDa fragment, the partially unfolded S1 molecules do not form amorphous aggregates but assemble into spherical particles. The native regions in partially unfolded S1 may be a determinant of aggregate morphology.

Amyloid↗

Adenoid glioblastoma arising in a patient with neurofibromatosis type-1.

An unusual case of glioblastoma with adenoid structures arising in a 30-year-old Japanese woman with neurofibromatosis type-1 (NF1) is reported. The patient was admitted to University of Miyazaki Hospital, complaining of headache, nausea and vomiting. From the neuroradiological findings the patient was diagnosed as having glioblastoma, and the tumor was surgically resected. Histologically, the tumor consisted mainly of dark basophilic cells showing prominent tubular or glandular structures surrounded by large eosinophilic cells, in addition to the typical glioblastoma features in the periphery of the tumor. Both cells showed strong stainability with glial fibrillary acidic protein (GFAP) and S-100 protein immunohistochemically, so that the tumor was classified as adenoid glioblastoma. Several cases of glioblastoma have been reported to reveal the adenoid or epithelioid differentiation. The patients with NF1 are prone to develop malignant tumors including glioblastoma, but no cases representing adenoid glioblastoma associated with NF1 have been reported. This report is considered to be the first case of adenoid glioblastoma arising in a patient with NF1. The recognition of the existence of epithelial features of glioblastoma would be important in differential diagnosis of epithelioid tumors of the brain including metastatic carcinomas.

Adult↗

Myosin-induced volume increase of the hyper-mobile water surrounding actin filaments.

Microwave dielectric spectroscopy can measure the rotational mobility of water molecules that hydrate proteins and the hydration-shell volume. Using this technique, we have recently shown that apart from typical hydrating water molecules with lowered mobility there are other water molecules around the actin filaments (F-actin) which have a much higher mobility than that of bulk water [Biophys. J. 85 (2003) 3154]. We report here that the volume of this water component (hyper-mobile water) markedly increases without significant change of the volume of the ordinary hydration shell when the myosin motor-domain (S1, myosin subfragment-1) binds to F-actin. No hyper-mobile component was found in the hydration shell of S1 itself. The present results strongly suggest that the solvent space around S1 bound to F-actin is diffusionally asymmetric, which supports our model of force generation by actomyosin proposed previously [op. cit.].

Actin Cytoskeleton↗

Cerebral blood flow abnormalities induced by transient hypothyroidism after thyroidectomy--analysis by tc-99m-HMPAO and SPM96.

UNLABELLED: The current study is an investigation of alterations in regional cerebral blood flow (rCBF) distribution in patients with transient hypothyroidism after thyroidectomy. In addition, the effects of thyroxine treatment on rCBF changes were studied. METHODS: Noninvasive rCBF measurements using 99mTc-HMPAO SPECT were performed on 24 post-thyroidectomy patients who were in a hypothyroidic state. The measurements were conducted before 131I therapy and after thyroid hormone (thyroxine) replacement. We used adjusted rCBF images (normalization of global CBF for each subject to 50 ml/100 g/min with proportional scaling) to compare these data with age-matched normal control groups (n =15) using SPM96. We also compared the absolute rCBF value of hypothyroidic patients with those of normal control groups. In addition, the association between rCBF alteration and the severity of depression was also analyzed. Finally, the effect of thyroid hormone replacement on rCBF was investigated individually using the Jack-knife test, in which patient data were compared with those from healthy volunteers. According to the result of this test, all cases were categorized into three subgroups, namely, improved, unchanged group and normal. To prove the reversibility of rCBF alteration after thyroid hormone replacement, a group comparison test between the normal controls and the improved group was done before and after thyroid hormone replacement. Similarly a group comparison test between the unchanged group and normal controls was also performed. RESULTS: In the hypothyroidic condition, there was a significant decrease in the posterior part of the bilateral parietal lobes and in part of the bilateral occipital lobes, including the cuneus. These decreased rCBF areas extended to the bilateral prefrontal cortices as deterioration became more profound. On individual analysis, 16 of 24 patients (66.7%) demonstrated rCBF reduction, while 8 patient did not show significant rCBF change (33.3%, the normal group). After thyroxine replacement, improvement of rCBF was noted in nine of 16 patients (56.3%, the improved group). In seven of 16 patients (43.7% the unchanged group), the significant low rCBF area remained unchanged. Compared with the normal controls, the improved group showed significantly decreased rCBF of the bilateral parietal lobe and the occipital lobe in the hypothyroic condition. After thyroid hormone replacement, these abnormal rCBF areas disappeared. In contrast, in the unchanged group, the significant hypoperfusion area became localized but remained. CONCLUSION: 99mTc-HMPAO SPECT and SPM96 analysis demonstrated a significant rCBF decrease in the parietal lobe and part of the occipital lobe in patients with induced transient hypothyroidism after thyroidectomy. This phenomenon might contribute to understanding of the depressive state. Recovery of rCBF after thyroid hormone replacement was confirmed in some patients. However, rCBF improvement did not always occur in every patient during the follow up period. The reversibility of rCBF in transient hypothyroidism may be dependent on individual characteristics during a short-term period.

Adult↗

Correlation of CT analysis and audiometry in Japanese otosclerosis.

OBJECTIVE: To determine the extent of audiometric correlation with CT findings. METHODS: Forty-four patients (82 ears) with surgically confirmed otosclerosis underwent preoperative CT examination. Based on the computed tomography (CT) findings, the ears were classified into five groups as follows: Group A, the group with no pathological CT findings; Group B1, the group with demineralization localized in the region of the fissula antefenestram; Group B2, the group with demineralization extending towards the cochleariform process from the anterior region of the oval window; Group B3, the group with extensive demineralization surrounding the cochlea; and Group C, the group with thick anterior and posterior calcified plaques. RESULTS: There were 32 ears (39.0%) in Group A, 21 ears (25.6%) in Group B1, 16 ears (19.5%) in Group B2, 7 ears (8.5%) in Group B3, and 6 ears (7.3%) in Group C. The mean bone conduction levels were greater in the order of the extent of demineralization: Groups A, B1-B3 suggesting positive relationship between the cochlear function and the degree of labyrhinthine otosclerosis. CONCLUSION: A good correlation between the preoperative CT findings and audiometry findings suggests that CT with a slice intervals between 0.5 and 1mm could provide useful informations in assuming the extent of otosclerosis in the inner ear.

Adolescent↗

Modulation of actomyosin motor function by 1-hexanol.

This study examines the effects of 1-hexanol as a perturbing agent on actomyosin ATPase and its related functions in the concentration range between 0 and 20 mM. In this range the denaturation of myosin subfragment 1 (S1), as measured by the inactivation rate of its K-EDTA-ATPase, and depolymerization of F-actin were insignificant. Major findings showed that hexanol had the following effects which were fully reversible, (a) a marked activation of S1 MgATPase (approximately 10-fold at 20 mM) without greatly affecting the enhancement of tryptophan fluorescence by formation of S1.ADP.Pi intermediate and the rate of ADP release from S1.ADP; (b) an inhibition of the maximum actin-activated ATPase activity; (c) an increase in the affinity of S1 for actin in the presence of ATP and a decrease in the presence of ADP or the absence of nucleotide; (d) a reduction in the sliding velocity of actin filaments in in vitro motility assays with myosin, and (e) a decrease in isometric tension of single skinned muscle fibers. Thus, the effects of hexanol on actomyosin interaction are distinct for the weak and strong binding states, consistent with a change in the hydrophobic interaction in the interface between myosin and actin accompanying the transition from the weak to the strong binding state. Hexanol also accelerates the Pi release from S1.ADP.Pi, which is the transition step from the weak to the strong binding state. The fact that hexanol accelerates Pi release suggests that this alcohol perturbs the S1.ADP.Pi conformation. We speculate that this intermediate-specific structural perturbation is related to the inhibition of the maximum actin-activated ATPase, in vitro motility, and isometric tension.

Actins↗

Single-molecule imaging of the dynamic interactions between macromolecules.

In recent years, the development of single-molecule detection techniques has allowed the dynamic properties of biomolecules, which are normally obscured in conventional ensemble measurements, to be measured. One of these single-molecule detection techniques allows the measurement of dissociation and association events of individual molecules to be measured. This technique is based on the unique premise that the mobility between molecules that are bound and the mobility between those that are free in solution are different. The binding of ATP at the beginning and its dissociation at the end of the hydrolysis reaction were detected at the single-molecule level in real time. In this study, we extended this technique to image the dynamic interactions between large biomolecules (protein/protein and protein/polysaccharide). The binding and dissociation of fluorescently labeled macromolecules to partner molecules fixed on a glass surface were visualized by total internal reflection fluorescence microscopy. The dynamic interactions between the proteins in two energy conversion systems, that is, signaling proteins and enzyme molecules moving on dextran, have been measured. In these systems, the dynamic interactions were sensitive to the factors determining the chemical reactions. Thus, the dynamic interactions monitored in the single-molecule measurements provided useful information to further the understanding of the underlying mechanisms of energy conversion systems.

Adenosine Triphosphate↗

Hyper-mobile water is induced around actin filaments.

When introduced into water, some molecules and ions (solutes) enforce the hydrogen-bonded network of neighboring water molecules that are thus restrained from thermal motions and are less mobile than those in the bulk phase (structure-making or positive hydration effect), and other solutes cause the opposite effect (structure-breaking or negative hydration effect). Using a method of microwave dielectric spectroscopy recently developed to measure the rotational mobility (dielectric relaxation frequency) of water hydrating proteins and the volume of hydration shells, the hydration of actin filament (F-actin) has been studied. The results indicate that F-actin exhibits both the structure-making and structure-breaking effects. Thus, apart from the water molecules with lowered rotational mobility that make up a typical hydration shell, there are other water molecules around the F-actin which have a much higher mobility than that of bulk water. No such dual hydration has been observed for myoglobin studied as the representative example of globular proteins which all showed qualitatively similar dielectric spectra. The volume fraction of the mobilized (hyper-mobile) water is roughly equal to that of the restrained water, which is two-thirds of the molecular volume of G-actin in size. The dielectric spectra of aqueous solutions of urea and potassium-halide salts have also been studied. The results suggest that urea and I(-) induce the hyper-mobile states of water, which is consistent with their well-known structure-breaking effect. The molecular surface of actin is rich in negative charges, which along with its filamentous structure provides a structural basis for the induction of a hyper-mobile state of water. A possible implication of the findings of the present study is discussed in relation to the chemomechanical energy transduction through interaction with myosin in the presence of ATP.

Actin Cytoskeleton↗

Osteoma of the frontal sinus complicated by intracranial mucocele.

We present a rare case of intracranial mucocele associated with frontal sinus osteoma in a patient suffering from generalized convulsion. The intracranial mucocele occurs as a complication of obstruction of sinus drainage caused by osteoma, but it is often diagnosed preoperatively as an intracranial or intracerebral cyst because of the rarity of these combined lesions in neurosurgical practice. However, once the mucocele extends intracranially, several other complications, including infections and/or a convulsion, can occur, indicating the necessity for surgical treatment. Moreover, the differentiation of the mucocele from the intracranial endodermal cyst predominantly depends upon its continuity with the intracranial osteoma portion or the sinus. Thus, knowledge of this rare lesion is important for accurate diagnosis and clinical management.

Brain Diseases↗

Hepatocyte nuclear factor-4 alpha/gamma and hepatocyte nuclear factor-1 alpha as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers.

Human dihydrodiol dehydrogenase (DD) catalyses the oxidation of trans-dihydrodiols of polycyclic aromatic hydrocarbons and the reduction of several ketone-containing drugs. About 40-fold interindividual difference in DD activities has been noted. Recently, we found that transcriptional factors, hepatocyte nuclear factor (HNF)-1 alpha, HNF-4 alpha and HNF-4 gamma were essential for the expression of DD4 mRNA, which is a major form of DDs. Thus, to clarify a possible mechanism(s) underlying the interindividual difference in DD activities, we investigated the sequences of genes and the expression levels of mRNA for DD4 and HNFs in human livers. We found no clear relationship between the genotypes of DD4 and HNF genes and the expression levels of DD4 mRNA in the subjects. The expression level of DD4 mRNA significantly correlated with that of HNF-1 alpha, HNF-4 alpha or HNF-4 gamma. These results suggest that the expression level of DD4 mRNA is cooperatively regulated by the amounts of HNF-1 alpha, HNF-4 alpha and HNF-4 gamma.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

CYP2D6.10 present in human liver microsomes shows low catalytic activity and thermal stability.

Comparing bufuralol 1'-hydroxylase activity among liver microsomes prepared from individuals whose CYP2D6 genotypes had been determined, we found that the activity tended to decrease depending on the number of the CYP2D6*10 allele. Pre-incubation of liver microsomes from individuals homozygous for the CYP2D6*10 allele resulted in a decrease in the enzyme activity more rapidly than those from individuals homozygous for the CYP2D6*1, suggesting that not only the catalytic activity but also the thermal stability of the enzyme appeared to be affected by the genetic polymorphism. To confirm this hypothesis, the kinetic parameters of CYP2D6.1 and CYP2D6.10 were compared for bufuralol 1'-hydroxylation and dextromethorphan O-demethylation using microsomes prepared from yeast transformed with plasmids carrying CYP2D6 cDNAs (*1A and *10B). Kinetic studies of these CYP2D6 forms indicated clear differences in the metabolic activities between the wild (CYP2D6.1) and the mutant enzymes (CYP2D6.10). Bufuralol 1(')-hydroxylase activity in microsomes of yeast expressing CYP2D6.10 was rapidly decreased by heat treatment, supporting the idea that the thermal stability of the enzyme was reduced by amino acid replacement from Pro (CYP2D6.1) to Ser (CYP2D6.10). These data strongly suggest that the thermal instability together with the reduced intrinsic clearance of CYP2D6.10 is one of the causes responsible for the known fact that Orientals show lower metabolic activities than Caucasians for drugs metabolized mainly by CYP2D6, because of a high frequency of CYP2D6*10 in Orientals.

Alleles↗