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Biomedical subjects

H Fukuyama

Publications and source records attributed to H Fukuyama.

At least 145 records · Page 8Linked to original sources
PubMed1995

A novel point mutation in the mitochondrial tRNA(Ser(UCN)) gene detected in a family with MERRF/MELAS overlap syndrome.

We found a new point mutation in the mitochondrial tRNA(Ser(UCN)) gene in a family with MERRF/MELAS overlap syndrome by screening for heteroplasmy by means of chemical cleavage of mismatch (CCM). Our strategy was based on the previous observations that most pathogenic mtDNA mutations in mitochondrial encephalomyopathies are heteroplasmic, whereas almost all neutral mitochondrial polymorphisms are homoplasmic. CCM followed by nucleotide sequencing of the corresponding region of the mitochondrial genome revealed a heteroplasmic mutation at nt 7512 in the tRNA(Ser(UCN)) gene. The 7512 (T to C) mutation disrupts a highly conserved base pair in the acceptor stem, and this mutation was not found in any of 120 normal controls, or in 43 patients with mitochondrial diseases. The proportion of the mutant mtDNA was 93% in muscle, 76 and 87% in the blood of the patients. A family member without apparent neuromuscular symptoms carried less mutant mtDNA. These findings support the view that this mutation is pathogenic in this family. Detection of heteroplasmy by CCM is an efficient means of screening pathogenic mtDNA point mutations.

Adult↗
PubMed1995

Presence of alternative 5' untranslated sequences and identification of cells expressing ctk transcripts in the brain and testis.

From a mouse brain cDNA library, two species of the Csk-type tyrosine kinase (ctk) gene containing different 5' untranslated sequences were cloned. Using the common as well as specific nucleotide sequences of the two clones as probes, we examined the expression of ctk in various mouse tissues by Northern blot analysis. The results indicated that both species of ctk were expressed in the brain, testis and bone marrow. By in situ histochemistry of the brain, ctk transcript was detected in neurons throughout the entire brain, especially those of the cortex, the hippocampus and the cerebellum. This distribution pattern is similar to that of the Src family kinases including Yes, Src, Fyn and Lyn. In the testis, the major transcript (0.7 kb) was shorter than that expressed in the brain and the bone marrow (2.0 kb). A subsequent Northern blot analysis of fractionated germ cell populations and in situ histochemistry revealed that the short and long transcripts were expressed in germ cells and somatic cells, respectively, and that the expression level was quantitatively regulated during germ cell development. These results suggest that Ctk is involved in the regulation of neural function and differentiation of male germ cells through interactions with member(s) of the Src family kinases.

Alternative Splicing↗
PubMed1995

Initial clinical experiences with dopamine D2 receptor imaging by means of 2'-iodospiperone and single-photon emission computed tomography.

Dopamine D2 receptor imaging was performed with 123I labeled 2'-iodospiperone (2'-ISP) and single-photon emission computed tomography (SPECT) in 9 patients: 4 with idiopathic Parkinson's disease, 2 with parkinsonism, 1 with Wilson's disease and 2 with pituitary tumor, and the results were compared with the data for 9 normal subjects. Following an intravenous injection of 123I-2'-ISP, early (within 30 min) and late (between 2 and 4 hr) SPECT images were obtained by means of a multi-detector SPECT scanner or a rotating gamma camera. In normal subjects, early SPECT images demonstrated uniform distribution of radioactivity in the cerebral gray matter and cerebellum reflecting regional cerebral blood flow, whereas late SPECT images showed high radioactivity only in the basal ganglia. All the patients with Parkinson's disease also demonstrated symmetrical basal ganglia uptake in the late SPECT images, but it was diminished in parkinsonism and Wilson's disease. One patient with a growth hormone-producing pituitary tumor had a positive uptake in the tumor. These preliminary clinical data demonstrated that 2'-ISP can be used for SPECT imaging of D2 dopamine receptors and may be of clinical value for the diagnosis and planning of the treatment of neurological diseases.

Adenoma↗
PubMed1995

Corpus callosum atrophy in amyotrophic lateral sclerosis.

Recent studies have suggested widespread involvement of the cerebral regions other than the primary motor cortex in amyotrophic lateral sclerosis. To investigate atrophy of the corpus callosum as a measure of cerebral pathology, we studied 25 right-handed patients with sporadic amyotrophic lateral sclerosis using magnetic resonance imaging. Five patients had cognitive decline or emotional and personality changes. The ratios of mid-sagittal corpus callosum areas to the midline internal skull surface area on T1-weighted images were analysed. Compared with 25 age- and sex-matched right-handed control subjects, the patients had significantly decreased callosal/skull area ratio, with anterior predominance of the degree of atrophy. The patients with cognitive decline or psychiatric symptoms had substantial atrophy of the anterior fourth of the corpus callosum. These findings suggest that atrophy of the corpus callosum, especially in the anterior half, is present in amyotrophic lateral sclerosis, and that severe atrophy in the anterior fourth is associated with cognitive decline and psychiatric symptoms. Callosal atrophy may reflect the widespread distribution of pathological changes in the cerebral cortex, which are accentuated in the frontal cortex.

Adult↗
PubMed1995

Localization in impaired spatial vision.

The present study provides clear clinico-anatomical evidence for localization of the spatial vision pathway. We report the case of a 29-year-old woman with severe spatial vision impairment. Magnetic resonance imaging revealed distinct bilateral and symmetrical occipito-parietal damage. The right lesion affected the superior parietal lobule, the dorsolateral portion of the occipital lobe, the precuneus, and the cuneus. The left lesion affected the superior parietal lobule, the dorsolateral portion of the occipital lobe, the precuneus, an upper part of the cuneus, and the posterior portion of the middle and inferior temporal gyri.

Adult↗
PubMed1995

Induction of CL100 protein tyrosine phosphatase following transient forebrain ischemia in the rat brain.

Protein tyrosine phosphorylation is thought to play an important role in the regulation of neural function. To elucidate the role that protein tyrosine phosphatases (PTPs) may play in the postischemic brain, PTPs expressed in regions of the rat brain vulnerable to transient forebrain ischemia were examined. With the reverse-transcriptase polymerase chain reaction using degenerate primers, three PTPs, STEP, PTP delta, and SH-PTP2, were identified. They were expressed in the hippocampus 12 h after transient ischemia for 20 min. During the reperfusion period, the mRNA levels of these PTPs were not different from those in sham-operated rats. In contrast, a fourfold increase in the mRNA level of CL100 (3CH134), a PTP that is inducible by oxidative stress, was detected by Northern blotting in the hippocampus and cerebral cortex 1 h after the onset of reperfusion. In situ hybridization histochemistry showed a slight increase in the level of CL100 mRNA in neuronal cells in the hippocampus and cortex of postischemic rats compared to control rats. These findings suggest that PTPs play a role in the normal function of the hippocampus and cerebral cortex and demonstrate that ischemia induced CL100 expression.

Amino Acid Sequence↗
PubMed1995

Progression of atrophy of the corpus callosum with deterioration of cerebral cortical oxygen metabolism after carotid artery occlusion: a follow up study with MRI and PET.

In cerebrovascular disease, progression of brain atrophy may reflect an increase in ischaemic changes. The purpose of this study was to determine whether atrophy of the corpus callosum progresses in association with a deterioration in cerebral cortical oxygen metabolism after occlusion of the carotid artery. Magnetic resonance imaging and PET were used to serially evaluate six patients with occlusion of the unilateral internal carotid artery at intervals ranging from 12 to 50 months. One patient had no symptoms, one had a transient ischaemic attack, and four had a minor stroke. All patients had presented at most only subcortical lesions at the first evaluation. During follow up, no patient showed extension of subcortical lesions or recurrent stroke. The initial total callosal area:skull area ratio for the patients was significantly less than that for 14 age matched normal control subjects. The yearly decrease of callosal size in the patients, which differed significantly from zero and exceeded that in the controls, was significantly correlated with the deterioration in mean cerebral cortical oxygen metabolism. Three of the four patients who showed significant progression of callosal atrophy presented deterioration in haemodynamic states as well. It is concluded that in some patients atrophy of the corpus callosum progresses after occlusion of the carotid artery even in the absence of any overt episode of stroke, and that this atrophy is associated with deterioration in cerebral cortical oxygen metabolism. An increase in cerebral morphological changes with deterioration in cerebral metabolism related to ischaemia may occur after occlusion of the carotid artery, even in the absence of symptoms.

Aged↗
PubMed1995

[An epidemiologic examination on the prevalence of the periodontal diseases and oral pigmentation in Yusho patients].

An epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in Yusho patients 26 years after PCB exposure. The results obtained were as follows. 1) 158 teeth of the total 284 examined teeth had the periodontal pockets deeper than 3 mm and the lower left first molar showed the highest prevalence of the periodontal pocket among the examined six index teeth. There was no definitive difference not only between sexes but also between age groups. However, 42 teeth had the periodontal pockets deeper than 4 mm. 2) Oral pigmentation was observed in 25 Yusho patients (33.8%). Chronological examination revealed that the prevalence of oral pigmentation seemed to be higher in the patients below the age of 49 than in those beyond the age of 50, but there was no definitive difference between sexes. It was of particular interest that the incidence of oral pigmentation appeared to decrease with decrease of the teeth present in number.

Adult↗
PubMed1995

[Cerebral blood flow and metabolism in Lafora disease].

An 18-year-old male manifesting intellectual deterioration and negative myoclonus was diagnosed as Lafora disease by the demonstration of Lafora bodies in the skin and muscle biopsy. The cortical evoked potential to electric stimulation of the median nerve at wrist showed the giant SEP, suggesting hyperexcitability of the sensory motor cortex. Cerebral blood flow, and cerebral glucose and oxygen metabolism were investigated by positron emission tomography (PET) in order to clarify the pathophysiological process in Lafora disease. The result showed diffusely decreased cortical glucose metabolic rate and cerebral blood flow, and moderately lowered oxygen metabolic rate. There was no increase in blood flow or glucose and oxygen metabolism in the sensorimotor cortex in spite of the presence of giant SEP. The ratio of the glucose to oxygen metabolism was not different from the mean value obtained from nine normal subjects. Based on these findings and review of the literature, it is unlikely that there is a significant deficit in cortical energy metabolism in patients with Lafora disease and it would be less plausible to have some enzymatic deficits in glucose metabolic process.

Adolescent↗
PubMed1995

SPECT imaging of dopamine D2 receptors with 2'-iodospiperone.

UNLABELLED: SPECT imaging of dopamine D2 receptors was performed using 123I-labeled 2'-iodospiperone (2'-ISP). METHODS: Iodine-123-2'-ISP was administered to 12 normal subjects. Serial SPECT scans were obtained in six normal subjects for kinetic studies and static SPECT images were obtained in four normal subjects. Two additional normal subjects had serial whole-body imaging to calculate radiation dosimetry. RESULTS: Serial SPECT scans demonstrated rapid initial brain uptake followed by gradual washout from the cerebral cortex and cerebellum, while the activity in the basal ganglia was stable for 2 hr and gradually decreased thereafter. There was fast clearance of blood activity with rapid conversion of 2'-ISP to the hydrophilic metabolites. The basal ganglia-to-frontal cortex ratio increased with time and plateaued between 2 and 4 hr postinjection. The basal ganglia-to-frontal cortex ratio obtained during this period demonstrated an age-dependent decrease similar to other D2 ligands. CONCLUSION: 2'-ISP can be used for mapping dopamine D2 receptors in human brain with SPECT. The relatively high background activity, however, suggests that further modification of the compound may be needed prior to widespread clinical use.

Adult↗
PubMed1995

[Positron emission tomography and single photon CT in the diagnosis of cerebrovascular disorders].

The positron emission tomography (PET) and single photon emission CT (SPECT) revealed the pathophysiology of ischemic brain in the transaxial images. There are several limitations in PET studies by continuous inhalation method using oxygen-15 labeled gases. There has been a suspicion about the constancy between the red cell volume and plasma volume in the ischemic brain. We measured plasma volume by PET using Cu-62 labeled human serum albumin in cases of internal carotid artery occlusion. There was no remarkable plasma volume alterations between the ischemic and non-ischemic hemisphere. Powers et al demonstrated the relationships between the intracranial perfusion pressure changes and vascular or metabolic adaptations. The important issue in acute stage of stroke is to differentiate the truly alive and completely destroyed tissue. Cerebral blood flow change might be affected during acute stage by diaschisis. Recent examination using benzodiazepine receptor imaging by SPECT might have a potential to depict the damaged tissues, because cortical neuronal cell bodies have a lot of the receptors and an ischemic insult induces the loss of the receptors. The relationship of crossed cerebellar hypoperfusion (CCH) and supratentorial circulatory conditions is attractive, because supratentorial hypometabolism of oxygen induced more severe CCH in internal carotid artery occlusion. Therefore, we can predict the supratentorial oxygen metabolism by CCH in a case of internal artery occlusion. We have a lots of tools to explore the pathophysiological states of ischemic brain. These must be dedicated to develop the more effective therapeutic procedures.

Brain↗
PubMed1995

[The correlation of the thalamic lesions on MRI with cerebral cortical blood flow in patients with lacunar infarction].

We performed MRI and measured cerebral blood flow (CBF) using 123I-IMP SPECT microsphere model in twenty three right-handed patients with lacunar infarction. Twelve of 23 patients showed chronic deterioration of dysarthria and gait disturbance. The mental function of the patients was evaluated by the Mini-Mental State (MMS) examination. The area of high intensity on T2-weighted images was quantitatively analyzed in the cerebral white matter (WM), lenticular nucleus (LN) and thalamus (THA). The score of MMS was positively correlated with the local CBF in the bilateral frontal, parietal, temporal and occipital cortices (p < 0.05). Also, the area of high intensity in the left THA showed a significant negative correlation with local CBF of the bilateral frontal, parietal, temporal and occipital cortices (p < 0.001). The high intensity areas of the bilateral LN, right WM and right THA had a significant but weaker negative correlation with local CBF of some cortices. These findings suggest that thalamic lesions on the dominant side play an important role in the reduction of cortical blood flow and the deterioration of mental functions in patients with lacunar infarction.

Aged↗
PubMed1995

A pilot/introducer needle for central vein cannulation.

A kit for safe and easy insertion of a central vein cannula was devised. A small gauge (22 gauge) metal pilot needle was equipped with a Y-shaped hub which had a side-port to accept a small gauge (0.46 mm) Seldinger guide wire. Once the needle reached the vein, guidewire was threaded in through the side-port. There was no need to remove the pilot needle and no need to repeat vein puncture with a larger-bore needle. Three puncture methods were used with the kit: (1) the central approach via the internal jugular vein, (2) the supraclavicular approach via the junction of the internal jugular vein and subclavian vein, and (3) the infraclavicular approach via the subclavian vein. Each method was used on 20 patients, for total of 60 patients, with a high success rate. Less than 3 minutes were required from puncture to catheter insertion. No serious complications were encountered.

Catheterization, Central Venous↗
PubMed1994

Scopolamine abolishes cerebral blood flow response to somatosensory stimulation in anesthetized cats: PET study.

The effect of the cholinergic blocker, scopolamine on the cerebral blood flow (CBF) response to vibrotactile stimulation of a fore paw was studied using high-resolution positron emission tomography and H2 15O in 5 pentobarbital-anesthetized cats. Before scopolamine injection, the CBF response to the stimulation was found in the contralateral somatosensory cortex (mean ratio (contralateral/ipsilateral) control: stimulated 1.02 +/- 0.02: 1.17 +/- 0.05; P < 0.01). After intravenous injection of scopolamine (0.35 mg/kg), the CBF response was abolished. However, the cerebral metabolic rate of glucose (CMRGlu) response to the same stimulation was unchanged after scopolamine injection in the same cats. We concluded that scopolamine abolishes the CBF response but not neuronal response to stimulation. We suggest that cholinergic mechanisms may play an important role for mediating CBF coupling to neuronal activity during physiological stimulation.

Anesthesia↗