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Biomedical subjects

H Tohgi

Publications and source records attributed to H Tohgi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Reduced size of right hippocampus in 39- to 80-year-old normal subjects carrying the apolipoprotein E epsilon4 allele.

Hippocampal size on magnetic resonance imaging was compared between normal subjects with the apolipoprotein E (apo E) epsilon4 allele (epsilon4/4, epsilon4/3, and epsilon4/2) and those without the epsilon4 allele (epsilon3/3, epsilon3/2, and epsilon2/2) in the age range of 39-80 years. The Mini-Mental State Examination (MMSE) scores did not differ between the two groups. The right hippocampal area and its ratio to hemisphere area and intracranial cavity area were significantly smaller in epsilon4 carriers than non-carriers, whereas hemisphere area did not differ between the two groups. These results suggest that as early as their forties, apo E epsilon4 allele carriers have a markedly smaller right hippocampus with no apparent cognitive impairment, which may have some significance in the high prevalence of the epsilon4 allele in Alzheimer's disease as well as other conditions that cause dementia.

Adult↗
PubMed1997

Reduction in the ratio of beta-preprotachykinin to preproenkephalin messenger RNA expression in postmortem human putamen during aging and in patients with status lacunaris. Implications for the susceptibility to parkinsonism.

Gamma-aminobutyric acid (GABA)/substance P (SP) neurons and GABA/enkephalin (Enk) neurons in the striatum exert opposing influence on the regulation of movement. The loss of GABA/SP neurons results in hypokinetic disorders (parkinsonism), whereas the loss of GABA/Enk neurons results in hyperkinetic disorders (e.g. chorea). The present study determined age-related changes in the beta-preprotachykinin (the precursor of SP) and preproenkaphalin (the precursor of Enk) messenger RNA (mRNA) ratio in the postmortem human putamen using the reverse transcription-polymerase chain reaction (RT-PCR). The ratio of beta-preprotachykinin to preproenkephalin mRNA expression decreased with age. The reduction in the beta-preprotachykinin/preproenkephalin mRNA ratio was more marked in cases with multiple small infarcts (status lacunaris) in the putamen. These findings may in part explain the susceptibility of the elderly, particularly of those with ischemic changes in the striatum to hypokinetic disorders.

Adult↗
PubMed1997

Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease.

The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p = 0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p = 0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p = 0.0001) and the Cmax (maximum concentration) was also decreased by 80%d after the administration (p = 0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.

Aged↗
PubMed1997

Concentration of catecholamines and indoleamines in the cerebrospinal fluid of patients with vascular parkinsonism compared to Parkinson's disease patients.

The concentration of catecholamines and indoleamines in the cerebrospinal fluid of patients with vascular parkinsonism (VP) was compared to that in patients with Parkinson's disease (PD) and controls. Compared to the controls, the concentration of tyrosine was significantly higher, and the concentration of L-dopa and 3-O-methyldopa (3-OMD) was significantly lower in both VP and PD patients. The balance between the 3-OMD/L-dopa and dopamine (DA)/L-dopa ratios was changed in favor of 3-OMD/L-dopa in both VP patients and PD patients suggesting the preservation of a compensatory mechanism. All these changes were less marked in VP patients than in PD patients. A remarkable finding was that in contrast to PD patients the concentration of DA and norepinephrine (NE) was significantly higher in VP patients than in the controls. The decrease in the concentration of 5-hydroxytryptamine (5-HT) was significantly greater in VP patients than in PD patients. In PD patients, the concentration of DA, NE, and 5-HT showed significant correlation with the severity of motor symptoms. In VP patients, the concentration of 5-HT alone showed significant correlation with the severity of motor symptoms and cognitive dysfunction. These findings suggest that VP patients may have similar disturbances in the DA synthesis pathway as PD patients, but differ from PD patients in that the concentrations of DA and NE are elevated and the decrease in the 5-HT concentration is greater in VP patients.

Aged↗
PubMed1997

[Effects of CTG repeat expansion on quantitative muscle histopathology in myotonic dystrophy].

The CTG trinucleotide repeat (CTG repeat) length in leukocytes and muscles shows significant correlations with muscle weakness, an increase in type 1 fiber proportion, and reductions in type 2A and 2B fiber proportions in patients with myotonic dystrophy (DM). The correlations are generally greater for CTG repeat length in muscles than in leukocytes. However, relatively small absolute values of correlation coefficients (r2 = 0.13-0.43) suggest that the CTG repeat length is not a role variable that may explain clinical and histopathological changes in DM patients.

Adult↗
PubMed1996

alpha-Tocopherol quinone level is remarkably low in the cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis.

In order to investigate the role of free radicals in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS), the concentrations of alpha-tocopherol (alpha-TOH) and its oxidized form alpha-tocopherol quinone (alpha-TQ) in the cerebrospinal fluid (CSF) of SALS patients were determined. The alpha-TOH level was 31% lower (P < 0.05) and the alpha-TQ level was 75% lower (P < 0.001) in SALS patients than in normal subjects. The results of the present study do not support the hypothesis that activated lipid peroxidation accelerates oxidation of alpha-TOH into alpha-TQ in SALS patients.

Aged↗
PubMed1996

A dopaminergic neurotoxin, (R)-N-methylsalsolinol, increases in Parkinsonian cerebrospinal fluid.

The concentration of (R)-N-methylsalsolinol, which is a dopamine-derived neurotoxin selective to dopamine neurons and induces parkinsonism in rats, was found to be increased significantly in the cerebrospinal fluid of untreated patients with Parkinson's disease. The enantio-specific occurrence of (R)-N-methylsalsolinol in cerebrospinal fluid suggests its enzymatic synthesis in the human brain. The individual differences in the activities of the enzymes determining the metabolism of (R)-N-methylsalsolinol in the brain might be involved in the pathogenesis of Parkinson's disease.

Aged↗
PubMed1996

Cerebrospinal fluid acetylcholine and choline in vascular dementia of Binswanger and multiple small infarct types as compared with Alzheimer-type dementia.

The acetylcholine (ACh) and choline (Ch) concentrations in the cerebrospinal fluid were investigated in patients with vascular dementia of the Binswanger type (VDBT) or multiple small infarct type (MSID) as compared with patients with Alzheimer-type dementia (ATD). The ACh concentration in patients with ATD was found to be significantly lower than in controls (73%, p < 0.0001), and showed a significant positive correlation with dementia scale scores (rs = 0.63, p < 0.03). The Ch concentration in the CSF of ATD patients was approximately the same as in controls. In VDBT/MSID patients, the ACh concentration was significantly lower than in controls (p < 0.001) also showing a significant positive correlation with dementia scale scores (rs = 0.62, p < 0.02), but was significantly higher than in ATD patients (p < 0.001). Moreover, the Ch concentration in VDBT/MSID patients was significantly higher than in controls (p < 0.001) or ATD patients (p < 0.001). These results suggest that simultaneous determination of ACh and Ch concentrations in CSF may be useful for differentiating VDBT/MSID from ATD and that increasing the ACh level using cholinergic agents may be a beneficial therapeutic strategy for the treatment of ATD as well as VDBT/MSIT, and is worthy of further investigation.

Acetylcholine↗
PubMed1996

The side and somatotopical location of single small infarcts in the corona radiata and pontine base in relation to contralateral limb paresis and dysarthria.

The aim of this study was to investigate whether the side and location of single small infarcts (< or = 3 cm) in the corona radiata (28 patients) and pontine base (36 patients) influence the incidence of contralateral upper or lower limb paresis and dysarthria. While the severity of contralateral limb paresis was not significantly different between right and left corona radiata lesions, infarcts presenting with contralateral limb paresis and/or dysarthria presented significantly more often in the left than in the right hemisphere, and left infarcts were significantly smaller than right infarcts. Lesions related to dysarthria and upper and lower limb paresis were arranged anterior-posteriorly in the paraventricular corona radiata region. Pontine base infarcts presenting with dysarthria also presented significantly more often in the left than in the right pons. Dysarthria showed a significant correlation with lesions presenting in the dorsomedial portion of the pontine base, upper limb paresis with those in the dorsomedial and dorsolateral portions, and lower limb paresis with lesions in the ventromedial portion. These results suggest greater influence of the left descending motor fibers on contralateral limb movement and articulation than of the right and face-arm-leg somatotopy of motor fibers in the paraventricular corona radiata region (anteroposterior) and in the pontine base (dorsoventral).

Adult↗
PubMed1996

[Problems in vascular dementia].

Vascular dementia (VD) and Alzheimer's type dementia are two main causes of dementia in the aged. Considering historical backgrounds and ethnic differences, a simplified classification of VD is suggested. First, poststroke dementia of acute onset associated with an infarct that is large enough to impair general cognitive functions, or strategically located. Second, multi-infarct dementia that develops incrementally with increasing numbers of infarcts, and which should be classified as multiple cortical infarct dementia and multiple small infarctor lacunar dementia. Third, vascular dementia of the Binswanger type (VDBT). We compared two types of white matter lesions, periventricular hyperintensity (PVH) and confluent centrum semiovale hyperintensity (CCSH) in lacunar stroke patients with regard to the cerebral blood flow (CBF). In patients with PVH, there was a significant positive correlation between the dementia scores and the CBF in the parietal and temporal areas but not in the frontal area. In CCSH patients, there was a significant positive correlation in the frontal area but not in the parieto-temporal areas. Therefore, dementia in most patients with PVH may not be primarily related to the PVH, but may possibly be due to coexisting Alzheimer's type dementia, and dementia in most CCSH patients may be related to cerebrovascular disease. VDBT is unique clinically in its slowly progressive intellectual deterioration and pathologically in diffuse, confluent, and almost symmetrical white matter lesions. For the pathogenesis of VDBT, our studies suggest that hypertension, short-term variations in blood pressure, and a sustained nighttime elevation of blood pressure promote small vessel disease and cause ischemia of the cerebral white matter that is located in the end-fields of penetrating arteries; this leads to an imparied integrity of the blood-brain barrier and free radical generation, both of which may have important roles in producing diffuse white matter degeneration.

Blood Pressure↗
PubMed1996

Development of large platelet aggregates from small aggregates as determined by laser-light scattering: effects of aggregant concentration and antiplatelet medication.

Particle-counting methods that employ light scattering (LS) quantify changes in the number of platelet aggregates of different sizes after the application of an aggregating stimulus. Using the LS method, we studied the effects of aggregant concentration, aspirin administration, and ticlopidine administration on aggregate formation and compared the results with those obtained using the conventional optical density (OD) method. Subjects were 47 controls, 31 patients treated with aspirin (330 mg/day), and 37 patients treated with ticlopidine (200 mg/day). Platelet aggregation after stimulation by 0.5, 1.0 or 5.0 muM ADP, or 0.5, 1.0 or 2.0 micrograms/ml collagen was determined using both methods. Using the LS method, small (9-25 micrograms), medium (25-50 micrograms), and large (50-70 micrograms) aggregates were counted. In patients untreated with antiplatelet medication, greater concentrations of ADP or collagen generated larger aggregates. Generation of small and medium-sized aggregates showed a significant positive correlation with OD levels after stimulation with 0.5 or 1.0 muM ADP, or 0.5 or 1.0 micrograms/ml collagen. In patients treated with aspirin, the development of small aggregates into large aggregates was inhibited. Thus, the number of small aggregates increased. Inhibition induced by aspirin was more effective against aggregation after stimulation with collagen than with ADP. In patients treated with ticlopidine, small and medium-sized aggregate formation was inhibited after stimulation with low concentrations of ADP or collagen, but was promoted after stimulation with high aggregant concentrations. The capability of the LS method to quantify different sizes of aggregates after stimulation with low concentration agonists may facilitate investigation of the aggregation process, and of how this process is affected by antiplatelet agents.

Aged↗
PubMed1996

[TCR alpha beta + CD4- CD8- T cells among the peripheral blood mononuclear cells of myasthenia gravis patients].

We investigated the occurrence of TCR alpha beta + CD4- CD8- mononuclear cells (DN alpha beta T cells) and TCR gamma delta + CD3+ mononuclear cells (gamma delta T cells) among the peripheral blood mononuclear cells of 22 myasthenia gravis patients (MG) and 22 controls in order to examine whether extrathymic T cell subpopulations might be responsible for the pathogenesis of MG. The differences between the mean percentages of both DN alpha beta T cells and gamma delta T cells in the MG patients (DN alpha beta T cells: 0.53 +/- 0.51%, gamma delta T cells: 3.45 +/- 2.79%) and the controls (DN alpha beta T cells: 0.32 +/- 0.16%, gamma delta T cells: 3.81 +/- 2.36%) were not significantly different. However, higher DN alpha beta T cells ratios (1.48 approximately 1.84%) were noted in three MG patients. Thymectomy and subsequent thorough dissection of the anterior mediastinum 3 years after thymectomy had no effect on the symptoms of one patient, a 25-year-old woman without thymoma. The other two patients, a 45-year-old man and a 41-year-old woman without thymoma, had recurrences despite long-term remissions (14 years and 30 years, respectively) after thymectomy. Examination of DN alpha beta T cells, which are probably generated extrathymically without negative selection, may play an important role in understanding the pathogenesis in these three cases of MG.

Adult↗
PubMed1996

[A case of progressive hemifacial and hemispheric atrophy with multiple hemi-intracerebral calcifications presenting with occipital lobe epilepsy].

A 30-year-old man with progressive hemifacial atrophy is described. He had right hemifacial atrophy and epileptic seizures first noted at the age of about 15 years. Examination revealed atrophy of the right half of the tongue, skin pigmentation in the right neck, grizzled hair on the right side of the head, and left upper temporal homonymous hemianopsia. CT and MRI revealed multiple intracerebral calcifications, and EEG showed spike discharges predominantly in the right occipital lobe, ipsilateral to the hemifacial atrophy. The epileptic seizures were associated with visual hallucinations that are characteristic of occipital epilepsy. A skin biopsy obtained from the pigmented region in the right neck showed chronic inflammatory changes consisting of severe atrophy of the epidermis, dermis, and fatty tissue, marked proliferation of collagen fibers, and perivascular infiltration by round cells and giant phagocytes. Previous descriptions on the pathogenesis of hemiatrophy of the face and brain were reviewed in relation to the present case.

Adult↗
PubMed1995

Effects of age on messenger RNA expression of glucocorticoid, thyroid hormone, androgen, and estrogen receptors in postmortem human hippocampus.

We studied messenger RNA (mRNA) expressions of receptors for glucocorticoid (GR), thyroid hormone (TR), androgen (AR), and estrogen (ER) and their changes with age in the hippocampal subregions in postmortem human brain. In situ hybridization was done with biotin-labeled antisense synthetic oligonucleotide probes. About 80% or more of the pyramidal neurons in the hippocampal subregions expressed mRNAs for individual receptors in the brains of subjects younger than 65. The ratio of mRNA-containing neuron density to total neuron density significantly decreased with age for GR in CA1 and CA3, and for AR in CA1. Non-significant trends in the reduction with age in the ratio of ER mRNA-containing neurons in CA1 and the ratio of GR mRNA-containing neurons in the hilus also were found. Age-related reductions in nuclear receptor protein mRNA expression in neurons in the hippocampal subfields may be important in the impairments of cognition, emotion, and responses to acute stress in the aged.

Adult↗
PubMed1995

Heat-shock cognate 70 messenger RNA expression in postmortem human hippocampus: regional differences and age-related changes.

In situ hybridization of postmortem human brain tissue showed that constitutive heat-shock cognate 70 (hsc 70) mRNA was expressed in more than 50% of the pyramidal neurons in the hippocampal subfields. The ratio (%) of the hsc 70 mRNA-expressing neurons to the total neurons was significantly greater in CA3 and the hilus than in CA1 and CA2. The lower ratio in CA1 may be related to its vulnerability to various stresses. The ratio of hsc 70 mRNA-expressing neurons in CA1 was significantly greater in the older subjects than in the younger ones. This may reflect the up-regulated hsc 70 mRNA induction in response to a reduction in free hsc 70 because the binding of hsc 70 to aberrant proteins may be increased in aged persons.

Adult↗
PubMed1995

Effects of the catechol-O-methyltransferase inhibitor tolcapone in Parkinson's disease: correlations between concentrations of dopaminergic substances in the plasma and cerebrospinal fluid and clinical improvement.

We compared the concentrations of dopaminergic substances in the plasma and cerebrospinal fluid (CSF) with clinical severity in patients with Parkinson's disease (PD) under L-dopa/carbidopa treatment and under L-dopa/carbidopa+tolcapone treatment. Compared with treatment with L-dopa/carbidopa alone, the co-administration of tolcapone produced a significant decrease in clinical severity; a remarkable reduction in the 3-O-methyldopa (3-OMD) concentration and significant increase in the L-dopa concentration both in the plasma and CSF; and a significant increase in the dopamine concentration in the CSF. The clinical effects of tolcapone were closely correlated with the reduction in the 3-OMD concentration, but not with the increase in the dopamine and L-dopa concentrations in the CSF.

3,4-Dihydroxyphenylacetic Acid↗