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Biomedical subjects

N Takahata

Publications and source records attributed to N Takahata.

At least 91 records · Page 5Linked to original sources
PubMed1994

Residual neurobehavioural effects associated with chronic exposure to mercury vapour.

To find the residual effects of long term exposure to mercury vapour, neurobehavioural tests were given to ex-mercury miners about 18 years after the end of mercury exposure. Seventy six male ex-mercury miners who had been exposed to high concentrations of mercury vapour (over 1.0 mg/m3) and with a history of mercury intoxication were compared with controls matched for age (within 3 years), sex, and education. Although the extent of the workers' symptoms caused by mercury poisoning, termed erethismus merculialis, decreased considerably after the end of exposure, matched paired comparison showed that performances of motor coordination, simple reaction time, and short term memory had deteriorated significantly in the exposed group. Multiple linear regression analysis of exposure variables with neurological examination measures showed positive correlations between poorer neurological performance and variables related to mercury exposure. Thus the duration of exposure correlated with poorer performance of hand-eye coordination, tapping, and a colour card reading test. Job categories classified by exposure to mercury also had a significant negative correlation with these performances. The period of years after the end of exposure had a significant correlation with better performance of reaction time and digit span. On the other hand, the history of intoxication itself had no significant correlation with any of the current neurobehavioural performances. These results suggest that there are slight but persistent effects on neurobehavioural function, especially on motor coordination, among mercury miners even more than 10 years after the end of exposure.

Aged↗
PubMed1994

[Disorganized eye movements and visuospatial dysfunctions in an early stage of the patients with Alzheimer's disease--the effects of language and visual information processing on constructional performances].

In Alzheimer's disease higher brain function disorders such as geographical disorientation, visual agnosia and constructional disability are frequently observed in addition to the progressive memory loss. Visual information processing was studied through newly developed technology, vision analyzer, since visuospatial functions play an important role in the pathophysiology underlying these neuropsychiatric symptoms and dementia itself. We found characteristic findings as to eye movements of focus indicating visual cognitive disorders. Language or language functions, however, are considered to be essentially involved in visuospatial functions. We examined eye movements of patients suffering from Alzheimer's disease (15 cases), MID (5 cases), Parkinson's disease (5 cases) and 10 control subjects during constructional behavior under various conditions in terms of visual information processing. 1. Alzheimer's disease (n = 15): All patients showed constructional disabilities when copying geometrical figures. 1) Three dimensional drawing was possible following verbal instructions in 7 out of 15 patients. 2) Three dimensional drawing was successful when the model figure to be copied was covered in 4 out of these 7 patients. 3) Three dimensional drawing was possible following verbal instruction in a dark room, although they were not so accurate but better than those when copied in 4 out of 7 patients. 4) The analysis of eye movements revealed that typical eye movements were confirmed during copying geometric figures. The distribution of the gazing points of focus, and the average eye movement velocity distribution were also distinctive. But these disorganized eye movements in description of graphic figures following verbal instruction became more similar to those of healthy controls when compared to those in the copying graphic figures. 2. MID (n = 5), Parkinson disease (n = 5), healthy controls (n = 10): 1) No subject showed constructional disability when copying a graphic figure. They were also capable to describe a graphic figure both in the dark and following verbal instruction. 2) No remarkable change was observed in the distribution of the eye movement, or in the average eye movement velocity on these subjects. 3. These results indicate that in an early stage of the patients with Alzheimer's disease, primary or fundamental disorders seem to lay in the verification process of visual information, which results in the difficulties in categorization process of the visual objects. The categorization process is involved with language function, which was preserved in a certain period at an early stage of the disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Alzheimer Disease↗
PubMed1994

[A case of Wernicke's encephalopathy which accompanied a passing blindness].

The case of a chronic alcoholic patient with Wernicke's encephalopathy accompanied by passing blindness is reported and the alcoholic amblyopia is discussed in this study. The patient was a 39 year-old male who had been a heavy drinker for 13 years, and was habitually inebriated for the last one year. Disturbance of consciousness ataxia of gait, nystagmus and blindness were manifested on admission. Decreased level of serum vitamin B1 was also recognized at admission. The symptoms diminished from about a month after admission except for horizontal nystagmus. Since the patient had racket-like scotoma in his central visual field, his blindness was thought to be alcoholic amblyopia. Although alcohol dependence is associated with many physical disabilities, there are few reports about Wernicke's encephalopathy with alcoholic amblyopia. This case demonstrates the importance of careful physical examination for understanding alcohol-related disabilities and alcohol dependence.

Adult↗
PubMed1994

Alterations of receptor-G protein-adenylyl cyclase coupling in alcoholics.

This study investigated alterations in the receptor adenylyl cyclase system in the brain and platelets of alcoholics through the study of GTP binding (G) protein, which has a key role in the system, in the membranes of the post-mortem brain and platelets. Quantitative examination of G protein by immunoblotting showed that GsH alpha in the temporal cortex of the post-mortem alcoholic brain was significantly decreased with controls. Moreover, the extent of ethanol enhancement of functional photoaffinity GTP(azidoanilido GTP) labeling to Gs alpha and Gi alpha was decreased in all cortical regions (frontal, temporal, parietal, occipital cortex) from alcoholics. In the platelet membrane, a quantitative reduction in GsH alpha and GsL alpha levels as assessed by immunoblotting was seen in family history positive (FHP) alcoholics. A reduction in ethanol enhancement of AAGTP labeling to Gs alpha and Gi alpha was also observed in the FHP group. These alterations of G protein were not found in the platelets from family history negative (FHN) alcoholics. The dysfunctions of Gs protein occurring in platelet membranes of the FHP group are likely to parallel those that occur in the alcoholic brain. These results suggest that disturbances of G protein-mediated signal transduction may be involved in the pathophysiology of alcoholics and that platelet G protein may be used as a trait marker of alcoholics.

Adenylyl Cyclases↗
PubMed1994

Reduced sensitivity to ethanol of Gs alpha and Gi/o alpha in the cerebral cortex of alcoholic patients.

In this study, we examined the quantity and quality of G proteins in membrane preparations from cortical regions (frontal, parietal, temporal and occipital cortex) in post-mortem brains obtained from subjects with chronic alcoholism and controls matched with respect to age and post-mortem delay (PMDT). Immunoblot analysis showed that the level of GsH alpha (52 kDa) was significantly decreased in temporal cortical membranes from alcoholics compared with controls, while no differences were observed in the amount of any G protein in frontal, parietal and occipital regions. Additionally, ethanol enhanced photoaffinity guanine nucleotide binding to both G alpha and Gi/o alpha in human cortical membranes. The percentage of increase in ethanol-stimulated photoaffinity GTP labeling of Gs alpha and Gi/o alpha was decreased in alcoholic patients in all cortical regions. These observations indicated that subsensitivities to ethanol-induced stimulation in G protein may contribute to impaired trans-signaling in cortical membranes of chronic alcoholics.

Alcoholism↗
PubMed1993

Alterations of guanine nucleotide-binding proteins in post-mortem human brain in alcoholics.

Qualitative and quantitative alterations of G proteins in membrane preparations from parietal and temporal cortex regions in post-mortem brains obtained from alcoholics and controls matched with respect to age and post-mortem delay were investigated by Western-blotting with polyclonal antibodies against specific G protein subunits and functional photoaffinity GTP binding. Quantitative immunoblotting showed that only Gs alpha (52 kDa species) in temporal cortex was significantly decreased (30%, P < 0.05) in alcoholics compared with controls. Moreover, ethanol-stimulated photoaffinity GTP labeling of Gs alpha and Gi/o alpha was decreased in alcoholics in both cortex regions. These results suggest that disturbances of G protein-mediated signal transduction may be involved in the pathophysiology of alcoholics.

Aged↗
PubMed1993

The synonymous substitution rate of the major histocompatibility complex loci in primates.

Because the divergence of many allelic lineages at the major histocompatibility complex (MHC) loci predates species divergence, standard methods of calculating synonymous substitution rates are not applicable to this system. We used three alternative methods of rate estimation: one based on the minimum number of substitutions (Dm), another on the nucleotide difference (Dxy), and the third on the net nucleotide difference (Dn). We applied these methods to the protein-encoding sequences of primate MHC class I (A, B, and C) and class II (DRB1) genes. To determine the reliability of the different estimates, we carried out computer simulation. The distribution of the estimates based on Dxy or Dn is generally much broader than that based on Dm. More importantly, the Dm-based method nearly always has the highest probability of recovering true rates, provided that Dm is not smaller than 5. Because of its desirable statistical properties, we used the Dm-based method to estimate the rate of synonymous substitutions. The rate is 1.37 +/- 0.61 for A, 1.84 +/- 0.40 for B, 3.87 +/- 1.05 for C, and 1.18 +/- 0.36 for DRB1 loci, always per site per 10(9) years. Hence despite the extraordinary polymorphism, the mutation rate at the primate MHC loci is no higher than that of other loci.

Alleles↗
PubMed1993

Subjective symptoms and neurobehavioral performances of ex-mercury miners at an average of 18 years after the cessation of chronic exposure to mercury vapor. Mercury Workers Study Group.

In order to determine if there are any residual effects of long-term exposure to mercury vapor, neurobehavioral tests were given to ex-mercury miners about 18 years after the cessation of mercury exposure. Seventy-six male ex-mercury miners who had been exposed to relatively high concentrations of mercury vapor (over 1.0 mg/m3) and with a past history of mercury intoxication were compared to age (+/- 3 years)-, sex-, and years of education-matched controls. Although the extent of the workers' symptoms caused by mercury poisoning, termed erethismus merculialis, markedly decreased after the cessation of exposure, the prevalence of neurological symptoms (such as hand tremors, headaches, and slurred speech) and symptoms of senility (such as low-back pain, loss of sexual desire) in the ex-miners was significantly higher than those in the controls. Matched-pair analysis showed that performances of motor coordination, Simple reaction time, and Short-term memory in the ex-miners were significantly deteriorated compared to those of controls. There are slight but persistent effects on neurobehavioral function, especially on motor coordination function, among mercury miners more than 10 years after the cessation of exposure.

Aged↗
PubMed1993

Effective population size, genetic diversity, and coalescence time in subdivided populations.

A formula for the effective population size for the finite island model of subdivided populations is derived. The formula indicates that the effective size can be substantially greater than the actual number of individuals in the entire population when the migration rate among subpopulations is small. It is shown that the mean nucleotide diversity, coalescence time, and heterozygosity for genes sampled from the entire population can be predicted fairly well from the theory for randomly mating populations if the effective population size for the finite island model is used.

Animals↗
PubMed1993

Evolution of hominoid mitochondrial DNA with special reference to the silent substitution rate over the genome.

Focusing on the synonymous substitution rate, we carried out detailed sequence analyses of hominoid mitochondrial (mt) DNAs of ca. 5-kb length. Owing to the outnumbered transitions and strong biases in the base compositions, synonymous substitutions in mtDNA reach rapidly a rather low saturation level. The extent of the compositional biases differs from gene to gene. Such changes in base compositions, even if small, can bring about considerable variation in observed synonymous differences and may result in the region-dependent estimate of the synonymous substitution rate. We demonstrate that such a region dependency is due to a failure to take proper account of heterogeneous compositional biases from gene to gene but that the actual synonymous substitution rate is rather uniform. The synonymous substitution rate thus estimated is 2.37 +/- 0.11 x 10(-8) per site per year and comparable to the overall rate for the noncoding region. On the other hand, the rate of nonsynonymous substitutions differs considerably from gene to gene, as expected under the neutral theory of molecular evolution. The lowest rate is 0.8 x 10(-9) per site per year for COI and the highest rate is 4.5 x 10(-9) for ATPase 8, the degree of functional constraints (measured by the ratio of the nonsynonymous to the synonymous substitution rate) being 0.03 and 0.19, respectively. Transfer RNA (tRNA) genes also show variability in the base contents and thus in the nucleotide differences. The average rate for 11 tRNAs contained in the 5-kb region is 3.9 x 10(-9) per site per year. The nucleotide substitutions in the genome suggest that the transition rate is about 17 times faster than the transversion rate.

Adenosine Triphosphatases↗
PubMed1993

Motor neuron disease and past poliomyelitis. Geographic study in Hokkaido, the northern-most island of Japan. ALS Study Group.

We carried out a survey on the cases of motor neuron disease (MND) occurring in Hokkaido between 1980 and 1989 in order to establish whether there is a relationship between MND and poliomyelitis. Hokkaido, the northern-most island of Japan, was one of the most affected areas during the poliomyelitis epidemic of the late 1940s to 1950s. We ascertained 389 cases of MND for these 10 years and 2,171 cases of paralytic poliomyelitis for the period 1949-1958, and analysed their geographic distributions. No significant correlation was found between MND and poliomyelitis in their geographic distributions.

Adult↗
PubMed1993

Magnetic field responses to visual stimulation in human parietal association cortex.

The neural activities of the parietal association cortex were studied in humans through the use of a 37-channel SQUID magnetometer system. The magnetic field responses were recorded in the parietal association cortex following visual stimulation with LED light. Main responses peaking at about 120, 170 and 220 msec after LED onset were observed. The estimated current dipole sources of the magnetic field responses at latencies of 160-190 and 210-270 msec were revealed to be located in the intraparietal sulcus. A change in the magnetic field responses with the eye position was found in the amplitude.

Adult↗
PubMed1993

Allelic genealogy and human evolution.

Genetic variation at most loci examined in human populations indicates that the (effective) population size has been approximately 10(4) for the past 1 Myr and that individuals have been genetically united rather tightly. Also suggested is that the population size has never dropped to a few individuals, even in a single generation. These impose important requirements for the hypotheses for the origin of modern humans: a relatively large population size and frequent migration if populations were geographically subdivided. Any hypothesis that assumes a small number of founding individuals throughout the late Pleistocene can be rejected. Extraordinary polymorphism at some loci of the major histocompatibility complex (Mhc) rules out the past action of severe bottlenecks, or the so-called founder principle, which invokes only a small number of founding individuals when a new species emerges. This conclusion may be extended to the 35-Myr-old history of the human lineage, because some polymorphism at Mhc loci seems to have lasted that long. Furthermore, although the population structure prior to the late Pleistocene is less clear, owing to the insensitivity of Mhc alleles, even to low levels of migration, the nature of Mhc polymorphism suggests that the effective size of populations leading to humans was as large as 10(5). Hence, the effective population size of humans might have become somewhat smaller in most of the late Pleistocene. The reduction could be due either to the then adverse environment in the Old World and/or to the increased migration rate. It is also argued that population explosion fostered by the agriculture revolution has had significant effects on incorporating new alleles into human populations.

Alleles↗
PubMed1993

The molecular descent of the major histocompatibility complex.

In the last few years, more than 500 primate major histocompatibility complex (Mhc) genes or parts thereof have been sequenced. The extraordinary sequence information is used here to draw conclusions about the manner of Mhc evolution. The Mhc genes are found to evolve at a relatively slow rate with the regularity of a clock. It takes from 1 to 6 million years for a new mutation to be incorporated into an Mhc allele, and the mutation rate is comparable to that of most other primate genes. The nonsynonymous sites coding for the peptide-binding region (PBR) are under relatively weak positive selection pressure (selection coefficient of a few percent only); the nonsynonymous non-PBR sites are under moderate negative selection pressure. The positive pressure is probably provided by parasites and is responsible for the trans-species persistence of allelic lineages at functional Mhc loci for more than 40 million years.

Alleles↗