A 200-m All-out Front-crawl Swim Modifies Competitive Swimmers' Shoulder Joint Position Sense.

We tested the hypothesis that an all-out-effort 200-m front-crawl swim trial affects competitive swimmers' shoulder joint position sense. On Day 1, we measured shoulder joint position sense before and after the swim trial, and on Day 2 before and after 2 min of seated rest. On both days, shoulder joint position sense was measured in the seated position using electromagnetic movement sensors in a position-matching paradigm. An investigator abducted participants' left (reference) shoulder joint in the frontal plane to test angles of 90°, 135°, and 180°. Participants then actively abducted the right (indicator) shoulder joint to match the position of the left, reference arm. After the 200-m all-out front-crawl swim trial, the indicator relative to the reference angle differed by 4.4° toward adduction at the 180° (vertical) testing position (P<0.05). Variation in absolute matching error was 3.2° or 2.2 times greater after swim compared with the no-swim control trial. An all-out 200-m front-crawl swim trial can selectively increase competitive swimmers' shoulder joint position sense error and increase variation in matching error in horizontal arm position.

Detecting sweet and umami tastes in the gastrointestinal tract.

Information about nutrients is a critical part of food selection in living creatures. Each animal species has developed its own way to safely seek and obtain the foods necessary for them to survive and propagate. Necessarily, humans and other vertebrates have developed special chemosensory organs such as taste and olfactory organs. Much attention, recently, has been given to the gastrointestinal (GI) tract as another chemosensory organ. Although the GI tract had been considered to be solely for digestion and absorption of foods and nutrients, researchers have recently found taste-signalling elements, including receptors, in this tissue. Further studies have revealed that taste cells in the oral cavity and taste-like cells in the GI tract appear to share common characteristics. Major receptors to detect umami, sweet and bitter are found in the GI tract, and it is now proposed that taste-like cells reside in the GI tract to sense nutrients and help maintain homeostasis. In this review, we summarize recent findings of chemoreception especially through sweet and umami sensors in the GI tract. In addition, the possibility of purinergic transmission from taste-like cells in the GI tract to vagus nerves is discussed.

The role of the GABAergic and dopaminergic systems in the brain response to an intragastric load of alcohol in conscious rats.

The brain's response to ethanol intake has been extensively investigated using electrophysiological recordings, brain lesion techniques, and c-Fos immunoreactivity. However, few studies have investigated this phenomenon using functional magnetic resonance imaging (fMRI). In the present study, we used fMRI to investigate the blood oxygenation level-dependent (BOLD) signal response to an intragastric (IG) load of ethanol in conscious, ethanol-naive rats. An intragastrically infused 10% ethanol solution induced a significant decrease in the intensity of the BOLD signal in several regions of the brain, including the bilateral amygdala (AMG), nucleus accumbens (NAc), hippocampus, ventral pallidum, insular cortex, and cingulate cortex, and an increase in the BOLD signal in the ventral tegmental area (VTA) and hypothalamic regions. Treatment with bicuculline, which is an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, increased the BOLD signal intensity in the regions that had shown decreases in the BOLD signal after the IG infusion of 10% ethanol solution, but it did not affect the BOLD signal increase in the hypothalamus. Treatment with SCH39166, which is an antagonist of D1-like receptors, eliminated the increase in the BOLD signal intensity in the hypothalamic areas but did not affect the BOLD signal decrease following the 10% ethanol infusion. These results indicate that an IG load of ethanol caused both a GABA(A) receptor-mediated BOLD decrease in the limbic system and the cortex and a D1-like receptor-mediated BOLD increase in the hypothalamic regions in ethanol-naive rats.

Effects of isoflurane and alpha-chloralose anesthesia on BOLD fMRI responses to ingested L-glutamate in rats.

It is important to investigate the effect of anesthesia on blood oxygenation level-dependent (BOLD) signals in an animal model. Many researchers have investigated the BOLD response to visual, sensory, and chemical stimuli in anesthetized rats. There are no reports, however, comparing the differences in the BOLD signal change between anesthetized and conscious rats when a visceral nutrient signal arises. Here, using functional magnetic resonance imaging (fMRI), we investigated the differences in the BOLD signal changes after intragastric administration of l-glutamate (Glu) under three anesthesia conditions: conscious, alpha-chloralose-anesthetized, and isoflurane-anesthetized condition. Under the conscious and alpha-chloralose condition, we observed the significant BOLD signal increase in the medial prefrontal cortex (mPFC), insular cortex (IC), hippocampus, and several hypothalamic regions including the lateral and ventromedial nucleus. In chloralose group, however, gut Glu stimulation induced BOLD signal increase in the prelimbic cortex and orbital cortex, which did not activate in conscious condition. Meanwhile, under isoflurane-anesthetized condition, we did not observe the BOLD signal increase in these areas. BOLD signal intensity in the nucleus of the solitary tract (NTS), to which vagus nerve transmits the visceral information from the gastrointestinal tract, increased in all conditions. Importantly, under conscious condition, we observed increased BOLD signal intensity in several regions related to the metabolic state (i.e. hunger or satiety), such as the mPFC, ventromedial and lateral hypothalamus (LH). Our results suggest that alpha-chloralose and isoflurane anesthesia caused distinct effects on BOLD response to the gut l-Glu stimulation in several brain regions.

Molecular and clinical analysis of Japanese patients with 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency.

Deficiency of mitochondrial 3-hydroxy-3-methylglutaryl CoA lyase (HL, EC4.1.3.4.) is an autosomal recessive genetic disorder characterized by acute episodes of vomiting, hypotonia, and lethargy in the neonatal period or in infancy. Except in Saudi Arabia, where HL deficiency is the most common organic acidemia, the disorder is quite rare with only 41 cases being reported in the English literature, and only five known cases among Japanese. In this study, we present the results of a molecular analysis of all five Japanese patients together with their clinical phenotypes. Five different mutations in the HL gene were identified: one large deletion, one nonsense mutation, one missense mutation, and two splice mutations. Except for G835A (E279K) with its relatively common occurrence among Japanese, these mutations were unique to each family. The results of expression studies with mutated HL cDNAs confirmed the pathogenicity of these mutations and supported the importance of previously identified functional domains of the HL molecule, i.e., the putative catalytic site or dimerization site. In addition, we identified an alternative splicing event that resulted in the skipping of exons 5 and 6. This alternatively spliced product did not show HL activity and was present in various tissues of normal subjects. Clinically, all patients presented with similar symptoms, except that the timing of the initial presentation varied considerably, from 1 day to 1 year 3 months. In general, patients with null-activity mutations presented earlier in life, whereas those with residual activities presented later.

Living-related liver transplantation for neonatal-onset propionic acidemia.

We report a child with neonatal-onset propionic acidemia treated with living-related liver transplantation. Despite minimal improvement in the levels of circulating propionyl CoA metabolites, hyperammonemia was corrected, and no episode of metabolic decompensation was experienced after the transplantation was performed. Natural protein intake could be increased from 0.5 g/kg per day to 2 g/kg per day. Anemia was corrected, and the growth rate and mental development improved significantly.

Hyperinsulinism-hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics.

Hyperinsulinism-hyperammonemia syndrome (HHS) is a recently identified genetic disorder characterized by hyperinsulinemic hypoglycemia with concomitant hyperammonemia. In patients with HHS, activating mutations in the glutamate dehydrogenase (GDH) gene have been identified. GDH is a key enzyme linking glutamate metabolism with the Krebs cycle and catalyzes the conversion of glutamate to alpha-ketoglutarate. The activity of GDH is controlled by allosteric inhibition by GTP and, so far, all the mutations of HHS patients have been located within the GTP-binding site. Characteristically, GDH from these individuals have therefore normal basal activity in conjunction with a loss of GTP inhibition. In this study, however, we have identified a novel variant GDH in a patient with a more severe form of HHS. The mutation is located outside the GTP-binding site and the patient's GDH shows consistently higher activity, even in the absence of allosteric effectors. These results further support the hypothesis that the activating mutation of GDH is the cause of HHS. The mechanism leading to the activation of GDH, however, is not always related to the loss of GTP inhibition as was originally suggested.

Identification of a novel single base-pair polymorphism in the glutamate dehydrogenase (GLUD1) gene.

A novel single base-pair polymorphism, G/A at ntd 955, was identified within the coding region of the glutamate dehydrogenase gene (GLUD1). This polymorphism should prove useful for the study of human disorders with altered ammonia and/or blood glucose levels.

Relatively longer hand in patients with Ullrich-Turner syndrome.

We analyzed the total hand length (HL) and length of noncarpal bones (NCL) in 50 Japanese patients with Ullrich-Turner syndrome (UTS) and in 443 other patients with short stature used as controls. In each patient group we calculated relative HL (RHL= HL/height) and relative NCL (RNCL= NCL/height). UTS patients had significantly greater RHL than controls. The greater RHL in UTS patients is mainly due to their longer, short tubular bones. The RHL is not affected by ages and karyotypes of UTS patients or growth hormone treatments given to them. We conclude that relatively longer hands are a common manifestation of UTS and that this parameter is useful for the diagnosis of the syndrome among short females, who usually need chromosome analysis.

X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency.

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It is X-linked and hemizygous new-born males usually suffer fatal hyperammonemia. In contrast, carrier females manifest variable phenotypes, ranging from asymptomatic carriers to those with severe hyperammonemia. In order to understand the correlation between X-inactivation status and the clinical phenotype of carrier females with this disorder, we analyzed the X-inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and two daughters with severe manifestation. In addition, we obtained tissue samples from various parts of the liver of one of these daughters and analyzed X-inactivation patterns and the residual OTC activities. The X-inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype. However, the X-inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. Interestingly, the degree of X-inactivation varied considerably, even within the same liver.

Uniparental and functional X disomy in Turner syndrome patients with unexplained mental retardation and X derived marker chromosomes.

We analysed parental origin and X inactivation status of X derived marker (mar(X)) or ring X (r(X)) chromosomes in six Turner syndrome patients. Two of these patients had mental retardation of unknown cause in addition to the usual Turner syndrome phenotype. By FISH analysis, the mar(X)/r(X) chromosomes of all patients retained the X centromere and the XIST locus at Xq13.2. By polymorphic marker analysis, both patients with mental retardation were shown to have uniparental X disomy while the others had both a maternal and paternal contribution of X chromosomes. By RT-PCR analysis and the androgen receptor assay, it was shown that in one of these mentally retarded patients, the XIST on the mar(X) was not transcribed and consequently the mar(X) was not inactivated, leading to functional disomy X. In the other patient, the XIST was transcribed but the r(X) appeared to be active by the androgen receptor assay. Our results suggest that uniparental disomy X may not be uncommon in mentally retarded patients with Turner syndrome. Functional disomy X seems to be the cause of mental retardation in these patients, although the underlying molecular basis could be diverse. In addition, even without unusual dysmorphic features, Turner syndrome patients with unexplained mental retardation need to be investigated for possible mosaicism including these mar(X)/r(X) chromosomes.

[A case of pulmonary metastasis of ovarian leiomyosarcoma responsive to CTP therapy].

One case of pulmonary metastasis of leiomyosarcoma responsive to CTP therapy was reported. The patient was a 44-year-old woman who had undergone total simple hysterectomy for uterine myoma 6 years before. Five years after the operation she underwent ovariectomy for ovarian tumor. Based on the histopathological findings, she was diagnosed to have leiomyosarcoma. One year later the patient was referred to use because of pulmonary metastasis. After admission to our hospital CTP therapy was started. Disappearance of the metastatic lesion was demonstrated by the chest X-ray findings at the end of five courses of treatment.

[The incidence of pulmonary tuberculosis in an urban area].

The incidence and prevalence of pulmonary tuberculosis has declined steadily in Japan, but the trends differ greatly by area according to epidemiological status. We studied the incidence and trends of pulmonary tuberculosis in an urban area (population approx. 150,000) during the period of 1979-1988. The area studied is a part of a large commercial city, characterized as having the most prevalent rate of tuberculosis area in that city. Of 1245 newly registered cases, 80% were over 40 years of age. While the incidence rate decreased to 57% in the last 10 years in this area, compared to 69% decrease for all of Japan, it was still considerably higher than the national average. Especially in the 20-59 age group it continued to be 2 times higher than that of the whole of Japan. Moreover, the positive rate of tubercle bacilli at the time of registration had increased remarkably from 27% in 1979 to 62% in 1988. These results suggest the tuberculosis continues to be a significant problem in this urban area, although the steady decline in the incidence of tuberculosis had led to a lack of awareness of this disease.

Application of a local drug delivery system to periodontal therapy: I. Development of collagen preparations with immobilized tetracycline.

For the purpose of applying a local drug delivery system to periodontal therapy, atelocollagen preparations with immobilized tetracycline (TC) were prepared by modifying the form of the collagen, the concentration of the immobilized TC, and the time of the cross-link process with glutaraldehyde. The course of the TC release from the collagen preparations into an aqueous solution was determined in relation to time. The preparations were also inserted into periodontal pockets, and the amount of TC remaining in the pocket was determined daily. The results obtained were as follows: 1) The degree of drug release could be controlled to some extent by adjusting the TC concentration and the time of the cross-link process; and 2) an amount of TC exceeding the effective dose in the gingival crevicular fluid was present in the periodontal pocket even 10 days after the insertion of TC fixed in the cross-linked processed collagen film in the periodontal pockets.