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Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 55 records · Page 3Linked to original sources
PubMed2001

Evidence for metaboreceptor stimulation of sweating in normothermic and heat-stressed humans.

1. Isometric handgrip (IHG) exercise increases sweat rate and arterial blood pressure, and both remain elevated during post-exercise ischaemia. The purpose of this study was to identify whether the elevation in arterial blood pressure during post-exercise ischaemia contributes to the increase in sweating. 2. In normothermia and during whole-body heating, 2 min IHG exercise at 40% maximal voluntary contraction, followed by 2 min post-exercise ischaemia, was performed with and without bolus intravenous administration of sodium nitroprusside during the ischaemic period. Sodium nitroprusside was administered to reduce blood pressure during post-exercise ischaemia to pre-exercise levels. Sweat rate was monitored over two microdialysis membranes placed in the dermal space of forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine, while the other was perfused with the vehicle. 3. In normothermia, IHG exercise increased sweat rate at the neostigmine-treated site but not at the control site. Sweat rate remained elevated during post-exercise ischaemia even after mean arterial blood pressure returned to the pre-IHG exercise baseline. Subsequent removal of the ischaemia stimulus returned sweat rate to pre-IHG exercise levels. Sweat rate during post-exercise ischaemia without sodium nitroprusside administration followed a similar pattern. 4. During whole-body heating, IHG exercise increased sweat rate at both neostigmine-treated and untreated sites. Similarly, regardless of whether mean arterial blood pressure remained elevated or was reduced during post-exercise ischaemia, sweat rate remained elevated during the ischaemic period. 5. These results suggest that sweating in non-glabrous skin during post-IHG exercise ischaemia is activated by metaboreflex stimulation and not via baroreceptor loading.

Adult↗
PubMed2001

Urinary organic acids in peroxisomal disorders: a simple screening method.

Using GC-MS, we studied urinary organic acids in 20 Japanese patients with peroxisomal disorders, including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy, and single deficiency of peroxisomal beta-oxidation enzymes. Non-ketotic dicarboxylic aciduria with elevated sebacate/adipate molar ratio was observed in 19 of the 20 patients. Elevation of 2-hydroxysebacate and epoxydicarboxylic acids were seen in 13 and 18, respectively. Tyrosyluria was remarkable in all patients. In two ZS patients, we tracked the time course from birth to infancy, and all the above stated findings were detected, except for one sample. Urinary organic acid analysis is indeed useful for screening subjects with peroxisomal disorders.

Acids↗
PubMed2001

The clinical phenotype and outcome of mitochondrial acetoacetyl-CoA thiolase deficiency (beta-ketothiolase or T2 deficiency) in 26 enzymatically proved and mutation-defined patients.

Mitochondrial acetoacetyl-CoA thiolase (T2 enzyme) deficiency (MIM 203750) is an autosomal recessive disorder of isoleucine and ketone-body metabolism. We determined the molecular basis of T2 enzyme deficiency in 26 patients at the levels of skin fibroblast enzyme activity, protein integrity, and DNA nucleotide sequence. Thirty different disease-associated alleles were identified. From these data we predicted that T2 in 6 of the 26 patients would have a mild effect on the enzyme protein and 20 would have a severe effect from their mutant genotypes. The corresponding clinical data were collected (by interviews and questionnaires) for the patients in the two groups. We found that genotype does not predict clinical severity and mutant sibs can have different clinical phenotypes; there were no consistent differences in clinical severity between patients with null-conferring or residual-conferring genotypes for T2 activity; only the absence of or a low urinary excretion of tiglyglycine during ketoacidosis correlated with a mild genotype. In general, T2 deficiency has a favorable outcome and 23 of 26 patients developed normally; one died during the first ketoacidotic episode and two have developmental delay. The median age at onset for the first ketoacidotic episode is 15 months (range 3 days to 48 months). The frequency of attacks falls with age, the last in our series occurring at 10 years of age; 11 patients had only one episode and 3 patients had none. We conclude that clinical consequences of T2 deficiency are avoidable with early diagnosis, appropriate management of ketoacidosis, and modest protein restriction.

Acetyl-CoA C-Acyltransferase↗
PubMed2001

A novel single-base substitution (380C>T) that activates a 5-base downstream cryptic splice-acceptor site within exon 5 in almost all transcripts in the human mitochondrial acetoacetyl-CoA thiolase gene.

Most mutation-related aberrant splicing occurs in the conserved splice-acceptor and -donor sites and some exonic mutations also affect splicing. We identified and characterized a point mutation (380C>T) in a Spanish patient (GK25) with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. GK25 is a homozygote of 380C>T, which activates a cryptic splice-acceptor site 5 bases downstream from 380C>T within exon 5, causing aberrant splicing in 94% of transcripts. The aberrant splicing results in a 17-amino acids deletion, including the active-site 126Cys. The 380C>T mutation also results in A127V mutation in 6% of transcripts. Transient expression analysis showed that the A127V mutation did not retain T2 activity, indicating that 380C>T was a null mutation. Although this cryptic splice site has a higher Shapiro and Senapathy's score (86) in even a normal sequence than the authentic splice-acceptor site of intron 4 (78), it is not used in normal controls. While the 380C>T mutation increases the score slightly (90), the cryptic splice site is used in almost all transcripts in GK25 fibroblasts. This is an example in which a point mutation activates a cryptic splice-acceptor site motif that is used preferentially over the upstream authentic splice site.

Acetyl-CoA C-Acyltransferase↗
PubMed2001

The cell surface-expressed HSC70-like molecule preferentially reacts with the rat T-cell receptor Vdelta6 family.

We previously showed that the cell surface-expressed Mr 70,000 heat shock cognate (hsc70, a constitutively expressed member of the hsp70 family) protein-like molecule (#067 molecule) interacts with rat CD3+, CD4-, CD8-, T-cell receptor (TCR)alphabeta-, natural killer recetor-P1- T cells. This 70hsc-like molecule was also suggested to present cellular peptide antigens to these T cells. In the present study, we identified the genetic structure of the TCR by establishing T-cell hybridomas between these T cells and mouse BW5147 cells. Our data indicated that these T cells preferentially used TCRs with the Vdelta6 family. Analysis of the nucleotide sequence of the CDR3 junctional portion showed that there are substantial diversities, with insertion of seven to nine amino acid residues. These data provide indirect evidences for our hypothesis that an hsc70-like molecule could be presented together with cellular peptide antigens to particular T cells with TCR gammadelta chains. Since the expression of this hsc70-like #067 antigen on the cell surface is usually induced along with cell transformation by activated oncogenes, T cells with the TCR Vdelta6 family are likely to contribute to host resistance to tumor cells.

Amino Acid Sequence↗
PubMed2001

The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6.

Human genetic peroxisomal biogenesis disorders (PBDs), such as Zellweger syndrome, comprise 13 different complementation groups (CGs). Eleven peroxin genes, termed PEXs, responsible for PBDs have been identified, whereas pathogenic genes for PBDs of 2CGs, CG-A (the same CG as CG8 in the United States and Europe) and CG6, remained unidentified. We herein provide several lines of novel evidence indicating that PEX6, the pathogenic gene for CG4, is impaired in PBD of CG6. Expression of PEX6 restored peroxisome assembly in fibroblasts from a CG6 PBD patient. This patient was a compound heterozygote for PEX6 gene alleles. Accordingly, by merging CG6 with CG4, human PBDs are now classified into 12CGs.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2001

Acute idiopathic blind spot enlargement syndrome: prolonged retinal dysfunction revealed by multifocal electroretinogram technique.

PURPOSE: To report the multifocal electroretinographic findings of a patient with acute idiopathic blind spot enlargement syndrome recorded at 2 weeks and 4 months after the onset. METHODS: A 35-year-old patient underwent static visual field (Humphrey, 30-2) and multifocal electroretinogram testing at 2 weeks and 4 months after the onset of acute idiopathic blind spot enlargement. The stimulus array for the multifocal electroretinogram consisted of 61 hexagons, and the total recording time was about 4 minutes. RESULTS: At 2 weeks, the patient had a large, well-demarcated scotoma centered on the blind spot, and its margin extended to within 5 degrees of fixation. The multifocal electroretinograms were depressed in the areas corresponding to the scotoma. At 4 months, her visual symptoms disappeared and static visual fields showed normal sensitivities at almost all locations. However, the multifocal electroretinograms still revealed reduced focal responses in a broad area around the blind spot. CONCLUSION: These results suggest that multifocal electroretinograms may be used to detect subclinical retinal dysfunction in patients with acute idiopathic blind spot enlargement.

Acute Disease↗
PubMed2001

Excision of an invasive thymoma: a cure for ulcerative colitis?

Thymoma is often associated with other diseases, including autoimmune diseases and endocrine disorders. Ulcerative colitis is a nonspecific inflammatory disease and is thought to be an immune-mediated disorder; however, coincidence of thymoma and ulcerative colitis is rare. We treated a 51-year-old woman with invasive thymoma and ulcerative colitis. After excision of the invasive thymoma with partial resections of pericardium, left lung, brachiocephalic vein, and left phrenic nerve, the ulcerative colitis was cured.

Colitis, Ulcerative↗
PubMed2001

Multifocal pupillary light response fields in normal subjects and patients with visual field defects.

The optimal conditions for recording focal pupillary light responses with a multifocal stimulation technique were determined, and the technique was applied to normal subjects and patients with visual field defects. Thirty-seven hexagonal stimuli were presented on a TV monitor with a visual field of 40 degrees diameter under a constant background illumination. Using a slow (4.7 Hz) m-sequence, reliable focal responses were obtained in both normal subjects and patients. The pupillary field and visual field were well correlated in patients with retinal diseases, but the correlation was not strong in patients with optic-nerve diseases. Pupillary light responses were reduced in the blind hemifield in patients with post-geniculate lesions. These results indicate that the multifocal stimulation technique can be used clinically to obtain a pupillary field for objective visual field testing.

Adult↗
PubMed2001

Effects of dioxins and polychlorinated biphenyls (PCBs) on thyroid function in infants born in Japan--the second report from research on environmental health.

Dioxins (PCDD + PCDF) and polychlorinated biphenyl (PCB) are potentially hazardous compounds and have structural similarity to thyroid hormones. Our research group on "Dioxins and PCB in Human Milk" was organized in 1997 and has been active for the past three years. We collected breast milk from 80 mothers living in Tokyo, Saitama, Ishikawa and Osaka Prefecture in Japan at 5, 30, 150, 300 postpartum days and measured PCDDs, PCDFs and PCBs during 1998-1999. We added another 20 prefectures and cities during 1999-2000. Breast milk was obtained from 415 mothers at 30 postpartum days (breast-feeding group). Blood was taken from infants who were breast-fed at the age of 1 year for evaluation of thyroid and immune functions. Blood was also taken from 53 infants who were bottle-fed (bottle-feeding group) as a control. Serum T4, T3, FT4 and TSH levels in the breast-feeding (n = 337) and bottle-feeding (n = 53) groups were within normal ranges and were not significantly different between the two groups. Although there were a large geographic differences of dioxins and co-PCB content in breast milk, there were no differences in serum T4, T3, FT4, TSH levels and no significant correlation between the mean serum levels of TSH and TEQ in breast milk. There was a significant correlation between serum TSH at 1 year of age and that from blood on dried filter paper TSH at 5 days of age. We concluded that dioxin intake from breast milk in Japanese infants did not impair thyroid function. However, long-term effects remain to be evaluated.

Adult↗
PubMed2001

The clinical course of childhood and adolescent adrenoleukodystrophy before and after Lorenzo's oil.

The clinical course of Japanese patients with childhood and adolescent adrenoleukodystrophy (ALD) who were treated with Lorenzo's oil after the progression of early symptoms was investigated by Kaplan-Meier analyses. Many of the early symptoms, including visual, personality, hearing, mental and speech disturbances, had already appeared when the oil therapy was started. These early symptoms appeared significantly faster than bed-ridden state or dysphagia (P<0.01). Gait disturbance appeared faster than bed-ridden state and dysphagia (P<0.05), and tended to appear later than the early symptoms. These results would reflect the early natural course of childhood and adolescent ALD before treatment, and provide a basis for the evaluation of therapeutic trials for ALD.

Adolescent↗
PubMed2001

Epileptic seizures and structural abnormalities in a patient with holoprosencephaly.

In a patient with holoprosencephaly, partial seizures had various initial ictal symptoms, and ictal EEGs showed epileptogenic foci in the right and left brain. Partial seizures did not culminate in secondary generalized tonic-clonic convulsions. Characteristic malformed structures contribute to the absence of secondary generalization and the presence of Jacksonian-type propagation.

Brain↗
PubMed2001

Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders.

Peroxisome biogenesis disorders (PBDs) are severe autosomal recessive neurological diseases caused by a defect of peroxisomal assembly factors. Zellweger syndrome, the most severe phenotype, is characterized by hypotonia, psychomotor retardation and neuronal migration disorder. Neonatal adrenoleukodystrophy and infantile Refsum disease are milder phenotypes of this disease. Thirteen complementation groups have been established since the genetic heterogeneity of PBDs was elucidated in 1988. Eleven genes for PBDs have been identified either by a functional complementation cloning or by EST homology searches. In 1992, the first gene for PBDs, PEX2, was identified. It encodes peroxisomal integral membrane protein with a RING finger domain. PEX5 and PEX7 are the genes for peroxisomal targeting signal (PTS)-1 and -2 receptors, respectively. PEX3, PEX16 and PEX19 are considered to be required for the early stage of peroxisome biogenesis. PEX13 protein has an SH3 docking site that binds to the PTS-1 receptor. PEX1 and PEX6 encode ABC protein, and PEX10 and PEX12 also encode integral membrane protein, with RING finger. Temperature-sensitivity, whereby peroxisomal biogenesis and metabolic dysfunctions are restored at 30 degrees C in cells from mild phenotypes, is a useful event for predicting the clinical severity and for elucidation of peroxisome biogenesis. Investigations using knockout mice are expected to facilitate understanding of migration disorders.

Animals↗
PubMed2001

Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency.

Succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization, characterized by intermittent ketoacidotic crises and persistent ketosis. The diagnosis was suspected in a patient who presented with hypoglycaemia, ketoacidosis and coma at 4 days of age. The hypoglycaemic tendency was only observed during the first month of life. A novel macromolecular labelling assay in cultured skin fibroblasts using D-3-hydroxy[3-14C]butyrate supported the diagnosis. Subsequently, 9% residual SCOT activity and undetectable cross-reactive protein were noted in fibroblasts and the patient was found to be homozygous for the G324E SCOT gene mutation. By 7 years of age, recurrent episodes of ketoacidosis superimposed on persistent hyperketonaemia had resulted in over 25 hospitalizations requiring intravenous fluid, glucose and sodium bicarbonate therapy. He has had normal growth but developmental delay and attention deficit-hyperactivity disorder. A continuous intravenous glucose infusion at 38 microlmol (6.8 mg)/kg per min reduced plasma total ketone levels from greater than 1.5 mmol/L to less than 0.5 mmol/L after 48 h. This indicates that patients with SCOT deficiency do not always manifest ketosis with administration of a sufficient amount of carbohydrates, but that even under such conditions hyperketonaemia is difficult to eliminate completely. The presence of hypoglycaemia does not exclude the diagnosis of SCOT deficiency in infancy.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Long-wavelength red light emission from TV and photosensitive siezures.

PURPOSE: We investigated a role of long-wavelength red light emission from TV in the induction of photosensitive seizures by an animated TV program called "Pocket Monsters". METHODS: The luminance energy of recorded color bar was measured by a spectroradiometer in cathode-ray tubes (CRTs) of photosensitive patients with and without seizures on the program (induced patients and photosensitive controls). RESULTS: The mean ratio of long-wavelength red light to total visible range was significantly higher in the CRTs of induced patients than in the CRTs of photosensitive controls. The ratio of luminance energy between at turn-on and at 60 min after turn-on of the CRTs indicated that luminance energy in long-wavelength red range from the CRTs of induced patients increased significantly after turn-on of CRTs. CONCLUSIONS: High amounts of long-wavelength red light emitted from CRTs might play an important role in induction of photosensitive seizures in "Pokemon" incident.

Adolescent↗
PubMed2001

Successful unrelated BMT in a patient with Kostmann syndrome complicated by pre-transplant pulmonary 'bacterial' abscesses.

Kostmann syndrome, severe congenital neutropenia, is often associated with life-threatening bacterial infections. A 5-year-old girl with Kostmann syndrome developed pulmonary abscesses. She was refractory to granulocyte colony-stimulating factor and antibiotics. She underwent unrelated HLA-matched BMT. Myeloablative conditioning consisted of 12-Gy TBI with lung shielding, antithymocyte globulin, etoposide, and cyclophosphamide. After successful engraftment, the pulmonary abscesses resolved by day 75 post-transplant. Although the option of transplantation is not established in the setting of unrelated HLA-matched BMT in Kostmann syndrome, this case may provide useful information. Furthermore, pre-transplant pulmonary bacterial abscesses may not be a contraindication for BMT in some patients with Kostmann syndrome.

Bone Marrow Transplantation↗