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Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 307 records · Page 17Linked to original sources
PubMed1996

Carrier identification of X-linked adrenoleukodystrophy by measurement of very long chain fatty acids and lignoceric acid oxidation.

Because identification of carriers of X-linked adrenoleukodystrophy (ALD) results in 5-15% false negatives with very long chain fatty acids (VLCFA) assay in plasma, and mutation analysis of plasma VLCFA combined with of the ALD gene is not always practical, we studied whether the analysis of plasma VLCFA combined with lignoceric acid oxidation study in fibroblasts could improve the rate of carrier detection. Lignoceric acid oxidation was abnormal in 19 out of 19 patients (ALD or adrenomyeloneuropathy) and in three out of three obligate heterozygous women. Among ten women at risk of being a carrier, three women who had normal plasma VLCFA had abnormal lignoceric acid oxidation in fibroblasts. These data suggest that this combined biochemical procedure may help to improve carrier detection in families when the ALD gene mutation has not been identified.

Adrenoleukodystrophy↗
PubMed1996

Life-threatening cardiac involvement throughout life in a case of Costello syndrome.

Costello syndrome is characterized by poor postnatal growth, mental retardation, curly hair, coarse face, loose skin of the hands and feet, and nasal papillomata. Patients with Costello syndrome have a high incidence of cardiac involvement, such as arrhythmias, hypertrophic cardiomyopathy, or congenital anomalies. The importance of cardiac involvement in Costello syndrome has not been strongly emphasized thus far, although arrhythmia and hypertrophic cardiomyopathy are both serious forms of cardiac involvement. We report the case of a Japanese girl with Costello syndrome, who experienced life-threatening cardiac involvement throughout her life.

Anus Neoplasms↗
PubMed1996

Mild form of beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase deficiency) in two Japanese siblings: identification of detectable residual activity and cross-reactive material in EB-transformed lymphocytes.

Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is an inherited metabolic disorder of isoleucine and ketone body catabolism. We report the cases of two siblings who showed clinically mild forms of this disorder. They did not excrete tiglylglycine in urine. Their EB-transformed lymphocytes contained residual T2 activity, which was confirmed by immunotitration analysis. In immunoblot analysis, the bands corresponding to T2 in the samples of the cell lines from two patients were the most intensely detected among those from 19 T2-deficient cell lines tested.

Acetyl-CoA C-Acyltransferase↗
PubMed1996

Trial of docosahexaenoic acid supplementation on a Japanese patient with a peroxisome biogenesis defect.

A female Japanese patient diagnosed with peroxisome biogenesis defect (PBD), who had hypotonia and craniofacial dysmorphism, was given supplementation of docosahexaenoic acid (DHA). Accumulation of very long chain fatty acids was revealed, and a diagnosis of PBD was made at 2 months of age because of the absence of peroxisomes, a defect in peroxisomal beta-oxidation enzymes and a decreased level of DHA in the erythrocytes. Supplementation of DHA was introduced at 3 months of age. For the first several months, psychomotor development was fairly good. The patient could laugh, brush off a blanket and play with toys at 6 months of age. However, neurological regression and convulsions occurred after 7 months of age. After recurrent respiratory infections and disturbance of the circadian rhythm, the patient died of liver failure and disseminated intravascular coagulopathy at 20 months of age. DHA may have a favorable effect on the early development of patients with PBD, but neurological deterioration cannot be prevented. Patients with a milder phenotype would be better candidates for DHA supplementation.

Docosahexaenoic Acids↗
PubMed1996

Suppression of methicillin resistance in a mecA-containing pre-methicillin-resistant Staphylococcus aureus strain is caused by the mecI-mediated repression of PBP 2' production.

The mechanism of methicillin susceptibility was studied in Staphylococcus aureus N315P, a pre-methicillin-resistant S. aureus strain that is susceptible to methicillin, despite the presence of mecA in the chromosome. In the presence of mec regulator genes mecI and mecR1, transcription of the mecA gene was not inducible by the addition of methicillin to the culture medium. Inactivation of the mecI gene function by replacing it with tetL made N315P express heterogeneous-type methicillin resistance. The subclone, in which the mecI gene was replaced, subclone P delta I, produced 12 times greater amounts of mecA gene transcripts and 8.5 times more PBP 2' protein than N315P. These data indicate that the mecI gene-encoded repression of mecA gene transcription is responsible for the apparent methicillin susceptibility phenotype of pre-methicillin-resistant S. aureus N315P.

Bacterial Proteins↗
PubMed1996

Reexamination of tympanic membrane temperature as a core temperature.

Controversies surrounding tympanic temperature (Tty) itself and techniques for measuring it have dampened the potential usefulness of Tty in determining core temperature (operationally defined here as the body temperature taken at a deep body site). The present study was designed to address the following questions. 1) Can a tympanic membrane probe be made that is safer and more reliable than its predecessors? 2) Why is the effect of facial cooling and heating on Tty so inconsistent in reports from different laboratories? 3) Is Tty still useful as a measure of core temperature? Data from this study, obtained with a modified thermocouple probe, suggest that the widely reported facial skin cooling effect on Tty is most probably due to thermal contamination from the surrounding ear canal wall and/or suboptimal contact of the probe sensor with the tympanic membrane because 1) Tty that fell during facial cooling was increased to the precooling level by the repositioning of the probe sensor; 2) Tty determined by using a probe with a larger sensor area (the sensor soldered to a steel wire ring)tended to fall in response to facial cooling, whereas Tty determined with a thermally insulated probe ring did not; and 3) Tty obtained under careful positioning of the insulated probe was relatively insensitive to facial cooling or heating. Because Tty was practically identical to esophageal temperature (Tes) in the steady state, i.e., 36.83 +/- 0.20 (SD) degrees C for Tty and 36.87 +/- 0.16 degrees C for Tes at room temperature (n = 11), and because facial cooling had little effect on both Tty and Tes (36.86 +/- 0.17 degrees C for Tty and 36.86 +/- 0.26 degrees C for Tes during facial or scalp skin cooling), we support the postulate that Tty is a good measure of core temperature. The temperature transient in response to foot warming was detected 5 min (n = 2) faster with Tty than with Tes. Thus, with further improvements in the design of the probe. Tty can become a standard for determination of core body temperature.

Adult↗
PubMed1996

Correction by gene expression of biochemical abnormalities in fibroblasts from Zellweger patients.

Zellweger syndrome is a prototype of peroxisomal biogenesis disorders and a fatal autosomal recessive disease with no effective therapy. We identified nine genetic complementation groups of these disorders, and mutations in peroxisome assembly factor-1 (PAF-1) and the 70-kD peroxisomal membrane protein (PMP70) genes have been detected by our group F and Roscher's group 1, respectively. We now describe permanent recovery from generalized peroxisomal abnormalities in fibroblasts of a Zellweger patient from group F, such as biochemical defects of peroxisomal beta-oxidation, plasmalogen biosynthesis, and morphologic absence of peroxisomes, by stable transfection of human cDNA encoding PAF-1. In the light of these observations, we designed a gene expression system using fibroblasts from patients with peroxisomal biogenesis disorders. In Zellweger fibroblasts obtained from Roscher's group 1 and transfected with human cDNA encoding PMP70, peroxisomes were not morphologically identifiable, and peroxisomal function did not normalize.

ATP-Binding Cassette Transporters↗
PubMed1996

Immunotitration analysis of cytosolic acetoacetyl-coenzyme A thiolase activity in human fibroblasts.

There are five known thiolases in human fibroblasts, and all but mitochondrial trifunctional protein (TFP) have thiolase activity toward acetoacetyl-CoA (AACoA). We investigated the contribution of mitochondrial acetoacetyl-CoA thiolase (AACoAT) (T2), cytosolic AACoAT (CT), and mitochondrial 3-ketoacyl-CoA thiolase (T1) to the total AACoAT activity in control human fibroblasts. Immunotitration of AACoAT activity with antibodies against T2, CT, or T1 was carried out in control fibroblasts, with the following results. In the case of AACoAT activity in the absence of potassium ion, 26-38%, 40-47%, and 11-20% of the total activity derived from CT, T1, and T2, respectively. The residual 6-9% total activity was not immunotitrated when three antibodies were used in combination. Hence, the contribution of peroxisomal 3-ketoacyl-CoA thiolase to the total AACoAT activity in the absence of potassium ion was at least less than 6-9%. Because the normal range of total AACoAT activity is relatively wide, it is difficult to evaluate CT defects based on a decrease of total AACoAT activity. Immunotitration with anti-CT antibody in six control fibroblasts revealed that CT activity ranges between 1.3 and 2.4 nmol/min/mg of protein. Immunotitration proved to be an accurate method to evaluate CT activity. The two cell lines from patients with CT deficiency have become extinct.

Acetyl-CoA C-Acetyltransferase↗
PubMed1996

Pulmonary oxygen uptake kinetics in nonsteady state.

The body does not always achieve a steady state and is more often kept in a nonsteady state. It is important not only in terms of physiological anthropology but also in its application to rehabilitation and training to clarify whether oxygen transport or utilization is the limiting factor in oxygen uptake in the nonsteady state. Hypotheses concerning the limiting factor in oxygen uptake have their own rationales, and it is still controversial as to which is actually responsible. The limiting factor in oxygen uptake may vary according to exercise conditions. Under certain conditions, oxygen transport would be responsible for limiting the oxygen uptake, and under others, oxygen utilization or both oxygen transport and utilization would be responsible. These conditions differ according to the type of exercise (e.g. step exercise vs. cycling, leg vs. arm exercise, and dynamic vs. static exercise), posture, recruited muscle fibers, and other experimental conditions. Considering that oxygen uptake is regulated by coupling among respiration, circulation, and metabolism, it may be possible that interactions among these functions vary in a complicated manner according to exercise conditions, which may require a different limiting factor in regulating oxygen uptake.

Biological Transport↗
PubMed1996

The influence of work loads on regional differences in sweating rates.

The influence of work loads (20, 40 and 60% VO2max) on regional differences in sweating rates was investigated in six healthy male students. The ratios of local sweating rate (msw) on the chest and back to estimated total sweating rate (mean msw of four sites examined x body surface area) at 20% work load were significantly greater than those on the forearm and forehead, whereas the ratio on the forehead at 60% work load was greater than at the other sites. The ratios on the forearm at 40 and 60% work loads were significantly greater than at 20% work load. The regional differences in sweating rates change with the increase in work load as seen by the greater variation in the ratios of msw on each site at 20% work load compared with 40 and 60% work loads. The results indicate that redistribution of this sweat activity to whole body or head with the rise in work load induces favorable conditions for evaporation and controlling brain temperature.

Adult↗
PubMed1996

Mucopolysaccharidosis IVA: four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency.

We report four new mutations in Japanese patients with mucopolysaccharidosis IVA (MPSIVA) who were heterozygous for a common double gene deletion. A nonsense mutation of CAG to TAG at codon 148 in exon 4 was identified, resulting in a change of Q to a stop codon and three missense mutations. V (GTC) to A (GCC) at codon 138 in exon 4, P (CCC) to S (TCC) at codon 151 in exon 5, and P (CCC) to L (CTC) at codon 151 in exon 5. Introduction of these mutations into the normal GALNS cDNA and transient expression in cultured fibroblasts resulted in a significant decrease in the enzyme activity. V138A and Q148X mutations result in changes of restriction site, which were analyzed by restriction-enzyme assay. P151S and P151L mutations that did not alter the restriction site were detected by direct sequencing or allele specific oligohybridization. Detection of the double gene deletion was initially done using Southern blots and was confirmed by PCR. Haplotypes were determined using seven polymorphisms to the GALNS locus in families with the double gene deletion. Haplotype analysis showed that the common double gene deletion occurred on a single haplotype, except for some variation in a VNTR-like polymorphism. This finding is consistent with a common founder for all individuals with this mutation.

Adolescent↗
PubMed1996

[QOL and nursing care of a ventilator-assisted child at home].

QOL is the important issue for chronically ill children. We visited a girl, 8 years old and 24 hours dependent on a ventilator. We talked to her, and observed her daily life, mainly on the following points: (1) what she is doing; and (2) how often, and what kind of care she needs at school and at home. Then we discussed the problems, QOL and nursing care. She enjoyed her school life with her many friends, and received respiratory care, sanitary care, and other care for 11 hours and 19 minutes in average per day. 93.1% of the care was taken by her parents and volunteer care givers, so that they wanted to have nurses care for her. Many kinds of nursing care service were necessary as soon as possible.

Child↗
PubMed1996

[A case of penile cancer treated with combination of chemotherapy, radiation and radical operation].

A 60-year-old [correction of 68] male was referred to our hospital because of a penile tumor with necrosis. Pathological examination of the penile tumor and superficial inguinal lymph nodes in biopsy revealed well differentiated squamous cell carcinoma (SCC) and the SCC tumor marker was elevated. TNM classification was T2, N2, M0 according to findings obtained by computed tomography (CT) and magnetic resonance imaging (MRI). We diagnosed the tumor inoperable radically and administered 10 mg peplomycin once a week for 10 weeks intravenously. The SCC marker level was not reduced and the tumor was not changed on MRI. Then, we performed combined pirarubicin treatment and radiotherapy. The patient received linac radiotherapy between 40 Gy/4 weeks/20 fractions. Pirarubicin, 10 mg/m2, was administered once a week for 4 weeks during irradiation intravenously. After the combined therapy, the SCC marked level was reduced to the normal range and the tumor was reduced. We performed radical operation. Pathological diagnosis revealed no viable tumor cells. The patient was alive with no evidence of disease a year later. This combined therapy is suggested to be useful.

Antibiotics, Antineoplastic↗
PubMed1996

Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient.

Succinyl CoA: 3-oxoacid CoA transferase (SCOT; E.C.2.8.3.5) mediates the rate-determining step of ketolysis in extrahepatic tissues, the esterification of acetoacetate to CoA for use in energy production. Hereditary SCOT deficiency in humans causes episodes of severe ketoacidosis. We obtained human-heart SCOT cDNA clones spanning the entire 1,560-nt coding sequence. Sequence alignment of the human SCOT peptides with other known CoA transferases revealed several conserved regions of potential functional importance. A single approximately 3.2-kb SCOT mRNA is present in human tissues (heart > leukocytes >> fibroblasts), but no signal is detectable in the human hepatoma cell line HepG2. We mapped the human SCOT locus (OXCT) to the cytogenetic band 5p13 by in situ hybridization. From fibroblasts of a patient with hereditary SCOT deficiency, we amplified and cloned cDNA fragments containing the entire SCOT coding sequence. We found a homozygous C-to-G transversion at nt 848, which changes the Ser 283 codon to a stop codon. This mutation (S283X) is incompatible with normal enzyme function and represents the first documentation of a pathogenic mutation in SCOT deficiency.

Amino Acid Sequence↗
PubMed1996

Abnormal B cell response of protein kinase C in some common variable immunodeficiency.

The localization of protein kinase C (PKC) was investigated in B cells or B cell lines derived from patients with common variable immunodeficiency (CVI) and healthy controls. Stimulation of the healthy control B cells by phorbol ester or anti-mu induced PKC activation and translocation to the plasma membrane after 10 min. In contrast, in the CVI-B cells, no apparent PKC translocation was induced by either phorbol ester or anti-mu stimulation. These results suggest that the pathogenesis in some CVI patients might involve defects in the pathway of PKC activation.

Adult↗
PubMed1996

Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans.

Peroxisome-biogenesis disorders (PBD) are genetically heterogeneous and can be classified into at least ten complementation groups. We recently isolated the cDNA for rat peroxisome assembly factor-2 (PAF-2) by functional complementation using the peroxisome-deficient Chinese-hamster-ovary cell mutant, ZP92. To clarify the novel pathogenic gene of PBD, we cloned the full-length human PAF-2 cDNA that morphologically and biochemically restores peroxisomes of group C Zellweger fibroblasts (the same as group 4 in the Kennedy-Krieger Institute) and identified two pathogenic mutations in the PAF-2 gene in two patients with group C Zellweger syndrome. The 2,940-bp open reading frame of the human PAF-2 cDNA encodes a 980-amino-acid protein that shows 87.1% identity with rat PAF-2 and also restored the peroxisome assembly after gene transfer to fibroblasts of group C patients. Direct sequencing of the PAF-2 gene revealed a homozygous 1-bp insertion at nucleotide 511 (511 insT) in one patient with group C Zellweger syndrome (ZS), which introduces a premature termination codon in the PAF-2 gene, and, in the second patient, revealed a splice-site mutation in intron 3 (IVS3+1G-->A), which skipped exon 3, an event that leads to peroxisome deficiency. Chromosome mapping utilizing FISH indicates that PAF-2 is located on chromosome 6p21.1. These results confirm that human PAF-2 cDNA restores peroxisome of group C cells and that defects in the PAF-2 produce peroxisome deficiency of group C PBD.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1995

Genomic DNA organization of human mitochondrial very-long-chain acyl-CoA dehydrogenase and mutation analysis.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a major enzyme catalyzing long-chain fatty acids in the first step of mitochondrial beta-oxidation system. Inborn error of this enzyme can cause sudden infant death syndrome and hypertrophic cardiomyopathy is present at a significantly high frequency. To investigate VLCAD deficiency at the genomic DNA level, we cloned the VLCAD gene and analyzed the structure. The gene is about 5.4 kb long and contains 20 exons. We performed mutation analysis in two patients, both having a 105 bp deletion encompassing bases 1078-1182 in cDNA. A point mutation (GT-->AT) at 5' splice site of intron 11 was identified in both patients. This mutation seems to cause skipping of exon 11 corresponding to the 105 bp deletion. This is the first documentation of aberrant splicing in the VLCAD gene.

Acyl-CoA Dehydrogenase, Long-Chain↗