Female patient showing hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID).
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Ectodermal Dysplasia↗
Biomedical subjects
N Matsuo
Publications and source records attributed to N Matsuo.
Long-term ingestion of dietary diacylglycerol lowers serum triacylglycerol in type II diabetic patients with hypertriglyceridemia.
We examined the effect of daily consumption of dietary diacylglycerol (DG) oil on serum lipid concentrations in patients with diabetes whose serum triacylglycerol (TG) levels were persistently increased despite continuous nutritional counseling at the outpatient clinic. Patients (n = 16) were divided into DG and control groups (n = 8 each). DG was incorporated (target dose 10 g/d) by substituting DG oil (80 g DG/100 g oil) for the ordinary TG cooking oil used at home for 12 wk. The control group continued consuming ordinary TG cooking oil. Dietary records indicated that there were no differences between groups in total energy intake or percentage of energy from fat. In the DG group, TG intake decreased from 26.8 +/- 9.3 to 15.7 +/- 8.9 g/d, whereas DG intake increased from 0.3 +/- 0.1 to 10.6 +/- 3.9 g/d. No differences between groups were observed in body weight, total fat intake or total oil consumption throughout the study period. In the DG group, serum TG levels decreased 39.4% from 2.51 +/- 0.75 mmol/L to 1.52 +/- 0.28 mmol/L. Serum glycohemoglobin A(1c) (HbA(1c)) concentration also decreased 9.7%. In contrast, there were no changes in these variables in the control group. Serum total and HDL cholesterol were not affected in either group. These results indicate that DG oil may be useful as an adjunct to the standard diet therapy of fat restriction in the management of diabetics with hypertriglyceridemia.
Blood Glucose↗
SHOX haploinsufficiency and overdosage: impact of gonadal function status.
Since its discovery in 1997, knowledge about the SHOX gene has rapidly increased. In this review, we summarise clinical features and diagnostic and therapeutic implications in SHOX haploinsufficiency and overdosage. SHOX haploinsufficiency usually results in mesomelic short stature and Turner skeletal features, including Madelung deformity with puberty, in subjects with normal gonadal function. Thus, identification of early or mild signs of Madelung deformity is pivotal for the diagnosis, and gonadal suppression therapy may serve to mitigate the clinical features. By contrast, SHOX overdosage usually leads to long limbs and tall stature resulting from continued growth into the late teens in subjects with gonadal dysgenesis. Thus, the combination of tall stature and poor pubertal development is the key to diagnosis, and oestrogen therapy can help the prevention of unfavourably tall stature as well as the induction of sexual development. These findings, in conjunction with skeletal assessment in Turner syndrome and expression analysis during human embryogenesis, imply that SHOX functions as a repressor for growth plate fusion and skeletal maturation in the distal limbs and, thus, counteracts the skeletal maturing effects of oestrogens.
Female↗
Fat-soluble vitamin status is not affected by diacylglycerol consumption.
OBJECTIVE: The objective of this study was to examine the effect of dietary diacylglycerol (DAG) on the bioavailability of fat-soluble vitamins in comparison with triacylglycerol (TAG). METHODS: We conducted a long-term administration test of DAG and TAG in 27 healthy men aged 27-47 years. After measuring baseline values, subjects were randomized into two groups, one group (n = 15) was given DAG and the other (n = 12) was given TAG. Subjects ingested 20 g of DAG or TAG either in mayonnaise or an emulsion drink of their own choice at meals once a day for 12 weeks. At 4, 8 and 12 weeks, fasting blood samples were drawn and serum levels of vitamin A, E, and D were measured. RESULTS: There were no significant changes in vitamin A levels throughout the study period. Compared to the initial values (using a Student's t test for paired values), significant differences of vitamin E and D were seen at some points during the experiment. According to a two-way repeated measures analysis of variance, however, DAG and TAG (lipid) and time had no effect on fat-soluble vitamin levels. CONCLUSIONS: Our results indicate that DAG does not affect the absorption of the fat-soluble vitamins in diets.
Adult↗
Effects of amphotericin B gargles on oral colonization of Candida albicans in asthmatic patients on steroid inhalation therapy.
BACKGROUND: Early use of inhaled steroids is recommended for bronchial asthma. The side effects are rare, but oral discomfort and candidiasis are clinically important complications. Most previous studies reported that the use of spacer and water gargling was necessary to prevent oral complications. However, in some patients, this may fail to prevent such complications. OBJECTIVE: To compare the effects of water gargling with those of amphotericin B, in the prevention of oral complications in asthmatics using inhaled steroids. METHODS: Pharyngeal swab samples were obtained aseptically from the posterior pharyngeal wall of 128 asthmatics who have been using inhaled steroids (beclomethasone dipropionate) for more than 1 year. The amount of Candida albicans in cultured swabs was evaluated based on the following criteria: oral symptoms, method of gargling, dose of inhaled steroids, type of spacer and serum cortisol level. RESULTS: The number of isolated C. albicans was significantly higher in asthmatics with oral symptoms than in those free of symptoms. It was also significantly higher in patients who gargled with water or 1,000 times dilution than in those who gargled with 100 or 50 times dilutions of amphotericin B. Moreover, it was significantly higher in patients with low levels of serum cortisol than in those with normal serum cortisol. CONCLUSION: We demonstrated that at least in a subgroup of asthmatics using steroid inhalers, gargling with water or even weak concentrations of amphotericin B does not prevent colonization of the throat with C. albicans. This group at high risk of developing oral candidiasis should gargle with amphotericin B at concentrations higher than 100 times dilution that can prevent clinically detectable oral candidiasis.
Administration, Oral↗
Micropenis and the AR Gene: mutation and CAG repeat-length analysis.
Various mutations of the AR gene and expanded CAG repeats at exon 1 of that gene have been reported in patients with hypospadias or genital ambiguity. However, the role of the AR gene has not been systemically studied in those with isolated micropenis lacking hypospadias or genital ambiguity. We studied 64 Japanese boys with isolated micropenis (age, 0-14 yr; median, 7 yr), whose stretched penile lengths were between -2.5 and -2.0 SD (borderline micropenis) in 31 patients (age, 0-13 yr; median, 8 yr) and below -2.5 SD (definite micropenis) in 33 patients (age, 0-14 yr; median, 6 yr). Mutation analysis of the AR gene was performed for exons 1-8 and their flanking introns, except for the CAG and GGC repeat regions at exon 1, by denaturing HPLC and direct sequencing, identifying a substitution of cytosine to thymine at a position -3 in the 3' splice site of intron 1 in a patient with definite micropenis. CAG repeat length at exon 1 was determined by electrophoresis with internal size markers and direct sequencing, revealing no statistically significant difference in the distribution of CAG repeat lengths [median (range) and mean +/- SE: total patients with isolated micropenis, 24 (14-34) and 23.5 +/- 0.38; patients with borderline micropenis, 24 (15-29) and 23.5 +/- 0.53; patients with definite micropenis, 23 (14-34) and 23.5 +/- 0.56; and 100 control males, 23 (16-32) and 23.5 +/- 0.29] or in the frequency of long CAG repeats (percentage of CAG repeats > or =26 and > or =28: total patients with isolated micropenis, 17.2 and 4.7%; patients with borderline micropenis, 19.4 and 6.5%; patients with definite micropenis, 15.2 and 3.0%; and 100 control males, 21.0 and 10.0%). These results suggest that an AR gene mutation is rare and that CAG repeat length is not expanded in children with isolated micropenis.
Adolescent↗
Turner syndrome and Xp deletions: clinical and molecular studies in 47 patients.
Although clinical features of Turner syndrome have primarily been explained by the dosage effects of SHOX (short stature homeobox-containing gene) and the putative lymphogenic gene together with chromosomal effects leading to nonspecific features, several matters remain to be determined, including modifying factors for the effects of SHOX haploinsufficiency, chromosomal location of the lymphogenic gene, and genetic factors for miscellaneous features such as multiple pigmented nevi. To clarify such unresolved issues, we examined clinical findings in 47 patients with molecularly defined Xp deletion chromosomes accompanied by the breakpoints on Xp21-22 (group 1; n = 19), those accompanied by the breakpoints on Xp11 (group 2; n = 16), i(Xq) or idic(X)(p11) chromosomes (group 3; n = 8), and interstitial Xp deletion chromosomes (group 4; n = 4). The deletion size of each patient was determined by fluorescence in situ hybridization and microsatellite analyses for 38 Xp loci including SHOX, which was deleted in groups 1-3 and preserved in group 4. The mean GH-untreated adult height was -2.2 SD in group 1 and -2.7 SD in group 2 (GH-untreated adult heights were scanty in group 3). The prevalence of spontaneous breast development in patients aged 12.8 yr or more (mean +/- 2 SD for B2 stage) was 11 of 11 in group 1, 7 of 12 in group 2, and 1 of 7 in group 3. The prevalence of wrist abnormality suggestive of Madelung deformity was 8 of 18 in group 1 and 2 of 23 in groups 2 and 3, and 9 of 18 in patients with spontaneous puberty and 1 of 23 in those without spontaneous puberty. The prevalence of short neck was 1 of 19 in group 1 and 7 of 24 in groups 2 and 3. Soft tissue and visceral anomalies were absent in group 1 preserving the region proximal to Duchenne muscular dystrophy and were often present in groups 2 and 3 missing the region distal to monoamine oxidase A (MAOA). Multiple pigmented nevi were observed in groups 1-3, with the prevalence of 0 of 7 in patients less than 10 yr of age and 15 of 36 in those 10 yr or older regardless of the presence or absence of spontaneous puberty. Turner phenotype was absent in group 4, including a fetus aborted at 21 wk gestation who preserved the region distal to MAOA. The results provide further support for the idea that clinical features in X chromosome aberrations are primarily explained by haploinsufficiency of SHOX and the lymphogenic gene and by the extent of chromosome imbalance in mitotic cells and pairing failure in meiotic cells. Furthermore, it is suggested that 1) expressivity of SHOX haploinsufficiency in the limb and faciocervical regions is primarily influenced by gonadal function status and the presence or absence of the lymphogenic gene, respectively; 2) the lymphogenic gene for soft tissue and visceral stigmata is located between Duchenne muscular dystrophy and MAOA; and 3) multiple pigmented nevi may primarily be ascribed to cooperation between a hitherto unknown genetic factor and an age-dependent factor other than gonadal E.
Adult↗
Growth hormone and gonadotropin-releasing hormone analog therapy in haploinsufficiency of SHOX.
We report on GH (0.5 IU or 0.17 mg/kg/week) and GnRH analog (GnRHa, 60 microg/kg, every 4 weeks) therapy in SHOX haploinsufficiency. Case 1 was a 46,XY boy with microdeletion of the Y chromosomal pseudoautosomal region. At 7 years of age, he exhibited short stature (-3.9 SD) with a reduced growth rate (3.8 cm/year), short 4th metacarpals, and mild Madelung deformity. GH therapy resulted in a marked increase in height velocity (10.7 cm/year in the first year). Case 2 was a 46,XX girl with a heterozygous nonsense mutation of SHOX (C674T). At 6 years of age, she presented with short stature (-3.3 SD) with a low height velocity (4.0 cm/year). GH therapy caused a moderate increase in height velocity (6.6 cm/year in the first year and 6.0 cm/year in the second year) before puberty. Because of breast development, she received GnRHa from 9 8/12 years of age. At 10 10/12 years of age, she had mild shortening and borderline curvature of radius. Case 3 was a girl with a 46,X,der(X)t(X;2)(p22.3;p21) karyotype. She was treated with GH from 6 to 14 years of age, and also with GnRHa from 12 to 15 years of age. Her height remained around mean -4 SD, with no discernible alteration of height velocity. At 17 years of age, she had short stature (-4.1 SD), bilateral cubitus valgus, Madelung deformity, and full breast development. The results suggest that GH therapy may have variable statural effects in SHOX haploinsufficiency as in most disorders including Turner syndrome, and that GnRHa therapy after pubertal entry may be insufficient to prevent the development of skeletal lesions such as Madelung deformity.
Body Height↗
Standard growth curves for Japanese patients with Prader-Willi syndrome.
We constructed the standard growth (length/height and weight) curves for Japanese individuals with Prader-Willi syndrome (PWS). Crude height and weight data were collected from 153 males and 99 females with the syndrome, and the collected data were arranged by a mathematical method to construct the curves. Height growth patterns were quite different between PWS and normal children. Mean height of individuals with the syndrome by puberty is -2 SD for normal children, and it drops off far below -2 SD value after puberty. Final mean height is 141.2 +/- 4.8 cm for females (n = 13) and 147.7 +/- 7.7 cm for males (n = 17), showing 15.8 and 21.9 cm below the average height for normal Japanese girls and boys, respectively. Thus, the degree of shortness is more pronounced in male than in female patients. There was no difference in height between those with chromosome 15q deletion and those without. Mean weight at birth of girls (n = 88) and boys (n = 131) were 2.70 +/- 0.45 Kg and 2.62 +/- 0.47 Kg, respectively. These values were smaller than those for normal neonates (P < 0.05, t-test). The weight of PWS children was under the mean value for normal infants by age 2 years, but gradually increase above the mean values for normal children around ages 2-4 years. Overweight in both males and females becomes obvious during prepuberty. Growth patterns are not different between Japanese and Caucasian children with the syndrome. Short stature is more prominent in boys of both ethnic groups, whereas the degree of overweight appears much more severe in Caucasians.
Adolescent↗
X-linked lissencephaly with ambiguous genitalia: delineation of further case.
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Abnormalities, Multiple↗
Imprinting of human GRB10 and its mutations in two patients with Russell-Silver syndrome.
Documentation of maternal uniparental disomy of chromosome 7 in 10% of patients with Russell-Silver syndrome (RSS), characterized by prenatal and postnatal growth retardation and dysmorphic features, has suggested the presence of an imprinted gene on chromosome 7 whose mutation is responsible for the RSS phenotype. Human GRB10 on chromosome 7, a homologue of the mouse imprinted gene Grb10, is a candidate, because GRB10 has a suppressive effect on growth, through its interaction with either the IGF-I receptor or the GH receptor, and two patients with RSS were shown to have a maternally derived duplication of 7p11-p13, encompassing GRB10. In the present study, we first demonstrated that the GRB10 gene is also monoallelically expressed in human fetal brain tissues and is transcribed from the maternally derived allele in somatic-cell hybrids. Hence, human GRB10 is imprinted. A mutation analysis of GRB10 in 58 unrelated patients with RSS identified, within the N-terminal domain of the protein, a P95S substitution in two patients with RSS. In these two cases, the mutant allele was inherited from the mother. The fact that monoallelic GRB10 expression was observed from the maternal allele in this study suggests but does not prove that these maternally transmitted mutant alleles contribute to the RSS phenotype.
Abnormalities, Multiple↗
Synthesis and reactivity of pyridylpyridone derivatives.
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Fluorides↗
Purification, characterization and gene cloning of two alpha-L-arabinofuranosidases from streptomyces chartreusis GS901.
alpha-L-Arabinofuranosidases I and II were purified from the culture filtrate of Streptomyces chartreusis GS901 and were found to have molecular masses of 80 and 37 kDa and pI values of 6.6 and 7.5 respectively. Both enzymes demonstrated slight reactivity towards arabinoxylan and arabinogalactan as substrates but did not hydrolyse gum arabic or arabinoxylo-oligosaccharides. alpha-L-Arabinofuranosidase I hydrolysed all of the alpha-linkage types that normally occur between two alpha-L-arabinofuranosyl residues, with the following decreasing order of reactivity being observed for the respective disaccharide linkages: alpha-(1-->2) alpha-(1-->3) alpha-(1-->5). This enzyme cleaved the (1-->3) linkages of the arabinosyl side-chains of methyl 3, 5-di-O-alpha-L-arabinofuranosyl-alpha-L-arabinofuranoside in preference to the (1-->5) linkages. alpha-L-Arabinofuranosidase I hydrolysed approx. 30% of the arabinan but hydrolysed hardly any linear arabinan. In contrast, alpha-L-Arabinofuranosidase II hydrolysed only (1-->5)-arabinofuranobioside among the regioisomeric methyl arabinobiosides and did not hydrolyse the arabinotrioside. Linear 1-->5-linked arabinan was a good substrate for this enzyme, but it hydrolysed hardly any of the arabinan. Synergism between the two enzymes was observed in the conversion of arabinan and debranched arabinan into arabinose. Complete amino acid sequencing of alpha-L-arabinofuranosidase I indicated that the enzyme consists of a central catalytic domain that belongs to family 51 of the glycoside hydrolases and additionally that unknown functional domains exist in the N-terminal and C-terminal regions. The amino acid sequence of alpha-L-arabinofuranosidase II indicated that this enzyme belongs to family 43 of the glycoside hydrolase family and, as this is the first report of an exo-1, 5-alpha-L-arabinofuranosidase, it represents a novel type of enzyme.
Amino Acid Sequence↗
Adenovirus-mediated gene therapy for mucopolysaccharidosis VII: involvement of cross-correction in wide-spread distribution of the gene products and long-term effects of CTLA-4Ig coexpression.
Recombinant adenoviruses expressing human beta-glucuronidase (AxCAhGUS) and CTLA-4Ig (AxCACTLA-4Ig) were generated and therapeutic efficacy was investigated using a murine model of mucopolysaccharidosis type VII (MPSVII). Seven days after the intravenous administration of AxCAhGUS, high levels of beta-glucuronidase (GUSB) activity were observed in the liver, spleen, heart, lung, kidney, and serum, while viral DNA was predominantly detected in the liver. To investigate the contribution of in vivo cross-correction of GUSB between the liver and other organs, we injected the serum obtained from the transduced mice into untreated MPSVII mice. Similar distributions of GUSB activity were observed in the serum-injected mice, suggesting that GUSB activities detected in the extrahepatic organs were due to the cross-correction rather than the direct gene transduction. This result also suggested that maintaining high levels of GUSB in the systemic circulation was essential for the effective treatment of MPSVII. To achieve this, we injected AxCAhGUS and AxCACTLA-4Ig into MPSVII mice. Serum GUSB activity was sustained at high levels for more than 200 days and morphological normalization of the liver and spleen was observed for a year. This suggests that long-term therapeutic efficacy in visceral organs of MPSVII is achievable by coexpression of CTLA-4Ig through an in vivo cross-correction pathway.
Abatacept↗
Testicular volume in Japanese boys up to the age of 15 years.
UNLABELLED: Previous studies have indicated that Japanese children grow and mature significantly faster than Caucasian children, thus calling for a separate reference standard for each skeletal and sexual maturity index. To establish normal reference values for testicular volume in Japanese boys, we studied from 1985 to 1995, 900 healthy male children of 0 to 15 years of age for medical history, physical examination, height, weight, sitting height, and head circumference measurements, Tanner sex maturity stage, and testicular size. The testicular volume was determined using a Prader orchidometer by the same observer (N.M.). Based on these data, we established the cross-sectional percentile growth curves (90th, 50th, 10th percentiles) for testicular volume of Japanese boys. The testicular volume of 3 ml was attained at 9.3 years of age (90th percentile), 11.0 years of age (50th percentile), and 12.1 years of age (10th percentile), respectively. CONCLUSION: Swelling of the testis in Japanese children begins approximately 1 year earlier than in Swiss children in accordance with the earlier skeletal maturation in Japanese children.
Adolescent↗
Clinical and molecular studies in 15 females with ring X chromosomes: implications for r(X) formation and mental development.
We report clinical and molecular findings in 15 Japanese mosaic females with r(X) chromosomes, 45,X/46,X,r(X), confirmed by fluorescence in situ hybridization (FISH) analysis for DXZ1 and whole X chromosome painting. Cases 1-3, 5-7, and 11-13 had mental retardation (MR), the remaining cases being free from MR. FISH analysis showed that XIST was absent from the r(X) chromosomes in cases 1-4 and was present on the r(X) chromosomes in cases 5-15. X-inactivation analysis for the methylation status of the AR gene indicated that, of eight cases with XIST-positive r(X) chromosomes in more than 10% (23%-62%) of lymphocytes (cases 5-12), cases 5-10 had selective X-inactivation, whereas cases 11 and 12 had active X disomy. Microsatellite analysis for multiple loci on the pericentromeric region revealed that, of 11 cases with r(X) chromosomes in more than 10% (13%-62%) of lymphocytes (cases 1, 2, and 4-12), cases 1, 2, and 5-10 had heterozygous alleles for at least one locus, whereas cases 4, 11, and 12 had single alleles for all the loci examined. The results suggest that the r(X) and normal X chromosomes could be of biparental or uniparental origin, and that mental status in females with r(X) chromosomes is determined by multiple factors, including the presence or absence of XIST on the r(X) chromosomes and the size and frequency of active r(X) chromosomes, in addition to co-incidental genetic and environmental factors.
Adolescent↗
A novel nonsense mutation of the PEPD gene in a Japanese patient with prolidase deficiency.
A nonsense mutation at amino acid residue 184 in the human peptidase D (PEPD) gene caused the production of a truncated polypeptide. Characterizing molecular defects in patients provides clues to elucidate the relationship between the phenotype and the genotype.
Amino Acid Sequence↗
Absent circadian variation of blood pressure in patients with anorexia nervosa.
OBJECTIVE: To examine whether circadian rhythm of blood pressure (BP) is altered in patients with anorexia nervosa (AN), and if so, to determine whether it is reversible after refeeding. STUDY DESIGN: Ambulatory BP monitoring was performed on 17 female inpatients with AN (mean age, 13.3 +/- 1.9 years) at the time of admission and serially during refeeding; 17 age-matched normal weight, normotensive female inpatients served as control subjects. RESULTS: Patients with AN had lost an average of 23.4% +/- 11.5% of body weight before the illness. Weight after refeeding was 105.6% +/- 9. 2% of that before illness. Mean 24-hour systolic BP (SBP) (96.5 +/- 8.6 mm Hg) and diastolic BP (DBP) (53.4 +/- 5.8 mm Hg) were significantly lower in patients with AN compared with those of control subjects (SBP, 106.1 +/- 6.5 mm Hg; DBP, 60.2 +/- 5.8 mm Hg). Although awake SBP and DBP were also lower in patients with AN, asleep SBP and DBP were not statistically different from those of control subjects. Night/day BP ratio in the control group was 0.93 +/- 0.06 in systolic and 0.92 +/- 0.09 in diastolic. Those values were significantly elevated in patients with AN (systolic 1.00 +/- 0. 09 and diastolic 1.00 +/- 0.09). After refeeding, the ratio decreased to 0.88 +/- 0.09 and 0.90 +/- 0.08,respectively (both P <. 05 vs baseline). CONCLUSIONS: In patients with AN, circadian variation of BP is absent. This reverts to normal after refeeding.
Adolescent↗