In typical Fukuyama congenital muscular dystrophy (FCMD), peak motor function is usually only unassisted sitting or sliding on the buttocks, though a few patients are able to walk at some point. However, a few patients have a severe phenotype and never acquire head control. In addition, it is clinically difficult to differentiate this severe FCMD from Walker-Warburg syndrome (WWS) or from muscle-eye-brain disease (MEBD). In order to establish a genotype-phenotype correlation, we performed haplotype analysis using microsatellite markers closest to the FCMD gene (FCMD) in 56 Japanese FCMD families, including 35 families whose children were diagnosed as FCMD with the typical phenotype, 12 families with a mild phenotype, and 9 families with a severe phenotype. Of the 12 propositi with the mild phenotype, 8 could walk and the other 4 could stand with support; 10 cases were homozygous for the ancestral founder (A-F) haplotype whereas the other 2 were heterozygous for the haplotype. In the 9 severe cases, who had never acquired head control or the ability to sit without support, 3 had progressive hydrocephalus, 2 required a shunt operation, and 7 had ophthalmological abnormalities. Haplotype analysis showed that 8 of the 9 cases of the severe phenotype are heterozygous for the A-F haplotype, and the other one homozygous for the haplotype. We confirmed that at least one chromosome in each of the 56 FCMD patients has the A-F haplotype. The rate of heterozygosity for the A-F haplotypes was significantly higher in severe cases than in typical or mild cases (P < 0.005). Severe FCMD patients appeared to be compound heterozygotes for the founder mutation and another mutation. Thus, the present study yielded molecular genetic evidence of a broad clinical spectrum in FCMD.

Brain↗

PubMed2000

Retreatment with interferon for chronic hepatitis C after transient response.

Approximately half of all patients with chronic hepatitis C show an initial biochemical response to interferon, but only 15% to 20% of patients achieve a sustained response. We studied the efficacy of retreatment with interferon for patients with chronic hepatitis C who showed transient biochemical responses to initial treatment. Thirty patients who relapsed were retreated 1 to 52 months (median 14) after the end of initial treatment, according to the previously used regimens. The responses were correlated with the pre-retreatment patient data. The liver histologic grades, compared with those found before the initial treatment, were better in eight (27%) patients but worse in six (20%), whereas the fibrosis stage was improved in five (17%) but worsened in eight (27%). All patients displayed end-of-retreatment biochemical responses. Of the 30 patients, 10 (33%) achieved sustained aminotransferase normalization and serum hepatitis C virus (HCV) RNA clearance, but the remaining 20 patients showed relapse within 1 year after cessation of retreatment. Univariate analysis associated the sustained response with low pre-retreatment viral loads (0.8 +/- 0.7 MEq/mL vs. 9.1 +/- 6.5 MEq/mL; p = 0.006), short treatment intervals (13 +/- 13 months vs. 22 +/- 14 months; p = 0.031), and low histologic grades (1.3 +/- 0.7 vs. 1.9 +/- 0.7; p = 0.039). However, multivariate analysis indicated that only the pre-retreatment viral load was predictive of the sustained response (p = 0.049). These findings suggest that transient responders to interferon are likely to respond to retreatment but the achievement of a sustained response depends on the HCV viral load before retreatment.

Adult↗

PubMed2000

Bis[N-phenyl(dicyclohexylthiophosphinoyl)thiomethanamido-S, S']copper(II).

The ligands in [Cu(C(19)H(27)NPS(2))(2)] adopt an S,S'-chelation mode leading to an S(4) donor set which defines a square-planar geometry about the Cu atom, which lies on an inversion centre.

Journal Article↗

PubMed2000

Structure-activity relationships of neuromedin U. IV. Absolute requirement of the arginine residue at position 7 of dog neuromedin U-8 for contractile activity.

To examine the role of both Arg residues at positions 5 and 7 of dog neuromedin U-8 (d-NMU-8; pGlu1-Phe-Leu-Phe-Arg5-Pro-Arg7-Asn8-NH2) for smooth muscle contractile activity on isolated chicken crop, d-NMU-8 analogs were synthesized where either Arg residue was systematically replaced by various amino acids [X: Ala, Thr, Glu, Gln, Lys, Orn, His, citrulline (Cit) or homoarginine (Har)]. All [X5]-d-NMU-8, except for [Glu5]- and [Des-Arg5]-d-NMU-8, were full agonists, although their affinities to NMU receptors were decreased. No [X7]-d-NMU-8 showed contractile activity even at concentrations of 10(-5) mol/l, except for [Har7]-d-NMU-8, which retained weak biological activity. These analogs had no antagonistic activity against porcine neuromedin U-8 (p-NMU-8). The results revealed that Arg7 of d-NMU-8 is indispensable for receptor binding and activation to induce smooth muscle contraction, and the guanidino group of the side chain at position 7, but not at position 5, is strictly recognized by NMU receptors in the chicken crop.

Animals↗

PubMed2000

[Clinical spectrum and management of holoprosencephaly].

To study the phenotypic spectrum and management of holoprosencephaly (HPE), we reviewed the findings of eight children with HPE from 3 to 10 years of age, who underwent intervention programs and rehabilitation at our center. One patient had alobar HPE, three semilobar HPE, and four lobar HPE. All patients had postnatal growth retardation, and seven showed a decreased BMI (< 25% tile). All patients had severe developmental delay and mental retardation (DQ < 40), showing no obvious correlation between their severity and the type of HPE. Neurologically seven patients had spasticity (3 spastic quadriplegia, 2 spastic diplegia, 2 mixed-type), except one patient with a 7q deletion [46,XY,del(7) (q35)] who had generalized hypotonia. Seven had variable types of seizures. All patients had feeding difficulties and were assessed by speech-language therapists. Four patients required tube feeding, four had gastroesophageal reflux disease. Recurrent respiratory tract infection was common. Three patients had abnormal serum sodium concentration (1 diabetes insipidus, 1 idiopathic hypernatremia, 1 hyponatremia). No family history of HPE was elicited. In conclusion, patients with HPE should be followed up closely for complications such as feeding difficulty, malnutrition, seizures, spasticity, infection, and osmoreceptor-hypothalamus-hypophyseal axis abnormalities.

Child↗

PubMed2000

[X-linked mental retardation syndromes].

Explore the source record for details and available documents.

Genetic Linkage↗

PubMed1999

Clinical and molecular analysis of Japanese patients with neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinosis (NCL) is one of the most common inherited neurological diseases in childhood. It occurs every 12,500 births in northern-European populations. Mental retardation, visual impairment, and seizures are common symptoms. The prevalence of NCL is variable depending upon the races or countries. Although a wealth information is available in Caucasian populations, there is little information about NCL in Asian people. Because a nationwide survey in Japanese patients with NCL has never been performed, we pursued an epidemiological survey. We identified 36 NCL patients in Japan. Patients with infantile, late infantile, juvenile, and adult type accounted for 2, 15, 15, and 4 cases, respectively. Seizures were a major initial symptom in the late infantile type. In the juvenile type, visual failure was present in 73% at onset. Recently, the juvenile NCL (Batten disease) gene has been isolated. Studies of the mutations in this gene demonstrated that a 1.02-kb deletion was the most prevalent mutation among Caucasian patients, accounting for 81% of total alleles. To determine the prevalence of this 1.02-kb deletion in Japanese patients, we performed a rapid allele-specific polymerase chain reaction test. No 1.02-kb major deletion was detected in 5 Japanese juvenile NCL cases. These data suggest that the distribution of NCL and clinical findings are similar to those of Caucasian subjects; however, prevalence of mutations in Japanese patients with NCL would be distinct from that observed in Caucasians.

Adolescent↗

PubMed1999

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature.

We report a male infant with multiple congenital anomalies and mosaic variegated aneuploidy; a rare cytogenetic abnormality characterized by mosaicism for several different aneuploidies involving many different chromosomes. He had prenatal-onset growth retardation, microcephaly, dysmorphic face, seizures, hypotonia, feeding difficulty, and developmental delay. In addition, he developed bilateral Wilms tumors. Neuroradiological examination revealed Dandy-Walker malformation and hypoplasia of the cerebral hemisphere and pons. Cytogenetic analysis revealed various multiple numerical aneuploidies in blood lymphocytes, fibroblasts, and bone marrow cells, together with premature centromere division (PCD). Peripheral blood chromosome analysis from his parents also showed PCD, but no aneuploid cells. The clinical phenotype and multiple aneuploidies of the patient may be a consequence of the homozygous PCD trait inherited from his parents. Comparison with previously reported cases of multiple aneuploidy suggests that mosaic variegated aneuploidy with PCD may be a clinically recognizable syndrome with major phenotypes being mental retardation, microcephaly, structural brain anomalies (including Dandy-Walker malformation), and possible cancer predisposition.

Abnormalities, Multiple↗

PubMed1999

Stool smears for diagnosis of intestinal acute graft-versus-host disease.

A patient with severe diarrhea was successfully diagnosed as having acute intestinal GVHD on stool smear through detection of detached intestinal epithelial cells with apoptosis. Since a stool smear can be easily obtained non-invasively, it is a possible tool for the diagnosis of acute intestinal GVHD.

Acute Disease↗

PubMed1999

Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia.

A 26-year-old Japanese woman slowly developed a change of character such as hypospontaneity and blunted affect, followed by obvious mental deterioration. She was diagnosed as having a disorganized type of schizophrenia at the first examination. Brain magnetic resonance imaging demonstrated diffuse high intensity in the cerebral white matter, particularly in the frontal lobes. The single photon emission computed tomography images using 123I-IMP disclosed diffuse cerebral hypofusion, especially in the frontal lobes. Electroencephalogram showed a moderate amount of 5-6Hz theta waves on the background of alpha activity. Nerve conduction velocities in the extremities were delayed. The level of leucocyte arylsulphatase was low. In the arylsulphatase A gene analysis, a compound heterozygote having the 99Gly-->Asp and 409Thr-->Ile mutations was confirmed. The patient was diagnosed as having metachromatic leukodystrophy. She gradually showed obvious dementing symptoms such as memory disturbance and disorientation. The characteristics of the psychiatric symptoms in the leukodystrophy are discussed.

Adult↗

PubMed1999

Development of restriction fragment-length polymorphism method to differentiate five subtypes of feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) isolates have been classified into five subtypes (A to E) based on the sequences of the env variable V3 to V5 region. In this study, we sequenced a partial gag region of 4 and 3 isolates belonging to subtypes C and E, respectively. Phylogenetic analysis revealed that the branching pattern based on the region was similar to that based on the env V3 to V5 region. Here, we propose a protocol to differentiate five subtypes by polymerase chain reaction amplifying 329 bp within the region followed by restriction fragment-length polymorphism analysis using four restriction enzymes.

Animals↗

PubMed1998

Osteogenesis imperfecta-like syndrome with severe mental retardation and extrapyramidal tract signs.

We report a girl with a unique combination of malformations, including recurrent fractures, mental retardation with extrapyramidal tract signs and minor facial abnormalities. Generalised osteoporosis with overtubulation of long bones was similar to that of osteogenesis imperfecta (OI). However, the short tubular bones were distinctively undertubulated and wormian bones were not found. Based on clinical, laboratory and neuroradiological examinations, it was less likely that bone fragility was attributable to disuse bone atrophy related to her physical handicap and the neurological abnormalities secondary to brain insult. She is presumed to have a previously undescribed OI-like syndrome.

Basal Ganglia Diseases↗

PubMed1998

Purification and properties of the raw-starch-digesting glucoamylases from Corticium rolfsii.

Corticium rolfsii AHU 9627, isolated from a tomato stem, is one of the strongest producers of raw-starch-digesting amylase. The amylase system secreted by C. rolfsii AHU 9627 consisted of five forms of glucoamylase (G1-G5) and a small amount of alpha-amylase. Among these amylases, G1, G2 and G3 were able to hydrolyze raw starch. Five forms of glucoamylase were separated from each other and purified to an electrophoretically homogeneous state. The molecular masses were: G1 78 kDa, G2 78 kDa, G3 79 kDa, G4 70 kDa, and G5 69 kDa. The isoelectric points were: G1 3.85, G2 3.90, G3 3.85, G4 4.0, and G5 4.1. These glucoamylases showed nearly identical characteristics except that G4 and G5 were unable to hydrolyze raw starch.

Amino Acid Sequence↗