Biomedical subjects
Publications and source records attributed to A Fujimoto.
A 23-year-old woman from Honduras was diagnosed to have hepatoerythropoietic porphyria. She had photosensitive skin of early onset, hypertrichosis, and severe scleroderma-like lesions of the hands. Erythrocyte uroporphyrinogen decarboxylase activity was reduced to about 10% of the normal activity.
Trisomy 14 mosaicism produces a distinct phenotype. Among the 13 reported and 2 additional patients, the following findings were present in more than 90%: growth retardation (15/15), psychomotor retardation (10/10), broad nose (13/14), "dysplastic" and/or apparently low-set ears (15/15), micrognathia (15/15), short neck (11/12), congenital heart disease (14/15), and micropenis and cryptorchidism (6/6). Other frequent findings were prominent forehead (12/14), hypertelorism (8/13), narrow palpebral fissure (7/9), large mouth (10/14), cleft or highly arched palate (10/14), body asymmetry (8/12), and abnormal skin pigmentation (6/10). Sex ratio was 6M:9F. Four patients died before age 4 months, while at least 2 patients survived through teens. One boy died at age 3 years following cardiac surgery. One girl with tetralogy of Fallot showed a remarkable improvement in health after Blalock-Taussig procedure. Although the surviving patients showed moderate growth and mental retardation, the oldest surviving woman at 29 years demonstrates functional language and appropriate self help skills.
1. Sequential patterns of abuse were analyzed in 222 subjects of substance abuse who had admitted mental hospitals. They were classified into four patterns and seven sub-patterns. 2. Alcohol alone type (Pattern I) was different from other patterns of abuse in their initiating ages, family status and the levels of social life. A marked tendency to multiple abuse was found in Pattern II and III including organic solvents and/or methamphetamine. 3. However, even in Pattern II and III, alcohol abuse was found in 18% of the subjects. This suggests alcohol is an important hidden substance in multiple drug abusers. 4. Many substance abusers without alcohol had also alcoholics in their family members. Especially those who initiated their abuse in early ages are supposed to have constitutional and family factors which are common to alcohol and drugs. 5. Patterns II and III of organic solvents and methamphetamine abuse, the existence of peers and their strong influence upon users were of prime importance. Initiation of abuse from an early age and disruption of social life were marked in those patterns. 6. Many alcoholics started their abuse in earlier ages than expected. The study shows that there were two groups; the group whose social lives had been disrupted at early ages, and the one whose level of social life had been maintained. 7. Physical illnesses were mostly found in the patterns which include alcohol abuse.
Hallermann-Streiff syndrome (HSS) is a rare disorder with an associated constellation of radiological findings that may aid in the diagnosis of affected individuals. We reviewed the skeletal surveys of 5 affected individuals and noted some characteristic and constant findings. Radiological findings can include a large, poorly ossified skull with decreased ossification in the sutural areas. There was an increase in the number of Wormian bones. Severe mid-facial hypoplasia was present along with a prominent nasal bone. The skull films also showed an abnormally obtuse or nearly straight gonial angle. The teeth appeared small. The long bones were thin and gracile in appearance and often showed poor demarcation of the cortex from the medullary portion. Abnormal bowing of the radius and ulna was seen neonatally in 2 cases. There was widening at the metaphyseal ends of the long bones. The ribs were thin, but normal in length. The vertebral bodies were noted to be small and 3 cases had platyspondyly. There was a decreased number of sternal ossification enters. The metacarpals were also thin and gracile in appearance with metaphyseal widening. We conclude that these characteristic radiological findings in the newborn with HSS can aid in the diagnosis, and a skeletal survey in suspected individuals may be valuable in confirming the diagnosis.
A female twin with short stature, unusual facial appearance, widely spaced nipples, and coarctation of the aorta was found to have a peripheral blood lymphocyte karyotype of 45,X(43%)/46,X,idic(Y)(p11). Her twin brother, also short with similar facial appearance, had the same mosaicism (40% 45,X). Cultured skin fibroblast studies showed discrepant karyotypes of 45,X (100%) in the girl and 45,X (78%)/46,X,idic(Y)(p11) in the boy. The mother and the father had normal chromosomes. Comparison of 27 biochemical markers yielded a likelihood of monozygosity of 0.9977. This report documents the occurrence of discordant phenotypic sex in monozygotic twins, involving gonadal dysgenesis with an abnormal dicentric Y, which presumably occurred de novo, followed by anaphase lag probably before the occurrence of twinning. Unequal distribution of the two resultant cell lines in various tissues of each twin could account for the development of the very different phenotypes, apparently normal boy and Ullrich-Turner girl.
The mutant c-erbB-2 gene encoding a protein with Glu instead of Val-659 in the transmembrane domain is able to transform NIH3T3 cells, while the wild type c-erbB-2 unless overexpressed does not. The mutant c-erbB-2 protein shows enhanced tyrosine kinase activity in vitro. Transient expression of this active c-erbB-2 stimulated the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element, serum response element, and cyclic AMP response element. Particularly, stimulation of the TPA response element by active c-erbB-2 was prominent. In contrast, transient expression of wild type c-erbB-2 stimulated none of these elements. Transactivation of the TPA response element was also observed in a cell line that stably expresses active c-erbB-2. The active c-erbB-2-induced transactivation of the TPA response element was partially prevented either by down-regulation of protein kinase C or by the protein kinase C inhibitor H7. These results indicate that protein kinase C is partly involved in oncogenic signalling of the active c-erbB-2 protein that leads to Jun/Fos-mediated transcriptional activation in nuclei.
An arthroscopic and histological investigation of patellar chondropathy in adolescents was performed in 98 knees of 83 patients who were classified into three clinical types of patellofemoral disorder. These were the anterior knee pain syndrome, idiopathic chondropathy, and unstable patella. Histological findings suggested little evidence of progression to high-grade chondropathy in the patients with anterior knee pain syndrome, and this may account for the resolution of clinical symptoms in this group. Even in patients with high-grade lesions in the idiopathic chondropathy and unstable patella groups, histological observations indicated that these lesions could heal either by intrinsic (fibrous metaplasia of chondrocytes and regeneration of matrix) or extrinsic repair. Chondropathy in adolescents may be similar to the early changes of osteoarthritis of the knee. However, chondropathy shows far more potential for repair by the synovium and/or the cartilage itself than does osteoarthritis.
1. There was no significant difference between the systolic blood pressure (SBP) of offspring derived from SHRSP mother and WKY father and the SBP of offspring derived from WKY mother and SHRSP father at the developing stage (5-13 weeks of age). 2. The degree of genetic determinations of SBP in stroke-prone spontaneously hypertensive rat (SHRSP) at 5, 7, 10 and 13 weeks of age, determined by genetic crosses between SHRSP and WKY, was 73.9, 70.8, 50.2 and 55.3% respectively. 3. Significant correlations between SBP at 5 and 7 weeks, 7 and 10 weeks, 10 and 13 weeks, also at 5 and 13 weeks of age in F2 generation crossed between SHRSP and WKY were observed. SBP falling at or above the 80th percentile group in F2 generation at 5 weeks of age were constantly higher than SBP falling at or below the 20th percentile group from 7 weeks of age onwards. 4. These results indicate that there exists 'tracking phenomenon of SBP in SHRSP' and that genetic factors regulate the rise in SBP. Tracking of SBP in F2 generation gives us new methodological insight into hypertensive mechanism in SHR.
The presence of the t haplotypes in strains derived from the Japanese wild mice (Mus musculus molossinus) was investigated. Crosses between the T/+ heterozygous short tailed mice and five normal tailed molossinus strains (MOL-ANJ, MOA, MOL-NEM, MOM and Mns) produced no tailless mice, indicating that these strains possess no t haplotype. In contrast, tailless mice were produced by a cross between the T/+ heterozygotes and a MOL-NIS strain. Mating experiments showed that the tailless character was due to an interaction between the T gene and an autosomal recessive gene carried by the MOL-NIS strain that expresses the short tail character under the homozygous condition. We have tentatively named this gene brachyury-interacting tail length modifier (btm). It remains to be investigated whether the btm gene is located in the t complex region or in the other locus.
Adolescent patellofemoral disorders which are associated with recognizable change in the articular cartilage of the patella are called chondromalacia patellae. This is a clinical syndrome characterized by persistent retropatellar pain, but not always associated with histopathological changes of the articular cartilage. When lateral retinacular release is performed in such patients, pain is frequently eased even though lateral release does not always cause an appreciable change in patellofemoral contact pressure. This suggests that pain, at times, may emanate from the peripatellar retinacular supports themselves. Thirty-five knees of 22 patients suffering from anterior knee pain (with or without an unstable patella) were investigated histologically. Pathological changes in nerves were graded on a 0 to 3 + scale of severity. There was severe degenerative neuropathy in nine knees, moderate change in nine, and slight change in 11; the remaining six knees were normal. Histological investigation of the resected lateral retinaculum suggested that pain originated in the lateral retinaculum in many patients, and that degenerative changes in the nerves of the lateral retinaculum may be an important cause of pain in patients with patellofemoral disorders.
A pregnant woman with indeterminate Duchenne muscular dystrophy (DMD) carrier status, but with DMD diagnosed in her deceased brother (unavailable for study), presented for prenatal diagnosis, intending to continue the pregnancy only if proven unaffected with DMD with near absolute certainty. Creatine kinase (CK) assays to clarify carrier status were inconclusive. Male sex in the fetus was identified, but DNA restriction fragment length polymorphism (RFLP) analysis was not yet available to this centre to investigate the possible transmission of the DMD gene, and the pregnancy was terminated. Tissue histology and dystrophin protein analysis demonstrated the absence of DMD. In a situation with proven maternal carrier status, future fetal inheritance of the opposite maternal X chromosome would indicate the presence of DMD. However, maternal carrier status remained in doubt through a second pregnancy, even with RFLP studies, and was finally established when dystrophin analysis confirmed the presence of DMD in the second fetus. Histologic findings are presented, contrasting features in the two fetuses. The value of dystrophin analysis for establishing the diagnosis of fetal DMD, in this case proving maternal carrier status in a difficult situation, and for demonstrating DMD gene:RFLP haplotype relationships is illustrated.
Postnatal growth records of 13 patients with Wolf-Hirschhorn syndrome indicate that the syndrome is associated with continuing severe growth retardation and marked microcephaly. In spite of severe retardation, these patients (with one exception) survived beyond infancy.
Cytogenetic studies showed 47,XY, + mar in a developmentally retarded child with some features of Prader-Willi syndrome, and 46,XX in his mother. The marker chromosome showed a single subterminal primary constriction, bisatellites, and two C-bands. DA/DAPI staining showed two intense bands in the marker chromosome, which most likely was derived from chromosome 15. Intense DA/DAPI fluorescence was also found in one chromosome 13 in the child, and one 13 and one 10 in his mother. The present results confirm the reports of DA/DAPI heteromorphism in acrocentric chromosomes other than the 15, and demonstrate a pericentric DA/DAPI heteromorphism in chromosome 10.
We have previously shown that purified T4 DNA topoisomerase promotes illegitimate recombination between two lambda DNA molecules, or between lambda and plasmid DNA in vitro (Ikeda, H. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 922-926). Since the recombinant DNA contains a duplication or deletion, it is inferred that the cross-overs take place between nonhomologous sequences of lambda DNA. In this paper, we have examined the sequences of the recombination junctions produced by the recombination between two lambda DNA molecules mediated by T4 DNA topoisomerase. We have shown that there is either no homology or there are 1-5-base pair homologies between the parental DNAs in seven combinations of lambda recombination sites, indicating that homology is not essential for the recombination. Next, we have shown an association of the recombination sites with the topoisomerase cleavage sites, indicating that a capacity of the topoisomerase to make a transient double-stranded break in DNA plays a role in the illegitimate recombination. A consensus sequence for T4 topoisomerase cleavage sites, RNAY decreases NNNNRTNY, was deduced. The cleavage experiment showed that T4 topoisomerase-mediated cleavage takes place in a 4-base pair staggered fashion and produces 5'-protruding ends.
Multiple cell-multiple flask mosaicism was found in 0.20% of 6,000 amniocenteses, and multiple cell-single flask mosaicism was found in 0.92%. Multiple cell-multiple flask mosaicism usually was found in fetal or infant tissues at delivery or elective abortion. Most multiple cell-multiple flask mosaicism involved sex chromosomes and was either 45, X/46, XY or 45, X/46, XX. Except for one fetus with 45, X/46, XX and an aortic coarctation, phenotypic abnormalities associated with sex chromosome mosaicism were not found in these patients. One normal boy has continued to show 45,X mosaicism during the first 4 years of life. Autosome abnormalities found in multiple cell-multiple flask mosaicism included del(18q) associated with fetal anomalies. Apparently normal phenotypes were associated with prenatal trisomy 17, two de novo supernumerary marker chromosomes, and monosomy 21. Since an aberrant cell line present in only one primary amniotic fluid cell culture was occasionally identified from another amniocentesis or at birth, multiple cell-single flask mosaicism involving a sex chromosome or a viable autosome abnormality cannot be assumed to be an in vitro event. Maternal cell contamination, which was found in 0.49% of amniocenteses, could have resulted in an erroneous diagnosis of fetal sex in two cases if cells from independent culture vessels were not examined.
This article reports a rare case of pigmented villonodular synovitis (PVS) arising from the plica synovialis mediopatellaris that impeded the knee joint when it was extended. This lesion was diagnosed and treated by arthroscopy.
Four human female fibroblast strains with an i(Xq) or derivative X chromosome as a cytological marker for the inactive X chromosome were used to determine the frequency of sister chromatid exchanges (SCEs) in the active and inactive X chromosomes. No significant difference in SCE frequency between the active and inactive X chromosomes was observed. Therefore, the state of chromatin condensation and the late DNA replication in the facultative heterochromatin of the inactive X chromosome do not appear to influence the SCE frequency.
This paper represent one of the important index of gingival color to various conditions. Generally the gingival color is very difficult problem to measure, so experimental gingivitis has to be treated by special technique such as Discriminant Analysis in spectrum pattern analysing. On measuring gingiva, Standard Measuring System is used in our department. Tissue Spectrum Analyzer TS-200 is used for measuring gingival color and spectrum pattern. Spectrum patterns are classified by its strength into three categories, that is Normal, Slightly-Redness and Redness. Discriminant Analysis and Graph Analysis (Constellation Graph) showed each group of property. The following results were obtained; Spectrum patterns have two peaks, that is 542 nm and 577 nm. With gingivitis change on three steps, that is Normal, Slightly-Redness and Redness, spectrum powers and difference of absorption in spectrum degrees and brightness is down. With gingivitis change, the Z1 value was obtained by Discriminant Analysis and showed a tendency to sign change from minus to plus. In the result of Discriminant Analysis distinction rate is 97.4% in N Group, 98.5% in SR Group and 100% in R Group. Constellation Graph represented each group of property clearly.