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Biomedical subjects

Y Mashima

Publications and source records attributed to Y Mashima.

At least 109 records · Page 6Linked to original sources
PubMed1995

Lack of differences among mitochondrial DNA in family members with Leber's hereditary optic neuropathy and differing visual outcomes.

Investigation of a maternal family of three generations of Leber's hereditary optic neuropathy (LHON) showed four affected and three unaffected individuals. Two of the four patients had recovered near-normal vision, one spontaneously, and one following treatment with idebenone, a quinol compound. One patient whose visual impairment persisted was a heavy consumer of alcohol and tobacco. Molecular genetic analysis of 12 known primary or secondary mutations in mitochondrial DNA (mtDNA) associated with LHON revealed only the 11778 mutation in a homoplasmic fashion with no secondary mutations. The variations in clinical outcome thus could not be explained by synergistically interacting secondary mutations in mtDNA. Environmental factors may play an etiologic role in the development of optic atrophy.

Adult↗
PubMed1995

Quantitative determination of heteroplasmy in Leber's hereditary optic neuropathy by single-strand conformation polymorphism.

PURPOSE: The maternal inheritance of Leber's hereditary optic neuropathy (LHON) is caused by defects in the genes of mitochondrial DNA (mtDNA). The most prevalent mtDNA mutation, present in 40% to 90% of families with this disease, is a G to A substitution at nucleotide position 11778. The rapid and accurate quantification of heteroplasmy of this mutation will help determine the relative risk for disease expression. METHODS: The authors conducted screening tests for heteroplasmy in 44 visually affected patients with the 11778 mutation and 34 unaffected members of 36 Japanese families with LHON using the single-strand conformation polymorphism analysis. This method can detect even a single base difference between the sequences of wild type and mutant DNA strands. The percentage of mutant mtDNA was calculated using an image analyzer. RESULTS: Single-strand conformation polymorphism analysis allowed the detection of heteroplasmy ranging from 5% to 95%. Five (14%) of the 36 families showed heteroplasmy, and 14 (18%) of the 78 persons tested had heteroplasmy ranging from 10% to 94%. Seven patients with heteroplasmy with visual loss had mutant mtDNA ranging from 62% to 94%. CONCLUSIONS: Single-strand conformation polymorphism analysis is rapid, efficient, and accurate for detecting point mutations and quantifying heteroplasmy in mtDNA. Individuals with heteroplasmy with less than 60% of mutant mtDNA in circulating leukocytes are probably at lesser risk for developing optic atrophy.

Adult↗
PubMed1995

[Molecular genetic analysis of Leber's hereditary optic neuropathy with the 3460 mutation in Japanese pedigrees].

We have identified a point mutation at nucleotide position 3460 in the ND1 gene of complex I in a Japanese pedigree with Leber's hereditary optic neuropathy by sequencing the ND genes in mitochondrial DNA. None of the 60 healthy Japanese had the 3460 mutation. The proband and his mother also had the 7444 mutation in the COI gene of complex IV and became nearly blind at age 19 with visual acuities of 0.02 OD and 0.04 OS We screened 30 patients with bilateral optic atrophy for the 3460 mutation, and identified one male patient who had the 3460 mutation in heteroplasmic fashion without carrying the 7444 mutation. He lost his sight at age 14 but it recovered to 1.2 OD and 0.7 OS about two years and half after the onset. The difference in final visual acuity between these two patients may reflect the degree of reduction in mitochondrial energy production.

Adolescent↗
PubMed1995

Clinical features of Japanese Leber's hereditary optic neuropathy with 11778 mutation of mitochondrial DNA.

The G to A transition of nucleotide position (nt) 11778 of mitochondrial DNA (mtDNA) has been frequently observed in Japanese Leber's hereditary optic neuropathy (LHON) cases. Therefore, we performed a multi-institutional study in Japan of LHON cases with this 11778 mutation of the mtDNA. Genetic and clinical data on 108 cases (90 affected and 18 carriers) in 79 unrelated families were obtained from 64 Japanese institutions. Detection of the nt11778 mutation was performed using restriction enzymes (74 cases) or dot blot with allele specific oligonucleotide (34 cases). Heteroplasmy was observed in 13 of the 90 affected cases and in 8 of the 18 carrier cases. Forty-five families had family history of LHON (44 maternal inheritance, 1 undetermined), and in 28 families (35.9%) there were isolated cases. The male-to-female ratio in the affected was 82:7 (92.1% male). The age at onset of visual loss ranged from 7 to 59 years (average: 23.4 years). All cases had bilateral involvement except one case with a blind eye resulting from ocular infection during childhood. Onset interval between the two eyes ranged from simultaneous to 17 months (average: 2.5 months), in 91.3% of cases being under 6 months. Visual acuity was 0.1 or worse in 152 (85.9%) of 177 eyes, only 6 eyes showing over 0.5. Progression of visual loss ranged from 0 to 48 months (average: 6.2 months). Central visual field abnormality was observed in 162 eyes (96.4%) of 168 eyes. Nonsuspect fundus in the ophthalmoscopic examination constituted 22.8% of eyes. Systemic corticosteroid was given to 45 (52.9%) of 85 cases and visual acuity was improved in only 2 cases (4.4%). Arrhythmia, neurological and muscular abnormality were observed as rare general complications. The present survey indicates that the male-to-female ratio is higher than the previous Japanese LHON statistics and that the visual outcome is better than in American LHON cases with the 11778 mutation.

Adolescent↗
PubMed1995

[Effects of insulin-like growth factor-I in burned rats].

Effect of insulin-like growth factor-I (IGF-I) on protein metabolism was investigated in burned rats receiving TPN. Twenty-six male SD rats were divided into two groups. IGF-I was administered to group IGF (IGF-I group, n = 14), but not to group C (Control group, n = 12). Loss of body weight after burn in group IGF was significantly lower than group C (p < 0.01). Cumulative nitrogen balance for 2 postburn days in group IGF was significantly higher than group C (p < 0.01). Rate of whole body protein turnover, synthesis and breakdown increased significantly in group IGF compared with group C. On the other hand, blood glucose was decreased significantly in group IGF (p < 0.05). Water balance made no significant difference between two groups. In group IGF, weight of the spleen, kidney, small intestine and colon increased significantly. Fractional synthesis rate and protein content of mucosa of the small intestine were significantly higher in group IGF than group C. From the histological point of view, mucosal layer was thickened and hyperplastic. Catabolism and surgical diabetes are caused in the surgical stress, and the administration of IGF-I are thought to be effective for improvement of those conditions. And IGF-I has the most remarkable effect on the small intestine of all organs studied in our experiment.

Animals↗
PubMed1995

Corneal epithelium in keratoconus.

Specular microscopy was employed to study the corneal epithelium of 20 keratoconus patients (17 male, 3 female, average age 23.9 +/- 6.6 years). The patients were divided into three groups based on the severity of the keratoconus; early, intermediate, and advanced. Initially, epithelial changes were limited to enlargement of the superficial cells. As the disease progressed, elongated cells became prominent. Irregularly configurated and nucleated epithelial cells were observed in all cases. Morphomeric analysis showed that the mean area of the corneal epithelial cells was 906 +/- 203 microns 2 in the early stage, 1,416 +/- 521 microns 2 in the intermediate stage, and 1,641 +/- 372 microns 2 in the advanced stage. The shape factor was 0.32 +/- 0.05, 0.76 +/- 0.22, and 0.81 +/- 0.17, respectively. Controls were chronic wearers of hard contact lenses without corneal pathology. Analysis of their epithelium revealed no abnormalities. This finding suggests that the epithelial changes observed in keratoconus are not due to the wearing of contact lenses, but rather to the disease itself.

Adolescent↗
PubMed1995

[Changes in proliferation and differentiation of basal cells during wound healing of rabbit corneal epithelial abrasions].

Changes in the mitotic rate and epithelial keratin expression of corneal epithelial basal cells following corneal abrasion (7.0 mm in diameter) in rabbits were studied immunohistochemically using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody and anti-epithelial keratin 1 (AE1). In the non-wounded control, the mitotic rate (PCNA positive cells in the basal cell layer) was approximately 4%, and only the superficial cells were stained by AE1 monoclonal antibody. One day after wounding, migrating epithelial cells at the leading edge, which reacted to AE1, showed low mitotic activity. At days 3 and 7, the mitotic rates of basal cells of regenerating epithelium were 3 times higher than that of controls. These basal cells displayed intensive staining with AE1, while the epithelium over the unwounded cornea exhibited a normal pattern limited to superficial cells. By 14 days after injury, the mitotic rate returned to normal and all epithelial cells expressed a normal AE1 staining pattern. Theses results suggest that regeneration of corneal epithelial basal cells involves changes in keratin expression, which might correlate with changes in the mitotic rate.

Animals↗
PubMed1995

[The role of the basal cell layer in the maintenance of normal corneal epithelium].

A method of desquamating single layers of corneal epithelial cells through the use of digitonin allowed the observation of the basal cell layer by scanning electron microscope. Basal cells of normal rabbit corneal epithelium were observed as small, round, and columnar-shaped cells, and the mean cell areas of superficial and basal cell layers were 507. 3 +/- 46.6 microns 2, and 39.5 +/- 2.8 microns 2, respectively. The mitotic rate of basal cells was also evaluated immunohistochemically using anti-PCNA (proliferating cell nuclear antigen) monoclonal antibody and the flat preparations of corneal epithelium. The mitotic rate (PCNA positive cells in the basal cell layer) was approximately 4%, and showed no difference between the center and peripheral portion of the cornea. We think these two new methods are useful for the analysis of morphological and functional characteristics of corneal epithelial basal cells.

Animals↗
PubMed1994

A piggyback contact lens for the correction of irregular astigmatism in keratoconus.

PURPOSE: Although the combination of a hard contact lens "piggybacked" on a soft lens base for the correction of severe astigmatism in keratoconus has existed for two decades, little is known about its effect on the corneal epithelium and endothelium. This study involves two parts: the measure of oxygen pressure in rabbits, and the long-term effects on patients with keratoconus wearing these hybrid lenses. METHODS: A polarographic sensor was used to measure the oxygen pressure on rabbit corneas under two types of piggyback lenses: oxygen-permeable hard lenses on high water-content soft lenses, and polymethylmethacrylate (PMMA) lenses on low water-content soft lenses. In the clinical evaluation, 11 patients with keratoconus (8 men, 3 women; 25.1 +/- 4.9 years of age) who could not wear hard contact lenses due to constant pain or inadequate lens fitting were given oxygen-permeable piggyback contact lenses and were observed for at least 9 months. RESULTS: In the animal study, the oxygen pressure under piggybacked oxygen-permeable hard contact lenses was 95 +/- 14 mmHg after 5 minutes wear, but it was only 34 +/- 14 mmHg when PMMA and low water-content lenses were used. Ten of 11 patients were successfully treated using this technique, whereas one patient had persistent contact lens loss, requiring penetrating keratoplasty. Specular microscopic observation of the corneal epithelium and endothelium did not show any changes during the follow-up period. CONCLUSIONS: These results suggest the efficacy and safety of the piggyback combination of oxygen-permeable hard and soft contact lenses for the correction of astigmatism in patients with keratoconus.

Adolescent↗
PubMed1994

Autosomal dominant retinitis pigmentosa. A mutation in codon 181 (Glu-->Lys) of the rhodopsin gene in a Japanese family.

The PCR/restriction endonuclease digestion (RE) assay and PCR/SSCP analysis of the rhodopsin gene in 13 Japanese families with autosomal dominant retinitis pigmentosa (ad RP) revealed a G-A substitution of the first nucleotide of codon 181, replacing Glu (GAG) with Lys (AAG), in one family. The proband showed an early onset of symptoms in childhood with a diffuse loss of rod and cone function and a relatively good preservation of cone function, corresponding to the type with relatively rapid progression to blindness (type I category of ad RP).

Adult↗
PubMed1994

[Radiation therapy of carcinoma of the esophagus in the aged--its results and problems].

Clinical records of 128 non-selected patients with esophageal cancer treated by radiation were reviewed to investigate reasons why treatment had to be discontinued, relationship between age and survival, and factors influencing prognosis. Radiation therapy was completed in 77 patients but was discontinued in 27 patients. Preoperative radiation was attempted in 24 patients. An overall median survival of 128 patients was 6.4 months, with 8.5 and 3.3 percent surviving 3 and 5 years. Median survivals of incomplete RT, completed Rt and RT + Surgery were 1.3, 7.7 and 11.3 months. By Kaplan-Meier analysis significant difference was observed in survival rate between incomplete RT and the other two groups, but not between RT and RT + surgery. T1 tumor cases with incomplete RT were characterized by a higher C-Score (higher incidence of comorbidity and complications), lower albumin concentration and poor performance status. Median survivals of 60 years, 70 and 80 were 12, 5.4 and 6.2 months, respectively. Performance status and C-score were significantly different between the 60 yr and 80 yr groups. Survival rates were also apparently affected by the size of the primary tumor and metastasis. Thus important factors influencing prognosis were performance status, albumin concentration, and comorbidity and complications, in addition to stage of tumor itself. Although performance status and albumin concentration were considered directly related to tumor stage, old age may have an adverse effect on these factors through increase of comorbidity and complication. The data may be useful for decision making for treatment of esophageal cancer of the aged.

Age Factors↗
PubMed1994

[Monitoring tumor response to therapy by means of 31P magnetic resonance spectroscopy. A case of advanced prostatic cancer with metastatic chest wall tumor].

The response of advanced prostatic cancer with metastatic chest wall tumor to high-dose diethylstilbestrol diphosphate (DESP) therapy was monitored by in vivo 31P magnetic resonance spectroscopy (31P MRS) study. A eighty-three year old man with Stage D2 prostatic cancer had been treated with chlormadinone acetate and cyclophosphamide since 1984. He was admitted to our hospital with a chest wall tumor and anemia on May 9, 1992. The elevated PAP, PSA and gamma-Sm levels were also observed. Needle biopsy of the tumor revealed poorly differentiated adenocarcinoma metastatic from the prostatic cancer. The patient received 500 mg of DESP by DIV daily for 10 days, and the tumor was reduced by 54% clinically. The abnormal PAP, PSA and gamma-Sm levels returned to almost normal range by three weeks after the initiation of high-dose DESP therapy, and regression of the tumor was confirmed by the MRI. After the first administration of DESP, the MR spectra of the chest wall tumor showed elevated peaks of phosphomonoesters and phosphodiesters. These substances are related to the membrane metabolism and their increase represents the membranous degeneration of tumor cells. The same changes continued consecuitively for three weeks, and corresponded with the regression of the tumor. In conclusion, these results suggest that in vivo 31P MRS of malignant tumors can be useful for evaluating early response to therapy prior to other clinical examinations.

Adenocarcinoma↗
PubMed1994

Rapid and efficient molecular analysis of gyrate atrophy using denaturing gradient gel electrophoresis.

PURPOSE: A generalized biochemical deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) is the inborn error in gyrate atrophy (GA), an autosomal recessive blinding disease of the retina and choroid of the eye. Because mutations in the OAT gene show a high degree of molecular heterogeneity in GA, the authors set out to determine the mutations by rapid and efficient methods. METHODS: The mutations in the OAT gene were determined by a combination of polymerase chain reaction (PCR) amplification of gene sequences, analysis by denaturing gradient gel electrophoresis (DGGE), and direct DNA sequencing. RESULTS: Eleven different mutations in 21 (95.5%) out of 22 mutant OAT alleles from 11 patients were identified: six missense mutations, three nonsense mutations, one 2 bp-deletion, and one splice acceptor mutation. A silent polymorphism of Asn (AAC)378 to Asn (AAT) was also observed. CONCLUSIONS. The combination of PCR amplification of the gene sequences, DGGE analysis, and direct sequencing is a rapid and efficient method for detection of mutations in GA cases. The diversity of the mutations attests to the enormous genetic heterogeneity in this disease.

Alleles↗
PubMed1993

High frequency of mutations at position 11778 in mitochondrial ND4 gene in Japanese families with Leber's hereditary optic neuropathy.

We have investigated the presence of a point mutation at position 11778 in the ND4 gene of mitochondrial DNA in 17 Japanese families with Leber's hereditary optic neuropathy (LHON), and have identified the mutation in 14 (82.4%) of the 17 families. The prevalence of this mutation appears to be much higher in Japanese patients with LHON than in patients of other ethnic origins, such as Finnish, Dutch, German, and English families.

Base Sequence↗
PubMed1993

A novel Cys-214-Ser mutation in the peripherin/RDS gene in a Japanese family with autosomal dominant retinitis pigmentosa.

We have screened for possible disease-causing mutations in the peripherin/retinal degeneration slow (RDS) gene in 13 Japanese families with autosomal dominant retinitis pigmentosa (ADRP). Using polymerase chain reaction-single strand conformation polymorphism analysis, a novel mutation at codon 214 was found in which the highly conserved cysteine was replaced with a serine in one family. The mutation at codon 214 was found in all three affected siblings of this family, but none of the 40 normal control individuals had this mutation. These results strongly suggest that the mutation is pathogenic for RP in this family. The clinical phenotype for this family is a late-onset form of ADRP.

Age of Onset↗
PubMed1993

[Clinical evaluation of age-related changes of bone mineral content of cortical and trabecular bones by dual energy QCT].

The potential capability of a new dual energy (DE) quantitative computed tomography (QCT) method, 4-equation 4-unknown method (DEQCT4E-4U), was evaluated for estimation of bone mineral density (BMD) as well as bone mineral content/cm width (BMC) in trabecular bone of lumbar vertebrae. Cortical BMD and BMC were also estimated by the single energy QCT method (SEQCT 80 kVp) and the age-related change of cortical BMD and the cortical BMC/trabecular BMC ratio was also studied. The result indicated that the estimation of the BMD combining analysis of BMC in trabecular bone obtained by the present method provides further knowledge concerning vertebral trabecular bone mineral status. The profiles of the age-related changes of the cortical BMD and cortical BMC/trabecular BMC ratio in females were markedly different from those in males. These results indicated that our method combining analysis of BMC (BMD) of cortical bone and trabecular bone was also found to provide valuable information to evaluate the vertebral bone mineral status.

Absorptiometry, Photon↗