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Biomedical subjects

K Fujiki

Publications and source records attributed to K Fujiki.

At least 73 records · Page 4Linked to original sources

Cloning and high expression of rabbit FKBP25 in cornea.

Rabbit 25 kDa FK-506/rapamycin binding protein (FKBP25) cDNA was isolated during a screening of rabbit corneal endothelial cDNA library. The cDNA clone was a 955 bp fragment with a 670 bp open reading frame and a 285 bp 3' non-coding region. The cDNA and deduced amino acid sequences were 91.7 and 96.4% identical, respectively, to previously reported human FKBP25B sequences. The lysine-rich region KK(X)7KK(X)26KKKK, which plays an important role in nuclear translocation in rabbit FKBP25, was recognized. Reverse transcription-polymerase chain reaction (RT-PCR) amplification of rabbit FKBP25 and FKBP12 in selected rabbit organs, including total cornea, showed higher expressions in cornea, retina, cerebrum and cerebellum than other compared tissues. RT-PCR amplification in rabbit cultured corneal cells showed expressions in all cultured corneal epithelial, stromal, endothelial, and especially in SV40-adenovirus vector-immortalized epithelial cells. The higher expressions of FKBP25 and FKBP12 suggest significant roles for FKBPs in those tissues.

Amino Acid Sequence↗

Freeze-fracture and immunohistochemical studies of gap junctions in human gastric mucosa with special reference to their relationship to gastric ulcer and gastric carcinoma.

Our aim was to determine whether the development of gap junctions in the human gastric mucosa has any relation to gastric ulcer and gastric carcinoma. Freeze-fracture replicas were prepared from the endoscopic biopsy specimens of 20 patients with gastric ulcer and 7 healthy volunteers. Large fractured areas of lateral cell membranes of surface mucous cells were examined randomly under an electron microscope. Small gap junctions were observed between gastric surface mucous cells in all healthy volunteers. Gap junctions in the patients with gastric ulcer were significantly fewer than in the healthy volunteers. In addition, gap junctions in patients with recurrent ulcer were significantly fewer than in those with first-onset ulcer. There was no obvious relationship between age and the development of gap junctions in patients with gastric ulcer or in healthy volunteers. In the areas of intestinal metaplasia, gap junctions were occasionally seen between absorptive cells of the villi, but not in the lateral membranes of goblet cells. Fresh frozen sections for indirect immunofluorescence were prepared from the endoscopic biopsy specimens of 19 patients with gastric ulcer and 5 patients with gastric cancer. Monoclonal antibody against liver gap junction protein (anti-connexin 32, 6-3G11) was used for the indirect immunofluorescence. On the border of gastric ulcer, fluorescent spots in the surface mucous cells were significantly fewer than in the surface mucous cells of the body and antrum which were distant from the ulcer area in the same patients. In gastric cancer tissue specimens, fluorescent spots were not observed at all.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Detection of Helicobacter pylori infection in early stage gastric cancer. A comparison between intestinal- and diffuse-type gastric adenocarcinomas.

BACKGROUND: Helicobacter pylori (H pylori) infection has been suggested to be a risk factor for gastric carcinogenesis. However, those previous studies have been concerned with advanced cancer cases. To the authors' knowledge, no detailed investigation on the prevalence of H pylori in early stage gastric cancer tissue has been performed. The relationship between early stage gastric cancer and the prevalence of H pylori was studied by a immunohistochemical staining analysis. METHODS: Sixty-eight patients who were endoscopically and surgically diagnosed as having early stage gastric cancer were enrolled in this study. All tissue specimens were obtained from patients by endoscopic biopsy, and were classified histopathologically as the intestinal-type of early stage gastric cancer in 34 patients (male-to-female ratio, 28:6; age, 64 +/- 11 years) and the diffuse-type of early stage gastric cancer (male-to-female ratio, 23:11; age, 57 +/- 14 years) in the other 34 patients. The amount of H pylori in tissue samples was graded from 0 (no characteristic bacteria) to 3 (numerous bacteria) using the fluorescent microscopic and an immunohistochemical technique. RESULTS: Twenty-nine of the 34 cases of the intestinal-type of gastric cancer had H pylori infection, as compared with 11 of the 34 cases of diffuse-type early stage gastric cancer. A significantly higher incidence (85%; P < 0.001) of H pylori infection and, thus, higher grading scores of the number of H pylori were found in the intestinal-type early stage gastric cancer. CONCLUSIONS: These findings suggest that the infection of H pylori may have a crucial relationship to the early stages of carcinogenesis of intestinal-type gastric cancer.

Adenocarcinoma↗

Prediction of relapses after interferon-alpha therapy by hepatitis C virus RNA in peripheral blood mononuclear cells.

To investigate the predictive value of hepatitis C virus (HCV)-RNA in peripheral blood mononuclear cells in the response to interferon therapy in patients with chronic hepatitis C, 15 patients with histologically proven chronic active hepatitis and who were positive for serum HCV-RNA were treated with interferon-alpha (6 million units; i.m.) every day for two weeks and then three times a week for 22 weeks. Ten of the 15 patients were responders whose alanine aminotransferase levels decreased to the normal range at the end of interferon therapy. In four of the 10 responders, HCV-RNA was not detected by reverse transcription-polymerase chain reaction in peripheral blood mononuclear cells nor in serum at the end of treatment. These four patients were complete responders, with alanine aminotransferase levels remaining normal for the next 24 weeks. In five of the 10 responders, HCV-RNA was detected in peripheral blood mononuclear cells but not in serum at the end of treatment. All of these relapsed within the next 24 weeks. In the remaining responder, HCV-RNA was detected both in peripheral blood mononuclear cells and in serum at the end of treatment. This responder also had a relapse within the next 24 weeks. Five of the 15 patients were non-responders, in whom HCV-RNA was detected both in peripheral blood mononuclear cells and in serum. Thus, detection of HCV-RNA in peripheral blood mononuclear cells may be a good clinical marker to predict relapse after interferon treatment.

Adult↗

Missense mutation of rhodopsin gene codon 15 found in Japanese autosomal dominant retinitis pigmentosa.

Heterozygous missense mutation in codon 15 of the rhodopsin gene was detected in a patient with autosomal dominant retinitis pigmentosa (ADRP), where a transition of adenine to guanine at the second nucleotide in codon 15 (AAT-->AGT), corresponding to a substitution of serine residue for asparagine residue (Asn-15-Ser) was detected. None of the remaining unrelated 42 ADRP, 24 autosomal recessive RP (ARRP) and 34 normal individuals had this alteration. Her funduscopic findings were sectorial in type similar to that of the patients with the same mutation found in an Australian pedigree (Sullivan et al., 1993). This study shows phenotypic similarities in patients with the same mutation of a different ancestry.

Amino Acid Sequence↗

Evaluation of the effects of esophageal varicosclerosants on local vascular occlusion and systemic blood coagulation.

The efficacy and safety of the various sclerosants available for esophageal sclerotherapy have not been adequately investigated. In the present study, we experimentally evaluated the effects on local vascular occlusion and systemic blood coagulation of five sclerosants: 5% ethanolamine oleate, 99.5% ethanol, 2% aethoxysclerol, thrombin, and n-butyl-2-cyanoacrylate. The effects were tested after injection into the auricular vein of rabbits. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen level, and peripheral blood platelet count were measured before injection and 5 minutes, 1 hour, 1 day, and 7 days later. Histologic examinations were then made of the auricular vein, lungs, liver, spleen, and kidneys. In the initial period after injection of ethanol or thrombin, fibrinogen level and platelet count were significantly reduced. Except for thrombin, none of the drugs affected prothrombin time or partial thromboplastin time. Local thrombosis took place after the injection of ethanolamine oleate, ethanol, and aethoxysclerol, whereas thrombin injection did not result in local thrombosis or vascular occlusion. Cyanoacrylate produced no local thrombus formation but caused vascular occlusion. Over-dosing of thrombin and ethanol led to sudden death of animals. These findings suggest that it is necessary to assess further the safety of intravascular use of thrombin, that the other drugs seem to be usable, and that careful consideration should be given to the excess use of ethanol in clinical settings. The present animal model may be useful for evaluating various sclerosants, although findings may not be applicable to humans because of differences in vascular size.

Animals↗

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↗

[A study on the rhodopsin gene in Japanese retinitis pigmentosa--screening of mutation by restriction endonucreases and frequencies of DNA polymorphisms].

We analyzed 11 sites of the rhodopsin gene using polymerase chain reaction (PCR) amplification and restriction endonucleases in 30 unrelated Japanese patients with autosomal dominant retinitis pigmentosa (ADRP). No point mutation was found in any patient. The frequencies of the single nucleotide (nt) substitution at nt 269, nt 5145 and nt 5321 were examined in three groups, 38 unrelated patients with ADRP, 23 patients with autosomal recessive retinitis pigmentosa (ARRP), and 67 normal controls. There was no significant difference in the frequencies of substitution among these three groups. The frequencies of A269G, G5145A, and C5321A were 52%, 36%, and 5%, respectively. These values were different from those of the American population. The polymorphisms, A269G and G5145A, are useful as DNA makers for linkage analysis.

Asian People↗

[Leber's hereditary optic neuropathy with onset at the age of 54 years].

We report a 55-year-old Japanese man who had an onset of bilateral progressive blurring of vision at age 54 years. His younger sister had diminished visual acuity since 14 years of age. On neurologic examination, bilateral optic atrophy was present. He could only count the digit numbers at 40 cm-distance with his right eye, and the visual acuity of the left eye was 0.08. Otherwise, neurologic examination was unremarkable. The PCR analysis of mitochondrial DNA prepared from whole blood revealed a G to A mutation at the nucleotide 11,778; the so-called Wallace's mutation. He was diagnosed as Leber's hereditary optic neuropathy. It is rare to see a patient with LHON with the onset after 50 years of age.

Age Factors↗

Clinical features of autosomal dominant retinitis pigmentosa with rhodopsin gene codon 17 mutation and retinal neovascularization in a Japanese patient.

A 49-year-old Japanese man had autosomal dominant retinitis pigmentosa with a point mutation in codon 17 of the rhodopsin gene, resulting in a threonine-to-methionine change, and retinal neovascularization in both eyes. Pigmentary degeneration mainly in the inferior area of the fundus, and severe loss in the upper portion of the visual field were observed. Moderately preserved rod and cone functions were demonstrated by electroretinograms. These findings differed from those of Japanese and white patients with autosomal dominant retinitis pigmentosa with a codon 347 mutation and were almost the same as those of white patients with the codon 17 mutation. Our study indicates that phenotypic similarities exist among patients with the same mutation, but of different racial backgrounds. The neovascularization in the right eye diminished over a two-year period in conjunction with the progression of retinal degeneration.

Adaptation, Ocular↗

A multicenter study of typical retinitis pigmentosa in Japan.

A nationwide, multicenter study of typical retinitis pigmentosa was carried out in collaboration with 13 university hospitals throughout Japan. A total of 253 patients, 122 males and 131 females, with a wide range of ages (mean 48 years), were registered during a two-month period in 1989. Determination of inheritance pattern revealed 30.2% autosomal recessive cases, 15.4% autosomal dominant, 0.5% X-linked, and 48.9% simplex, indicating a relative decrease in autosomal recessive cases and a relative increase in simplex cases in recent decades. The age at onset, initial symptom, and visual functions including visual acuity, visual field and electroretinogram showed a marked interindividual variability, but statistical analysis demonstrated that visual defects progressed with increasing age and disease duration. A correlation between the phenotypic variation and the genetic type was observed. This survey of retinitis pigmentosa in Japan provides information for counseling and rehabilitation of patients and encourages basic and clinical research of this genetic disease.

Adolescent↗

Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP).

The mutations of codon 17, 23, 58, and 347 of rhodopsin gene were investigated in 24 unrelated Japanese families including 33 patients with autosomal dominant retinitis pigmentosa (ADRP). A patient with codon 17 mutation (Thr-17-Met, ACG-->ATG) and a family including 4 patients with codon 347 mutation (Pro-347-Leu, CCG-->CTG) were detected among them. Their clinical findings were extremely different between the two mutations. The former showed type 2 and the latter showed type 1 ADRP. No mutation of codon 23 and 58 was detected in any families so far analyzed in the present study. Clinical findings associated with the mutation in codon 17 and 347 of the rhodopsin gene show an existence of allelic heterogeneity.

Adolescent↗

Multiple births and congenital anomalies in Tokyo Metropolitan Hospitals, 1979-1990.

The rate of multiple births and the incidence of congenital anomalies in Tokyo Metropolitan Hospitals were studied during the period 1979-1990. The number of twins was 968 pairs (8.23 per 1,000 deliveries) and of triplets 18 sets (15.3 per 100,000 deliveries) among 117,672 deliveries including 1,587 stillbirths after 16 weeks gestation. Multiple birth rates increased yearly. Stillbirth rates in twins and triplets were 5.5% and 16.7% respectively, which were both significantly higher than that in singletons (1.3%). The number of congenital anomalies was 42 in 1,936 twins (2.17%), 2 in 54 triplets (3.7%) and 1721 in 116,686 singletons (1.47%). The most common defects in twins were those of the cardiovascular system (0.72% in twins vs 0.52% in singletons) and of the musculoskeletal system (0.72% in twins vs 0.50% in singletons), followed by upper respiratory tract and/or mouth conditions (0.67% in twins vs 0.35% in singletons), all of which had no significant difference in frequency between twins and singletons. Though some anomalies had a significantly higher frequency in twins than in singletons, the concordance rate in the like-sexed twins was very low.

Congenital Abnormalities↗