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Biomedical subjects

N Adachi

Publications and source records attributed to N Adachi.

At least 55 records · Page 3Linked to original sources

A fatal case of infantile scurvy.

We report a case of infant death due to scurvy, which is very rare in Japan. We initially had little knowledge of the disease and suspected that the bleeding in the body was caused by domestic violence. The case did not fall under the category of the battered child syndrome but the death was caused by ignorance with respect to child care. In addition the parents usually locked the child alone in a room during the day and this is probably a case of neglect.

Autopsy↗

A human homologue of yeast anti-silencing factor has histone chaperone activity.

BACKGROUND: Structural changes in chromatin play essential roles in regulating eukaryotic gene expression. Silencing, potent repression of transcription in Saccharomyces cerevisiae, occurs near telomeres and at the silent mating-type loci, as well as at rDNA loci. This type of repression relates to the condensation of chromatin that occurs in the heterochromatin of multicellular organisms. Anti-silencing is a reaction by which silenced loci are de-repressed. Genetic studies revealed that several factors participate in the anti-silencing reaction. However, actions of factors and molecular mechanisms underlying anti-silencing remain unknown. RESULTS: Here we report the functional activity of a highly evolutionarily conserved human factor termed CIA (CCG1-interacting factor A), whose budding yeast homologue ASF1 has anti-silencing activity. Using yeast two-hybrid screening, we isolated histone H3 as an interacting factor of CIA. We also showed that CIA binds to histones H3/H4 in vitro, and that the interacting region of histone H3 is located in the C-terminal helices. Considering the functional role of CIA as a histone-interacting protein, we found that CIA forms a nucleosome-like structure with DNA and histones. CONCLUSIONS: These results show that human CIA, whose yeast homologue ASF1 is an anti-silencing factor, possesses histone chaperone activity. This leads to a better understanding of the relationship between chromatin structural changes and anti-silencing processes.

Amino Acid Sequence↗

Hyperperfusion in the lateral temporal cortex, the striatum and the thalamus during complex visual hallucinations: single photon emission computed tomography findings in patients with Charles Bonnet syndrome.

We report the findings of single photon emission computed tomography using 123I-IMP and magnetic resonance image studies of five patients with Charles Bonnet syndrome (CBS) while they were having visual hallucinations. All patients developed complex visual hallucinations after suffering from eye disease. The mean age at onset of CBS was 71.6 years. Single photon emission computed tomography studies in all patients disclosed hyperperfusion areas with some asymmetrical appearances in the lateral temporal cortex, striatum and thalamus. These results suggest that when elderly people suffer from eye disease, subsequent excessive cortical compensation in the lateral temporal cortex, striatum and thalamus may precipitate the development of visual hallucinations.

Aged↗

Inter-ictal and post-ictal psychoses in frontal lobe epilepsy: a retrospective comparison with psychoses in temporal lobe epilepsy.

There have been few studies of the psychopathology of patients with frontal lobe epilepsy (FLE). The majority of studies of both inter-ictal and post-ictal psychoses have strongly suggested the influence of temporal lobe disturbance on psychoses. Patients with organic brain damage or schizophrenia, however, sometimes show frontal lobe dysfunction. The purpose of this study was to better understand the effect, if any, of frontal lobe disturbance and seizure on psychopathology. Patients were divided into four groups based on epilepsy type and preceding seizures; 8 with FLE/inter-ictal psychosis, 3 with FLE/post-ictal psychosis, 29 with temporal lobe epilepsy (TLE)/inter-ictal psychosis, and 8 with TLE/post-ictal psychosis. Psychopathologic symptoms were retrospectively reviewed based on case notes, using a modified brief psychiatric rating scale (BPRS). Psychomotor excitement, hostility, suspiciousness, and hallucinatory behaviour were prominent features in all four groups. Six orthogonal factors were derived by factor analysis from the original data based on the 18 BPRS items. FLE patients with inter-ictal psychosis showed marked hebephrenic characteristics (i.e. emotional withdrawal and blunted effect). Our findings suggest that patients with FLE can exhibit various psychiatric symptoms. However, their psychotic symptoms, hebephrenic symptoms in particular, may often be overlooked.

Adult↗

Proprioceptive improvement in knees with anterior cruciate ligament reconstruction.

The correlation between the prospective course of proprioceptive improvement and knee stability after anterior cruciate ligament reconstruction was investigated in 38 patients. Proprioception, on the basis of the patient's capacity to reposition the limb accurately, was evaluated at 3-month intervals for 24 months after hamstring graft anterior cruciate ligament surgery. Knee stability was evaluated concurrently with a KT-2000 knee arthrometer. Thirty patients experienced improvement in postoperative position sense in at least one of the examinations, although eight patients had no improvement at any time. Of the 30 patients who had improvement, 28 maintained improved position sense from 18 months to the final followup. Thirty patients maintained significantly better knee stability for a postoperative period of at least 24 months. These results indicated that a minimum of 18 months after anterior cruciate ligament reconstruction may be needed for complete restoration of the proprioceptive function in knees, although the mean position sense in all patients gradually improved from 9 months. Improvement in postoperative knee stability may have facilitated recovery of proprioception.

Adolescent↗

Antibodies against mycobacterial antigens in the synovial fluid of patients with temporomandibular disorders.

In the absence of active pulmonary disease, mycobacterial infection frequently causes arthritis and can be considered to initiate autoimmune diseases such as rheumatoid arthritis. Temporomandibular disorder (TMD) is a disease in which pain and impaired mandibular movement appear to arise directly from degenerative or inflammatory changes within the temporomandibular joint, but its precise pathogeny has not been elucidated. Here we examined whether mycobacterial infection is related to the pathology of TMD. The antibody levels against mycobacterial antigen in the synovial fluid (SF) of patients with TMD were assessed by enzyme-linked immunosorbent assay (ELISA). Six of 17 TMD patients (35%) were found to possess mycobacterial antigen-specific immunoglobulin (Ig) G but not IgM, while the six healthy volunteers possessed neither. Western-blot analysis was used to isolate the reacted antigen, and the IgG reacted strongly to 44-kDa antigen. The first 14 N-terminal amino acid sequences were determined, and computer analysis revealed that it was homologous to translational elongation factor Tu (EF-Tu) of Mycobacterium tuberculosis, which was a major target antigen for these antibodies. The 44-kDa protein of Mycobacterium bovis BCG (BCG) was identical with the EF-Tu of M. tuberculosis. We cloned the gene encoding the EF-Tu of BCG by using the synthesized oligonucleotide primers by means of polymerase chain-reaction. The gene was expressed in Escherichia coli. The protein was purified, and the antibody levels against this recombinant protein in the SF of TMD patients were assessed by ELISA. Our findings suggest that some cases of TMD are concerned with the synovial IgG against the EF-Tu of M. tuberculosis, and that the existence of the antibody is a clinical indication of TMD.

Adolescent↗

Stereocontrolled reduction of alpha- and beta-keto esters with micro green algae, Chlorella strains.

The stereocontrolled reduction of alpha- and beta-keto esters using micro green algae was accomplished by a combination of the cultivation method and the introduction of an additive. The reduction of ethyl pyruvate and ethyl benzoylformate by the photoautotrophically cultivated Chlorella sorokiniana gave the corresponding alcohol in high e.e. (>99% e.e. (S) and >99% e.e. (R), respectively). In the presence of glucose as an additive, the reduction of ethyl 3-methyl-2-oxobutanoate by the heterotrophically cultivated C. sorokiniana afforded the corresponding (R)-alcohol. On the other hand, the reduction in the presence of ethyl propionate gave the (S)-alcohol. Ethyl 2-methyl-3-oxobutanoate was reduced in the presence of glycerol by the photoautotrophically cultivated C. sorokiniana or the heterotrophically cultivated C. sorokiniana to the corresponding syn-(2R,3S)-hydroxy ester with high diastereo- and enantiomeric excess (e.e.). Some additives altered the stereochemical course in the reduction of alpha- and beta-keto esters.

Chlorella↗

Role of tyrosine 114 of L-methionine gamma-lyase from Pseudomonas putida.

L-Methionine gamma-lyase from Pseudomonas putida has a conserved tyrosine residue (Tyr114) in the active site as in all known sequences of y-family pyridoxal 5'-phosphate dependent enzymes. A mutant form of L-methionine y-lyase in which Tyr114 was replaced by phenylalanine (Y114F) resulted in 910-fold decrease in kcat for alpha,gamma-elimination of L-methionine, while the Km remained the same as the wild type enzyme. The Y114F mutant had the reduced kcat by only 28- and 16-fold for substrates with an electron-withdrawing group at the gamma-position, namely O-acetyl-L-homoserine and L-methionine sulfone, respectively, and also the similar reduction of kcat for alpha,beta-elimination and deamination substrates. The hydrogen exchange reactions of substrate and the spectral changes of the substrate-enzyme complex catalyzed by the mutant enzyme suggested that gamma-elimination process for L-methionine is the rate-limiting determination step in alpha,gamma-elimination overall reaction of the Y114F mutant. These results indicate that Tyr114 of L-methionine gamma-lyase is important in y-elimination of the substrate.

Carbon-Sulfur Lyases↗

Effectiveness of an insole with a lateral wedge for idiopathic osteonecrosis of the knee.

For the purpose of investigating the effect of an insole with a lateral wedge, we studied 30 patients (31 knees) aged from 46 to 78 years with idiopathic osteonecrosis of the knee for at least three years. The 18 knees treated with an insole (group I) were matched by age, gender, obesity index, area of lesion, femorotibial angle, stage, and clinical evaluation with 13 treated conservatively without an insole (group II). The clinical results, as rated by a knee score, improved significantly more in group I than in group II. Radiologically, the necrotic area and ratio decreased in group I, whereas in group II they increased. In advanced cases, with stage 4 or a femorotibial angle of more than 180 degrees, the use of an insole did not improve the clinical or radiological findings. The insole is a valuable method of conservative treatment for the early stages of osteonecrosis of the medial femoral condyle.

Aged↗

[Genetic analysis of a patient with dyskeratosis congenita].

Dyskeratosis congenita (DKC) is a rare inherited disease characterized by reticulated pigmentation of the skin, nail dystrophy and oral leukoplakia. More than 90% of DKC cases are inherited as an X-linked recessive trait. Half the patients develop progressive pancytopenia by the age of 11 yr, and this is the leading cause of death. We experienced a 11-year-old boy with the above symptomatic triad of DKC, complicated by progressive pancytopenia as well as cerebellar ataxia. Genetic analysis of mRNA from his cultured peripheral lymphocytes revealed a missense mutation resulting in substitution of 1,150 C with T in the DKC1 gene. This is identical to the mutation reported by Knight et al. to be prevalent in X-linked cases of DKC (11 out of 21 patients). Existence of the identical mutation in Japan suggests that this mutation has been selected on the basis of not only the DNA structural sequence of dyskerin, but also its biological function. We report the detailed clinical course of this Japanese DKC patient with a mutation in the DKC1 gene, and describe the results of genetic analysis.

Cerebellar Ataxia↗

[The HSV-TK/GCV gene therapy in five cases of recurrent glioblastoma multiforme].

Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy was performed in five cases of recurrent glioblastoma multiforme. The mean age of cases, three males and two females, was 60 +/- 5 years old. All of the tumors were confirmed pathologically as glioblastoma multiforme and recurred after the initial treatments (surgery and irradiation). A total number of 1 x 10(9) vector producer cells (VPCs), which produce retroviral vectors containing the HSV-TK gene, was inoculated into the tumor-bed spaces after removal of the recurrent tumors. From the following 14th day to the 27th day, GCV was transfused 5 mg/kg i.v. twice a day. The effect of the HSV-TK/GCV gene therapy was evaluated by the Karnofsky performance scale and MRI findings sequentially, before the therapy and in the 1st, 2nd, 4th and 6th month after the VPCs inoculation. During the follow-up period of 12 months, two cases died (survival period; 8.4 and 9.9 months), whereas the other three are still alive for over 12 months (1-year survival; 60%). Karnofsky performance scale showed the maximum at the 2nd and 4th month in all cases; the mean performance rating of living cases was 80% and that of dead cases was 70%. MRI revealed progression in none of the cases until the 2nd month. These results obtained in five cases suggest that the HSV-TK/GCV gene therapy may promise a feasible approach against glioblastoma multiforme.

Adult↗

[The biosafety of the HSV-TK/GCV gene therapy in five cases of recurrent glioblastoma multiforme].

Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) therapy was performed in five cases of recurrent glioblastoma multiforme. In the last study, the authors demonstrated response of the HSV-TK/GCV therapy against tumor progression (Adachi N, et al.: No Shinkei Geka). The aim of this study is to estimate the biosafety of in vivo HSV-TK gene transfer and GCV administration in five cases. Six parameters were analyzed sequentially up to the 6th month after the vector producer cells (VPCs) inoculation as follows; i) clinical symptom, ii) vital sign, iii) peripheral blood cell count, iv) blood biochemical analysis, v) serological test, vi) molecular biological test in peripheral leukocytes. In addition, ten systemic organs extracted from the two subjects in whom death occurred were also analyzed biologically. One case suffered from transient deterioration of left hemiparesis on the 34th day, which could be considered a probably-related but not adverse event. Serological tests detected anti-VPC antibody at the 1st month in one case and anti-vector antibody at the 1st and 4th month in another. The other examinations revealed no abnormal findings at all. These data indicate that the HSV-TK/GCV therapy might be a satisfactorily safe approach against glioblastoma multiforme.

Adult↗

[Effects of intravenous nicardipine, prostaglandin E1, nitroglycerin, sodium nitroprusside, and epidural lidocaine on hepatic and renal blood flow during hypotensive anesthesia].

We studied the effects of intravenous nicardipine (NIC), prostaglandin E1 (PGE1), nitroglycerin (TNG), sodium nitroprusside (SNP) and epidural lidocaine (LID) on hepatic and renal blood flow during general anesthesia (nitrous oxide-oxygen-sevoflurane) in 46 female patients undergoing unilateral total hip arthroplasty. During operations, hepatic blood flow, glomerular filtration rate, renal plasma flow, and renal tubular injury were measured by R 15 ICG (15 minutes retention rate of indocyanine green), CCR (creatinine clearance), CPAH (para-aminohippuric acid clearance), and urinary excretion of NAG and beta 2-microglobulin. Significant elevation of R 15 ICG was observed in the hypotensive state in the TNG group and the elevation of R 15 ICG indicates that blood flow to the liver has decreased during hypotensive anesthesia. Urine volume in the PGE1 group was larger than that in the TNG, SNP or LID group. CCR in the PGE1 group was larger than that in the NIC, TNG or SNP groups. CPAH in the PGE1 group was larger than that in the SNP or LID group. The value of urine NAG in the TNG group was larger than that in the NIC or PGE1 group. The value of urine beta 2-microglobulin in the NIC group was larger than that in the PGE1 or SNP group. The results of urine volume, CCR, CPAH, urine NAG, and urine beta 2-microglobulin indicate that blood flow to the kidneys was greater in the PGE1 group as compared to other groups. This study indicates that prostaglandin E1 is the best hypotensive drug for hepatic and renal blood flow during hypotensive anesthesia.

Aged↗

Characterization of the 5'-flanking region of the gene encoding bovine adenylate kinase isozyme 3.

We have characterized the 5'-flanking region of the gene encoding bovine adenylate kinase isozyme 3 (AK3). S1 mapping analysis revealed multiple transcription start points in the bovine AK3 gene. The promoter activities were tested in HeLa cells using the chloramphenicol acetyltransferase (CAT) gene as a reporter. The CAT analysis showed that the basal promoter sequence was located within the region from -189 to +228. In the presence of short DNA fragments of the 5'-flanking region as competitors, the transcriptional activity of the bovine AK3 promoter changed depending on the fragments used. The results identified the basal regulatory elements in the proximal promoter region.

Adenylate Kinase↗

Cloning and functional characterization of the promoter region of the gene encoding human adenylate kinase isozyme 3.

The 5'-flanking region of the gene encoding human adenylate kinase isozyme 3 was isolated and compared with that of the bovine AK3 gene previously characterized. Four conserved DNA sequences (elements-a, -b, -c, and -d) were found in both the regions. The promoter activities were analyzed in HeLa cells using promoter-CAT reporter constructs. The proximal promoter region (-217 to +261), which contains three of four conserved elements, gave a maximum promoter activity. In a series of electrophoretic mobility-shift assays, DNA fragments and double-stranded oligodeoxyribonucleotides containing sequences of the four conserved elements interacted with nuclear extracts of HeLa cells. The a-element contained the W-element, while the d-element, which had a high G + C content, was a novel regulatory cis-element distinct from the GC box. The b- and c-elements were homologous to each other and had a motif resembling downstream promoter element. Mutations of the c- and d-elements significantly reduced the promoter activity, indicating that the c- and d-elements in the AK3 promoter are crucial. These elements may also be involved in the transcriptional regulation of other TATA-less genes.

Adenylate Kinase↗

Metyrapone alleviates ischemic neuronal damage in the gerbil hippocampus.

Transient forebrain ischemia was induced in gerbils, and the effect of a pre-ischemic treatment with metyrapone (100 mg/kg) on delayed neuronal death in hippocampal CA1 neurons was evaluated. The effect of metyrapone on the ischemic release of amino acids in the CA1 region was also examined by microdialysis. Hippocampal slices were used for the evaluation of the hypoxia-induced intracellular Ca2+ increase by microfluorometry. The metyrapone treatment morphologically improved the damage provoked by 3 min of ischemia, although it did not alleviate the damage by 5 min. Ischemia for 3 min produced a 306% increase in the glutamate concentration in perfusates, and metyrapone suppressed the peak value to 42% of that in the control group. The extent of the increase in fluorescence intensity by intracellular Ca2+ was lower by 16% in slices from metyrapone-treated animals than in controls 600 s after induction of hypoxia. The removal of Ca2+ from the perfusion medium suppressed the hypoxic Ca2+ increase, and the increase was further reduced in slices pretreated with metyrapone. The increase in the level of endogenous glucocorticoids, which occurs in cerebral ischemia, may aggravate ischemic neuronal damage.

Amino Acids↗