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Biomedical subjects

N Fukuhara

Publications and source records attributed to N Fukuhara.

At least 55 records · Page 3Linked to original sources

Uniform tissue distribution of tRNA(Lys) mutation in mitochondrial DNA in MERRF patients.

We documented the presence of a point mutation in the tRNA(Lys) gene of mitochondrial DNA (mtDNA) in various postmortem tissues from two patients with myoclonus epilepsy associated with ragged-red fibers (MERRF). The percentages of the mutant mtDNA were similar (93 to 99%) in both clinically affected and unaffected tissues, suggesting that preferential clinical involvement of certain tissues in MERRF is based not only on the variation of distribution of the mutant mtDNA, but also on other factors such as differences in the threshold in various CNS regions and organs.

Adult↗

[Familial juvenile parkinsonism with dementia and autonomic failure--a case report].

A case of familial juvenile parkinsonism with dementia, orthostatic hypotension, neurogenic bladder and constipation was reported. He had been in a good health until the age of 28 when a finger tremor occurred on effort to hold hands in a definite position, and disturbances in gait and speech were noted. These symptoms were relieved by levodopa treatment followed by dyskinesia and motor fluctuations. Three years later, he complained of faintness, constipation and urinary frequency. The neurological examination revealed mentally sound male with masked face, tremor and rigidity in his extremities, and short step gait with lateropulsion. Urodynamic study showed uninhibited bladder. In the following years, orthostatic hypotension, dysuria and urinary retention developed gradually. He became mentally loose and was unable to take medicines appropriately. When in the Nishiojiya Byoin National Sanatorium, he tried to snake out the hospital many times. His parents and a brother suffered from Parkinson's disease and juvenile parkinsonism, respectively, suggesting an autosomal dominant inheritance. On admission to our hospital, he was apathetic. He had masked face, bilateral postural tremor, frozen gait and dyskinesia in the right lower extremity. Little bradykinesia or rigidity was noted. His muscle tone and deep tendon reflexes were decreased but neither muscular wasting, weakness, ataxia nor sensory disturbance was observed. Laboratory data including ceruloplasmin, copper, dopamine-beta-hydroxylase and lysosomal enzyme activities were normal except for mild anemia. A cranial CT scan revealed mild cortical atrophy in the frontal and temporal lobes, but nerve conduction study and cortical evoked potentials showed no abnormality. While in the hospital, his mental functions deteriorated to the state of dementia and orthostatic hypotension became apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Marinesco-Sjögren syndrome--report of two patients in a family with muscle CT study].

Two patients with Marinesco-Sjögren syndrome in a family were characterized by autosomal recessive inheritance, congenital cataract, cerebellar ataxia, mental retardation, short stature and variable skeletal abnormalities. Muscle biopsy specimens showed replacement of muscle fibers by fat and fibrous tissue, a marked variation of fiber size and a rimmed vacuole formation. Nerve biopsy specimens showed a reduced number of myelinated nerve fibers in the sural nerves. Muscle CT revealed atrophy of the quadriceps femoris, semitendinosus, gastrocnemius and soleus muscles. Accordingly, extensor muscles in the thighs were more preferentially involved than flexor muscles in the legs.

Adult↗

Effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on hemopoiesis and survival rate following allogeneic bone marrow transplantation in mice.

The effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the survival rate and hemopoiesis after allogeneic bone marrow transplantation (BMT) were examined. Specific pathogen-free (SPF) C3H mice and germ-free C3H mice, kept in an isolator for germ-free animals, received 10 Gy of total body irradiation (TBI) and all the mice died by day 9 after TBI. These survival rates were improved by BMT. In the case of SPF mice, survival rates at 14 and 100 days were 33% (12/36), 17% (6/36) and in the case of germ-free mice they were 79% (15/19), 74% (14/19) respectively. When SPF mice received rhG-CSF (30 micrograms/kg/day) subcutaneously for 14 consecutive days following BMT, their survival rates were improved to 79% (30/38), 79% (30/38) respectively. The survival rate of rhG-CSF treated SPF mice were equal to that of germ-free mice. When the effect of rhG-CSF treatment on hemopoiesis of SPF mice after allogeneic BMT was examined various hematopoietic progenitor cells in the bone marrow and spleen increased until day 10 after, BMT, while only neutrophils increased in the peripheral blood during the period. No adverse effects of rhG-CSF were observed throughout the study period. It was suggested that in SPF mice treated with rhG-CSF after BMT, the neutrophil recovered in counts quickly and increased neutrophil prevented endogenous infections and improved the survival rate without apparent complications.

Animals↗

C33 antigen recognized by monoclonal antibodies inhibitory to human T cell leukemia virus type 1-induced syncytium formation is a member of a new family of transmembrane proteins including CD9, CD37, CD53, and CD63.

C33 Ag was originally identified by mAb inhibitory to syncytium formation induced by human T cell leukemia virus type 1. The Ag was shown to be a highly heterogeneous glycoprotein consisting of a 28-kDa protein and N-linked oligosaccharides ranging from 10 to 50 kDa. In the present study, cDNA clones were isolated from a human T cell cDNA expression library in Escherichia coli by using mAb C33. The identity of cDNA was verified by immunostaining and immunoprecipitation of transfected NIH3T3 cells with mAb. The cDNA contained an open reading frame of a 267-amino acid sequence which was a type III integral membrane protein of 29.6 kDa with four putative transmembrane domains and three putative N-glycosylation sites. The C33 gene was found to belong to a newly defined family of genes for membrane proteins, such as CD9, CD37, CD53, CD63, and TAPA-1, and was identical to R2, a cDNA recently isolated because of its strong up-regulation after T cell activation. Availability of mAb for C33 Ag enabled us to define its distribution in human leukocytes. C33 Ag was expressed in CD4+ T cells, CD19+ B cells, CD14+ monocytes, and CD16+ granulocytes. Its expression was low in CD8+ T cells and mostly negative in CD16+ NK cells. PHA stimulation enhanced the expression of C33 Ag in CD4+ T cells by about 5-fold and in CD8+ T cells by about 20-fold. PHA stimulation also induced the dramatic size changes in the N-linked sugars previously shown to accompany human T cell leukemia virus type 1-induced transformation of CD4+ T cells.

Amino Acid Sequence↗

Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived cell lines.

Sixteen human T-cell lines were studied for the expression of a cell-adhesion molecule ICAM-1 and its counter-receptor LFA-1. The cell lines included 3 human T-cell-leukemia-virus-type-I (HTLV-1)-negative cell lines derived from acute lymphoblastic leukemia (ALL) and 13 HTLV-1-positive cell lines, 7 of them established from cord- or peripheral-blood T cells by in vitro transformation with HTLV-1, 2 derived from HTLV-1 carriers, and 4 derived from patients with adult T-cell leukemia (ATL). In sharp contrast to a basal level of ICAM-1 in 3 HTLV-1-negative ALL cell lines, strong induction of ICAM-1 was seen in all HTLV-1-positive T-cell lines except for MT-1, one of the 4 ATL cell lines used in the present study. On the other hand, the expression of LFA-1 (CD11a and CD18) was more or less similar among the cell lines with and without HTLV-1. Interestingly, however, 3 out of 4 ATL cell lines (TL-Om1, H582, HUT102) revealed striking depression of LFA-1 expression. Several lines of evidence strongly argued against direct involvement of the viral transactivator p40tax or some autocrine cytokines in the induction of ICAM-1 in HTLV-1-positive T-cell lines. It was also found that ICAM-1 and LFA-1 were involved in syncytium formation induced in the co-culture of HTLV-1-positive and HTLV-1-negative human T-cell lines. Implications of constitutive expression of ICAM-1 for certain clinical manifestations of ATL and of depression of either ICAM-1 or LFA-1 during progression of ATL are discussed.

Animals↗

Thymic carcinoma associated with pinealoma and terminating with peroxidase-negative acute myeloid leukemia.

Thymoma is associated with a wide variety of syndromes. However, an association with peroxidase-negative acute myeloid leukemia and pinealoma, although feasible due to the marked influence of this tumor on the lymphoid system, has not been described previously. A patient with thymic carcinoma and pinealoma who developed peroxidase-negative acute myeloid leukemia as a late event is presented in this report.

Adult↗

Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy.

To analyze the genetic abnormality in a Japanese patient with adult-type metachromatic leukodystrophy (MLD), we first elucidated the genomic organization of the human arylsulfatase A (ASA) gene and then compared the nucleotide sequences of exons and splice junctions of the mutant ASA gene to those of a normal control. We have identified a new mutation, a G-to-A transition in exon 2, which results in amino acid substitution of Asp for 99Gly. In a transient expression study, COS cells transfected with the mutant cDNA carrying 99Gly----Asp did not show an increase of ASA activity, which confirms that the mutation is a cause of adult-type MLD.

Adult↗

[A case of spinal osteomyelitis detected by MRI].

A 75-year-old man was admitted because of chest pain and gait disturbance. He noticed pain in the left anterior chest regardless of exercise 3 months prior to admission. Two months later, the chest became smart with motion, followed by sensory disturbance of the lower extremities. On admission, he was anemic. His lower extremities showed exaggerated deep tendon reflexes with positive Babinski signs and an impairment of superficial and deep sense with sensory ataxia. Muscular weakness, muscular wasting, or urinary disturbance was not found. An X-ray film of his thoracic spine disclosed compression fracture and protein content of his cerebrospinal fluid was increased. Magnetic resonance image (MRI) of the ill spines revealed fusion of the bodies of the fifth and sixth thoracic vertebrae with a low signal intensity on T1-weighted images and a partially high signal intensity on T2-weighted images. The intervertebral disc was destroyed. Although histological or bacteriological confirmation was absent, characteristic MRI findings were compatible with spinal osteomyelitis. After antibacterial chemotherapy, his clinical symptoms improved and he came to be able to walk again.

Aged↗

MERRF: a clinicopathological study. Relationships between myoclonus epilepsies and mitochondrial myopathies.

Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a degenerative disease involving dentate nuclei of the cerebellum, globus pallidus, the posterior columns and spinocerebellar tracts of the spinal cord, and skeletal muscles. Abnormal mitochondria were observed in the cells of the cerebellar cortex and of the dentate nuclei. The main symptoms of this disease include cerebellar ataxia and myoclonus in addition to muscular wasting. Patients with MELAS occasionally have myoclonus, but they never have myoclonus as their initial symptoms. Most of the patients with both clinical features of MERRF and MELAS were regarded as belonging to the category of MELAS.

Brain↗

Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on allogeneic bone marrow transplantation in mice.

The effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the survival rate and hemopoiesis after allogeneic bone marrow transplantation (BMT) was examined. Specific pathogen-free (SPF) C3H mice, kept in a flexible isolator for germ-free animals, received 10Gy of total body irradiation (TBI), and an allogeneic BMT 24 hours later. The 14 day survival rate was 33%. When the mice were received rhG-CSF (30 micrograms/kg/day subcutaneously) daily for 2 weeks following BMT, the 14 day survival rate rose to 79%. The effect of rhG-CSF treatment on hemopoiesis in BMT mice resulted in higher neutrophil counts in the peripheral blood by day 14 post-BMT. Administration of rhG-CSF after allogeneic BMT benefited survival rate and neutrophil recovery without any apparent complications.

Animals↗

Enzymatic production of L-tryptophan from DL-serine and indole by a coupled reaction of tryptophan synthase and amino acid racemase.

Enzymatic production of L-tryptophan from DL-serine and indole by a coupled reaction of tryptophan synthase and amino acid racemase was studied. The tryptophan synthase (EC 4.2.1.20) of Escherichia coli catalyzed beta-substitution reaction of L-serine into L-tryptophan and the amino acid racemase (EC 5.1.1.10) of Pseudomonas putida catalyzed the racemization of D-serine simultaneously in one reactor. Under optimal conditions established for L-tryptophan production, a large-scale production of L-tryptophan was carried out in a 200-liter reactor using intact cells of E. coli and P. putida. After 24 h of incubation with intermittent indole feeding, 110 g liter-1 of L-tryptophan was formed in molar yields of 91 and 100% for added DL-serine and indole, respectively. Continuous production of L-tryptophan was also carried out using immobilized cells of E. coli and P. putida. The maximum concentration of L-tryptophan formed was 5.2 g liter-1 (99% molar yield for indole), and the concentration decreased to 4.2 g liter-1 after continuous operation for 20 days.

Amino Acid Isomerases↗

Evidence of duplication and deletion in super short segment 11 of rabbit rotavirus Alabama strain.

The complete nucleotide sequence of genome segment 11, of the Alabama strain of rabbit rotavirus, was determined by sequencing dsRNA and mRNA using the dideoxy chain termination method. This strain has a "super short" RNA pattern. Its segment 11 is 1036 bp in length, 369 nucleotides longer than that reported for rotavirus strains with a "long" electropherotype. Sequence analysis indicated that the shift in genome segment 11 of Alabama strain to a "super short" RNA pattern results from a simple duplication followed by a simple deletion. The positive strand of segment 11 contains two non-overlapping open reading frames of 594 bases (198 amino acids) starting at base 22 and a second of 273 bases (91 amino acids) starting at base 712. The polypeptide from the latter reading frame is the result of a partial duplication of the nucleotide sequence encoding amino acids 110 to 198 of gene 11.

Amino Acid Sequence↗

VP4 protein of porcine rotavirus strain OSU expressed by a baculovirus recombinant induces neutralizing antibodies.

The complete VP4 gene of porcine rotavirus strain OSU has been inserted into a baculovirus expression vector under the control of the polyhedrin promoter. The VP4 outer capsid protein, which is a major neutralization antigen in rotavirus, was expressed in high yield in Spodoptera frugiperda cells. Reactivity with polyclonal and monoclonal antibodies suggested that neutralizing epitopes were functionally unaltered on the expressed VP4. The VP4 produced in this system also induced antibodies in guinea pigs which inhibited hemagglutination of OSU and neutralized its infectivity to high titer. The available evidence suggests that the VP4 expressed in insect cells maintained its antigenic configuration and may prove useful in elucidation of (1) the extent of VP4 polymorphism among human and animal rotaviruses and (2) the distribution of VP4 among these viruses.

Animals↗

Nucleotide sequence of gene segment 1 of a porcine rotavirus strain.

The nucleotide sequence of gene segment 1, which encodes VP1 of porcine rotavirus strain Gottfried, was determined. VP1 is associated with single-shelled rotavirus particles and has been linked to virus transcriptase and replicase enzymatic activities. Gene segment 1 is 3302 nucleotides long with a single open reading frame capable of coding for a protein of 1088 amino acids (calculated mol wt 125 kDa). The predicted amino acid sequence revealed that VP1 is basic, with a net positive charge of 18 at pH 7.0. It shares five consensus sequences with several well-characterized RNA-dependent RNA polymerases. Gottfried VP1 also shares consensus sequences with certain GTP-binding proteins; however, we could not detect any GTP-binding activity in VP1. Our preliminary experiments suggest that VP3, another polypeptide located in single-shelled rotavirus particles, possesses GTP-binding activity. These results suggest that mRNA synthesis and capping enzyme activities are related to VP1 and VP3, respectively.

Amino Acid Sequence↗

Experimental chloroquine myopathy: morphological and biochemical studies.

Morphological and biochemical studies were performed on the soleus muscles of rats receiving a daily intraperitoneal injection of 50 mg chloroquine chloride (CQ) per kilogram of body weight. Light microscopy showed mild to moderate variations in fiber size, numerous dense membranous bodies and vacuoles. The vacuoles were ringed by material that was intensely basophilic in hematoxylin-eosin preparations, resembling rimmed vacuoles in the muscle fibers of distal myopathy. Segmental degradation or necrosis was often observed. The 3H-leucine uptake by myofibrillar and soluble sarcoplasmic fractions in CQ-treated muscles was the same as in the controls. The significant increases in lysosomal (cathepsin B & L, B and D) proteases and thiol protease inhibitor occurred in the earlier stages of CQ-induced myopathy, when hardly any autophagic vacuoles or dense bodies were observable by light microscopy. We conclude that the over-development of autophagic vacuoles and the significant increases in lysosomal protease activity in muscle tissues may be important in the development of the focal degradation and necrosis of CQ-treated muscles.

Animals↗

A Creutzfeldt-Jakob disease agent (Echigo-1 strain) recovered from brain tissue showing the 'panencephalopathic type' disease.

We used histologic evidence of degenerative changes in both the gray and white matter of the brain to diagnose a patient as having the panencephalopathic type of Creutzfeldt-Jakob disease (CJD). This type of CJD is relatively common in Japan, but not in North America or Europe. We recovered a transmissible pathogen (Echigo-1 strain) from an autopsy specimen of the patient's brain and passed it serially in Hartley guinea pigs. After a long latent period, it caused degenerative changes, mainly in the thalamic area of the guinea pig brain. On the 4th passage, a substrain emerged with a short latent period. When cross-transmitted to Golden Syrian hamsters, this substrain induced severe degeneration in both the thalamus and cerebral cortex. We compare our results with those for other experimental CJDs produced by other types of this disease.

Adult↗

[Malignant tumors of the ethmoid sinuses--treatment and prognosis].

From 1981 to 1987, 15 cases of malignant tumors of the ethmoid sinuses were treated by radiotherapy, either with or without chemotherapy. Pathologically, these cases consisted of 7 squamous cells ca., 2 transitional cells ca., 3 anaplastic ca., 1 adenoid cystic ca., 1 malignant teratoma, and 1 rhabdomyosarcoma. The three-year survival in all cases 37%. Of eight patients determined to be in stages I and II, 4 patients had a localized relapse locally within 10 months after treatment and a distant metastases developed at a later time in 4 patients, whereas in 7 patients in stage III and IV, a distant metastases developed in 5 patients immediately after radiotherapy.

Adult↗