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Biomedical subjects

M Iijima

Publications and source records attributed to M Iijima.

At least 109 records · Page 6Linked to original sources

[Differential diagnosis of post-transfusion graft-versus-host disease (GVHD) by rapid immunopathologic examination of the skin].

The diagnosis of post-transfusion graft-versus-host disease (GVHD) in early period is critical for the prognosis of the patients. Exanthema and fever are the earliest symptom of the post-transfusion GVHD and usually precede the disturbance of the liver and bone marrow. Snap-frozen, cryostat-sectioned specimens from the lesional and perilesional skin were labeled by monoclonal antibodies against HLA-ABC, HLA- DR, ICAM-1, CD1a and CD8. The reaction was visualized by indirect immunofluorescence. Graft-versus-host reaction (GVHR) was immunopathologically characterized by extensive expression of HLA-DR and ICAM-1 in the epidermal keratinocytes, exocytosis of CD8 positive cytotoxic T-cell and the reduction or disappearance of CD1a expression by epidermal dendritic cells. The other GVHRs such as erythema exudativum multiforme (EEM), fixed drug eruption, toxic epidermal necrolysis (TEN) and lichen planus could not be separated. Our protocol of the immunopathologic examination could be done quickly (within 3 hours) and provides more detailed and useful information for the diagnosis of GVHD in early period compared with conventional histopathology.

Diagnosis, Differential↗

Short-term hemodialysis treatment in dogs and cats with total uretic obstruction.

This study evaluated the single-pass system for the short-term dialysis treatment of dogs and cats with experimental renal failure. The hemodialyzer was equipped with a thin and highly permeable Cuprophan membrane. Four animals (two dogs and two cats) with total uretic obstruction were dialyzed twice in a one-week period. The vascular access by venipuncture of external jugular vein delivered more than 5 ml/min/kg/body weight of blood repeatedly, even for the cats. The evaluation of the effects of the blood flow, dialysate flow and ultrafiltration pressure revealed that the blood flow was the most important factor for effective dialysis. A 300 ml/min dialysate flow provided enough clearance of blood urea nitrogen and creatinine. The ultrafiltration pressure played an important role in ensuring that the fluid removal was constant. Laboratory studies revealed a 50.0% (range 42.0 to 59.3%) reduction of blood urea nitrogen, a 48.7% (range 42.5 to 58.7%) reduction of creatinine, and a 49.8% (range 34.3 to 66.2%) reduction of inorganic phosphate during the dialysis treatment. No dialysis disequilibrium syndrome was shown by the clinical signs. We conclude that this short-term dialysis using a single-pass system for small animals was sufficiently applicable to dogs and cats, and that the optimal duration of the dialysis was 2 hours.

Animals↗

[Efficacy of nasal bi-level positive airway pressure ventilation in a patient with olivo-ponto-cerebellar atrophy suffering from sleep apnea syndrome].

Sleep apnea with neuromuscular disorders has been successfully treated with bi-level positive airway pressure ventilation (BiPAP), which, unlike continuous positive airway pressure ventilation (CPAP), creates pressure difference between expiratory and inspiratory phases. Hence if the respiration of patients stops longer than a pre-set duration, BiPAP can automatically force them to breath through a nasal mask. We report a 60-year-old woman with olivo-ponto-cerebellar atrophy (OPCA), whose mixed-type sleep apnea was difficult to treat with conventional CPAP. We therefore tried BiPAP on this patient at night. Nocturnal CO2 retention was nearly resolved, and unexpectedly daytime PaCO2 was also corrected with marked improvement of daytime somnolence. BiPAP is totally non-invasive, and may be one of the most effective treatments in patients with OPCA suffering from sleep apnea.

Female↗

Mutation in p53 and de-regulation of p53-related gene expression in three human cell lines immortalized with 4-nitroquinoline 1-oxide or 60Co gamma rays.

In vitro models of malignant transformation of human cells may provide considerable insight into the mechanisms of multi-step carcinogenesis. It is well established that normal human cells must be immortalized before they can be malignantly transformed; however, they are stringently destined for aging and are rarely immortalized. The mechanism of cellular aging and immortalization is still unknown. We detected expression of only mutated p53 mRNA by direct sequencing of the reverse-transcribed mRNA in 3 human cell lines immortalized either with 4-nitroquinoline 1-oxide or with 60Co gamma rays. Consequently, only the mutated pS3 protein was expressed in each immortalized cell line. The expression of sdiI/p21 and mdm2, both of which are positively regulated by wild-type p53, was significantly down-regulated in the immortalized cell lines, resulting in over-expression of cdk2 and cdk4. Introduction of the sdiI/p21 gene into these cells was followed by a remarkable decrease in their ability to synthesize DNA. These results indicate that the p53 cascade may play an important role in the immortalization of human cells.

4-Nitroquinoline-1-oxide↗

Plasma endothelin level in the acute stage of Bell palsy.

OBJECTIVE: To determine the plasma endothelin level in the acute stage in patients with Bell palsy (based on the hypothesis that endothelin, which is a potent vasoconstrictor, may play a role in the mechanism of the onset of facial nerve paralysis and in view of the fact that the etiology of Bell palsy is still a maze of unknowns). DESIGN: The study involved 62 patients with the acute stage (tested within 10 days of onset) of Bell palsy (i.e., idiopathic acute peripheral facial paralysis) and an additional 36 healthy persons who served as control subjects. To determine the content of endothelin, 2 ml of plasma samples was collected from each subject. Endothelin-1 was extracted and analyzed by a radioimmunoassay by using anti-endothelin-1 antibody. SETTING: Nihon University Itabashi Hospital, a referral and institutional center in Tokyo, Japan. RESULTS: The patients who were suffering from Bell palsy exhibited a statistically significant (P < .01) increase in the endothelin level compared with that in the 36 normal control subjects. An age-matched comparison (ranges, 20-29 years and 30-39 years) of patients with Bell palsy with normal control subjects revealed a significant difference between the normal group and the group with Bell palsy in the plasma endothelin level for both age groups that were tested (P < .01). The mean value of the endothelin level in patients with Bell palsy was maximal on day 5, and the percentage of patients with abnormally elevated endothelin levels was 100% from days 6 to 9. CONCLUSION: Endothelin, which has potent vasoconstrictive effects, may contribute to the pathogenesis of the microcirculatory impairment that occurs in patients with Bell palsy, mainly by promoting secondary ischemia.

Acute Disease↗

Effects of okadaic acid on cell growth, anchorage-independent growth, and co-cultures of normal (KMS-6), immortalized (KMST-6), and neoplastically transformed (KMST-6T and KMST-6/RAS) human fibroblasts.

The effects of okadaic acid (OA) on normal human (KMS-6), its immortalized (KMST-6) and neoplastically transformed (KMST-6T and KMST-6/RAS) cells were investigated as a model of two stage carcinogenesis. The presence of OA inhibited cell growth of the normal and immortalized cells but not that of the neoplastic KMST-6T cells. In contrast, cell growth of the other neoplastic KMST-6/RAS cells transformed with the Ha-ras oncogene was inhibited by OA. OA enhanced colony formation of KMST-6T cells in soft agar, but it suppressed that of KMST-6/RAS cells. Co-cultures of KMST-6T cells with normal KMS-6 cells showed an increase in focus formation of KMST-6T cells in the presence of OA, whereas focus formation of KMST-6/RAS cells decreased. These results indicate that OA has growth-promoting effects on certain types of transformed human cells.

Carcinogens↗

Fluoride analysis of apatite crystals with a central planar OCP inclusion: concerning the role of F- ions on apatite/OCP/apatite structure formation.

To study the roles of F- ions in the formation of apatite crystals embedding octacalcium phosphate (OCP) lamella in the center of apatite (Ap), a range of the Ap/OCP/Ap lamellar-mixed crystals were synthesized under various concentrations of fluoride ion (F-) from 0. 1-1.0 ppm at pH 6.5 and 37 degrees C. The products were analyzed for the F- incorporation, F- distribution, and the amount of OCP and Ap by chemical analysis, X-ray diffraction (XRD), electron probe microanalysis (EPMA), and nuclear magnetic resonance (NMR) techniques. The F- content and the amount of apatite in the crystalline product increased with an increase in the F- concentration in solution, whereas the amount of OCP and the yield of total product decreased. EPMA indicated that F- ions are distributed in the crystals almost homogeneously. The combined analysis suggested that a low-substituted fluoridated hydroxyapatite (FHAp) grew on a small amount of F--containing OCP or on a surface-reaction layer of OCP, which has accumulated a small amount of F-. The roles of F- ions were hypothesized as the reduction of the growth rate and/or the critical thickness in the a*-axis direction of OCP, the enhancement of hydrolysis of OCP, and the activation of the growth of FHAp, resulting in thinner OCP lamella and thicker apatite lamella in the a*-axis direction with an increase in F- concentration.

Apatites↗

Efficient production of Thermus protease aqualysin I in Escherichia coli: effects of cloned gene structure and two-stage culture.

The DNA sequence encoding Thermus protease aqualysin I was inserted downstream from a bacteriophage T7 promoter in an expression vector. In the T7 expression system, using a strain lacking an F' episome, aqualysin I was produced in soluble form without chemical induction. The deletions of part (30 amino acid residues) or all (105 residues) of the C-terminal pro-sequence from the C terminus significantly affected both cellular growth and the production of the enzyme. Complete deletion adversely affected both. In contrast, the 30-residue deletion markedly improved productivity by approximately four times compared to non-deletion, and shortened the time needed for the activation of a precursor to active enzyme. The concentration of inducer isopropyl beta-D-thiogalactopyrano-side (IPTG) was varied to examine its effects, and it was found that a low concentration of IPTG improved aqualysin I production. To avoid the inhibitory effects of acetic acid accumulation in the culture medium, the use of other carbon sources besides glucose was examined. When cells were cultivated with glycerol, the acetic acid level remained relatively low, and both good cellular growth and a high level of production were attained. The aqualysin I productivity for a fed-batch culture using two carbon sources, glucose and glycerol, reached more than 150 kU/ml enzymatically active aqualysin I.

Bacteriophage T7↗

Detection and comparison of viral antigens in measles and rubella rashes.

Measles and rubella skin lesions were immunocytochemically compared by the avidin-biotin-peroxidase complex method for detecting viral antigens. Cryostat sections of biopsied specimens of the skin were stained with mouse monoclonal antibodies to P protein of measles virus and to E1 protein of rubella virus. The measles virus antigen was concentrated in the corneal layer and the keratinocytes of the epidermis and in the surface part of the dermis in the biopsy secimens taken within 6 days after the onset of rash. On the other hand, the rubella virus antigen was dispersed in all parts of the dermis and the subcutaneous layer but not in the epidermis in the biopsy specimens taken within 2 days after the onset of rash. The differences in the distribution and density of the viral antigen and in the times of its detection suggest distinct patterns of spread of infection with each virus in the skin.

Adolescent↗

Enhancing effect of ultraviolet A on ornithine decarboxylase induction and dermatitis evoked by 12-o-tetradecanoylphorbol-13-acetate and its inhibition by curcumin in mouse skin.

BACKGROUND: Previous studies have demonstrated appreciable tumor induction in mouse skin by daily irradiation with high-power long-wavelength ultraviolet A (UVA). OBJECT: The aim of the present study was to examine the enhancing effects of UVA on changes in mouse skin mediated by the tumor promoter 12-o-tetradecanoylphorbol-13-acetate (TPA) by measurement of ornithine decarboxylase (ODC) activity and morphometric analysis. In addition, we examined the inhibitory effects of curcumin, a component of turmeric, on these changes. METHOD: ODC activity in the epidermis of CD-1 mice was determined by the method of Russell and Snyder. Epidermal and dermal thickness, and the number of dermal infiltrating inflammatory cells were quantified using a computer-assisted image analyzer. RESULTS: A combination of topical TPA application and UVA irradiation produced a greater increment of ODC activity at 4 h than TPA alone (p < 0.05). Histopathologically, TPA plus UVA tended to increase the dermal infiltrating inflammatory cells in contrast to TPA alone. Pretreatment of mice with curcumin significantly abrogated the TPA-induced changes in ODC activity and the dermal infiltrating inflammatory cells as well as the TPA plus UVA-mediated enhancement of these changes. CONCLUSION: Our data indicate that UVA irradiation (18.72 J/cm2) significantly enhances ODC induction at an early stage (4-6 h) after topical application of TPA, and aggravates the dermatitis elicited by TPA. Pretreatment with curcumin significantly inhibits these enhancing effects.

Animals↗

Selective expression of mutated p53 in human cells immortalized with either 4-nitroquinoline 1-oxide or 60Co gamma rays.

Many studies on in vitro transformation of human cells indicate that the cells must be immortalized before they can be neoplastically transformed, indicating that immortalization is a critical step in multistep neoplastic transformation of human cells. We immortalized three human cell lines by repeated treatment with either 60Co gamma rays or a chemical carcinogen, 4-nitroquinoline 1-oxide, and found that all three immortalized cell lines have mutations in the tumor suppressor gene, p53. Direct sequencing of the reverse-transcribed mRNA and immunoprecipitation of p53 protein revealed that mutant p53 is selectively expressed in all the immortalized cell lines, whereas the genomic fragments of the immortalized cells contain wild-type and mutated p53 alleles. Although the mutated p53 is selectively expressed in the immortalized cells, expression of the wild-type p53 was induced by treatment of the cells with a hypomethylating reagent, 5-azacytidine, indicating that the wild-type p53 allele might be inactivated by hypermethylation of DNA. Actually, the entire genomic locus including the promoter region of p53 is hypermethylated in all the immortalized cell lines. Expression and phosphorylation of Rb was normal in these three cell lines. Thus, inactivation of both wild type p53 alleles and selective expression of mutated p53 seem to be key factors in the immortalization of human fibroblasts.

4-Nitroquinoline-1-oxide↗

Cloning of cDNA with possible transcription factor activity at the G1-S phase transition in human fibroblast cell lines.

Normal human fibroblasts have a finite proliferative capacity in vitro. Thus, immortalization of human cells is associated with cellular aging. We have established an immortalization-sensitive cell line from fibroblasts of Wilms' tumor patients which have a partial deletion of chromosome 1 1p. This cell line was easily immortalized by introducing SV4OT. By differential hybridization using both SV4OT-introduced crisis cells and young cells, we cloned a gene that was highly expressed in 1 1p-cells at the time of the crisis and named this gene C-1. Nucleotide sequence analysis of C-1 revealed that it contains a helix-loop-helix domain, indicating that it may be a transcription factor. Expression of the C-1 gene was transiently induced early in the G0-to-S phase transition in two normal human (OUMS-24 and HSF-412) and a non-tumorigenic immortal human (OUMS-24F) fibroblast cell lines, while the other immortal SUSM-1 cells highly expressed the C-1 gene in the middle G1 phase. These results suggest that the C-1 gene product may function as a transcription factor related to the cell cycle.

Amino Acid Sequence↗

[A case of relapsing Guillain-Barré syndrome following Miller Fisher syndrome].

Miller Fisher syndrome (FS) is thought to be a variant of Gullain-Barré syndrome (GBS), both of which rarely relapse. We report a rare case of GBS that followed FS. A 38-year-old woman had ophthalmoplegia, ataxia and areflexia following an upper respiratory tract infection with a diagnosis of FS. Serum anti-GQ1b IgG antibody was found to be increased, but decreased through immunoadsorption as the neurological symptoms of the patient improved. She became completely asymptomatic three months after the onset of FS. Following a common cold two months later, however, she developed weakness of all four limbs and dysesthesia of hands and feet with albuminocytologic dissociation of cerebrospinal fluid, which was consistent with the diagnosis of GBS. Moreover, serum anti-GQ1b IgG antibody had increased again. Anti-GQ1b IgG antibody frequently becomes positive not only in FS but also GBS with ophthalmoplegia. However, the antibody was positive in this particular patient with GBS, even in the absence of ophthalmoplegia. This case suggests that anti-GQ1b IgG antibody might be a common pathogenesis of both FS and GBS.

Adult↗

[A case of atypical progressive supranuclear palsy with degeneration of the fronto-pontine tracts, and without grumose degeneration of the dentate nucleus].

An autopsy case of progressive supranuclear palsy (PSP) with degeneration of the fronto-pontine tracts of the midbrain and pons, and without grumose degeneration of the dentate nucleus is reported. A 72-year-old woman was suffering from dysarthria and gait disturbance. Moderate dementia was noted and gradually worsened. Pyramidal and extrapyramidal signs and cerebellar ataxia were not observed. Eye movements were fully preserved. Brain CT showed cerebellar atrophy. Three years later, she was unable to stand or move, and became mutistic. At the age of 75, she died suddenly. The duration of her illness was approximately 4 years. Clinical diagnosis was LCCA (late cortical cerebellar atrophy). Neuropathological examination revealed gliosis of the deep layers of the cerebral cortex around the precentral gyrus, fronto-pontine tracts degeneration (posterior part of the anterior crus, genu and anterior part of the posterior crus of the internal capsule, cerebral peduncles of the midbrain, pontine base and pyramis of the medulla oblongata). Also, atrophy of the pons and marked degeneration of the superior colliculi and substantia nigra were observed. Neurofibrillary tangles (NFTs) and glial fibrillary tangles (GFTs) were found in the subcortical nuclei. These findings were almost consistent with PSP. However, the following differed from those of previously reported typical PSP cases: firstly, mild gliosis in the reticular formation of the midbrain; secondly, few NFTs in the pontine nuclei and superior colliculi and; thirdly, no grumose degeneration in the dentate nucleus. In addition, clinical symptoms of the present case are not consistent with PSP. Therefore, we concluded this case to be an atypical PSP both clinically and neuropathologically.

Aged↗

[A case of neuroborreliosis with unilateral radiculoneuropathy and elevated serum antibodies for Borrelia garinii and Borrelia afzelii].

A 24-year-old male patient was admitted to our hospital because of dysesthesia and weakness of the right leg. Six weeks before admission he traveled to southern China. A week later he noticed multiple papules with itching on his right leg that were suspected to be insect bites. Four days later numbness of the right leg developed. Then he began to limp because of the leg weakness. Two weeks before admission severe pain in the right leg developed. On admission neurological examination revealed hypesthesia, muscle weakness and atrophy, areflexia, radicular pain and Lasègue sign of the right leg, and patchy hypesthesia of the left leg. The cranial nerves were intact, and meningeal signs were negative. Complete blood counts and serum biochemistry were unremarkable except for eosinophilia and mild elevation of IgE. A test for antinuclear antibody was positive. Cerebrospinal fluid was normal. Nerve conduction study and sural nerve biopsy showed multifocal severe axonopathy. Although antibody for Borrelia burgdorferi sensu stricto was negative, antibodies for B. garinii and for B. afzelii were positive in serum immunoblotting. Neurological symptoms improved after administration of intravenous ceftriaxon following oral doxycycline. In Japan, this is the second case of neuroborreliosis not due to B. burgdorferi sensu stricto. To test antibodies for B.garinii and for B. afzelii is recommended in patients with suspected neuroborreliosis.

Adult↗