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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 307 records · Page 17Linked to original sources

Rescue of the hairless phenotype in nude mice by transgenic insertion of the wild-type Hfh11 genomic locus.

Mice and rats homozygous for mutations at the nude (nu) locus exhibit the pleiotropic phenotypes of hairlessness and athymia. A recent positional cloning study identified, as a nude gene, a novel fork head transcription factor, Hfh11 (also called whn), that is expressed in skin and thymus, and is mutated in nude rodents. To obtain the direct biological proof that this gene is responsible for nude phenotype, we microinjected a cosmid clone containing the wild-type Hfh11 genomic locus into fertilized nude eggs. Two independent founder lines of transgenic mice were generated that corrected the hairless phenotype, but not the thymic defect. This partial rescue demonstrates that Hfh11 is the gene responsible for the hairless defect in the nude mouse. Taken together with previous genetic studies, this complementation result indicates that Hfh11 is indeed the nude gene and the Hfh11 locus is likely to be subject to complicated regulation.

Animals↗

Effects of transgenic mixed-haplotype MHC class II molecules A alpha d A beta z on autoimmune disease in New Zealand mice.

The MHC haplotype heterozygosity (H-2d/H-2z) acts as one major predisposing genetic element for autoimmune disease resembling systemic lupus erythematosus (SLE) in the F1 hybrid of NZB (H-2d) and NZW (H-2z) mice. To determine a possible role of mixed-haplotype A molecules, we introduced a transgene A beta z into H-2d/H-2d homozygous (NZB x NZW.H-2d)F1 mice, in which, compared with the original H-2d/H-2z heterozygotes, the incidence and titer of IgG anti-DNA antibodies, serum levels of nephritogenic retroviral gp70/anti-gp70 immune complexes (ICs) and the associated incidence of IC-type lupus nephritis were reduced. Evidence for the formation of mixed-haplotype A alpha d A beta z molecules in the transgenic mice was obtained by A beta z molecule expression on the cell surface of splenic B cells and macrophages, thymic epithelial cells and mature B cells in the bone marrow. A alpha d A beta z-restricted T cell clones showed good proliferative responses to spleen cells from the transgenic mice, to an extent much larger than seen in cells from the original (NZB x NZW)F1 mice, suggesting that the expression of functional A alpha d A beta z molecules on cells in transgenic mice is considerably high. Compared with findings in transgene-negative littermates and the original (NZB x NZW)F1 mice, the A beta z transgene to a greater extent promoted serum levels of IgM anti-double-stranded (ds) DNA antibodies and IgM anti-gp70/gp70 ICs in the transgenic mice. None the less, the production of IgG anti-dsDNA antibodies and IgG anti-gp70/gp70 ICs as well as the development of renal disease was markedly suppressed. Possible mechanisms of such effects of the transgene are discussed.

Animals↗

Subarachnoid hemorrhage caused by previously diagnosed, previously unruptured intracranial aneurysms: a retrospective analysis of 25 cases.

OBJECTIVE: We conducted a retrospective analysis of the clinical features of angiographically diagnosed unruptured intracranial aneurysms that were treated conservatively and subsequently ruptured. METHODS: At our center, we reviewed the angiographic and clinical features of 25 patients with subarachnoid hemorrhage caused by previously unruptured aneurysms. RESULTS: Eleven of the 25 patients died, including 1 patient who had undergone surgery. Ten patients had single aneurysms, and 15 had multiple aneurysms. Thus, multiple aneurysms were significantly more common than single aneurysms. The associated disease was cerebral infarction in 12 patients, previous subarachnoid hemorrhage from different aneurysm in 8 patients, intracerebral hemorrhage in 3 patients, and other conditions in 2 patients. Aneurysm size was able to be evaluated after rupture in 20 patients. At initial diagnosis, 16 aneurysms measured less than 5 mm in maximum diameter; the size of most aneurysms had increased by the time of rupture, although the aneurysm size remained less than 5 mm in five patients. No relationship was found between aneurysm rupture and patient age, aneurysm size at initial diagnosis, or time interval from diagnosis to rupture. The incidence of aneurysm rupture in patients with cerebrovascular disease, although higher than the incidence in patients with other underlying disease, was not significant. CONCLUSION: We conclude that small unruptured intracranial aneurysms measuring less than 5 mm are susceptible to the risk of rupture, so that radical treatment or careful follow-up examination should be considered.

Adult↗

Strangulated prolapsed ureterocele: a solid vulval mass in a woman.

We report a rare case of prolapsed ureterocele in an adult female, which had been identified as a small finger-tip sized orthotopic ureterocele 12 years earlier and recently presented a hard neoplastic mass due to strangulation at the urethra and long-standing inflammation.

Adult↗

Effects of a rhubarb (Rhei rhizoma) solution and its fractions on the formation of calcium phosphate precipitates.

Inhibitory effects of a rhubarb (Rhei rhizoma) solution and its fractions on the formation of calcium phosphate precipitates were studied. The rhubarb solution inhibited both the amorphous calcium phosphate (ACP) formation and the rate of hydroxyapatite (HAP) transformation, and extended the induction time. When the solution was fractionated using membrane filters, a filtrate with the molecular weight between 3 and 10 kDa (with 2/3 recovery of polyphenols) was found to be responsible for both the ACP formation and the extension of the induction time. Another filtrate with the molecular weight below 3 kDa (with 1/3 recovery of polyphenols) may be responsible for the inhibition of both the ACP formation and the rate of HAP transformation, and the extension of the induction time. When the extract of rhubarb was fractionated using a Sephadex LH-20 column chromatography, fraction IV greatly inhibited the formation of calcium phosphate precipitates, while fractions I, II and III slightly inhibited that reaction. Our finding suggests that fraction IV may contain useful substance(s) for the prevention of oral calcium phosphate precipitation (calculus formation). However, strong calcium chelating properties would limit the concentration that could be safely employed.

Analysis of Variance↗

Water transport in collecting ducts of Japanese quail.

Previously, we reported that the countercurrent urine concentration mechanism in birds appears to operate by recycling of a single solute (NaCl), in which the thick ascending limb of looped nephrons provides an energy source. To determine the importance of the medullary collecting duct (MCD) in the countercurrent multiplier system, we examined in isolated and perfused MCDs from Japanese quail, Coturnix coturnix, the osmotic and/or diffusional water permeability and whether arginine vasotocin (AVT) regulates water permeability. We noted that dark cells that possess electron-dense cytoplasm and numerous mitochondria and light mucus-secreting cells exist in the cortical collecting duct (CD), whereas only mucus-secreting cells are present in the MCDs. The volume flux (Jv) in the MCDs from intact birds and that from the water-deprived birds were nearly zero; after exposure to a hyperosmotic bath and AVT (2 x 10(-5) M), the Jv was significantly higher in water-deprived birds. The diffusional water permeability (Pdw) was moderately high in MCDs bathed in an isosmotic bath in which the Pdw was increased slightly by AVT (10(-5) M, bath) and more markedly (10(-5) M) by forskolin (Fsk), whereas 1,9-dideoxy Fsk (an inactive analogue) showed no effect. Furthermore, the basal adenosine 3',5'-cyclic monophosphate (cAMP) levels were higher in the medulla than in the cortex and were stimulated only slightly by AVT (10(-5) M) and markedly by Fsk (10(-4) M) in both the cortex and medulla. These results in the C. coturnix CD indicate the following. 1) Two types of cells are present; whereas dark cells resemble mammalian intercalated cells morphologically, it is not certain whether mucus-secreting cells are equivalent to principal cells. 2) AVT increases Pdw via a cAMP mechanism; the relatively high basal Pdw and minor effect of AVT on Jv and Pdw suggest, however, that diffusional water movement across the MCD may occur without significant direct control by AVT.

Animals↗

In vivo evaluation of antiplatelet agents in gerbil model of carotid artery thrombosis.

BACKGROUND AND PURPOSE: Antiplatelet agents are widely used for the prevention of ischemic stroke. However, their effects on thrombus formation have rarely been evaluated in experimental animals in vivo. We introduce methods for evaluating antithrombotic action in gerbils and the effects of several antiplatelet agents on thrombus formation. METHODS: In gerbils 8 to 10 weeks of age, we tightly compressed the unilateral common carotid artery for 2 minutes using the device prepared for this purpose to damage the endothelium. Thrombus formation in the damaged artery was observed directly through the microscope for 30 minutes. In six animals, the damaged artery was examined immediately after the experiments by electron microscopy. We studied the effects of antiplatelets by injecting the drugs intravenously 10 minutes before endothelial damage. RESULTS: In control studies, 70% to 90% of animals developed thrombi after arterial compression. The electron microscopic examination displayed endothelial damage in association with platelet thrombus at the damaged site. Administration of 2 mg/kg aspirin, 3 and 10 mg/kg ticlopidine, and 0.3 and 1.0 mg/kg ibudilast, a novel prostacyclin accelerator, decreased the frequency of thrombus formation significantly, whereas 20 mg/kg aspirin and 20 mg/kg dipyridamole failed to decrease thrombus formation. CONCLUSIONS: This model is considered useful for evaluating the antithrombotic effects of drugs because of its feasibility and high reproducibility. The present results support the view that a lower dose of aspirin may prevent cerebral vascular accidents as efficiently as a higher dose of aspirin.

Animals↗

Polyethylene glycol-modified pokeweed mitogen (PWM) as a potential non-immunogenic stimulator of lymphokine-activated killer cells.

Among the various plant lectins, pokeweed mitoge (PWM) is most effective in enhancing the cytotoxicity of human lymphokine-activated killer (LAK) cells. However, the use of PWM in adoptive immunotherapy has been limited due to the strong immune response against the protein of plant origin. Amino groups in PWM was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chioro-s-triazine, activated PEG2, to form PEG-PWM conjugates. Its immunoreactivity towards anti-PWM antibodies was reduced by increasing the degree of modification of amino groups in PWM. PEG-PWM, in which 54% of amino groups in PWM was modified with activated PEG2, had a nearly complete reduction of immunoreactivity. Intraperitoneal administration of PEG-PWM to mice did not produce substantial levels of anti-PWM antibodies. Nevertheless, PEG-PWM retained the ability to induce the maximum levels of cytotoxicity of human LAK cells in vitro.

Animals↗

Tolerogenic capacity of poly(ethylene glycol) (PEG)--modified ovalbumins in relation to their immunoreactivity towards anti-ovalbumin antibody.

Ovalbumin (OVA) was chemically modified with poly(ethylene glycol) (PEG) derivatives: activated PEG2, 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine and activated PM13, copolymer of poly(oxyethylene) allyl methyl diether and maleic anhydride. Pretreatment of BALB/c mice with PEG2- or PM13-OVA suppressed the production of both IgG- and IgE-class anti-OVA antibodies induced by subsequent immunizations with unmodified OVA. PEG2-OVA had higher potency to suppress OVA-specific immune response than PM13-OVA. Although extensive modification (62%) of amino groups in the OVA molecule with activated PEG2 was required to diminish most of its immunoreactivity towards anti-OVA antibodies, only a low degree of modification (27%) was sufficient to induce tolerogenicity to OVA. Thus, the loss of immunoreactivity of PEG2-OVA was not prerequisite for its tolerogenic capacity. Moreover, the use of completely denatured PEG2-OVA immunogen lead to the loss of its ability to induce immune tolerance to native OVA. These observations are discussed in relation to the regulatory mechanism of immune response.

Animals↗

Multimodal evoked potentials in Alzheimer's disease and Binswanger's disease.

Somatosensory evoked potentials (SEPs), brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs), and auditory event-related potentials (ERPs) were studied in 15 patients with Alzheimer's disease (AD), eight patients with Binswanger's disease (BD), and 15 normal subjects. Patients with BD showed significant prolongation of the interpeak latency between N13 and N20 (N13-N20) and N20-P40 of SEPs as compared with the normal controls, whereas patients with AD only demonstrated significant prolongation of N20-P40. The interpeak latency between waves I and V of BAEPs in patients with both AD and BD was significantly longer than that of controls. There were no significant differences in P100 latency of VEPs among these three groups. Both groups with dementia showed significant prolongation of N200 and P300 latencies of ERPs compared with normal controls. In addition, patients with AD showed significant prolongation of P200 latency. We conclude that these two dementing diseases have different electrophysiologic features that may be related to their underlying pathogenetic mechanisms. Furthermore, the measurement of multimodal evoked potentials may be helpful in the differential diagnosis of AD and BD.

Aged↗

Abnormal Q wave, ST-segment elevation, T-wave inversion, and widespread focal myocytolysis associated with subarachnoid hemorrhage.

A 74-year-old Japanese woman with subarachnoid hemorrhage was admitted to our hospital. During her hospitalization, serial electrocardiograms showed the combination of abnormal Q waves, ST-segment elevation, and T-wave inversion, which strongly suggested acute myocardial infarction. However, postmortem examination revealed widespread focal myocytolysis of the myocardium which was unrelated to vascular distribution.

Aged↗

Potent allelochemical falcalindiol from Glehnia littoralis F. Schm.

A potent allelochemical in Glehnia littoralis F. Schm. was investigated. Falcalindiol was isolated from G. littoralis; 859.9 mg/kg of fresh root and 62.5 mg/kg of fresh aerial parts. Its structure was elucidated by spectroscopic methods, and the antimicrobial activities of falcalindiol were evaluated by the paper disk method against several microorganisms. The plant growth inhibition of falcalindiol was also investigated.

Antifungal Agents↗

Method of obtaining mutants defective in immunoglobulin mu transcription factors.

A method of obtaining mutants defective in the regulatory function of Ig mu gene expression was developed. Such mutants are useful for discovering the functions of transcription factors and isolating their genes, especially those of DNA-unbinding factors. Cells expressing Ig mu and Eco-GPT simultaneously under control of each mu enhancer were prepared as follows: myeloma X63Ag8.653 cells were transfected with pSV-V mu Me delta CH1 encoding a mu gene modified for cell surface mu expression without light chains, selected by neomycin resistance, transfected with Eco-GPT gene connected to the mu enhancer, and selected with mycophenolic acid in a medium containing xanthine. The mu(m)/Eco-GPT cells were mutated with ethane methyl sulfonate (EMS), and selected with toxin-conjugated anti-mu antibody, and then with 6-thioguanine. The mu(M)-/Eco-GPT- mutants obtained were fused with X63Ag8.653 cells. Fusion caused the mutant to recover mu(M) expression, suggesting that some trans-acting transcription factor other than the mu-encoding gene itself was probably mutated.

3T3 Cells↗

Antimicrobial benzopyrans from the receptacle of sunflower.

The antimicrobial substances in sunflower (Helianthus annuus) were investigated. Two antifungal benzopyran derivatives, 6-acetyl-2,2-dimethyl-1,2-benzopyran (1) and 6-acetyl-7-hydroxy-2,2-dimethyl-1,2-benzopyran (2), were isolated from the ethanol extract of sunflower receptacles. The antimicrobial activities of isolated compounds 1 and 2 and their related compounds (precocenes) were evaluated by the paper disk method, using Pyricularia oryzae as the test fungus.

Anti-Infective Agents↗

Correlation of histology and dynamic MR imaging (MRI) of intracranial meningiomas with a 0.5 tesla MR system.

In 33 histologically verified intracranial meningiomas, the correlation between the pattern of the time-signal intensity curve (TIC) from dynamic MR imaging and the histological subtypes were studied. The patterns of TIC for meningiomas were classified into two types: type A with a steep rise to a peak within a short time; type B with a slow rise to a peak followed by a plateau. Of the 16 meningiomas of the meningothelial types, 14 (87%) were type A on the TIC. On the contrary, all of the fibroblastic meningiomas were type B. The others had an almost equal distribution between the two types. These results indicate that dynamic MRI does not always have a predictive value for the histological subtype of an intracranial meningioma or for the histological architecture of the meningothelial or fibroblastic components.

Brain Neoplasms↗

Reassessment of second look operation for epithelial ovarian cancer.

We retrospectively reviewed 91 patients with epithelial ovarian cancer who underwent second-look operation (SLO). SLO identified a persistent tumor in 18 (19.8%) of 91 patients. Of these 18 patients, 13 (72.2%) showed disease progression after SLO. Patients with a positive SLO in which the identification of the persistent disease was only possible by washing cytological study showed better prognosis than patients with macroscopic lesions. Of the 73 patients with a negative SLO, 12 (16.4%) developed recurrence after cessation of treatment. These 12 patients were from stage 1c to 3 with Grade 2 and 3 tumors. The SLO findings were more sensitive than the serum tumor marker in identifying persistent disease. Also we reviewed 55 patients having no SLO. Among 57 cases in stage 1 and 2 with Grade 1 tumor, there were no cases of recurrence, regardless of whether they had SLO or not. Our results suggest that SLO findings correlate well with the patient's prognosis. SLO may not be needed for patients in stage 1 and 2 with Grade 1 tumor. Patients with advanced stage disease with Grade 2 and 3 tumors have high-risk for recurrence after negative SLO. While SLO is still of benefit in management of ovarian cancer, refinements are needed to determine its indication and scheduling.

Adult↗

[A case of ACTH-producing thymic carcinoid tumor with Cushing syndrome].

ACTH-producing thymic carcinoid tumor with Cushing syndrome in a 41-year-old male was reported. Plasma ACTH and cortisol was high, and chest X-ray film and CT scan revealed a tumor mass in the anterior mediastinum. Extended thymectomy with pretracheal lymph node dissection was performed. The microscopic findings revealed that the mass was carcinoid tumor with metastasis of anterior mediastinal lymph node. ACTH and cortisol were restored to normal range 1 week after operation. Unfortunately, he admitted seven months later because of high level of ACTH and right supraclavicular lymph nodes swelling. He underwent right neck dissection. Pathological examination proved metastatic carcinoid tumors in the dissected nodes. It is important to perform supraclavicular lymph node dissection together with extended thymectomy for thymic carcinoid tumor.

Adrenocorticotropic Hormone↗