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Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 577 records · Page 32Linked to original sources

Lateral situated sinus pericranii. Case report.

We hereby report a case of a laterally situated sinus pericranii, which is rare. According to the articles regarding this kind of lesion, carotid angiograms revealed no pathological findings, and venograms taken with direct injection of contrast medium into the mass were useful. It should be stressed that the lesion could be demonstrated in the late phase of carotid angiograms, and digital subtraction angiography was especially useful for diagnosis. The literature is also reviewed.

Angiography, Digital Subtraction↗

A new microcatheter system for endovascular treatment of cerebral arteriovenous malformations.

A new microcatheter system was used for diagnostic and therapeutic purposes in three cases of arteriovenous malformation. This microcatheter is used with a steerable guidewire and provides high selectivity of the target vessels and greater catheter maneuverability than does balloon catheters. Tissue adhesive was safely injected for the therapeutic embolization in two of the cases. With this system, however, the utmost attention is necessary to prevent reflux of the tissue adhesive and to avoid lacerating the feeding vessels with the guidewire. This microcatheter system was found to be very useful for diagnostic and therapeutic procedures in endovascular treatment of cerebral arteriovenous malformations.

Adult↗

Identification of an intracellular protein that specifically interacts with photoaffinity-labeled oncogenic p21 protein.

An oncogenic 21-kDa (p21) protein (Harvey RAS protein with Val-12) has been covalently modified with a functional reagent that contains a photoactivatable aromatic azide group. This modified p21 protein has been introduced quantitatively into NIH 3T3 cells using an erythrocyte-mediated fusion technique. The introduced p21 protein was capable of inducing enhanced pinocytosis and DNA synthesis in the recipient cells. To identify the putative intracellular protein(s) that specifically interact with the modified p21 protein, the cells were pulsed with [35S]methionine at selected times after fusion and then UV-irradiated to activate the azide group. The resulting nitrene covalently binds to amino acid residues in adjacent proteins, thus linking the p21 protein to these proteins. The cells were then lysed, and the lysate was immunoprecipitated with the anti-p21 monoclonal antibody Y13-259. The immunoprecipitate was analyzed by SDS/PAGE to identify p21-protein complexes. By using this technique, we found that three protein complexes of 51, 64, and 82 kDa were labeled specifically and reproducibly. The most prominent band is the 64-kDa protein complex that shows a time-dependent rise and fall, peaking within a 5-hr period after introduction of the p21 protein into the cells. These studies provide evidence that in vitro the p21 protein becomes associated with a protein whose mass is about 43 kDa. We suggest that the formation of this complex may play a role in mediating early events involved with cell transformation induced by RAS oncogenes.

Affinity Labels↗

Isolation and characterization of s-myc, a member of the rat myc gene family.

A 9-kilobase-pair clone containing a myc-related gene that we have designated s-myc was isolated from a rat genomic library. The entire nucleotide sequence of the cloned DNA was determined, showing that the s-myc gene contains an open reading frame consisting of 1287 base pairs without introns. In vitro transcription-translation analysis of s-myc indicated that this gene produces a protein of approximately 50 kDa. The amino acid sequence predicted from the DNA sequence showed that the s-Myc protein is closely related to the murine N-Myc protein but lacks an acidic amino acid-rich sequence commonly present in the Myc-family proteins. Studies on transfection of s-myc into rat RT4-AC tumor cells revealed that the gene produces a polyadenylylated transcript of approximately 4.7 kilobases and that its high-level expression suppresses the tumor-igenicity of RT4-AC tumor cells in nude mice.

Amino Acid Sequence↗

Host-Specific Effects of Toxin from the Rough Lemon Pathotype of Alternaria alternata on Mitochondria.

Host-specific toxin from the rough lemon (Citrus jambhiri Lush) pathotype of Alternaria alternata (ACR toxin) was tested for effects on mitochondria isolated from several citrus species. The toxin caused uncoupling of oxidative phosphorylation and changes in membrane potential in mitochondria from leaves of the susceptible host (rough lemon); the effects differed from those of carbonylcyanide-m-chlorophenylhydrazone, a typical protonophore. ACR toxin also inhibited malate oxidation, apparently because of lack of NAD(+) in the matrix. In contrast, the toxin had no effect on mitochondria from citrus species (Dancy tangerine and Emperor mandarin [Citrus reticulata Blanco], and grapefruit [Citrus paradisi Macf.]) that are not hosts of the fungus. The effects of the toxin on mitochondria from rough lemon are similar to the effects of a host-specific toxin from Helminthosporium maydis (HMT) on mitochondria from T-cytoplasm maize. Both ACR and HMT toxins are highly selective for the respective host plants. HMT toxin and methomyl had no effect (toxic or protective) on the activity of ACR toxin against mitochondria from rough lemon.

Journal Article↗

Evaluation of production and characterization of monoclonal antibodies to human IgG of four subclasses.

Human IgG of four subclasses, semi-purified from pooled human serum by a series of DEAE ion exchange and protein A affinity chromatographies, were used as immunogens and initial screening antigens to produce subclass-specific and -restricted monoclonal antibodies (McAbs). These McAbs were bound to CNBr-activated Sepharose 4B and utilized in immunoaffinity chromatography to prepare four polyclonal human IgG subclasses of satisfactory purities, which were then used as final screening antigens. Subclass-specific McAbs thus chosen were further evaluated for subclass- and especially allotype-specificity using a panel of monoclonal IgG myeloma proteins with representative Gm markers for each subclass in micro enzyme-linked immunosorbent assay (ELISA). A total of 10 clones of subclass-specific McAbs (one for anti-IgG1, three anti-IgG2, two anti-IgG3, four anti-IgG4) were established. Among them, IgG2-specific clones of HG2-30F and HG2-56F, IgG3-specific HG3-7C and HG3-32C, and IgG4-specific HG4-53G McAbs were superior to the corresponding specificity standard McAbs chosen by the Human Immunoglobulins Subcommittee of the WHO/International Union of Immunological Societies (IUIS) in 1985. As allotype-specific McAbs, HG1-1E for G1m(az) and HG3-3B for G3m(b) were obtained. In micro ELISA of this study as well as all protocols of the previous WHO/IUIS collaborative study, antigens (myeloma IgG subclasses) were immobilized or fixed to a solid phase, resulting in possible variations in their epitope expressions. We developed a new assay system, micro radioimmunoassay (RIA), in which reactivities of McAbs against free IgG subclasses in solution can be evaluated. HG2-30F, having extremely high reactivities to coated IgG2 in micro ELISA, remarkably reduced its reactivities to free IgG2 in solution in micro RIA. Two other clones also showed some different reactivities in micro RIA and micro ELISA. We believe that this micro RIA is valuable for evaluation of McAbs reactivities against native human IgG subclasses in solution.

Animals↗

Frequency and types of point mutation at the 12th codon of the c-Ki-ras gene found in pancreatic cancers from Japanese patients.

Point mutations at the 12th codon of c-Ki-ras in pancreatic cancer from Japanese patients were examined using the polymerase chain reaction, followed by cloning of the amplified gene fragments in pTZ phagemid and nucleotide sequence determination. The frequency of the point mutations found in the tumors was quite high (75%). The mutation most frequently detected was a G---A transition at the second position of codon 12 (GGT---GAT), but other types of mutations such as GGT----GTT and GGT----CGT were also found. In one case, silent mutation of GGT to GGC was detected in addition to the frequent mutation of GGT to GAT. These observations suggest that the 12th codon of pancreatic c-Ki-ras is highly mutatable.

Adenocarcinoma↗

Inhibitory effect of chitin heparinoids on the lung metastasis of B16-BL6 melanoma.

Structure-function studies for the antimetastatic activity of chemically modified chitin heparinoids composed of N-acetyl glucosamine units were performed in an experimental lung metastasis model. 6-O-Sulfated chitin (S-chitin) significantly inhibited the lung tumor colonization in proportion to the degree of sulfation. However, 6-O- and N-sulfated but partially N-deacetylated chitin (S-chitosan), and 6-O-carboxymethylated chitin (CM-chitin) had no effect. 6-O-Sulfated CM-chitin (SCM-chitin), which exhibited fairly low levels of anticoagulant activity, was also more effective than intact heparin. Furthermore, SCM-chitin with a high degree of sulfation (SCM-chitin III) caused a marked decrease of the number of lung tumor colonies in the spontaneous lung metastasis model. These results strongly suggest that 6-O-sulfate and N-acetyl groups in the glucosamine unit were required for the anti-metastatic effect of chitin heparinoids as well as heparin, and SCM-chitin III may be of therapeutic benefit for the prevention of tumor metastasis.

Animals↗

Transformation of NIH3T3 cells with synthetic c-Ha-ras genes.

Synthetic human c-Ha-ras genes in which amino acid codons were altered to those which are frequently used in highly expressed Escherichia coli genes were ligated to the 3'-end of Rous sarcoma virus long terminal repeat. When NIH3T3 cells were transfected with the plasmids having those genes with valine at codon 12, leucine at codon 61 or arginine at codon 61, transformants were efficiently produced. These results indicated that the synthetic c-Ha-ras genes are expressed in a mammalian system even though their codon usage is altered to correspond with that of E. coli. This expression vector system should be useful for studies on the structure-function relationships of c-Ha-ras, since the synthetic gene can be easily modified to have multiple base alterations, and can also be used simultaneously for the production of large amounts of p21 in E. coli for biochemical and biophysical studies.

Avian Sarcoma Viruses↗

Inositol trisphosphate (IP3) receptors and epileptic seizure.

The effects of anticonvulsants and Ca2+ channel antagonists on the inositol trisphosphate (IP3) binding and IP3-induced Ca2+ release were examined in brain membrane fractions. Anticonvulsant (PHT and valproate) and Ca2+ channel antagonists (verapamil, diltiazem, flunarizine, nicardipine and cinnarizine), examined did not significantly inhibit the IP3-receptor binding. The Kd and Bmax values of the IP3 binding did not change significantly in the various brain regions of the amygdala-kindled rats, killed 10 days after the last seizure, compared to those of controls. On the other hand, PHT, PB and carbamazepine inhibited the Ca2+ releasing activity of IP3 in the cerebellar membrane fractions by approximately 20% at therapeutic concentrations.

Amygdala↗

Three-dimensional ultrastructural changes of acellular glomerular basement membrane in various types of human glomerulonephritis.

Using a cellular digestion technique combined with scanning electron microscopy, we examined the three-dimensional ultrastructural changes of the glomerular basement membrane (GBM) in various types of human glomerulonephritis (GN). Gaps of the GBM, which were not found by routine transmission electron microscopy, were observed in a patient with IgA nephropathy manifesting microscopic hematuria. The dense material of the GBM in dense deposit disease (DDD) was not affected by this cellular digestion technique, while the deposits in other immune complex diseases were almost removed. Thus the dense material in DDD differs in composition from the immune complex deposits in other GN. In membranous GN and lupus nephritis, the morphological changes of the urinary surface of the GBM varied from pinhole to craters and reticula, according to the severity of the disease stage. This technique is useful for examining ultrastructural changes of the GBM in various human GN.

Basement Membrane↗

Spontaneous and secretagogue-induced changes in cytosolic free Ca concentration measured by microfluorimetry with fura-2 on single bovine adrenal chromaffin cells.

The concentration of cytosolic Ca2+ ([Ca]in) was examined in single bovine adrenal chromaffin cells by monitoring fura-2 fluorescence with microspectrofluorimetry. To see the correlation between [Ca]in and secretion, we also measured the rates of catecholamine (CA) secretion and 45Ca efflux from populations of cells. [Ca]in was constant in the majority of single cells, but the small oscillatory changes in [Ca]in were observed in a population of cells. These spontaneous Ca oscillations, when observed, disappeared either after removal of extracellular Ca2+ or by addition of D-600 or Mn2+, but still persisted in the presence of tetrodotoxin (TTX) or after removal of extracellular Na+. In the silent cells the Ca fluctuations were often induced by Bay-K-8644. The characteristics of Bay-K-8644-induced Ca fluctuations were very similar to those of spontaneous ones. Low concentrations of nicotine (1 microM), acetylcholine (ACh; 1-2 microM), or KCl (12.5 mM) often induced oscillations riding on a steady rise in [Ca]in. These changes were rapidly suppressed by removal of either extracellular Ca2+ or Na+, or by addition of either D-600 (methoxyverapamil) or TTX. A low concentration of ACh (1 microM) or KCl (12.5 mM) also increased the rate of 45Ca efflux, but substantial secretion was not detected. On the other hand, the sustained rise in [Ca]in was evoked by 0.1 mM ACh, 20 microM nicotine, or 30 mM KCl, which was suppressed by removal of extracellular Ca2+, but was little affected by TTX. A sustained increase in 45Ca efflux upon exposure to ACh was observed, possibly reflecting the sustained rise in [Ca]in. ACh also stimulated CA secretion, which was faded out during the prolonged application. Veratridine, a Na channel activator, caused repetitive sequence of Ca transients followed by a sustained rise in [Ca]in. These results, together with the previous electrophysiological findings, suggest that: (1) the spontaneous Ca fluctuations are closely associated with occurrence of spontaneous Ca2+ and Na+ action potentials; (2) the rise in [Ca]in induced by a low concentration of nicotinic agonists of KCl is mediated by Na+ action potentials as well as gradual membrane depolarizations; (3) the oscillatory changes subsequent to a rise in [Ca]in reflect fluctuations in Ca2+ influx through the Ca2+ channels; (4) the critical [Ca]in needs to be attained before the CA secretion takes place.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Clivus and apicopetroclivus meningiomas--report of 24 cases.

The authors describe the clinical and radiological features, surgical procedures, and outcome of 18 cases of clivus meningiomas and six of apicopetroclivus meningiomas. There were 17 females and seven males, ranging in age from 26 to 69 years, with a mean age of 47 years. All except one showed cranial nerve deficits. Computed tomography accurately demonstrated tumor size and location. Cerebral angiography showed characteristic displacement of the basilar artery and its tributaries, with blood supply to the tumor largely via the meningohypophyseal trunk. Magnetic resonance imaging was excellent in delineating the relationship of the tumor to the brainstem and major vasculature. The surgical approaches used were transpetrosal-transtentorial (n = 9), combined transpetrosal-transtentorial-transzygomatic preauricular transpetrosal (n = 9), suboccipital-subtemporal (n = 2), suboccipital (n = 1), frontotemporal (first stage operation) followed by suboccipital (second stage operation) (n = 1), suboccipital-transpetrosal (n = 1), and orbitozygomatic-infratemporal preauricular transpetrosal (n = 1). Seventeen tumors were totally removed and seven subtotally. The operative mortality was 8% (two patients). Twenty patients developed new cranial nerve deficits within 1 month of surgery. The average follow-up period was 5 years, and the outcome was good or excellent in 12 cases. Transpetrosal approaches proved relatively safe and effective for radical tumor removal and, in two cases, permitted preservation of useful hearing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Magnetic resonance imaging of intracavernous pathology.

To evaluate the usefulness of magnetic resonance (MR) imaging of intracavernous pathology, T1-weighted spin echo images of four vascular lesions and 10 neoplastic lesions with surgically confirmed cavernous sinus (CS) invasion were reviewed retrospectively. In one case of traumatic carotid-cavernous fistula (CCF) and one of dural arteriovenous malformation (AVM), the internal carotid artery (ICA) and rapid shunted flow were depicted as signal voids, and the relationship between the ICA and shunted flow was clearly shown. Normal venous flow appeared as a low-intensity area and was observed even in the presence of the CCF and dural AVM. In two cases of thrombosed aneurysms, the thrombosis was clearly demonstrated, along with patent arterial flow in one case; in the other case, however, it was impossible to differentiate patent arterial flow from calcification. The intensity of all neoplastic lesions was similar to that of the cerebral cortex. The relationship between the ICA and the tumors was clearly demonstrated. The visual pathways were also plainly shown unless they were involved, or markedly compressed, by tumor. CS invasion was strongly associated with four findings: 1) encasement of the ICA by the tumor; 2) marked displacement of the ICA; 3) absence of low intensity, which reflects normal venous flow, in the CS; and 4) extension of extrasellar tumors to the medial wall or of intrasellar tumors to the lateral wall. MR imaging was judged promising in the evaluation of intracavernous pathology.

Adenoma↗

[A variant of persistent trigeminal artery associated with a petroclival meningioma. Case report].

A 52-year-old female was admitted with a chief complaint of progressive gait disturbance over the previous 16 months. Neurological examination revealed impairment of the Vth and VIIIth cranial nerve functions and cerebellar ataxia on the left side. Computed tomography showed a petroclival tumor of 5 x 5 x 4.5 cm. Left carotid angiography disclosed tumor staining fed by branches of the tentorial artery. Also, an anomalous artery branched from the internal carotid artery between the C5 and C6 portions and supplied the region usually fed by the anterior inferior cerebellar artery. The tumor was removed via a combination of transpetrosal-transtentorial and transzygomatic approaches. The anomalous artery was confirmed to course along the Vth cranial nerve, replacing the anterior inferior cerebellar artery. Twenty-seven cases of variant persistent trigeminal artery have been reported in the world literature, including this case. The embryological and clinical features of this anomaly are discussed.

Carotid Arteries↗

Trigeminal neurinomas: operative approach in eight cases.

The authors report eight cases of trigeminal neurinoma managed over the past 13 years with radical resection at a single-stage operation. Three patients were male and five were female, ranging in age from 25 to 56 years (mean 41.5 years). One had von Recklinghausen's disease. The tumors were located mainly within the middle fossa in two cases and within the posterior fossa in two, and extended both supra-and infratentorially in four cases. Facial pain and hearing disturbance were the main symptoms, with various other symptoms such as focal seizures, hemiparesis, gait disturbance, increased intracranial pressure, and visual disturbance also being noted. All patients underwent radical tumor resection with either a transpetrosal transtentorial or orbitozygomatic infratemporal surgical approach; the approach depended on the topography of the tumor. Total removal was performed in all cases. Only one patient, treated early in the series, required a second operation to remove the tumor completely. In another case the tumor recurred 5 years after the operation. There has been no operative mortality, but injury or permanent damage to the trigeminal branches was inevitable in many cases. The surgical results were excellent in three patients and good in five.

Adult↗

A combined orbitozygomatic infratemporal epidural and subdural approach for lesions involving the entire cavernous sinus.

The authors present four cases of vascular lesions and 10 cases of tumors involving the cavernous sinus. They were operated on via a combined orbitozygomatic infratemporal epidural and subdural approach. With this approach, multisided exposure of the cavernous sinus can be achieved via the shortest possible distance with minimal retraction of the neural structures in and around the cavernous sinus. In one patient the carotid artery had been occluded previously, but in the other 13 patients it was preserved. There was no mortality, and all patients except one returned to work within 6 months after surgery.

Brain Neoplasms↗