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Biomedical subjects

N Nishikawa

Publications and source records attributed to N Nishikawa.

At least 55 records · Page 3Linked to original sources
PubMed1996

Liposomal Arg-Gly-Asp analogs effectively inhibit metastatic B16 melanoma colonization in murine lungs.

Analogs of a synthetic peptide having the L-arginine-L-glycine-L-aspartic acid (RGD) sequence have been found to decrease metastatic colonization. To enhance the metastasis-suppressing efficacy of these analogs, we sought to stabilize these analogs and to prolong their circulation time by incorporating them into a liposomal formulation. Various structures of RGD analogs grafted to hydrophobic groups were synthesized and then incorporated into liposomes. Liposomes composed of distearoylphosphatidylcholine, cholesterol, dipalmitoylphosphatidylglycerol and appropriate RGD analogs were injected intravenously along with B16BL6 murine melanoma cells into mice. Liposomal RGD (0.6 mumol of the analog equivalent to ca. 200 micrograms RGD peptides) inhibited lung colonization up to 76%. This dose is an order of magnitude lower than that for comparable inhibition reported for free RGD. Multi-dose administration of liposomal RGD (0.15 mumol of the analog) also inhibited the spontaneous lung metastasis of cells from a primary tumor site of B16BL6 cells subcutaneously implanted into the footpad of mice. Taken together, our data indicate that liposomal RGD may serve as a useful anti-metastatic agent.

Amino Acid Sequence↗
PubMed1996

Inhibition of tumor invasion and metastasis by peptidic mimetics of Arg-Gly Asp (RGD) derived from the cell recognition site of fibronectin.

The partially modified retro- and retro-inverso peptides of the Arg-Gly Asp (RGD) sequence of fibronectin, in which the direction of the Arg residue is reversed and/or the chirality of the amino acid residue is inverted, i.e., mainly R(rev)-COCH2CO-D and DR(rev)-COCH2CO-D, have been synthesized to examine their antimetastatic effects in murine lung or liver metastasis models, as well as their inhibitory effect on tumor cell invasion in vitro. R(rev)-COCH2CO-D inhibited lung metastasis produced by i.v. coinjection with B16-BL6 melanoma more potently than did other pseudo-peptides or the original RGDS peptide. Rrev-COCH2CO-D also showed antimetastatic effects against several different types of tumor cells such as B16-BL6 melanoma, Colon26 M3.1 carcinoma, and L5178Y-ML25 lymphoma cells, in a dose-dependent manner, and multiple administrations had a therapeutic effect on spontaneous lung metastasis. The invasion of melanoma cells into reconstituted basement membrane Matrigel in vitro was suppressed by R(rev)-COCH2CO-D more effectively than by RGDS. These results indicate that the antimetastatic effect by R(rev)-COCH2CO-D was in part due to the inhibition of tumor invasion. The RGDS peptide decomposed when incubated with fresh plasma in vitro, whereas R(rev)-COCH2CO-D was not affected by this treatment. Thus, the reversion of the Arg-Gly linkage in the RGD sequence resulted in protease resistance leading to the retardation of the clearance of the peptide in vivo, and consequently augmented its antimetastatic and antiinvasive properties. Designed peptide analogues may provide various advantages and be useful for preventing cancer metastasis.

Animals↗
PubMed1995

Construction of a human genomic library of clones containing poly(dG-dA).poly(dT-dC) tracts by Mg(2+)-dependent triplex affinity capture. DNA polymorphism associated with the tracts.

Microsatellite DNA is a useful tool for detecting DNA polymorphisms among species or individuals, especially those among closely related individuals. We constructed a library of clones that contained poly(dG-dA).poly(dT-dC) tracts from human genomic DNA by Mg(2+)-dependent triplex DNA formation. Examination of triplex DNA formation in the presence of various metal ions Mg2+, Mn2+, or Zn2+ revealed that the procedure worked best in the presence of Mg2+. Affinity enrichment was performed with AluI-digested chromosomal DNA mixed with biotinylated (dG-dA)17 in the presence of Mg2+. A library constructed after three cycles of affinity enrichment showed that over 80% of the clones contained at least one poly(dG-dA).poly(dT-dC) tract. Most of them contained a perfect (dG-dA)n repeat 30-84 base pairs in length, while some contained variants such as (dC-dT)10-(dC)-(dC-dT)9. Using the clones from the library as a probe, we detected DNA polymorphisms associated with the repeat length of the tracts in the Japanese population. We also detected a microsatellite instability among the tracts in a cancer tissue sample.

Base Sequence↗
PubMed1995

Effect of acoustic overstimulation on the hydropic ear.

The effect of acoustic overstimulation (2 kHz pure tone) on the compound action potential (CAP) threshold was investigated at frequencies ranging from 2 to 16 kHz using albino guinea pigs, both normal and with experimentally induced endolymphatic hydrops. The hydropic ears were less susceptible to acoustic overstimulation than the normal ears. As the CAP threshold was raised, the frequency exhibiting the greatest CAP threshold shift increased in both animal groups. The tendency was more noticeable in the hydropic ears than in the normal ears. These results are discussed from the aspect of cochlear hydrodynamics.

Action Potentials↗
PubMed1995

Parasite nematode infections in Awassi adult sheep: distribution through Syrian farm flocks.

A survey was conducted on 1,474 adult sheep from 73 flocks distributed in the 13 provinces of Syria. Faecal egg and larval nematode outputs were studied. Marshallagia and Nematodirus infections were higher in the driest areas; infections by other nematodes, Dictyocaulus and small lungworms (Cystocaulus and Muellerius) were higher in the more rainy areas. A long transhumance limited small lungworm infections, which were higher in flocks using wet night shelters.

Analysis of Variance↗
PubMed1994

Enrichment of human DNAs that flank poly(dA).poly(dT) tracts by triplex DNA formation.

Human DNA fragments which contain poly(dA).poly(dT) tracts and their immediate flanking regions were enriched by means of triplex DNA formation. Human DNA fragments were mixed with biotinylated (dT)34 in the presence of Mg2+ and the triplex DNA [(dT)34.poly(dA).poly(dT)] was adsorbed onto streptavidin-coated magnetic beads and the DNA fragments which formed triplexes were eluted from the beads with a buffer containing EDTA. A control experiment using a plasmid with a poly(dA).poly(dT) tract indicated that DNA fragments with the tract could be enriched over 60-fold after one cycle of the treatment. After PCR amplification, the sample was subjected to the next cycle of the affinity enrichment. After four cycles, we obtained a human genomic DNA library of clones with inserts ranging from 500 to 1000 bp among which 86% had at least one poly(dA).poly(dT) tract. No less than 60% of the clones were close or distant members of the Alu family. Sequence determination of 25 clones revealed that the length of the poly(dA).poly(dT) tracts was 14 to 37 (average 28) bp and that they were located close to either end of the fragments. While 15 clones were identified as Alu family homologues and one as a human L1 family member, nine clones were of unknown origin. None of these nine clones were a highly repeated sequence nor a part of transcriptionally active regions.

Bacterial Proteins↗
PubMed1994

Chronic ocular ischemia associated with the Eisenmenger's syndrome.

We studied the ocular findings of two adult patients with the Eisenmenger's syndrome who had atrial septal defects that were diagnosed before the age of 10 years but not operated on and pulmonary hypertension. Both eyes of these patients showed microaneurysms, multiple small blot hemorrhages, or capillary dilation in the temporal peripheral fundus. Multiple microaneurysms and retinal collaterals were confirmed by fluorescein angiography. One of the patients developed bilateral rubeosis iridis with slow progression. These retinal lesions and the rubeosis iridis are probably related to chronic ocular ischemia caused by chronic systemic hypoxia.

Adult↗
PubMed1994

Effects of superficial temporal to middle cerebral artery bypass for ischaemic retinopathy due to internal carotid artery occlusion/stenosis.

The effects of superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis for retinopathy is discussed and analysed in 19 cases of occlusive internal carotid artery disease (4 with stenosis and 15 with occlusion) according to Doppler sonography (DS) of the retinal artery, optic fundi and visual impairment symptoms. Preoperatively, all cases showed abnormal DS findings (stenosis patterns in 2 cases and the reversed flow patterns in 17 cases). All cases showed ischaemic changes of the optic fundi. Visual symptoms were amaurosis fugax in 2 cases, decline of visual acuity in 13 cases and both in 4 cases. At one month after the bypass, two stenosis pattern cases showed almost normal DS findings. In the 17 reversed flow pattern cases, 13 cases had a marked improvement of the reversed flow. The ischaemic changes of the optic fundi were ameliorated in 12 cases. In the follow-up stage, greater improvement in the DS findings and the optic fundi could be seen in all cases. In all cases worsening of the visual acuity was prevented, and in some cases the decreased visual acuity improved. The above improvements correlated well with the improvement of DS findings. It is believed that this procedure should be performed to prevent and improve ischaemic retinopathy caused by ischaemic ICA lesion.

Aged↗
PubMed1993

Inhibition of tumor metastasis by Arg-Gly-Asp-Ser (RGDS) peptide conjugated with sulfated chitin derivative, SCM-chitin-RGDS.

We have synthesized a new compound in which Arg-Gly-Asp-Ser (RGDS) was conjugated with 6-O-sulfated and 6-O-carboxymethyl-chitin (SCM-chitin), i.e. SCM-chitin-RGDS, and tested the inhibitory effect on lung and liver metastases of three different types of tumors in mice. SCM-chitin-RGDS was more effective for the inhibition of liver metastasis of L5178Y-ML25 lymphoma and lung metastases of colon 26 M3.1 cells than SCM-chitin, RGDS or their mixture. GRGDS peptide, however, required a higher dose (3000 micrograms) to obtain a sufficiently antimetastatic effect. Intermittent i.v. administration of SCM-chitin-RGDS before or after the i.v. inoculation of L5178Y-ML25 cells caused significant inhibition of liver metastasis as compared with the multiple administration of RGDS, SCM-chitin or untreated control. Co-injection of lymphoma cells with SCM-chitin-RGDS or multiple treatment of SCM-chitin-RGDS after tumor inoculation showed significantly enhanced survival rate. SCM-chitin-RGDS also showed the spontaneous lung metastasis produced by intrafootpad injection of B16-BL6 melanoma cells by the multiple i.v. administrations. These results demonstrate that the conjugation of RGDS peptide with SCM-chitin led to augmentation of therapeutic potential to cancer metastasis, thus implying an importance of the conjugation of cell-adhesive RGDS peptide with structurally heparin-like SCM-chitin, which possess binding ability to the heparin-binding domain of fibronectin or laminin and extremely low anticoagulant properties.

Amino Acid Sequence↗
PubMed1992

Intracellular HRP study of nociceptive neurons within the ventrobasal complex of the cat thalamus.

Locations and morphological characteristics of nociceptive specific (NS) and wide dynamic range (WDR) neurons of the ventrobasal (VB) thalamic complex were studied using an intracellular HRP injection technique in cats anesthetized with urethane and chloralose. Both NS and WDR neurons were found within the marginal zone of the VB complex. Their somata were confined to the VB complex, but dendrites were extended into the structures of the thalamus surrounding the VB complex. NS neurons were found in the caudal part of the VB complex, whereas WDR neurons were found more rostrally. Examinations of their locations within the marginal zone of the VB complex confirmed the somatotopic organization, as found previously. We also confirmed the previous reports that there are 3 different types of low-threshold mechanoreceptive (LTM) neurons within the VB complex. They are type I, type II and type III neurons. Both NS and WDR neurons were either type I or type II neurons. Obvious morphological differences were not found between LTM neurons and two classes of nociceptive VB neurons investigated.

Animals↗
PubMed1992

The effect of crossed olivo-cochlear bundle stimulation on acoustic trauma.

To investigate whether the crossed olivo-cochlear bundle (COCB) functions in a protective manner, albino guinea pigs were exposed to sounds of varying intensity (110-130 dB SPL, 3-30 min) with or without electric stimulation of COCB, and the threshold shifts of the compound action potential (CAP) were examined. A statistically significant protective effect was observed in animals exposed to stimuli of intermediate intensity which induce threshold shifts of 50 to 55 dB on average. No protective effect was observed in the groups exposed to greater or milder stimuli. These results are discussed in the light of the available literature.

Acoustic Stimulation↗
PubMed1991

Trigeminal nociceptive neurons in the subnucleus reticularis ventralis. I. Response properties and afferent connections.

Trigeminal nociceptive neurons within the subnucleus reticularis ventralis medullae oblongatae (SRV), which lies ventral to the trigeminal subnucleus caudalis and subnucleus reticularis dorsalis medullae oblongatae, were studied in urethane/chloralose-anesthetized cats and monkeys. These neurons were called 'SRV neurons'. They were almost regularly excited by pressure to the ipsilateral cornea or to both corneas at a strength well above the human corneal pain threshold. Most of them were activated by noxious mechanical stimulation of the pinna, face and/or tongue. A significant fraction of SRV units was responsive to tapping of the ipsilateral dorsum of the nose and/or electrical stimulation of tooth pulp afferents. Evidence was obtained that responses to tapping of the dorsum of the nose were due to mechanical distortion of the nasal mucosa. Intracellular injection of HRP into SRV neurons demonstrated that injected neurons were large neurons characteristic of the SRV. Trigeminal tractotomy just rostral to the obex did not eliminate responses of SRV units to trigeminal inputs. Neurons relaying trigeminal inputs to SRV neurons were electrophysiologically identified in the nucleus reticularis parvocellularis which is ventromedially adjacent to the subnuclei oralis and interpolaris of the trigeminal spinal tract nucleus. These findings were supported by HRP injection into the SRV. Units having receptive fields similar to those of SRV neurons were found in lamina VII of the first cervical cord, suggesting that SRV neurons may be trigeminal lamina VII neurons.

Afferent Pathways↗
PubMed1991

Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes.

Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other.

Animals↗
PubMed1991

The effect of furosemide on the endocochlear potential in ears with experimentally induced endolymphatic hydrops.

The endocochlear potential (EP) was measured in 38 guinea pigs with experimentally induced endolymphatic hydrops at the 3rd, 6th, 12th and 24th postoperative weeks, and the effects of furosemide (FUR, 50 or 80 mg/kg) on the EP were examined. A time-related reduction of the EP from the normal value and increased susceptibility to FUR were disclosed in the hydropic animals. Furthermore, 24-week animals given 80 mg/kg FUR showed a significantly slower recovery rate of the EP than the other groups, indicating impairment of the strial function progressive with post-operative time. The negative component of the EP was considered to be unimpaired until at least 12 weeks after the surgery.

Animals↗
PubMed1989

Three cases of oral squamous cancer associated with leukocytosis, hypercalcemia, or both.

Three examples of malignant neoplasms primary to the oral cavity and associated with paraneoplastic syndromes are presented. The first case is a squamous cell carcinoma of the maxilla associated with leukocytosis. The second case is a mandibular squamous cell carcinoma associated with hypercalcemia in the absence of bony metastases. The third case is a squamous cancer of the tongue that metastasized to the lumbar vertebrae and right second rib and was associated with both hypercalcemia and leukocytosis. There was no evidence of acute infection or leukemia that could be expected to account for leukocytosis. Hypercalcemia in the second case was defined as humoral hypercalcemia of malignancy by biochemical and clinical evaluations. To our knowledge, this is the first definitive report of a carcinoma primary to the oral cavity associated with humoral hypercalcemia of malignancy. In each case, the severity of hypercalcemia, leukocytosis, or both very closely correlated with tumor growth. Surgical excision of the tumors or regression of tumor mass due to aggressive anticancer drug administration resulted in decreases in leukocyte number, serum calcium level, or both. In contrast, recurrence or regrowth of tumors induced further development of hypercalcemia, leukocytosis, or both. It is therefore likely that humoral factors released by these oral carcinomas are responsible for the hypercalcemia, leukocytosis, or both.

Adult↗
PubMed1989

[Results of vitrectomy for diabetic traction retinal detachment involving the macula; a comparison of six-month and three-year postoperative findings].

Three-year follow-up examinations were performed on 45 cases that underwent pars plana vitrectomies for diabetic retinopathy complications from 1982 to 1983. All of these cases had traction retinal detachment involving the macula. Visual improvement was noted in 27 eyes (60%) and 11 eyes (24%) had worse visual acuity at 6 months after surgery. Final visual improvement was noted in 21 eyes (47%) at the there-year follow-up examinations. Five (11%) of the 45 cases had better visual acuity at the three-year examination than at six months, 18 (40%) had the same visual acuity, but 22 (49%) had poorer vision at the three-year examination. Out of those cases, 28 eyes (62%) had totally attached retina 6 months after operation and the results in those eyes were quite stable at three years. Of these, 19 (68%) had the same or better visual acuity at three years compared with six months. But if retinal detachment was present at 6 months, the prognosis was very poor at the three-year examination with a visual acuity of less than hand motions. Reattachment of the retina is most important to maintain good prognosis for surgical treatment for diabetic retinopathy with traction retinal detachment.

Adult↗
PubMed1988

Restoration of microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit): stimulatory effects of GH restricted to the first 20 days of postnatal life.

We administered bovine growth hormone to the Little (lit), a promising model of isolated growth hormone deficiency, during the first and second 20 days after birth. Positive results were obtained only when bovine growth hormone was given during the first 20 days of postnatal life. We observed a distinct increase in cerebral weight, DNA content, and 2',3'-cyclic nucleotide 3'-phosphohydrolase activity. The latter administration of bovine growth hormone was ineffective. These data prove that growth hormone has an independent action on cerebral development, apart from the complementary or synergistic action of thyroid hormones, and that the administration of exogenous growth hormone led to increased myelinogenesis through its stimulatory effects on glial proliferation, as evidenced by the increase in cerebral DNA content.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗