Biomedical subjects

J Ishikawa

Publications and source records attributed to J Ishikawa.

At least 73 records · Page 4Linked to original sources

PubMed1997

Boundary lubrication between the tendon and the pulley in the finger.

The lubrication mechanism between the human flexor digitorum profundus tendon and the A2 pulley was investigated in vitro. The gliding resistance at the interface between the tendon and the pulley increased significantly after the tendon had been treated with a hyaluronidase solution. Alcian-blue staining of the surface of the tendon before and after it was treated with hyaluronidase suggested the presence of hyaluronate complex. Alcian blue-positive and hyaluronidase-sensitive materials, such as hyaluronate or proteoglycan, in the synovial membrane and the matrix of the tendon, may act as a boundary lubricant, facilitating the gliding and reducing the resistance between the tendon and the pulley.

Alcian Blue↗

PubMed1997

[A case of basilar impression treated with mandible splitting transoral approach].

We report a case of basilar impression treated with mandible splitting transoral approach surgery. A 39-year-old man presented a ten-year history of gait disturbance. He had experienced acceleration of his spastic paraparesis for the past few years. Neurological examination on admission demonstrated tetraparesis (MMT4/5), severe hyperreflexia in his arms and legs, severe sensory loss below C2, urinary retention and inability to open his mouth widely. Radiological findings showed the dens and the body of C2 are deeply invaginated to the atlas and the foramen magnum and medulla and upper cervical cord were markedly compressed by this basilar invagination. After carrying out posterior decompression and occipito-cervical fixation, we attempted to remove the invaginated dens and the C2 vertebral body using a conventional transoral approach. But limitation of mouth opening made operative fields narrow. Consequently because of insufficient anterior decompression his neurological deficits could not be alleviated. Employment of mandible splitting procedure brought about a wide operative view so that complete removal of the residual dens and 70% drilling out of the C2 body was made possible. Postoperative complications were negligible. Finally, great alleviation of his deficits was achieved. Mandible splitting procedure is effective for obtaining a wide operative field on the anterior approach to the craniocervical junction.

Adult↗

PubMed1997

[Analysis of mild barbiturate-moderate hypothermia therapy on the authors' 152 cases].

Mild barbiturate-moderate hypothermia therapy was established for severe head injury and cerebrovascular disease. This study was conducted on 152 patients from April 1984 through July 1995. In this study were included patients with Glagow Coma Scale score of less than 8 points but those with serious systemic complications and elderly and infantile patients were excluded. Our protocol consisted of administration of thiamylal Na 1.25-2.5 mg/kg/h and droperidol 20-40 micrograms/kg/h (mild barbiturate) while maintaining a core temperature of 32-34 degrees C (moderate hypothermia). The clinical outcome was good (GR, MD) in 58 cases, poor (SD) in 24 cases and bad (PVS, D) in 70 cases. This therapy was found to be particularly effective for preventing ischemic neurological damage in the vasospasm stage following SAH and severe head injury in young patients. However, this therapy did not prevent pneumonia, cardiac failure, arrhythmia and hypopotassemia from occurring frequently. We conclude that this therapy is contraindicated in the elderly, i.e., those older than 65 years.

Adolescent↗

PubMed1997

Genetic mutations of butyrylcholine esterase identified from phenotypic abnormalities in Japan.

We have identified 12 kinds of genetic mutations of butyrylcholine esterase (BCHE) from phenotypic abnormalities, showing that BCHE activities were deficient or diminished in sera. These genetic mutations, detected by PCR-single-strand conformation polymorphism analysis and direct sequencing, consisted of one deletion (BCHE*FS4), nine missense (BCHE*24 M, *1005, *250P, *267R, *330I, *365R, *418S, *515C, *539T), and two nonsense mutations (BCHE*119STOP, *465STOP). All of the individuals deficient in serum BCHE activity were homozygous for silent genes (6 of 6). Fifty-eight percent of the individuals (31 of 53) with slightly reduced serum BCHE activity were heterozygous for silent genes. They also showed a higher frequency (47% as allele frequency) of the K-variant than the general population (17.5%). Finally, we confirmed low serum BCHE activity in 10 of 23 individuals heterozygous for silent genes.

Butyrylcholinesterase↗

PubMed1997

[Wide craniotomy-small dural incisions and intentionally delayed removal of intracerebral contusional hemorrhage for acute subdural hematoma].

The outcome of acute subdural hematoma (ASDH), which can cause severe parenchymal injury, has generally been unsatisfactory. The standard surgical procedure for ASDH is a quick and wide opening by dural incision, removal of the subdural and contusional intracerebral hematoma, followed by large external and internal decompression. In this study, we assessed our therapeutic strategy, consisting of three principles: 1. Removal of subdural hematoma by wide craniotomy-small dural incisions, in well-decompressed case, connecting the small dural incisions and stanching the bleeding points on the cortical surface but not proceeding with contusional hemorrhage in emergency operations, 2. Post-operative induction of mild barbiturate-moderate hypothermia therapy and 3. Intentionally delayed evacuation of the intracerebral contusional hemorrhage when needed. The patients, profile is composed of an old therapy group (27 cases) and a new therapy group (20 cases) suffering from ASDH with cerebral contusion. The clinical outcome with the old therapeutic strategy was good recovery (GR) in 7 cases, moderate disability (MD) in 5, severe disability (SD) in 2, vegetative state (PVS) in 3 and death (D) in 10, whereas the outcome with the new strategy resulted in GR in 15 cases, MD in 3, D in 2. These clinical results indicate that the rates of mortality and severe morbidity were markedly reduced with our new therapeutic strategy.

Acute Disease↗

PubMed1996

Construction of pRES18 and pRES19, Streptomyces-Escherichia coli shuttle vectors carrying multiple cloning sites.

We developed two Streptomyces-Escherichia coli shuttle vectors. The plasmid pRES102, consisting of the essential region of pRES1 and the thiostrepton resistance gene (tsr) fragment of pIJ702, was combined with the E. coli plasmid vector pUC18 or pUC19. The resulting shuttle vectors, designated pRES18 and pRES19, respectively, have relatively compact size (6.25 kb), low copy number, multiple cloning sites reciprocally arranged in opposite directions, and selection markers for both Streptomyces (tsr) and E. coli (beta-lactamase (bla) and beta-galactosidase (lacZ). These shuttle vectors are capable of carrying DNA fragments as long as 10 kb, of being maintained in S. griseus, S. lavendulae and S. lividans, and are compatible with pIJ702.

Cloning, Molecular↗

PubMed1996

Inhibitory effect of fluvastatin at doses insufficient to lower serum lipids on the catheter-induced thickening of intima in rabbit femoral artery.

The anti-atherosclerotic effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors at doses insufficient to lower serum cholesterol was investigated in rabbit femoral artery denuded by balloon catheter. Fluvastatin and pravastatin were given orally at doses of 4 and 8 mg/kg per day, respectively, for 2 weeks after the catheterization. There was little change in serum cholesterol, triglyceride and phospholipid by chronic treatment with the drugs. The cross-sectional area of the intima, expressed as relative values to media (I/M ratio), was increased by the catheterization, showing intimal thickening in the denuded arteries. The I/M ratio was reduced by fluvastatin but not pravastatin: 0.327 +/- 0.060 for control, 0.116 +/- 0.035 for 4 mg/kg fluvastatin, 0.088 +/- 0.027 for 8 mg/kg fluvastatin and 0.22 +/- 0.069 for 8 mg/kg pravastatin. Fluvastatin (8 mg/kg)-induced effect on the I/M ratio, was prevented by the combined administration with 40 mg/kg per day mevalonate, a metabolite in the HMG-CoA reductase pathway. These results suggest that fluvastatin inhibits intimal thickening after catheterization-induced injury through percutaneous transluminal coronary angioplasty (PTCA) and that the inhibition is presumably attributed to reduced migration and proliferation of smooth muscle cells but not secondarily to a lowering of serum lipid.

Animals↗

PubMed1996

The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells.

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.

Acute Disease↗

PubMed1996

Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is crucial to hematopoiesis, melanogenesis, and gametogeneis. Although the enzymatic activity of the c-kit product (KIT) is regulated by its ligand, both the Val559-->Gly (G559) mutation in the juxtamembrane domain and the Asp814-->Val (V814) mutation in the phosphotransferase domain lead to constitutive activation of KIT. By retroviral infection of hematopoietic progenitor cells with KIT(G559) or KIT(V814), KIT(G559) induced development of granulocyte/macrophage and mast-cell colonies in vitro without the addition of exogenous growth factors. KIT(V814) induced factor-independent growth of various types of hematopoietic progenitor cells, resulting in the development of mixed erythroid/myeloid colonies in addition to granulocyte/macrophage and mast-cell colonies. Furthermore, transplantation of KIT(G559) and KIT(V814)-infected bone marrow cells led to development of acute leukemia in one of 10 and six of 10 transplanted mice, respectively. No mice developed hematologic malignancies after transplantation of wild-type KIT-infected cells. Furthermore, transgenic mice expressing KIT(V814) developed acute leukemia or malignant lymphoma. These results demonstrate a direct role of the mutant KITs, particularly KIT(V814), in tumorigenesis of hematopoietic cells and suggest that similar mutations may contribute to the development of human hematologic malignancies.

Animals↗

PubMed1996

Hypereosinophilic syndrome with generalized myasthenia gravis.

A patient with hypereosinophilic syndrome simultaneously had generalized myasthenia gravis. Ultrastructural and functional studies demonstrated an increase of the activated hypodense eosinophils. The eosinophilic cationic protein level in plasma and whole blood paralleled the severity of congestive heart failure. A high level of interleukin-5 was detected in both serum and in conditioned medium of T cells by interleukin-2 stimulation before therapy. The findings indicate that both diseases may be associated with a common T-cell abnormality.

Blood Proteins↗

PubMed1996

Endogenous nitric oxide modifies antigen-induced microvascular leakage in sensitized guinea pig airways.

To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (l-NAME), on antigen-induced airway microvascular leakage in actively sensitized guinea pigs by using Evans blue dye. Three weeks after sensitization with ovalbumin (10 micrograms), the tracheas were cannulated, and lungs were artificially ventilated. Animals were pretreated with atropine and propranolol (both 1 mg/kg, intravenously) to avoid neural modification. Ovalbumin inhalation (3 mg/ml, 1 minute) challenge caused significant microvascular leakage in all airways portions, which was significantly suppressed in a dose-dependent manner by pretreatment with intravenous injection of L-NAME (1 and 10 mg/kg) but not with the inactive enantiomer D-NAME (10 mg/kg). This inhibition by L-NAME was significantly reversed by co-administration of L-arginine (100 mg/kg, intravenously). Pretreatment with a vasoconstrictor, phenylephrine (20 micrograms/kg, intravenously), had no inhibitory effects on antigen-induced airway microvascular leakage despite increasing systemic blood pressure. Inhalation of representative mast cell-derived mediators, histamine (2 mg/ml, 1 minute) or leukotriene D4 (5 micrograms/ml, 1 minute), produced significant microvascular leakage in all airways. L-NAME (10 mg/kg, intravenously) partially but significantly inhibited leukotriene D4-induced leakage, whereas histamine-induced leakage was not affected. These results suggest that endogenous nitric oxide acts to increase airway microvascular leakage after airway allergic reaction.

Animals↗

PubMed1996

Clinical results of treatment of triangular fibrocartilage complex tears by arthroscopic debridement.

In order to determine indications for arthroscopic debridement and the management of triangular fibrocartilage complex (TFCC) tears, we reviewed 16 wrists retrospectively. The mean patient age was 30 years, with a range of 20 to 53 years. The follow-up period averaged 35 months. Two groups were identified: post-traumatic tears (n = 11) and degenerative tears (n = 5). The results of arthroscopic debridement were compared and analyzed based on the preoperative and postoperative evaluation of pain, range of motion, grip strength, return to work, patient acceptance, and complications. Failures were further evaluated to determine identifiable lesions or anatomic defects associated with poor results. Patients with positive ulnar variance and lunotriquentral interosseous ligament tears had a poor clinical outcome. Good results correlated with grip strength; all patients with post-traumatic TFCC tears had excellent results, while those with degenerative TFCC tears did poorly.

Adult↗

PubMed1996

Extracorporeal shock wave lithotripsy in von Willebrand's disease.

A renal calculus in a patient with von Willebrand's disease was successfully fragmented by extracorporeal shock wave lithotripsy (ESWL) with the administration of Haemate P. No serious bleeding was observed after ESWL. With supplementation of the missing von Willebrand's factor, ESWL may be applied to patients with this bleeding diathesis.

Adult↗

PubMed1996

Inhibitory effects of fluvastatin, a new HMG-CoA reductase inhibitor, on the increase in vascular ACE activity in cholesterol-fed rabbits.

1. The effects of fluvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on the vascular angiotensin converting enzyme (ACE) activity in hyperlipidaemic rabbits were compared with those of enalapril, an ACE inhibitor. 2. Rabbits were fed a 1.5% cholesterol containing diet or normal diet for 16 weeks and treated with either fluvastatin or enalapril in the diet at the respective doses of 2 and 10 mg kg-1 day-1. The total cholesterol, triglyceride and phospholipid levels in serum were significantly increased in rabbits fed the high cholesterol diet. Treatment with fluvastatin but not enalapril resulted in a decrease in serum lipids. 3. The vascular ACE activities assessed via the cleavage rate from synthetic substrate in the aortic arches and upper thoracic aortae were increased by 8 to 10 times when the rabbits were made hyperlipidaemic. Fluvastatin as well as enalapril significantly lowered the tissue ACE in the aortae. 4. The ACE activities in serum did not alter in hyperlipidaemic rabbits either in the presence or absence of fluvastatin. The serum ACE activity was lowered by enalapril. 5. The lipid peroxide in serum as well as the plaque area in the thoracic aorta was significantly increased in the cholesterol diet-fed rabbits. Treatment with fluvastatin or enalapril reduced both serum lipid peroxide and plaque formation. The relaxant responses to acetylcoholine (ACh) were significantly suppressed in the cholesterol-fed rabbits. Treatment with fluvastatin or enalapril significantly reversed the suppression of ACh-induced relaxation. 6. It seems that the reduction of vascular ACE is not coupled to lipids and ACE activity in serum, but rather to lipid peroxidation. Thus, the decrease in vascular ACE activity by fluvastatin as well as the lipid-lowering effect may reduce the risk of atherosclerosis progression in the vasculature.

Animals↗

PubMed1996

Effect of YM934, a novel potassium-channel opener, in various experimental asthma models in guinea-pigs.

YM934 is a novel synthetic potassium-channel opener. We have investigated its anti-asthma effect after intravenous (i.v.) and oral (p.o.) administration in various experimental asthma models in the guinea-pig, and compared the results with those for lemakalim, theophylline and salbutamol. In an ovalbumin-active sensitization anaphylaxis asthma model, YM934, lemakalim, theophylline and salbutamol dose-dependently prolonged the time before the occurrence of asthma attacks and reduced the mortality rate. The respective ED50 values (dose required to prolong by 50% the time before the occurrence of attacks) of the anti-asthma effects of YM934, lemakalim, theophylline and salbutamol were 6, 340, 30000, and 45 micrograms kg-1 (i.v.); the efficacy ratios were YM934 (1) > salbutamol (1/9) > lemakalim (1/57) > > theophylline (1/5000). YM934 also prolonged the period before the occurrence of attacks in the anti-BSA (bovine serum albumin) serum-passive sensitization anaphylaxis, histamine-induced and methacho-line-induced asthma models, with respective ED50 values for these models of 15, 22 and 20 micrograms kg-1 (i.v.). Among these models a reduction in mortality rate was seen in the histamine- and methacholine-induced asthma models. After oral administration, YM934 showed an anti-asthma effect in the ovalbumin-active sensitization anaphylaxis, histamine-induced and methacholine-induced asthma models, with respective ED50 values of 38, 44 and 193 micrograms kg-1. YM934 was 5-6 times more potent than salbutamol. These results indicate that YM934 has potent anti-asthma activity, and that this activity is mainly attributable to bronchodilation, most likely mediated through its potassium-channel opening activity.

Administration, Oral↗

PubMed1996

Involvement of endogenous tachykinins in LTD4-induced airway responses.

Leukotriene D4-(LTD4) has been reported to cause tachykinin release from airway sensory nerves. However, the functional significance of endogenously released tachykinins in LTD4-mediated airway responses has not been fully clarified. The aim of this study was to investigate whether LTD4-induced airway responses are due, in part, to tachykinin release in guinea-pigs. Airway plasma exudation and bronchoconstriction were assessed by measuring extravasation of Evans blue dye and by mean pulmonary resistance (RL) in the presence of atropine (1 mg.kg-1 i.v.) and propranolol (1 mg.kg-1 i.v.), respectively. LTD4 (5 micrograms.mL-1 for 1 min) inhalation caused increase in plasma exudation and RL. Capsaicin pretreatment of animals to deplete sensory neuropeptides significantly inhibited LTD4-induced plasma exudation in the main bronchi, but not in the central (cIPA) and peripheral intrapulmonary airways (pIPA). Pretreatment with specific tachykinin neurokinin-1 (NK1)-receptor antagonists, FK 888 (10 mg.kg-1 i.v.) and CP 96345 (4 mg.kg-1 i.v.), also significantly reduced LTD4-induced plasma exudation in the main bronchi, and in the main bronchi and cIPA, respectively. However, these antagonists did not significantly affect the LTD4-induced increase in RL. In contrast, neurokinin-2 (NK2)-receptor antagonist, SR 48968 (0.3 mg.kg-1 i.v.), significantly inhibited the bronchoconstriction after LTD4-inhalation. These results suggest that leukotriene D4-induced bronchoconstriction and plasma exudation in guinea-pigs are, in part, due to tachykinin release from airway sensory nerves.

Administration, Inhalation↗

PubMed1996

Repeated allergen exposure enhances excitatory nonadrenergic noncholinergic nerve-mediated bronchoconstriction in sensitized guinea-pigs.

The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.

Allergens↗

PubMed1996

Enzymatic 2'-N-acetylation of arbekacin and antibiotic activity of its product.

Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and antibiotic assay of the incubated reaction mixtures revealed that a modified compound retaining substantial antibiotic activity was formed from arbekacin (ABK), while modification of the other AGs resulted in the marked decrease in antibiotic activity. Structure determination following isolation from a large scale reaction mixture showed the modified ABK to be 2'-N-acetyl ABK. In addition, 2',6'-di-N-acetyl ABK was formed as a minor product. The same conversion also occurred with dibekacin (DKB) resulting in the formation of 2'-N-acetyl DKB and 2',6'-di-N-acetyl DKB. MIC determination showed antibacterial activity (1.56 approximately 3.13 micrograms/ml) of 2'-N-acetyl ABK against a variety of organisms. By contrast, 2'-N-acetyl DKB showed no substantial antibiotic activity. We believe 2'-N-acetyl ABK has the highest and broadest antibacterial activity, compared with known N-acetylated AGs.

Acetylation↗