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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 253 records · Page 14Linked to original sources
PubMed1994

Relationship of protein structure of isoleucyl-tRNA synthetase with pseudomonic acid resistance of Escherichia coli. A proposed mode of action of pseudomonic acid as an inhibitor of isoleucyl-tRNA synthetase.

To elucidate the mode of action of pseudomonic acid, we have compared the deduced amino acid sequences of isoleucyl-tRNA synthetases (ILeRS) from wild-type Escherichia coli strain MC4100, a pseudomonic acid-resistant mutant (strain PS102) of MC4100, and a pseudomonic acid-producing strain, Pseudomonas fluorescens. Compared with the wild-type enzyme, the deduced amino acid sequence of E. coli mutant ileS gene in strain PS102 shows a single amino acid substitution of leucine for phenylalanine at residue 594 of the IleRS. This mutational alteration in IleRS of an E. coli pseudomonic acid-resistant mutant resides in a region of the enzyme in close proximity to one of the consensus sequences of class I aminoacyl-tRNA synthetases, the KMSKS sequence between residues 602 and 606 of the E. coli IleRS. DNA sequence of the cloned ileS gene predicts that the P. fluorescens IleRS consists of 943 amino acids with 54% identity with the E. coli IleRS. The P. fluorescens ileS gene and the wild type and PS102 alleles of E. coli ileS were cloned into an expression vector, pEXPCR, and the sensitivities of E. coli DH5 alpha cells harboring each of these plasmids were compared. The cells harboring the P. fluorescens ileS were found to be most resistant to pseudomonic acid, while the transformants expressing the PS102 IleRS were more resistant than those containing the wild-type E. coli IleRS. IleRS purified from the wild-type E. coli was specifically cleaved by trypsin between Lys605 and Ser606 in the region of K602MSKS606. The protection of the IleRS from the trypsin digestion was found with pseudomonic acid or ATP, but not with isoleucine or tRNA(1Ile). Based on these results, we propose that pseudomonic acid binds to IleRS in the vicinity of the KMSKS sequence that is an ATP-binding subsite, and that pseudomonic acid is a bifunctional inhibitor with characteristics of both isoleucine and ATP, for example, an analog of isoleucyladenylate.

Adenosine Triphosphate↗
PubMed1994

DP-1904, a specific inhibitor of thromboxane A2 synthesizing enzyme, suppresses ICAM-1 expression by stimulated vascular endothelial cells.

Intercellular adhesion molecule-1 (ICAM-1) is an antigen that is strongly expressed by vascular endothelial cells at sites of local inflammation and participates in the development of inflammation. In the present study, vascular endothelial cells were stimulated by inflammatory cytokines that promote thromboxane A2 synthesis to observe their effects on the expression and shedding of ICAM-1 on the cell surface. In addition, the suppressive effects of DP-1904 ([+/-]-6-[1-imidazolylmethyl]-5,6,7,8-tetrahydronaphthalene-2- carboxylic acid hydrochloride hemihydrate), a thromboxane A2 synthesis inhibitor, on ICAM-1 expression were evaluated. ICAM-1 expression on the surface of human umbilical vein endothelial cells was increased significantly by stimulation with interleukin-1 beta, tumor necrosis factor alpha (TNF alpha), thrombin and platelet-activating factor (PAF). DP-1904, an inhibitor of thromboxane A2 synthesis, significantly suppressed the expression of ICAM-1 on the surface of human vascular endothelial cells that had been stimulated by TNF alpha or PAF. These findings suggest that an enhanced expression of thromboxane A2 on human vascular endothelial cells is closely related to the expression of ICAM-1 on the surface of these cells.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Experimental lumbar radiculopathy. Immunohistochemical and quantitative demonstrations of pain induced by lumbar nerve root irritation of the rat.

OBJECTIVE: A series of experiments were designed to develop and validate an animal model of lumbar radiculopathy. More specifically, these investigations introduced a model of chronic neuropathic pain in the rat associated with clinically relevant lumbar nerve root trauma and evaluated the ability of the model to effect symptoms and begin to understand the underlying neurochemical and neurophysiologic factors associated with these neurologic abnormalities. SUMMARY OF BACKGROUND DATA: A search of the literature suggested that these studies were a first attempt to distinguish and elucidate an experimental lumbar radiculopathy. METHODS: Two basic approaches to nerve trauma were considered, direct damage to the nerve via compression, and introduction of foreign materials in proximity to the nerve root that might cause irritation and inflammation leading to chronic symptoms. Ligature around the nerve (i.e., surrounding the nerve with a suture) was considered a plausible irritant that might behave in an animal model in a similar way that nerve root entrapment, often observed in HNP and stenosis cases, might function in humans. Further, varying levels of irritation was modeled by using 4-0 silk as a mild and 4-0 chromic gut as a more harsh irritant. STUDY DESIGN: Five distinct treatments of the nerve roots were investigated initially: 1) a sham intervention, where the surgery simply exposed the nerve roots and dorsal root ganglion followed by standard closing procedures; 2) nerve root clipping, where the nerve roots were clipped with a microhemoclip; 3) 4-0 silk ligature, where two loose ligatures of 4-0 silk were placed around the nerve roots; 4) 4-0 chromic gut 1, where one loose ligature of 4-0 chromic gut was placed around the nerve roots; and 5) 4-0 chromic gut 2, where four 0.3 cm pieces of 4-0 chromic gut were laid adjacent to the nerve roots and secured by two loose ligatures of 4-0 chromic gut. ANOVA techniques were used to test for differential effects across time for the five treatment groups in terms of animal function and biochemistry in the DRG. RESULTS: Rats treated with chromic gut ligature in large quantity demonstrated differential patterns of results on the injured and noninjured sides consistent with a lumbar radiculopathy. The injured side demonstrated significantly worse thermal hyperalgesia related to neuropathic pain (P < 0.0001); initial mechanical hypoalgesia (P < .001), and motor dysfunction (P < .001) resolving within 2 weeks; significantly increased c-fos counts (P < .0001) 2 weeks postoperatively, which showed a consistent trend toward baseline and return to baseline by 12 weeks; significantly greater and highly increased VIP concentrations in the dorsal root ganglia 2 weeks postoperatively (P < .0001) that did not resolve or tend towards baseline after 12 weeks of follow-up in conjunction with a trend toward VIP depletion in the spinal cord 2 weeks postoperatively that did resolve to baseline until a 12-week concentration indicated a significant increase in concentration (P < .002). Quantitative and qualitative changes in c-fos and VIP, correlated with the patterns of behavior and function. Thus, for the first time, evidence to link outcome behaviors and function with underlying neurochemical processes is suggested. CONCLUSIONS: When the same apparent conditions can be demonstrated in some situations to be causing pain and in other situations to be independent of pain, some additional factor or factors not considered in the original investigations may be mediating the outcome. Neurochemical consequences of nerve root irritation provide a theoretical framework for hypothesizing about various types of mediating events that might explain how similar apparent pathology might reasonably lead to different predictions about behavior consequences of the pathology.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Experimental lumbar radiculopathy. Behavioral and histologic changes in a model of radicular pain after spinal nerve root irritation with chromic gut ligatures in the rat.

OBJECTIVE: The recently proposed animal model of lumbar radiculopathy was used to investigate behavioral consequences and histologic changes in spinal nerve roots, dorsal root ganglia, and spinal nerves after the L4, L5, and L6 nerve roots were loosely ligated with either silk or chromic gut sutures in an attempt to better understand the pathophysiologic mechanisms that give rise to pain associated with lumbar radiculopathy. SUMMARY OF BACKGROUND DATA: Little is known about the pathophysiologic mechanisms that give rise to pain associated with lumbar radiculopathy. The recently proposed animal model of unilateral lumbar radiculopathy, which demonstrated an association with motor paresis and thermal hyperalgesia of the affected hind limb and showed evidence of spontaneous pain has been demonstrated, may serve as a vehicle to allow direct investigation of the nature of the pathophysiological mechanisms associated with lumbar radiculopathy. METHODS: Three distinct treatments of the nerve roots were initially investigated: 1) a sham intervention, where the surgery simply exposed the nerve roots and dorsal root ganglion followed by standard closing procedures; 2) 4-0 silk ligature, where two loose ligatures of 4-0 silk were placed around the nerve roots; and 3) 4-0 chromic gut 2, where four 0.3 cm pieces of 4-0 chromic gut were laid adjacent to the nerve roots and secured by two loose ligatures of 4-0 chromic gut. STUDY DESIGN: ANOVA techniques were used to test for differential effects across time for the three treatment groups in terms of animal function. A qualitative analysis of the histology of the ipsilateral and contralateral nerve roots, dorsal root ganglia, and spinal nerves was done to correlate histologic changes with behavioral changes. RESULTS: Behavioral results were consistent with the previous study. Rats treated with chromic gut, but not silk, reliably demonstrated a prolonged thermal hyperalgesia that was maximal 2 weeks after surgery and lasted for up to 12 weeks. These behavioral changes, however, were not correlated with histologic changes in myelinated fiber content in the L4, L5, and L6 nerve roots, dorsal root ganglia and spinal nerves, the ipsilateral spinal nerved, dorsal root ganglia, and nerve roots of rates ligated with silk or chromic gut showed similar, significant, decreased in the number of large diameter myelinated fibers. CONCLUSIONS: These results suggest that mechanical constriction of the L4, L5, and L6 spinal nerve roots, as evidenced by a loss of myelinated fibers, is not sufficient to produce the behavioral effects associated with this model of lumbar radiculopathy. It is hypothesized that chemical factors from the chromic gut play a role in the pathophysiology and development of the behavioral, but not histological, changes in this model of lumbar radiculopathy.

Animals↗
PubMed1994

A 100-kDa protein in the C4-activating component of Ra-reactive factor is a new serine protease having module organization similar to C1r and C1s.

Ra-reactive factor (RaRF), a C-dependent bactericidal factor in mice, is composed of one polysaccharide-binding component and one C4/C2-activating component. The former is an oligomer of 28-kDa protein corresponding to the mannose-binding protein of mice. The 100-kDa protein, P100, has been shown to be present in the C4/C2-activating component. This protein generates 29- and 70-kDa polypeptide chains when reduced. In this study, we determined the nucleotide sequence of cDNA coding for P100. cDNAs were prepared by reverse transcription PCR and cassette-ligation-mediated PCR on mRNA from BALB/c mouse liver, using primers synthesized by reference to the sequence determined in a previous study. The results of cDNA sequencing indicate that the precursor protein of P100 containing a 24-residue signal peptide consists of 704 amino acid residues. Taking the results of the previous electrophoretic study into consideration, it is thought that the cleavage of mature P100 protein generates a 29-kDa chain of 251 residues and a 70-kDa chain of 429 residues. Although homology in the amino acid sequence of P100 with that of human C1r and C1s subcomponents of C was less than 40%, a striking similarity in domain organization was found among these proteins, indicating that P100 is a new C4-activating serine protease structurally similar to C1r and C1s. Northern hybridization showed that the liver was the primary site of the expression of the P100 gene.

Amino Acid Sequence↗
PubMed1994

Elevated serum and urinary thrombomodulin levels in patients with non-insulin-dependent diabetes mellitus.

Increased plasma levels of soluble thrombomodulin have been reported in several disorders as a marker for vascular endothelial damage. Serum and urinary thrombomodulin levels were measured in 79 patients with non-insulin-dependent diabetes mellitus. Both levels were significantly higher (23.5 +/- 6.1 ng/ml and 146.6 +/- 64.9 ng/ml, respectively) than those of normal healthy controls (18.8 +/- 3.1 ng/ml, P < 0.001, and 96.8 +/- 60.3 ng/ml, P < 0.01). Serum thrombomodulin levels increased in keeping with urinary albumin levels. In urine thrombomodulin was lower in the macroalbuminuria group than in the microalbuminuria group, suggesting two mechanisms: intravascular overproduction and impaired renal clearance. Both serum and urinary thrombomodulin levels in diabetic patients might be predictors for very early nephropathy.

Adult↗
PubMed1994

Isolation, characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans.

We have isolated 13 fluoride-resistant mutants of the nematode Caenorhabditis elegans. All the mutations are recessive and mapped to five genes. Mutants in three of the genes (class 1 genes: flr-1 X, flr-3 IV, and flr-4 X) are resistant to 400 micrograms/ml NaF. Furthermore, they grow twice as slowly as and have smaller brood size than wild-type worms even in the absence of fluoride ion. In contrast, mutants in the other two genes (class 2 genes: flr-2 V and flr-5 V) are only partially resistant to 400 micrograms/ml NaF, and they have almost normal growth rates and brood sizes in the absence of fluoride ion. Studies on the phenotypes of double mutants showed that class 2 mutations are epistatic to class 1 mutations concerning growth rate and brood size but hypostatic with respect to fluoride resistance. We propose two models that can explain the epistasis. Since fluoride ion depletes calcium ion, inhibits some protein phosphatases and activates trimeric G-proteins, studies on these mutants may lead to discovery of a new signal transduction system that controls the growth of C. elegans.

Animals↗
PubMed1994

Characterization of mice bearing subclones of colon 26 adenocarcinoma disqualifies interleukin-6 as the sole inducer of cachexia.

A subclone (clone 20) of chemically induced, murine colon adenocarcinoma with a potent ability to induce cachexia and another subclone (clone 5) without such an activity were transplanted to syngeneic mice (CDF1) and their tissue weights, blood components and cytokine levels in sera were compared. Mice transplanted with clone 20 showed a profound body-weight loss by 15 days after inoculation when the tumor accounted for less than 1% of the body weight, along with marked reduction of food and water intakes. Thereafter, they transiently gained in body weight with restoration of food and water intakes. Thus, the change in body weight was biphasic and not proportional to the tumor size. Body fat was lost preferentially, accompanied with a decrease in plasma triglyceride levels. The thymus contracted remarkably, and the peripheral lymphocyte count decreased extensively. Mice transplanted with clone 5, in contrast, did not show any of these changes characteristic of cachexia. Serum concentration of interleukin-6, which has been proposed as the principal inducer of cachexia in mice with colon 26, increased in mice with clone 5 to levels comparable to those in mice with clone 20. The changes in mice bearing clone 20 could not all be explained in terms of known biological activities of interleukin-6. Additional unknown factors, therefore, are presumed to contribute to cachexia in mice with clone 20. Identification of them should be helpful in the care of cachectic patients.

Adenocarcinoma↗
PubMed1994

Test performances of three diagnostic procedures in evaluating thyroid nodules: physical examination, ultrasonography and fine needle aspiration cytology.

A retrospective study was performed to determine the reliability of physical examination (PE), ultrasonography (US) and fine-needle aspiration cytology (FNA) in the evaluation of thyroid nodules. Preoperative diagnoses of 252 euthyroid patients comprised 126 with benign lesions, 114 with papillary carcinoma and 12 with follicular carcinoma made by PE, US and FNA were reviewed. The specificity of PE, US and FNA for malignancy was 98%, 90% and 98%, respectively. The sensitivity of PE, US and FNA for malignancy was 63%, 78% and 80%. The sensitivity for papillary carcinoma of the three procedures was 68%, 83%, 88%, whereas that for follicular carcinoma was 25%, 25%, 8%, respectively. When all the test results were negative, the likelihood ratio favoring papillary carcinoma was 0.008 whereas that favoring follicular carcinoma was 0.6. The histological category of carcinoma should be considered when evaluating diagnostic procedures for thyroid nodules. No negative test result is conclusive for ruling out the possibility of follicular carcinoma.

Biopsy, Needle↗
PubMed1994

Amyloidosis secondary to rheumatoid arthritis associated with plexiform change in bilateral temporal lobes.

A 70-year-old woman with rheumatoid arthritis (RA) and secondary amyloidosis presented repeated consciousness loss. The pathological findings at autopsy revealed multi-organic deposits of amyloid A-protein and so-called 'plexiform change' of blood vessels in bilateral temporal lobes. The arterial plexiform change, which is found in the lung specimen of primary pulmonary hypertension, might be a new pathological cerebrovascular change associated with RA.

Aged↗
PubMed1994

Blood viscosity and plasma viscosity in patients with sudden deafness.

Blood viscosity and plasma viscosity were measured in 51 patients with sudden deafness (SD) and 70 controls with normal hearing. Blood viscosity and plasma viscosity in patients with SD at their first medical examination were significantly higher than in the control group. The difference in viscosimetry results between the two groups was greater at higher shear rates. The data obtained in viscosimetry and pure-tone audiometry were analyzed after dividing the patients into a high viscosity group and a normal viscosity group. The correlation between average hearing level in pure-tone audiogram and blood viscosity or plasma viscosity was positive. The values of the O2-transport capacity of the blood demonstrated a negative correlation with average hearing level in patients with SD before treatment. During the course of treatment, blood viscosity and plasma viscosity decreased with the improvement of hearing impairment. When the distribution of average hearing level was 40 to 79 dB, a few of the patients with "recovery" or "good improvement" and most of patients with "fair improvement" or "no change" belonged to the low viscosity group. And, most of the patients with flat type hearing impairment and a few patients with high tone type hearing impairment belonged to the high viscosity group. These results suggest that many patients with SD have increased blood viscosity and plasma viscosity, and that this increase may play a significant role in the etiology of SD. There are also some differences in etiologic factors concerning type of hearing impairment and prognosis. In conclusion, the present study points to the importance of measuring blood viscosity and plasma viscosity in patients with SD, since blood and/or plasma viscosity may be involved in its etiology and prognosis.

Adult↗
PubMed1994

[Radiation therapy of carcinoma of the esophagus in the aged--its results and problems].

Clinical records of 128 non-selected patients with esophageal cancer treated by radiation were reviewed to investigate reasons why treatment had to be discontinued, relationship between age and survival, and factors influencing prognosis. Radiation therapy was completed in 77 patients but was discontinued in 27 patients. Preoperative radiation was attempted in 24 patients. An overall median survival of 128 patients was 6.4 months, with 8.5 and 3.3 percent surviving 3 and 5 years. Median survivals of incomplete RT, completed Rt and RT + Surgery were 1.3, 7.7 and 11.3 months. By Kaplan-Meier analysis significant difference was observed in survival rate between incomplete RT and the other two groups, but not between RT and RT + surgery. T1 tumor cases with incomplete RT were characterized by a higher C-Score (higher incidence of comorbidity and complications), lower albumin concentration and poor performance status. Median survivals of 60 years, 70 and 80 were 12, 5.4 and 6.2 months, respectively. Performance status and C-score were significantly different between the 60 yr and 80 yr groups. Survival rates were also apparently affected by the size of the primary tumor and metastasis. Thus important factors influencing prognosis were performance status, albumin concentration, and comorbidity and complications, in addition to stage of tumor itself. Although performance status and albumin concentration were considered directly related to tumor stage, old age may have an adverse effect on these factors through increase of comorbidity and complication. The data may be useful for decision making for treatment of esophageal cancer of the aged.

Age Factors↗
PubMed1994

[Monitoring tumor response to therapy by means of 31P magnetic resonance spectroscopy. A case of advanced prostatic cancer with metastatic chest wall tumor].

The response of advanced prostatic cancer with metastatic chest wall tumor to high-dose diethylstilbestrol diphosphate (DESP) therapy was monitored by in vivo 31P magnetic resonance spectroscopy (31P MRS) study. A eighty-three year old man with Stage D2 prostatic cancer had been treated with chlormadinone acetate and cyclophosphamide since 1984. He was admitted to our hospital with a chest wall tumor and anemia on May 9, 1992. The elevated PAP, PSA and gamma-Sm levels were also observed. Needle biopsy of the tumor revealed poorly differentiated adenocarcinoma metastatic from the prostatic cancer. The patient received 500 mg of DESP by DIV daily for 10 days, and the tumor was reduced by 54% clinically. The abnormal PAP, PSA and gamma-Sm levels returned to almost normal range by three weeks after the initiation of high-dose DESP therapy, and regression of the tumor was confirmed by the MRI. After the first administration of DESP, the MR spectra of the chest wall tumor showed elevated peaks of phosphomonoesters and phosphodiesters. These substances are related to the membrane metabolism and their increase represents the membranous degeneration of tumor cells. The same changes continued consecuitively for three weeks, and corresponded with the regression of the tumor. In conclusion, these results suggest that in vivo 31P MRS of malignant tumors can be useful for evaluating early response to therapy prior to other clinical examinations.

Adenocarcinoma↗
PubMed1994

[Serum granulocyte-colony stimulating factor (G-CSF) levels in elderly patients with infections].

To clarify the clinical role of granulocyte-colony stimulating factor (G-CSF), we examined the levels of serum G-CSF in elderly patients with infection (n = 48) and elderly normal volunteers (n = 32). G-CSF levels were significantly higher in patients in acute infectious status (571.9 +/- 782.9 pg/ml, mean +/- SD) than in normal volunteers (25.3 +/- 19.7 pg/ml). There was no significant relationship between serum G-CSF levels and age or granulocyte count in normal volunteers. In acute infectious status, there was no relationship between serum G-CSF levels and granulocyte count or c-reactive protein (CRP). We compared the response of G-CSF to infection between patients with frequently repeated infection (repeaters) and others (non-repeaters). Repeaters showed relative lower elevation of G-CSF levels in acute infectious status compared with non-repeaters (197.6 +/- 370.0 pg/ml vs. 1014.1 +/- 927.4 pg/ml p < 0.001). In other clinical data, serum albumin was significantly lower in repeaters than in non-repeaters. There was no significant difference in age, serum total protein, white blood cell count, granulocyte count and CRP. In non-repeaters, G-CSF levels was significantly higher in acute phase of infection than in recovery phase (550 +/- 703 pg/ml vs. 37.5 +/- 39.2 pg/ml p < 0.01 n = 15). We determined the status which showed incomplete recovery of infectious symptoms as chronic phase. In twenty-two of repeaters, we examined serum G-CSF levels and clinical data in acute and chronic phase of infection. There was no significant difference in G-CSF levels between in acute and chronic phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Intrabullar suction-adhesion in a case of giant bulla of the lung with steroid--department intractable bronchial asthma].

We successfully reduced a giant bulla using an intrabullar suction-adhesion method in a case of steroid-dependent intractable bronchial asthma. A 53-year-old woman was hospitalized with an asthma attack, and suffered pneumonia in the area surrounding a giant bulla after remission of two episodes of asthma. After the pneumonia, we found that the giant bulla had increased in volume. It was readily apparent that the bulla should be reduced. At that time a right side pneumothorax occurred by accident, which improved the chest drainage. Immediately after that, we inserted a chest drainage tube directly into the bulla and instilled fibrin glue through the tube into the bulla. Intrabullar suction and bronchial embolization via bronchofiberscopy has been used to patients with inoperable giant bullae of the lung. If intrabullar suction with fibrin glue alone can reduce giant bulla, it would offer another option to patients with inoperable giant bullae without the risk of a surgical procedure.

Asthma↗
PubMed1994

[A case of synchronous double cancer in the same pulmonary lobe].

We have experienced a case of synchronous double cancer developing in the right lower lobe in a 75-year-old male. He was asymptomatic. His chest X-ray film showed two nodular shadows, one in the right proximal S8 and another in peripheral S9. The serum CEA level was elevated to 9.5 ng/ml. Bronchoscopic brush cytology revealed adenocarcinoma from the tumor in orifice of B8. He was therefore diagnosed preoperatively as having adenocarcinoma of the right S9 with metastasis to #12 hilar lymph node. Right lower lobectomy was performed. The final histological diagnosis was double primary lung cancer consisting of squamous cell carcinoma (S9) with rare mucoepidermoid carcinoma in the same lobe. His postoperative course was uneventful.

Aged↗
PubMed1994

[An adult case of congenital esophagobronchial fistula complicated with pyothorax].

A 64-year-old woman with congenital esophagobronchial fistula complicated with pyothorax is reported. She was admitted to our hospital because of high fever and cough. Chest X-ray showed a cavity with niveau in the right lower lobe. The next day she noticed right chest pain. Chest X-ray showed right pleural effusion. The diagnosis of left esophagobronchial fistula with pyothorax was confirmed by esophagography, esophagoscopy, chest X-ray and chest CT. After treatment of the pyothorax with antibiotics and drainage, fistulectomy and right lower lobectomy were performed. The postoperative course was uneventful. Histologically, the fistula had esophageal epithelium with a submucosal muscle layer and demonstrated a transitional zone between squamous epithelium and bronchial epithelium.

Bronchial Fistula↗