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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 235 records · Page 13Linked to original sources

Substrate specificities of the protease of mouse serum Ra-reactive factor.

Ra-reactive factor (RaRF) is a serum bactericidal factor whose function seems to be to activate C in a manner similar to that of C1, but with activation triggered by binding to bacterial polysaccharides instead of to immune complexes. It is composed of multiple polysaccharide-binding subunits associated with a novel serine protease, and its overall structural organization is similar to that of C1. This similarity extends to the serine protease component, which shares a similar modular construction and about 40% sequence identity with the C1r and C1s subcomponents of C1. In this study, we examined the substrate specificity of mouse RaRF by assaying its ability to cleave C components C3, C4, and C5, and its activity against the murine C4 isotype, sex-limited protein. Our results revealed that RaRF preferentially cleaves the C4 alpha-chain with specific activities 20- to 100-fold greater than either human or murine C1s, and that RaRF also cleaves the C3 alpha-chain, but with a lower efficiency than C4 alpha. We also found that RaRF is much less sensitive than C1s to mutations near the proteolytic site and that the two proteases show different reactivities against synthetic substrates. Hence, although the RaRF protease and C1s have similar structures and play similar roles in C activation, they also display clear differences in substrate range and in the details of their substrate recognition mechanisms. Finally, we found that RaRF does not cleave sex-limited protein even at a level 100-fold higher than necessary for C4 cleavage.

Amino Acid Sequence↗

Localization of the genes for the 100-kDa complement-activating components of Ra-reactive factor (CRARF and Crarf) to human 3q27-q28 and mouse 16B2-B3.

Human and mouse genes for the complement-activating component (P100) of Ra-reactive factor, a novel bactericidal factor (CRARF and Crarf), were mapped to R-banded metaphase chromosomes by fluorescence in situ hybridization with human and mouse P100 cDNA 2.7 and 2.0 kb long, respectively. The localization of fluorescent signals showed that CRARF and Crarf mapped to human 3q27-q28 and mouse 16B2-B3, respectively. This evidence is consistent with the previous assumption that the distal portion of the long arm of human chromosome 3 is homologous to the proximal portion of mouse chromosome 16.

Animals↗

Characterization of thermal hyperalgesia, c-fos expression, and alterations in neuropeptides after mechanical irritation of the dorsal root ganglion.

STUDY DESIGN: This study analyzed hypersensitization in sensory systems after mechanical irritation of the dorsal root ganglion. OBJECTIVES: To develop a reliable and reproducible animal model of hyperalgesia arising from the dorsal root ganglion and to understand the unique contributions of the dorsal root ganglion to clinical manifestations of sciatica. SUMMARY OF BACKGROUND DATA: The dorsal root ganglion likely plays an important role in disorders of sciatica. However, no previous study has analyzed sciatica after irritation of the dorsal root ganglion. Thermal hyperalgesia indicates a decrease in thermal nociceptive threshold and hypersensitization in sensory systems. METHODS: The left L4 and L5 dorsal root ganglia in rats (n = 22) were exposed circumferentially. Other rats (n = 22) also had the left L4 and L5 dorsal root ganglia ligated loosely with two 4-0 chromic gut sutures. Changes in thermal withdrawal latency were examined in the hindpaws across time. Substance P and vasoactive intestinal polypeptide contents were quantified in the dorsal root ganglion and spinal cord. Substance P, calcitonin gene-related peptide, and c-fos expression also were examined in the spinal cord by immunohistochemistry. In addition, histologic changes in myelinated nerve content were examined in the dorsal root ganglion. RESULTS: Thermal hyperalgesia occurred in rats with exposure of the dorsal root ganglion and in rats with loose ligation of the dorsal root ganglion, and was accompanied by an increase in c-fos expression and spontaneous pain-related behaviors. CONCLUSIONS: This experimental model reliably produced a disorder resembling an acute phase sciatica and should help further advance the understanding of pathomechanisms of spinal pain after irritation of the dorsal root ganglion in humans.

Animals↗

Splenectomy before tumor inoculation prolongs the survival time of cachectic mice.

The effects of splenectomy on the development of cachexia, tumor growth and animal survival were studied in tumor-bearing CDF1 mice. Mice were inoculated with two subclones of colon 26 adenocarcinoma, clone 20 (with a potent capacity to induce cachexia) and clone 5 (without such activity), and underwent splenectomy before or after tumor inoculation. Splenectomy significantly prolonged the survival of mice bearing clone 20 when it was performed prior to tumor inoculation, although the progression of cachexia and tumor growth were not affected. The survival rate was higher in splenectomized than it was in nonsplenectomized mice 20-40 days after tumor inoculation. Such effects on survival were not observed, however, in mice splenectomized after inoculation with clone 20 or in mice that underwent splenectomy either before or after inoculation with clone 5. The decrease of peripheral blood lymphocyte count observed in mice bearing clone 20 was magnified when splenectomy was performed before tumor inoculation, but the serum levels of tumor necrosis factor and interleukin-6 were comparable. These results indicate that cancer death from cachexia is not directly attributable to enhanced catabolism. The mechanism by which splenectomy ameliorates the survival of cachectic mice remains to be studied, although several changes observed in the splenectomized mice after inoculation, including decreases in the peripheral blood L3T4+ cells and Lyt-2+ cells on the 9th day and 15th day respectively, and increase in the L3T4+/Lyt-2+ cell ratio on the 15th day suggest the involvement of the modified host's immune response.

Adenocarcinoma↗

Bond strength, interfacial characterization, and fracture surface analysis for a new stress-breaking bonding agent.

Three commercial dentin bonding systems were analyzed by tensile bond testing, area analysis of fractured surfaces, and SEM analysis of the tooth-resin interfaces. Tensile bond strengths in megapascals(SD) were Tenure-Marathon V ([T-M]; 8.86[3.02]), new system with low-viscosity resin ([K-LVR-P]; 6.50[2.01]), and new system without low-viscosity resin ([K-P] = 7.28[1.75]), which were significantly greater than Scotch-bond 2-P50 ([SB-P50]; 3.96[1.02]). Gaps that ranged up to 5.6 microns (mean for the group) were observed around most of the restorations at dentin surfaces and less so at enamel surfaces, where some of the restorations remained free of gaps. The gaps near the dentin margin were significantly smaller for K-LVR-P than for SB-P50. The tensile test revealed mixed failure modes in all systems, and in the cross sections of class V restorations, the gaps were confined to the dentin-resin junction.

Analysis of Variance↗

Interleukin-8 and monocyte chemotactic activating factor responses to cardiopulmonary bypass.

Cardiac operations with cardiopulmonary bypass cause a systemic inflammatory response. Neutrophils and monocytes-macrophages play an important role in triggering the initiation of the inflammatory response. Recently, some kinds of cytokines that are powerful leukocyte chemotactic factors have been characterized concerning an inflammatory response: interleukin-8 has a potent chemoattractant activity for neutrophils, and monocyte chemoattractant factor has monocyte-macrophage chemotactic activity. To investigate the possible roles of the cytokines in the inflammatory response in cardiopulmonary bypass, 12 adult patients undergoing cardiopulmonary bypass were studied for measurement of interleukin-8 and monocyte chemoattractant factor. Systemic blood was collected before cardiopulmonary bypass, at the end of cardiopulmonary bypass, and at 3, 12, 24, and 48 hours after cardiopulmonary bypass from the patients' radial arteries. Significant increases in levels of interleukin-8 and monocyte chemoattractant factor were detected with a peak level at 3 hours after bypass compared with levels before cardiopulmonary bypass (p < 0.05). This study demonstrated that interleukin-8 and monocyte chemoattractant factor are released into the circulation after adult hypothermic cardiopulmonary bypass and reach a maximum level 3 hours after bypass.

Aged↗

Emphysematous cholecystitis after endoscopic wallstent placement complicated by distal migration of the stent.

Endoscopic placement of Wallstents was thought to be a less invasive procedure, and in previous publications serious complications were infrequent. We report here on the case of a 58-year-old man with unresectable pancreatic cancer who developed emphysematous cholecystitis after endoscopic placement of a Wallstent, which was further complicated by distal migration of the stent. A second stent had to be placed into the first to fully bridge the malignant stricture. Three days later, the patient developed cholecystitis and septic complications, and he finally died of septic shock with disseminated intravascular coagulation. This previously unreported complication should be considered if abdominal pain and high fever develop after Wallstent placement.

Cholecystitis↗

[A case of myelodysplastic syndrome who died of septic pulmonary embolism].

A case of myelodysplastic syndrome (MDS) complicated by septic pulmonary embolism is reported. A 61-year-old female who had been followed for refractory anemia with excess of blasts suddenly died of acute respiratory failure. An autopsy revealed massive pulmonary emboli with gram-positive cocci gathered in the emboli and alveolar spaces. Staphylococcus aureus was also detected through a blood culture from the right atrium. We speculate that pulmonary embolism was the result of septicemia induced by the immunosuppressive condition associated with MDS.

Fatal Outcome↗

Autolysis of methicillin-resistant Staphylococcus aureus is involved in synergism between imipenem and cefotiam.

Imipenem-induced autolysis and the activity of imipenem plus cefotiam were studied in 16 strains of methicillin-resistant Staphylococcus aureus (MRSA). The degree of imipenem-induced autolysis and the rate of synergistic action of imipenem plus cefotiam varied among strains and did not correlate with susceptibility to either imipenem or cefotiam. However, the degree of autolysis correlated well with susceptibility to the synergistic action of imipenem plus cefotiam. In methicillin-susceptible S. aureus strains, both imipenem-induced autolysis and the synergistic activity of the combined drugs were less than those observed in MRSA strains. Differences in the degree of autolysis were not due to differences in autolytic enzyme production. The autolysis of imipenem-pretreated MRSA was enhanced further by cefotiam, while treatment of cells in the reverse order did not enhance autolysis. These findings indicate that cell wall impairment in MRSA is caused by exposure to imipenem but not to cefotiam and that this difference in drug actions results in synergism between imipenem and cefotiam. The possible participation of penicillin-binding proteins PBP 2' and PBP4 in the observed effect is discussed.

Bacterial Proteins↗

A free smooth muscle graft for a continent urinary conduit in dogs.

We constructed a continent, catheterizable urinary conduit using a smooth muscle graft in dogs. One end of an isolated vascularized ileal segment was anastomosed to the bladder dome, and the other end was opened in the abdominal wall. The ileal conduit was tightly encircled with a free seromuscular flap of the ileum in 6 dogs and with a similar flap of colon in 6 other dogs. All smooth muscle grafts were alive 6 months after the operation. Pressure study showed that all but one ileal conduit had a pressure of more than 30 cm of water. Two dogs with a free ileal graft leaked urine when the bladder pressure increased, whereas all dogs with a colonic graft never leaked urine from the stoma. This smooth muscle graft will be available to reinforce the continent action of a plicated or narrowed intestinal tube for a urinary reservoir.

Animals↗

Synthesis and evaluation of novel pyrazolo[1,5-alpha]pyrimidine derivatives as nonpeptide angiotensin II receptor antagonists.

A novel series of 6-alkyl-7-oxo-4,7-dihydropyrazolo[1,5-alpha]pyrimidine-3-carboxyli c acid derivatives was prepared as angiotensin II (AII) receptor antagonists. When evaluated in an in vitro binding assay using COS cells transfected with a cDNA encoding a human AT1 angiotensin II receptor, the compounds in this series showed Ki values in the range of 0.4-4.0 nM. In anesthetized spontaneously hypertensive rats (SHRs), administration of the 6-propyl derivative 4d (1 mg/kg, i.v.) reduced the mean blood pressure (MBP) by a maximum of more than 30 mmHg from the normal value.

Angiotensin II↗

Effect of lidocaine injection of EOAE in patients with tinnitus.

In the present study, evoked otoacoustic emissions (EOAEs) were measured in 30 patients with tinnitus before and after intravenous lidocaine injection (1 mg/kg). For EOAE recordings, 1 kHz tone burst stimuli were used. Intravenous lidocaine injection resulted in suppression of tinnitus in 22 (73%) ears, and changes of EOAE amplitude (increase or decrease) in 18 (60%) ears. Of the 18 ears with EOAE amplitude changes, tinnitus disappeared or decreased in 17 (94%) ears. In 12 ears without changes of EOAE amplitude, tinnitus was suppressed in only 5 (42%). Changes in latency were not detected in any of the ears. These results indicate that there is a relationship between the effect of lidocaine in tinnitus suppression and changes in cochlear micromechanics caused by lidocaine.

Acoustic Stimulation↗

[Thyroid hormones in patients with acute exacerbations of pneumoconiosis].

Thyroid hormone levels in serum were measured in 34 patients with acute exacerbations of pneumoconiosis. Levels of free T3 were below the normal range in 26 patients, and 12 of those patients (46.2%) died. Levels of free T3 were within the normal range in 8 patients, and only of those patients died. Having a T3 level within the normal range was associated with a good outcome. Levels of free T3 measured during acute exacerbations were significantly lower than those measured when the disease was clinically stable. Patients who died tended to have lower levels of free T3 than did those who survived. These results suggest that levels of free T3 in serum samples taken during an acute exacerbation can helpful in predicting the outcome of pneumoconiosis.

Aged↗

[The effects of the treatment with oxitropium bromide after one month or more in patients with pulmonary emphysema--evaluation of pulmonary function tests, exercise tests, and a questionnaire].

Chronic effects of oxitropium bromide were studied in patients with pulmonary emphysema. Pulmonary function tests, an exercise test, and a questionnaire were used. Seven subjects underwent two successive studies, including a questionnaire on QOL, pulmonary function tests, and an exercise test before and after one month or more of regular inhalation of ocitropium bromide (600 micrograms/day). The complaint of breathlessness was significantly reduced and the ability to perform activities of daily living had improved slightly after the treatment. There were no significant differences in the values of arterial oxygen pressure at rest. The VC, RV/TLC, and peak expiratory flow rate improved. A significant decrease in oxygen uptake at rest, a slight decrease in minute ventilation at rest, and a significant prolongation of exercise time were observed after the treatment. No other changes were noted. We conclude that oxitropium bromide may improve lung mechanics and reduce the work of respiratory muscles.

Administration, Inhalation↗

[Studies concerning the pathogenesis of trigeminal neuralgia caused by cerebellopontine angle tumors].

It has been well recognized that neurovascular compression can elicit trigeminal neuralgia (TN) and microvascular decompression surgery has become popular as a radical treatment of this clinical symptom. Cerebellopontine (C-P) angle tumors, however, as well known, can also cause TN. Four hundred fifty six patients with TN underwent posterior fossa exploration between 1984 and 1992 in our clinic, and among them, 45 (9.9%) patients harbored C-P angle tumors which were causative of TN. They included 22 epidermoids, 18 meningiomas and 5 neurinomas. The patient population consisted of 35 women and 10 men, ranging in age from 28 to 73 years, with a mean age of 51.7 years. The mean age of the patients of TN with tumors is considerably lower than that of neurovascular compression patients (61.0 years), particularly in cases of neurinomas (44.4 years) and epidermoids (48.0 years) (p < 0.01). Such difference in ages at the onset of symptom may be explained by the fact that the tumor growth in the C-P angle develops earlier than changes of the vasculature of the vertebrobasilar artery system by aging. Anatomical relationships between the 5th cranial nerve and offending arteries or tumors verified at surgery are as follows; Type A: The nerve is totally encased by the tumor. Type B: The axis of the nerve is distorted by the tumor. Type C: The nerve is shifted by the tumor and is compressed by the artery contralaterally. Type D: The nerve is compressed by the artery which was displaced by the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinical evaluation of cefpodoxime proxetil, a new oral cephem, in the treatment of respiratory tract infections with the special reference to community-acquired Streptococcus Pneumoniae infections].

The clinical usefulness of cefpodoxime proxetil (CPDX-PR) was investigated in the treatment of pneumonia and chronic airway infections occurring in patients first visiting our outpatient clinic or those being treated at the outpatient clinic. CPDX-PR was orally administered twice a day after meals at a dose of 100-200 mg for acute respiratory tract infections and at a dose of 200 mg for chronic respiratory tract infections. Excellent, good, fair, and poor responses were observed in 20, 33, 10, and 3 of 66 patients (4 with acute bronchitis, 27 with pneumonia, and 35 with acute exacerbation of chronic airway infection), respectively, demonstrating an 80.3% efficacy rate (53/66). Causative organisms, including Streptococcus pneumoniae, were all eradicated from the patients whose causative organisms were examined over time, although 2 of the patients were superinfected with Pseudomonas aeruginosa. There were no serious adverse reactions or abnormal changes in laboratory test results. It was concluded that CPDX-PR could be used as a first-choice drug for the treatment of respiratory tract infections at an outpatient clinic, and that this drug should acquire greater importance in particular consideration of recent increases in infections with S. pneumoniae.

Adult↗

[Anesthetic management of a patient with congenital cystic adenomatoid malformation].

Congenital cystic adenomatoid malformation (CCAM) is a rare disease that is diagnosed by severe respiratory dysfunction from birth. A 5-day-old-boy with CCAM underwent removal of a large cyst which was present at lower lobe of right lung. Anesthesia was induced slowly and maintained with oxygen and sevoflurane. Severe airway obstruction occurred transiently by the secretion from the lung cyst. Thereafter, the surgery was completed safely and his postoperative course was uneventful. Perioperative anesthetic management of the patient with CCAM is also discussed.

Airway Obstruction↗

Chloroplast protein import. Chloroplast envelopes and thylakoids have different abilities to unfold proteins.

Proteins have to be at least partially unfolded upon passage through the biological membranes. Previous studies with a dihydrofolate reductase fusion protein containing a chloroplast transit peptide showed that stabilization of the tertiary structure of the fusion protein by binding of a ligand, methotrexate, failed to block its translocation across the envelopes, suggesting that chloroplast envelopes have strong activity to unfold proteins [America, T., Hageman, J., Guéra, A., Rook, F., Archer, K., Keegstra, K. & Weisbeek, P. (1994) Plant Mol. Biol. 24, 283-294]. In the present study, we have analyzed in vitro translocation of a fusion protein consisting of the entire plastocyanin precursor and dihydrofolate reductase across the chloroplast envelope membranes and the thylakoid membrane. In the presence of methotrexate, the fusion protein was imported into the stroma but its translocation across the thylakoid membrane was blocked. The fusion protein that bound to the envelope became susceptible to digestion by thermolysin. These results suggest that, while the envelope membranes can unfold the methotrexate-bound fusion protein to allow its passage, the thylakoid membrane cannot unfold the fusion protein that has re-bound to methotrexate in the stroma.

Amino Acid Sequence↗