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Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 73 records · Page 4Linked to original sources

Application of the fold plication method for unilateral lung volume reduction in pulmonary emphysema.

BACKGROUND: Unilateral lung volume reduction procedures are used to treat pulmonary emphysema. The most significant technical problem with this operation is an air leak from the pulmonary stump. Bovine pericardium has been used to prevent air leaks but is associated with interstitial pneumonia and a high cost. METHODS: The fold plication method was devised to prevent postoperative air leaks to avoid interstitial pneumonia, and to decrease cost. This technique was applied in 20 consecutive patients with emphysema who underwent a unilateral lung volume reduction operation via a thoracoscopic two windows approach. RESULTS: The operative time was approximately 1 hour. There was minimal postoperative bleeding, no persistent air leaks, and no evidence of pneumonia. Pulmonary function improved in all patients. CONCLUSIONS: The unilateral fold plication method is an economical and safe alternative to bovine pericardial patching after lung volume reduction operation to prevent stump air leaks.

Adult↗

Immature astrocytes in Fukuyama congenital muscular dystrophy: an immunohistochemical study.

Recent studies of Fukuyama congenital muscular dystrophy have focused on abnormalities of the basement membrane in muscle and brain. The cerebral cortex has a unique basement membrane at the glia limitans, which is intimately related to astrocytes in the developing brain, and the basement membrane may be partially produced by the astrocyte. In this study the cerebral astrocytes in six patients with Fukuyama congenital muscular dystrophy, including two fetal patients, were characterized by immunohistochemical study. In fetal Fukuyama congenital muscular dystrophy, astrocytes reacted less to antibodies of glial fibrillary acidic protein, S-100 protein, and alphaB-crystallin than control astrocytes, but in postnatal Fukuyama congenital muscular dystrophy, astrocytes reacted more to these antibodies and displayed beading of processes. Moreover, vimentin was positive in the astrocytes of two postnatal Fukuyama congenital muscular dystrophy patients. This astrocytic appearance may suggest immaturity of astrocytes in Fukuyama congenital muscular dystrophy. Astrocytes exhibiting beaded cytoplasmic processes were prominent at the subpia of the cortex and around vessels. The authors hypothesize that these immature astrocytes are unable to participate in the function of the cortical basement membrane, which is defective in Fukuyama congenital muscular dystrophy. Studies of neurons and meninges were similar to those of control subjects.

Adolescent↗

Physical and psychological improvements after phase II cardiac rehabilitation in patients with myocardial infarction.

We have designed a new 4-week hospitalized phase II cardiac rehabilitation program. The purpose of the present study is to clarify whether the physical and psychological status of patients with myocardial infarction (MI) improves after participation in our program. Twenty-nine patients (27 males, two females) with acute MI who enrolled in the 4-week hospitalized phase II rehabilitation program were assessed. All patients enrolled in this study had received coronary interventions. The rehabilitation consisted of exercise training, education and counseling. We evaluated the physical and psychological status of the patients before and just after the program, and at a 6-month follow up. The physical status was assessed by exercise tolerance measured by the peak oxygen consumption and anaerobic threshold, frequency of exercise, and serum concentrations of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol. The psychological status was assessed by the Spielberger state-trait anxiety inventory questionnaire (STAI) and the self-rating questionnaire for depression (SRQ-D). Thirty-four patients (27 men, seven women) with MI who did not participate in our rehabilitation program served as a control group. After participation in our rehabilitation program, exercise tolerance and the serum lipid profiles of the patients were improved compared with those before rehabilitation. These parameters had improved significantly 6 months after rehabilitation. The STAI anxiety score was improved significantly and the SRQ-D depression score tended to be improved just after the rehabilitation program. Regular physical activity was continued even 6 months after the completion of the program. Our hospitalized phase II cardiac rehabilitation program improved the management of cardiac risk factors and the psychological status in patients with MI. This comprehensive program may contribute to the secondary prevention of MI as well as the recovery of physical and psychological activities.

Adult↗

Renal-protective effect of non-depressor dose of cicletanine in streptozotocin diabetic rats.

OBJECTIVE: To assess the renal benefits of cicletanine (CIC) in diabetic rats with renal impairment. METHODS: Hemi-nephrectomized streptozotocin-diabetic Wistar-Kyoto Izmo rats (WKYIzm) (10 weeks old) were randomly assigned to receive vehicle or a low or high dose of CIC (30 or 100 mg/kg per day, orally) for 12 weeks. RESULTS: The blood pressure was raised slightly but not significantly in this model. An anti-hypertensive effect of CIC was not significantly observed. However, the sub-depressor doses of CIC significantly and dose-dependently decreased urinary albumin excretion. These results were confirmed by morphological analysis of kidneys in each group of rats. CIC treatment significantly and effectively protected against an increase in the percentage of focal glomerular sclerosis. CIC did not affect urinary and blood glucose concentrations at either dose. CONCLUSIONS: These results suggest that CIC has a renal-protective action, which is not related to improvement of diabetes or of high blood pressure in this model. The action might be due to the reduction of intraglomerular capillary pressure, although the mechanism remains to be further investigated.

Animals↗

Plasma platelet-activating factor acetylhydrolase deficiency in Japanese patients with asthma.

Platelet-activating factor (PAF), a phospholipid with a wide range of proinflammatory actions, is immediately degraded and inactivated in vivo by PAF acetylhydrolase (PAF-AH). Surprisingly, 4% of the Japanese population lacks the extracellular isoform of this enzyme, plasma PAF-AH, due to a genetic missense (V279F) mutation. We studied the association of this mutation with asthma prevalence and phenotypes in the Japanese adult population. The allele frequency of V279F mutation was 18.6% in 279 patients with asthma (28.7% heterozygotes and 4.3% homozygotes) and 21.7% in 217 healthy subjects (32.3% heterozygotes and 5.5% homozygotes). V279F mutant allele prevalence was consistent regardless of asthma type (16.3% in atopic [n = 156] and 21.6% in nonatopic [n = 123]), or the severity of disease (21.7% in patients with mild [n = 97], 17.5% in those with moderate [n = 131], and 15.8% in those with severe [n = 51] asthma). Plasma PAF-AH activity was inversely proportional to the number of mutant alleles, and did not correlate with asthma prevalence, type, or severity. We concluded that plasma PAF-AH deficiency due to V279F mutation is not essential to the pathophysiology of asthma in the Japanese adult population.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection.

The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated. Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM). The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils. Arterial oxygen tension (p<0.05), vital capacity (VC) (p<0.001), %VC (p<0.05) and forced expiratory volume in one second (p<0.01) were improved after RXM treatment, but airway bacteria were not eradicated. Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p<0.05 for each). RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients. In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils. In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells.

Anti-Bacterial Agents↗

The role of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotypes in alcohol-induced vasospastic angina.

Alcohol ingestion often provokes attacks in patients with vasospastic angina. Type 2 aldehyde dehydrogenase (ALDH2) deficiency, which is based on a single point mutation (Glu487Lys) of the ALDH2 gene, is common in the Japanese population, but rare among the Caucasian population. We investigated how the genotype of ALDH2 affects the characteristics of alcohol-induced vasospastic angina. Ninety-one patients with vasospastic angina who had ingested alcohol daily or occasionally were studied. Patients had been diagnosed as vasospastic angina by a provocation test with an intracoronary injection of ergonovine or acetylcholine during coronary angiography. The Glu487Lys mutation was detected by allele specific PCR. We interviewed the patients to obtain information concerning the relationship between alcohol ingestion and anginal attacks. Alcohol ingestion induced attacks in 16 of 66 patients without the Glu487Lys mutation, 8 of 22 in heterozygotes, and 1 of 3 in mutant homozygotes. The intervals between alcohol ingestion and the onset of anginal attacks were shorter in homozygotes (0.17 hours) and heterozygotes (1.5+/-0.6 hours) for ALDH2*2 than in normal homozygotes for ALDH2*1 (5.4+/-0.6 hours). The amount of ethanol which induced attacks was significantly greater in normal homozygotes than in homozygotes (11 ml) and heterozygotes (42.5+/-7.1 ml) for ALDH2*2 (96.1+/-13.4 ml in normal patients). The frequency of anginal attacks induced by alcohol ingestion did not differ between ALDH deficient and normal homozygotes. In ALDH deficient patients, however, anginal attacks were induced by a smaller amount of alcohol immediately after its ingestion. Thus, the ALDH2 genotype modifies the characteristics of the anginal attacks as a co-factor for the induction of vasospastic angina after alcohol ingestion.

Alcohol Dehydrogenase↗

Changes in neoplastic cell features and sensitivity to mitotane during mitotane-induced remission in a patient with recurrent, metastatic adrenocortical carcinoma.

A 58-year-old man had adrenocortical carcinoma in the right adrenal gland. The tumour secreted excessive cortisol and dehydroepiandrosterone-sulphate (DHEA-S), and had invaded the right hepatic lobe and vena cava. Eleven months after surgical tumour resection, the serum DHEA-S levels again increased. Local tumour recurrence and a metastasis was found in the lung. Eleven months after surgery chemotherapy with mitotane (o,p'-DDD) was initiated. Twelve weeks of mitotane reduced serum DHEA-S levels and caused these tumours to disappear. The patient was then treated with low-dose mitotane (1.5-2.0 g/day) for 2 years. Serum levels of mitotane remained at less than 10 microg/ml. Although such low serum levels of mitotane and delayed initiation of mitotane after surgery have been proposed to weaken the antineoplastic effect of mitotane, the patient had a remission for 2 years. However, there was then local re-recurrence with an increase in serum DHEA-S and death 4 months later. The histological features of neoplastic cells were quite different comparing tumour resected at surgery and tumour at autopsy. The latter had more frequent mitotic nuclei. This tumour was initially sensitive to mitotane, but later became insensitive.

Adrenal Cortex Neoplasms↗

The use of sevoflurane anesthesia during early pregnancy.

Sevoflurane has favorable pharmacodynamic properties such as a rapid, smooth induction and emergence from anesthesia. However, there is only one report of sevoflurane anesthesia during early pregnancy. We report the use of sevoflurane for maintenance of general anesthesia in a pregnant patient undergoing non-obstetric surgery. A 25-year-old, female patient, at 13 weeks gestation, was diagnosed as having a strangulated ileus. General anesthesia was performed and maintained with oxygen, nitrous oxide, and sevoflurane. Six months later a healthy infant without abnormalities was delivered.

Adult↗

Evaluation of cytotoxicity of UHMWPE wear debris.

We established a novel method to investigate the phagocytosis of ultra high molecular weight polyethylene using primary macrophage cells by an inverted cell culture method. Abundant wear debris derived from implant materials are generated in aseptic loosening and are deposited in periprosthetic tissues in which they are phagocytized by mono- and multi-nucleated macrophage like cells. Ultra-high-molecular-weight-polyethylene wear debris generated from different sources namely, from laboratory test wear machine, in vivo methods and from knee and hip simulator were mainly used in this investigation. The cytotoxicity index of the different UHMWPE particles obtained from various sources were compared with that of the PE beads and the control without particles by Alamar Blue and Neutral Red assays. The results showed that the cytotoxicity index was significantly lower for the wear debris from the in vivo experiments than that for other particles. SEM analysis were also done to understand the morphology of the wear debris and polyethylene beads and to confirm the phagocytosis process. The mean diameter of the wear debris obtained from the in vivo experiments as estimated from the imaging analysis of the SEM photographs was found to be the least. The inverted cell culture method may be regarded as one of the good methods to study the phagocytosis of UHMWPE by macrophage cells.

Animals↗

Development of a new catheter-tip pressure transducer.

Two major disadvantages of the conventional catheter-tip transducer have been incapability to calibrate baseline pressure and to adjust sensitivity after insertion. A vast majority of conventional catheter-tip transducers are classified as gauge type. Due to their structure they are inherently incapable of recalibrating after insertion. We have overcome this problem by developing a new differential type catheter-tip transducer equipped with a lumen that connects a small chamber at the backside of the transducer to another external port. This lumen is capable of pressure passage. The output of this type depends on the difference between the two imposed pressures. This passage makes a baseline standard possible, when the end of the lumen is exposed to atmospheric pressure. When pneumatic pressure is imposed to the end of the lumen using a syringe, for example, the transducer output shifts up and down in accordance to that pressure, enabling baseline pressure recalibration and verifying the degree of sensitivity after insertion. By obtaining the following data, we confirmed the stability and availability of this transducer: Baseline drift less than 0.04 mmHg/8 hour, frequency characteristics flat up to 60 Hz, and common mode rejection ratio more than 46 dB.

Catheterization, Peripheral↗

Functional analysis of human mitochondrial receptor Tom20 for protein import into mitochondria.

The mitochondrial import receptor translocase of the outer membrane of mitochondria (Tom20) consists of five segments, an N-terminal membrane-anchor segment, a linker segment rich in charged amino acids, a tetratricopeptide repeat motif, a glutamine-rich segment, and a C-terminal segment. To assess the role of each segment, four C-terminally truncated mutants of the human receptor (hTom20) were constructed, and the effect of their overexpression in COS-7 cells was analyzed. Expression of a mutant lacking the tetratricopeptide repeat motif inhibited preornithine transcarbamylase (pOTC) import to the same extent as the wild-type receptor. Thus, overexpression of the membrane-anchor and the linker segments is sufficient for the inhibition of import. Expression of either the wild-type receptor or a mutant lacking the C-terminal end of 20 amino acid residues stimulated import of pOTC-green fluorescent protein (GFP), a fusion protein in which the presequene of pOTC was fused to green fluorescent protein. On the other hand, expression of mutants lacking either the glutamine-rich segment or larger deletions inhibited pOTC-GFP import. In vitro import of pOTC was inhibited by the wild-type hTom20 and the mutant lacking the C-terminal end, but much less strongly by the mutant lacking the glutamine-rich segment. On the other hand, import of pOTC-GFP was little affected by any of the forms of hTom20. In binding assays, pOTC binding to hTom20 was only moderately decreased by the deletion of the glutamine-rich segment, whereas pOTC-GFP binding was completely lost by this deletion. Binding of pOTCN-GFP a construct that contains an additional 58 N-terminal residues of mature OTC, resembled that of pOTC. All of these results indicate that the region 106-125 containing the glutamine-rich segment of hTom20 is essential for binding and import stimulation in vivo of pOTC-GFP and for inhibition of in vitro import of pOTC. The results also indicate that this region is important for mitochondrial aggregation. The different behaviors of pOTC and the pOTC-GFP chimera toward hTom20 mutants is explicable on the basis of the conformation of the precursor proteins.

Animals↗

Pharmacological properties of the CO2/H+-sensitive area in the ventral medullary surface assessed by the effects of chemical stimulation on respiration.

We recently discovered that CO2/H+-sensitive neurons in the ventral medullary surface (VMS) are immunoreactive to glutamate, glutamic acid decarboxylase (GAD), calcineurin and cAMP. We then tested the hypothesis that glutamate, GABA, calcineurin and cAMP affect the activity of CO2/H+-sensitive neurons in the VMS. Using male Wistar rats anesthetized with urethane and pentobarbital, we checked for changes in relative tidal volume (VT) and respiratory frequency (f) in response to injecting the VMS with a variety of test agents dissolved in mock CSF. Respiratory changes occurred immediately and were dose-dependent. (1) 200-1600 pmol Glutamate increased VT but decreased f. The glutamate effect was never abolished by concomitant injection of AP5, a NMDA receptor antagonist, but was abolished by CNQX, an AMPA receptor antagonist, indicating predominance of AMPA receptors in the CO2/H+-sensitive neurons in the VMS. (2) 200-1600 pmol GABA decreased both VT and f. The GABA effect was never abolished by concomitant injection of saclofen, a GABA(B) receptor antagonist, but was abolished by bicuculline, a GABA(A) receptor antagonist, indicating predominance of GABA(A) receptors in the CO2/H+-sensitive neurons in the VMS. (3) 4-32 microg Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase 2B, and 200-1600 pmol FK506, selective inhibitor of calcineurin, had no effect on respiration when they were applied extracellularly, but 400-3200 pmol BAPTA-AM, an intracellular Ca2+-chelating agent, decreased both VT and f, indicating involvement of intracellular Ca2+ in the excitatory mechanisms of respiration. (4) 100-800 pmol IBMX, an enhancer of intracellular cAMP, decreased both VT and f, indicating involvement of cAMP in the inhibitory mechanisms of respiration. These results indicate that the CO2/H+-sensitive neurons in the VMS contain glutamate and/or GABA in cytoplasma, possess AMPA and/or GABA(A) receptors on surface of plasma membrane, and compose the internal circuit, and that their activities are regulated by Ca2+ and cAMP.

1-Methyl-3-isobutylxanthine↗

Topology and immunohistochemistry of proton-sensitive neurons in the ventral medullary surface of rats.

We aimed to clarify the topology and immunohistochemistry of CO2/H+-sensitive neurons in the ventral medullary surface (VMS), the central chemoreceptor area in rats. Inhalation of 3 and 7% CO2 in air significantly decreased pH in arterial blood and increased paCO2, which caused hyperpneic and tachypneic responses. Following inhalation of 3 and 7% CO2 in air for 5 min, the density of c-Fos-immunoreactive (IR) neurons increased stepwise not only in the 3rd-5th divisions of the VMS (between the caudal end of the nucleus corporis trapezoidei and the caudal end of the area postrema), but also in the rostroventromedial medulla (RVMM). Following inhalation of 7% CO2 in air for 5 min, glutamate-, glutamic acid decarboxylase (GAD)-, calcineurin- and cAMP-IR neurons were found not only in the VMS, but also in the RVMM. The topology of these neurons was similar to that of the c-Fos-IR neurons. No immunoreactivity was found for serotonin, substance P, somatostatin, cholecystokinin-octapeptide, methionine-enkephalin, choline acetyltransferase, tyrosine hydroxylase, phenylethanolamine N-methyltransferase, NO-synthase, S-100, calbindin-D, calmodulin, or parvalbumin. The densities of c-Fos-, glutamate-, GAD-, calcineurin- and cAMP-IR neurons were almost zero in the 1st division of the VMS, but became higher along the 2nd-4th divisions of the VMS. Regression lines of the density against the 1st-4th divisions of the VMS were significantly linear. These results indicate that H+-sensitive neurons are common in the 4th-5th divisions of the VMS, and that they are glutamatergic, GABAergic, and containing calcineurin and cAMP.

Administration, Inhalation↗

Inhibitory effects of prostaglandin D2 against the proliferation of human colon cancer cell lines and hepatic metastasis from colorectal cancer.

The inhibitory action of prostaglandin D2 (PGD2) and its effect on the cell cycle were examined in cell lines SW480 and LS174T of human colon cancer. The growth of the cell lines were assessed 24 h and 48 h after the addition of 1.0 microgram/ml and 10.0 micrograms/ml PGD2. The growth of SW480 cells was inhibited 48 h, but not 24 h, after the addition of 1.0 microgram/ml, and 24 h and 48 h after the addition of 10.0 micrograms/ml, while that of LS174T was inhibited by both doses after 24 h and 48 h. S-Phase DNA synthesis in the SW480 cells was significantly blocked 24 h after the addition of 10.0 micrograms/ml PGD2. The cell cycle of LS174T cells was arrested at the G0 + G1 phase 24 h after the addition of 1.0 microgram/ml and 10.0 micrograms/ml PGD2. The correlation between hepatic metastasis and PGD2 concentration in human cancer tissue was examined. The mean value of PGD2 concentrations in the primary cancer tissue was significantly lower in the hepatic metastasis group than that in the group without hepatic metastasis. These findings suggest that measuring the PGD2 in cancer tissue may be useful for detecting and predicting the hepatic metastasis from human colorectal cancer.

Biomarkers, Tumor↗

Expression analysis of two mutant human ornithine transcarbamylases in COS-7 cells.

Ornithine transcarbamylase (OTC) is located in the mitochondrial matrix of the liver and small intestine and catalyzes the second step of the urea cycle. OTC deficiency (OTCD) is an X-linked inborn error of metabolism and causes hyperammonemia. We reported in 1992 the A152V and G195R mutations in patients with OTCD. These mutant OTC cDNAs were prepared by site-directed mutagenesis using the polymerase chain reaction (PCR). The wild-type and mutant cDNAs were transiently expressed in COS-7 cells. The wild-type cDNA gave an OTC activity of 1180 +/- 47 nmol/min per mg protein. The OTC activities of the A152V and the G195R mutants were 3.7% and 2.5% of that of wild-type, respectively. Immunoblot analysis showed that the quantities of OTC proteins in the A152V and G195R mutants were 29% and 12% of that of wild-type, respectively. In pulse-labeling and pulse-chase experiments, the precursor form of OTC was synthesized and processed to the mature form. The A152V mutant OTC was processed to the mature form as rapidly as the wild-type precursor. However, the processed, mature form of the mutant OTC was rapidly degraded, presumably in the mitochondrial matrix. These results indicate that OTCD with the A152V mutation is due both to rapid degradation of the processed, mature form, and to a lower specific activity of the remaining protein.

Animals↗

Development and histologic characteristics of synovitis induced by trauma in the rat temporomandibular joint.

Histopathological changes caused by trauma to the rat temporomandibular joint synovium were examined by light microscopy. The trauma was induced by forced hypermobility of the condyle. Pathological changes of the synovium were found primarily in the anterior pouch of the upper joint compartment. The main findings included surface cell proliferation, increased capillary hyperemia, fibrin deposits on the surfaces of inflamed synovial membranes, and fibrinous adhesion between closely opposed synovial membranes. A gradual change from fibrinous adhesion to fibrous adhesion was also seen.

Animals↗