Search PubMed⌕ Search

Biomedical subjects

M Kawase

Publications and source records attributed to M Kawase.

At least 55 records · Page 3Linked to original sources
PubMed2000

Convenient synthesis of alpha-trifluoromethylated acyloins from alpha-hydroxy or alpha-amino acids.

Alpha-trifluoromethylated acyloins (2 and 6) have been prepared from alpha-hydroxy acids (1), N-acylprolines (5) or N-acyl-N-alkyl alpha-amino acids (8) by novel transformation reactions with trifluoroacetic anhydride (TFAA) in the presence of pyridine. The former reaction of 1 could proceed through mesoionic 1,3-dioxolium-4-olates, whereas the latter two reactions of alpha-amino acids (5 and 8) could involve mesoionic 1,3-oxazolium-5-olates. The reaction of 1 with TFAA shows more potential for practical applications because of the ready availability of the starting materials and ease of manipulation.

Acetic Anhydrides↗
PubMed2000

Antitumor potential and possible targets of phenothiazine-related compounds.

Phenothiazines and its related compounds have shown diverse biological activities including psychotropic, anticancer and other pharmacological activities. Recent studies have suggested the possible interactions between phenothiazines and their physiological targets or potential receptors. New types of phenothiazine, such as "half-mustard type" phenothiazines and benzo[a]phenothiazines, have been synthesized. These compounds stimulated T-cell blast formation, natural killer cell activity (possibly via activation of monocytes and macrophages) and antibody-dependent cellular cytotoxicity of human peripheral blood mononuclear cells, and showed cytotoxicity against several human cancer cell lines. Benzo[a]phenothiazines induced monocytic differentiation and apoptotic cell death (characterized by internucleosomal DNA fragmentation) in human myelogenous leukemic cell lines, but not in other cancer cell lines. These compounds also induced antimicrobial activity in vivo, possibly by host-mediated immunopotentiation. On the other hand, phenothiazines did not induce such immunopotentiation activity, but showed direct antibacterial activity in vitro. There was positive relation between their radical intensity and biological activities. These compounds did not show any apparent mutagenic activity, but rather be antimutagenic. These data suggest their possible applicability of "half-mustard type" phenothiazines and benzo[a]phenothiazines for cancer chemotherapy.

Animals↗
PubMed2000

Effect of administration of fermented milk containing whey protein concentrate to rats and healthy men on serum lipids and blood pressure.

The effect of fermented milk supplemented with whey protein concentrate on the serum lipid level of rats was investigated. The serum total cholesterol level for the group fed fermented milk with both Lactobacillus casei TMC0409 and Streptococcus thermophilus TMC 1543 was significantly lower than that of the control group (P<0.05) in rats. Furthermore, the effect of the longterm intake of this fermented milk on the serum lipid level of twenty healthy adult men was investigated. During the 8-wk study, the volunteers consumed 200 ml of fermented milk or placebo in the morning and evening. Blood samples were drawn for analysis three times, just before taking the experimental diet, and after 4 wk and 8 wk of consumption. After 8 wk, the high density lipoprotein cholesterol level for the fermented milk group showed a significant rise after 4 wk (P<0.05), whereas that of the placebo group showed no change even after 4 wk (P>0.05). The triglyceride level for the fermented milk group lowered significantly after 4 wk (<0.05), whereas that of the placebo group showed no change even after 4 wk (P>0.05). The atherogenic index [(total cholesterol - high density lipoprotein cholesterol)/high-density lipoprotein cholesterol] for the fermented milk group decreased significantly from 4.24 to 3.52 (P<0.05). The systolic blood pressure lowered significantly by the intake of fermented milk (P<0.05) On the other hand, such effect was not observed in the placebo group (P>0.05). These results indicate potential of the development of fermented milk with multiple therapeutic effects.

Adult↗
PubMed2000

[Surgical treatment for mitral regurgitation: mid-term outcome following mitral valve repair].

Mid-term results of mitral valve repair for mitral regurgitation were evaluated in 173 consecutive patients (mean age 53 years, 107 males, 66 females) treated from July 1991 to March 1998. Pathological causes of the mitral valve disease were degenerative in 118 patients, infective endocarditis in 25, rheumatic in 13, and ischemic in 8 (ischemic cardiomyopathy in 7). The principal technique was chordal replacement with expanded polytetrafluoroethylene sutures for prolapse of the anterior leaflet, and Carpentier's sliding leaflet technique for prolapse of the posterior leaflet. Most patients received ring annuloplasty with a rigid ring and flexible band (physiological remodeling annuloplasty). Intraoperative transesophageal echocardiography was used after 1993. There were 7 operative deaths (4%) and 7 mitral valve replacements (4%) during the same operation. Successful repair was achieved in 96% of patients with mitral regurgitation. Mean follow-up was 35 months (range 2 to 78 months). Survival at 6 years was 85 +/- 10% of all patients, 98 +/- 2% in degenerative cases. Six patients required reoperation (1.2%/patient-year) and mean time interval between initial operation and reoperation was 33.1 months. Four patients with atrial fibrillation had thromboembolic events (0.8%/patient-year). There were no anticoagulant-related complications. Freedom from reoperation and all valve-related event at 6 years was 88 +/- 6% and 84 +/- 6%. Late postoperative Doppler echocardiography revealed satisfactory results in 93% of the patients. Mitral valve repair using chordal replacement, sliding plasty and ring annuloplasty provides excellent mid-term results.

Disease-Free Survival↗
PubMed2000

[Spinal anesthesia for a patient with epidermolysis bullosa hereditaria dystrophica].

A 39-year-old male with epidermolysis bullosa hereditaria dystrophica was scheduled for surgical excision of squamous cell carcinoma in the lower leg. Spinal anesthesia was chosen, because the skin of the puncture site for spinal anesthesia appeared to be dry and scarred, and to have less chance of infection. To avoid shear stress to the skin, we carefully performed anesthetic management including attachment of equipments associated with anesthesia, monitoring and surgery. However, we experienced some troubles and complications associated with anesthetic technique, such as pain on removing a dressing sheet, burning sensations induced by alcoholic stimuli for cold sign test and tent-like traction of the punctured skin on withdrawing the spinal needle.

Adult↗
PubMed1999

Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme.

We examined the effects of the free radical scavenger, 21-aminosteroid, on apurinic/apyrimidinic endonuclease (APE/Ref-1) protein expression and subsequent infarction volume after photothrombotic cortical cerebral ischemia in mice. Immunohistochemistry and Western blot analysis showed a significant reduction in APE/Ref-1 expression 6 and 24 h after ischemia in untreated animals, whereas in drug-treated animals the reduction was much less at the same time points. The administration of 21-aminosteroid significantly decreased subsequent infarction volume 3 days after ischemia. These data suggest that 21-aminosteroid prevents the early decrease of APE/Ref-1 expression, thereby reducing cortical infarction after photothrombotic cerebral ischemia.

Animals↗
PubMed1999

Mitochondrial release of cytochrome c corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia.

Release of cytochrome c from mitochondria to the cytosol is a critical step in apoptotic cell death after focal cerebral ischemia. The relationship among cytochrome c release, selective vulnerability, and delayed death of hippocampal CA1 neurons after transient global ischemia was examined. Global ischemia was induced by 10 min of bilateral common carotid artery occlusion and hypotension in rats. Cytosolic expression of cytochrome c was evaluated by immunohistochemistry and Western blotting. Apoptosis after global ischemia was also characterized by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) staining and DNA gel electrophoresis. Immunohistochemistry showed cytosolic cytochrome c-positive cells exclusively in the CA1 subregion of the hippocampus as early as 2 hr after ischemia. Double fluorescent immunostaining confirmed that CA1 neurons and a small number of astrocytes expressed cytochrome c. Western blot analysis revealed a band (15 kDa) of cytochrome c in the cytosolic fraction and a corresponding decrease in the mitochondrial fraction. A significant number of TUNEL-positive cells appeared only in the CA1 pyramidal cell layer of the hippocampus, and DNA gel electrophoresis showed a significant amount of DNA fragmentation 3-5 d after ischemia. Our data provide the first evidence that cytochrome c was released to the cytosol from mitochondria in CA1 neurons after global ischemia and that the release preceded DNA fragmentation. These findings suggest cytochrome c involvement in the delayed death of hippocampal CA1 neurons in rats after transient global ischemia.

Animals↗
PubMed1999

Alpha-trifluoromethylated acyloins induce apoptosis in human oral tumor cell lines.

Cytotoxic activity of newly synthesized trifluoromethyl ketones and related compounds was studied using two human oral tumor cell lines (HSG and HSC-2). Among them, alpha-trifluoromethylacyloins (1 and 2) were found to induce apoptotic cell death, as judged by the terminal deoxynucleotidyl transferase (TdT) dUTP nick end-labeling (TUNEL) method which detects DNA nick or fragments. Furthermore, the cytoplasm of 1 or 2 treated HSG cells was stained by M30 monoclonal antibody, which detects the product resulting from the cleavage of cytokeratin 18 by activated caspase.

Antineoplastic Agents↗
PubMed1999

Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion.

Blood-brain barrier (BBB) disruption is thought to play a critical role in the pathophysiology of ischemia/reperfusion. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that can degrade all the components of the extracellular matrix when they are activated. Gelatinase A (MMP-2) and gelatinase B (MMP-9) are able to digest the endothelial basal lamina, which plays a major role in maintaining BBB impermeability. The present study examined the expression and activation of gelatinases before and after transient focal cerebral ischemia (FCI) in mice. Adult male CD1 mice were subjected to 60 min FCI and reperfusion. Zymography was performed from 1 to 23 h after reperfusion using the protein extraction method with detergent extraction and affinity-support purification. MMP-9 expression was also examined by both immunohistochemistry and Western blot analysis, and tissue inhibitors to metalloproteinase-1 was measured by reverse zymography. The BBB opening was evaluated by the Evans blue extravasation method. The 88-kDa activated MMP-9 was absent from the control specimens, while it appeared 3 h after transient ischemia by zymography. At this time point, the BBB permeability alteration was detected in the ischemic brain. Both pro-MMP-9 (96 kDa) and pro-MMP-2 (72 kDa) were seen in the control specimens, and were markedly increased after FCI. A significant induction of MMP-9 was confirmed by both immunohistochemistry and Western blot analysis. The early appearance of activated MMP-9, associated with evidence of BBB permeability alteration, suggests that activation of MMP-9 contributes to the early formation of vasogenic edema after transient FCI.

Animals↗
PubMed1999

Release of mitochondrial cytochrome c and DNA fragmentation after cold injury-induced brain trauma in mice: possible role in neuronal apoptosis.

Recent studies have shown that release of mitochondrial cytochrome c is a critical step in the apoptosis process. In this study, we examined the subcellular distribution of the cytochrome c protein after cold injury (CI), in which apoptosis is assumed to participate. Western blotting and immunohistochemistry showed cytosolic cytochrome c as early as 1 h after CI, and correspondingly, there was a reduction in mitochondrial cytochrome c after injury. Neuronal distribution of cytosolic cytochrome c was shown by double staining with a neuronal nuclear marker by immunohistochemistry. A significant amount of DNA laddering was detected 4 h after CI, and increased in a time-dependent manner. These data suggest that early cytochrome c release from mitochondria may contribute to apoptosis induction after traumatic brain injury.

Animals↗
PubMed1999

Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice.

Recent studies have shown that release of mitochondrial cytochrome c is a critical step in the apoptosis process. We have reported that cytosolic redistribution of cytochrome c in vivo occurred after transient focal cerebral ischemia (FCI) in rats and preceded the peak of DNA fragmentation. Although the involvement of reactive oxygen species in the cytosolic redistribution of cytochrome c in vitro has been suggested, the detailed mechanism by which cytochrome c release is mediated in vivo has not yet been established. Also, the role of mitochondrial oxidative stress in cytochrome c release is unknown. These issues can be addressed using knock-out mutants that are deficient in the level of the mitochondrial antioxidant manganese superoxide dismutase (Mn-SOD). In this study we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and heterozygous knock-outs of the Mn-SOD gene (Sod2 -/+) after permanent FCI, in which apoptosis is assumed to participate. Cytosolic cytochrome c was detected as early as 1 hr after ischemia, and correspondingly, mitochondrial cytochrome c showed a significant reduction 2 hr after ischemia (p < 0.01). Cytosolic accumulation of cytochrome c was significantly higher in Sod2 -/+ mice compared with wild-type animals (p < 0.05). N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone (z-VAD.FMK), a nonselective caspase inhibitor, did not affect cytochrome c release after ischemia. A significant amount of DNA laddering was detected 24 hr after ischemia and increased in Sod2 -/+ mice. These data suggest that Mn-SOD blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after permanent FCI.

Amino Acid Chloromethyl Ketones↗
PubMed1999

In vitro susceptibility of Helicobacter pylori to trifluoromethyl ketones.

Heteroaromatic trifluoromethyl ketones (TFMK's) showed strong inhibitory activity against Helicobacter pylori. The MIC50 observed for 2-trifluoroacetonylbenzoxazole (1) is 20-fold more active than metronidazole and is only twice as high as that of clarithromycin. The inhibitory mode of TFMK's on Hp growth was not related to inhibition of urease.

Benzoxazoles↗
PubMed1999

Transfer function analysis of the circulation in patients undergoing sevoflurane anesthesia.

PURPOSE: The effects of sevoflurane anesthesia on the interactions between heart rate, blood pressure and respiration were assessed using transfer function analysis. METHODS: Nine ASA 1 or 2 patients undergoing elective surgery were involved. They were paralysed and their lungs were mechanically ventilated during sevoflurane anesthesia. Instantaneous heart rate (IHR) from electrocardiogram, instantaneous lung volume (ILV) by respiratory inductive plethysmography and mean blood pressure (MBP) by arterial tonometry were obtained during conscious state, and 1MAC and 2MAC of sevoflurane anesthesia. Transfer function analysis for the relationships between ILV and IHR, ILV and MBP, MBP and IHR were made for five minute periods during which the respiratory rate was varied in a standardized fashion. RESULTS: In awake patients transfer magnitudes for the relationships between ILV and IHR and between MBP and IHR in the 0.04-0.5Hz frequency band were 8.9 +/- 7.7 bpm x l(-1) and 0.95 +/- 0.44 bpm x mmHg(-1) respectively. Sevoflurane 2MAC decreased these values to 1.2 +/- 0.7 (P = 0.014) and 0.26 +/- 0.14 (P < 0.01) respectively, but phases were not affected. Neither transfer magnitudes nor phases between ILV and MBP were affected during sevoflurane anesthesia. Coherence for the relationships between ILV and IHR and between MBP and IHR were decreased during 1MAC sevoflurane anesthesia but not affected during 2MAC sevoflurane anesthesia. CONCLUSIONS: The interactions between heart rate, blood pressure and respiration were altered by sevoflurane anesthesia. These findings could be explained by the attenuation of autonomic nervous system activity.

Adult↗
PubMed1999

Mitral valve repair by Carpentier-Edwards physio annuloplasty ring.

A semi-flexible annuloplasty ring (Physio-ring) was clinically used in 30 cases of mitral valve insufficiency. The Physio-ring has the characteristics in which the anterior section is rigid and has a saddle-shaped curve, while the posterior section is flexible to allow for changes in size and shape of the anulus during ventricular contraction. The patients were aged from 23 to 73 years (mean 53.8 +/- 12.5). The cause of mitral valve insufficiency was degenerative (in 24 patients), rheumatic (2), ischemic (1), endocarditis (1), congenital + degenerative (1), and traumatic (1). On the 6-month post-implant echocardiogram, 96.6% had grade 0 or +1 regurgitation. The effective valve orifice area was 2.61 +/- 0.82 cm2 (n = 19). There was no late death. However, there was 1 (3.3%) hospital death after the patient had received a simultaneous coronary artery bypass grafting, and then developed low output syndrome after surgery. Although there was no device-related complication, hemolysis of undetermined cause was observed in 1 (3.3%) patient. The findings from this study indicated a low incidence of device-related complication, while excellent valvular function was maintained.

Adult↗
PubMed1999

Early decrease in apurinic/apyrimidinic endonuclease is followed by DNA fragmentation after cold injury-induced brain trauma in mice.

Apurinic/apyrimidinic endonuclease, a multifunctional protein in the DNA base excision repair pathway, plays a central role in repairing DNA damage caused by reactive oxygen species. We examined protein expression of apurinic/apyrimidinic endonuclease before and after cold injury-induced brain trauma in mice, where we have previously shown reactive oxygen species to participate. Immunohistochemistry showed the nuclear expression of apurinic/apyrimidinic endonuclease in the entire region of control brains. One hour after cold injury-induced brain trauma, nuclear immunoreactivity was predominantly decreased in the inner boundary of the lesion, whereas there was a slight increase in the outer boundary area. Four hours after cold injury-induced brain trauma, nuclear immunoreactivity was almost absent in the entire lesion, and remained so until 24 h. At this time, a marked increase in apurinic/apyrimidinic endonuclease immunoreactivity was seen in the outer boundary zone. Western blot analysis of the sample from the non-ischemic area showed a characteristic 37,000 mol. wt band, which decreased markedly 24 h after cold injury-induced brain trauma. A time-dependent increase in DNA fragmentation was also observed after cold injury-induced brain trauma. Our data provide the first evidence that apurinic/apyrimidinic endonuclease decreased rapidly in the lesion after cold injury-induced brain trauma, whereas it was significantly increased at the outer boundary zone. Although further examination is necessary to elucidate the direct relationship between apurinic/apyrimidinic endonuclease alteration and the pathogenesis of cold injury-induced brain trauma, our results suggest the possibility that an early decrease in apurinic/apyrimidinic endonuclease and failure of the DNA repair mechanism may contribute to DNA-damaged neuronal cell death after cold injury-induced brain trauma.

Animals↗
PubMed1999

Effectiveness of polyamidoamine dendrimers modified with tripeptide growth factor, glycyl-L-histidyl-L-lysine, for enhancement of function of hepatoma cells.

Cationic polyamidoamine dendrimers are known to be highly branched cascade polymers. Tripeptide growth factor, glycyl-L-histidyl-L-lysine (GHK), was employed as a ligand for activation or attachment of cells from a rat hepatoma cell line, H4-H-E-C3, and immobilized at the terminus of the dendrimer (GHK-dendrimer) to develop a suitable surface for use as a culture substratum in the bioartificial liver support system (BAL). The growth of cells was inhibited by increasing the number of generations of GHK-dendrimers. On the other hand, urea synthesis and lidocaine clearance of the cells adhered on fifth generation GHK-dendrimers were enhanced much more than on first generation GHK-dendrimers. GHK was shown to act as a growth inhibitor and an activator of hepatoma cells. These properties of GHK are advantageous for the utilization of hepatoma cells in BAL. Ligand-modified dendrimers are very promising for the creation of a high-performance substratum for cell culture and high performance bioartificial organs, as well as for high-performance bioartificial liver systems. GHK may have the potential to be a highly useful ligand.

Journal Article↗