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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 91 records · Page 5Linked to original sources

[Partial nephrectomy using a microwave tissue coagulator for bilateral renal cell carcinomas: a case report].

We report a case of bilateral renal cell carcinomas in a 56-year-old male treated by partial nephrectomy at the same time using a microwave tissue coagulator technique. The patient did not need dialysis after the operation because we did not need to sacrifice the artery feeding to normal renal tissue during the operation. This technique has advantages of nephron sparing without occlusion of the renal artery, and decreased operation time and blood loss.

Carcinoma, Renal Cell↗

Overexpressed cell surface interleukin-4 receptor molecules can be successfully targeted for antitumor cytotoxin therapy.

A variety of human solid cancer cell lines and primary cell cultures has been reported to overexpress high-affinity receptors (R) for interleukin-4 (IL-4), a pleiotropic immunoregulatory cytokine. The significance of IL-4R expression is not known; however, IL-4 is able to upregulate adhesion molecules, inhibit cell proliferation, and mediate signal transduction in tumor cell lines. To target IL-4R, we produced a chimeric protein composed of a circular permuted IL-4 and a mutated form of Pseudomonas exotoxin [termed IL4(38-37)-PE38KDEL or cpIL4-PE]. The recombinant cpIL4-PE was highly cytotoxic to cancer cells, but not toxic to normal B cells, T cells, monocytes, and CD34+, even though these cells express detectable numbers of IL-4R. The cytotoxicity was specific because excess of recombinant IL-4 neutralized the cpIL4-PE effect. To further develop this molecule, in vivo antitumor activity was tested in animal models of human cancer. This agent showed remarkable antitumor activity in AIDS-Kaposi's sarcoma, glioblastoma multiforme, and breast cancer models in immunodeficient animals. cpIL4-PE caused partial or complete regression of established human tumors. Preclinical efficacy and toxicity studies provided a therapeutic window in which this cancer-targeted agent could be used. On the basis of these studies, we initiated a Phase I clinical trial for the treatment of recurrent glioblastoma multiforme. Our preliminary clinical results suggest that cpIL4-PE has antitumor activity against the deadliest form of brain tumors, without detectable toxicity to normal brain tissues. Thus, IL-4 receptors represent novel targets for cancer cytotoxin therapy.

Animals↗

[The effects of percutaneous endoscopic gastrostomy feeding in patients with swallowing disturbance].

BACKGROUND AND PURPOSE: Because the number of patients who need home healthcare has recently increased in Japan, Percutaneous endoscopic gastrostomy (PEG) will soon become more popular. This study aims to examine the effects of enteral alimentation via PEG. MATERIAL AND METHODS: The subjects were 18 patients who underwent PEG instead of receiving total parental nutrition (TPN) (TPN-to-PEG group), 13 patients who underwent PEG instead of receiving enteral nutrition through a naso gastric tube (NG-to-PEG group), and 11 healthy volunteers (control). Morphological changes of the small bowel mucosa and activities of daily life (ADL) after PEG were also investigated. RESULTS: In the TPN-to-PEG group, the serum level of total protein and albumin, length of duodenal villi, ration of positive proliferative cells, width of duodenal microvilli and ADL markedly increased. In the NG-to-PEG group, body weight and ADL were markedly improved after PEG. CONCLUSION: Nutrition via PEG is superior to TPN or enteral nutrition with an NG tube. I conclude that PEG will become the first choice for improving nutrition in patients with dysphasia and will contribute to continuous enteral nutrition for home care.

Activities of Daily Living↗

Erythropoietin inhibits calcium-induced neurotransmitter release from clonal neuronal cells.

Erythropoietin (EPO) and EPO receptor (EPO-R) are expressed in the brain but their neuronal functions are not yet clarified. The effects of EPO on neurosecretion were studied using clonal rat pheochromocytoma PC12 cells. EPO suppressed Ca(2+)-induced dopamine release from PC12 cells in a concentration- and time-dependent manner. Inhibition was also produced by an EPO mimetic peptide 1 (EMP1), a small synthetic peptide agonist of EPO-R, but not by its inactive analogue in which Cys residues were substituted with Ser. Inhibition was abolished by genistein but not by genistin. EPO and EMP1 induced autophosphorylation of Janus kinase 2 (JAK 2), a tyrosine kinase that associates with EPO-R, and dephosphorylation of GAP-43 in a tyrosine kinase-dependent fashion. These results suggest that EPO suppresses neurotransmitter release through activation of EPO-R linked to JAK2.

Animals↗

The characterization of the common fragile site FRA16D and its involvement in multiple myeloma translocations.

Fragile sites appear as breaks, gaps, or decondensations on metaphase chromosomes when cells are grown under specific culture conditions. The breaks are nonrandom, appearing in defined, conserved locations throughout the mammalian genome. Common fragile sites, as their name implies, are present in virtually all individuals. With three common fragile sites cloned, their mechanism of expression and the role, if any, they play in human disease are still unclear. We have assembled a BAC contig of >1 Mb across the second most active common fragile site, FRA16D (16q23.2). We fluorescently labeled these BACs and used them as probes on metaphases from aphidicolin-induced lymphocytes and demonstrated that FRA16D decondensation/breakage occurs over a region of at least 1 Mb. Thus, this is the largest common fragile site cloned to date. Microsatellite markers that map within FRA16D show a very high loss in prostate, breast, and ovarian tumors, indicating that loss within this fragile site may be important in the development or progression of these tumors. In addition, a common t(14q32;16q23) translocation is observed in up to 25% of all multiple myelomas (MM). We localized four of four such cloned t(14;16) MM breakpoints within the FRA16D region. This work further demonstrates that the common fragile sites may play an important role in cancer development.

Cells, Cultured↗

Current Awareness.

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of NMR in biomedicine. Each bibliography is divided into 9 sections: 1 Books, Reviews ' Symposia; 2 General; 3 Technology; 4 Brain and Nerves; 5 Neuropathology; 6 Cancer; 7 Cardiac, Vascular and Respiratory Systems; 8 Liver, Kidney and Other Organs; 9 Muscle and Orthopaedic. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

Journal Article↗

Magnetic resonance spectroscopy of cellular lipid extracts from sensitive, resistant and reverting K562 cells and flow cytometry for investigating the P-glycoprotein function in resistance reversion.

The proton NMR spectra of K562 cells contain resonances of lipids. When these cells acquire multidrug resistance phenotype, the NMR lipid signals are modified and partially recovered when the resistance is reversed. The goals of the present study are to elucidate the mechanism of the resistance phenotype reversion and to investigate the possible origin of lipid signals detected in whole cells with proton NMR spectroscopy. Therefore, the K562 drug-sensitive cell line, its adriamycin resistant counterpart and two reverting derivates, obtained by verapamil treatment and long term culture in drug-free medium, were used in this study. The P-glycoprotein (P-gp) pump function was measured by flow cytometry and lipids were extracted to be analysed by proton and phosphorus spectroscopy. The phenotype reversion is due to the decrease of the P-gp function and an increased entrance of anthracycline drug when compared with the resistant cells. The spectra obtained on extracts showed no modification of the fatty acid composition and of the ratio of total cholesterol to fatty acid content. A different phospholipid composition in sensitive and resistant cells was found, but the reversion of resistance did not produce a recovery of these lipids. Thus, the lipid NMR spectra of extracts could not explain the spectral modifications observed on whole cells, in relation to acquiring and reverting drug resistance. These results are in favour of a different lipid organization or of localization within the cell.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Characterization of native and recombinant peptidyl prolyl cis-trans isomerases derived from Methanococcus thermolithotrophicus based on cDNA sequence.

It is important to establish whether a recombinant protein is an authentic copy of the predicted cDNA sequence. In this study, recombinant protein for native peptidyl prolyl cis-trans isomerase (N-PPIase) and double-labeled (13C- and 15N-) protein (DL-PPIase) appeared on the sodium dodecyl sulfate (SDS) electropherograms as two bands for N-PPIase and four bands for DL-PPIase. Since the N-terminal amino acid residues of all bands were the same, we characterized these bands using the peptide mapping method and amino acid composition analysis. Peptide mapping of the proteins seemed to be almost identical but they could not reflect the whole amino acid sequences of the protein. The bands on the polyvinylidene difluoride (PVDF) membrane, electroblotted after SDS-polyacrylamide gel electrophoresis (SDS-PAGE), were hydrolyzed and their amino acid composition was analyzed using a highly sensitive 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) amino acid analysis and compared with the cDNA sequences for proteins. The matching score (sigma(T%-E%)2) for similarity of proteins was calculated by summation of the square difference between the theoretical (T%) and the experimental (E%) amino acid composition of the recombinant protein. The amino acid composition of all bands of both proteins showed more than 93% of the theoretical values. The major molecular weights of both proteins were 16812 and 17694 by electrospray ionization (ESI)-mass spectrometry. However, the purified proteins also contained minor compounds with Mr of 3721 for N-PPIase and 5285 for DL-PPIase. These compounds were considered to be nonpeptidyl products that comigrated with the protein. Similarities of the amino acid composition of the four bands were more than 98%. Our results indicate that AQC amino acid analysis is the most suitable method for characterization of a recombinant protein.

Amino Acids↗

Mechanical compression of the lumbar nerve root alters pain-related behaviors induced by the nucleus pulposus in the rat.

The purpose of this study was to refine a method of nerve-root injury in the rat to produce hyperalgesia, a pain-related behavior, and to determine if there were any relationships between the histological extent of nerve-root injury and the magnitude of hyperalgesia. Three methods were used to produce hyperalgesia: irritation of a nerve root by ectopic nucleus pulposus, silk loop alone, or both silk loop and ectopic nucleus pulposus. Autologous nucleus pulposus obtained from coccygeal intervertebral discs was relocated on the lumbar nerve roots after laminectomy. Two loops of 4-0 silk were placed around the exposed nerve roots. Hyperalgesia was measured preoperatively and postoperatively. The distribution of myelinated axons in the dorsal nerve roots was evaluated histologically. Mechanical hyperalgesia was detected in rats in which autologous nucleus pulposus was applied to the nerve root but not in those in which silk loops were used. Silk loops around the nerve root resulted in thermal hyperalgesia only in rats in which autologous nucleus pulposus was applied to the nerve root. Fewer large myelinated fibers were seen in the rats in which silk loops were used. Although a silk loop around the nerve root was not sufficient to produce hyperalgesia, supplemental application of autologous nucleus pulposus to the nerve root produced thermal hyperalgesia. It is possible that mechanical constriction of the nerve root alters the pain-related behavior elicited by chemical factors from the nucleus pulposus.

Animals↗

Mechanisms of tubulin modification by phosphatidylcholine hydroperoxides.

The interaction of lipid peroxides with cellular proteins has been postulated to contribute to cellular aging. A potential target for such effects is tubulin, the building block of microtubules. We examined the concentration-dependent effects of phosphatidylcholine hydroperoxides on the ability of tubulin to polymerize into microtubules. The results demonstrated that even very low concentrations of peroxides were sufficient to interfere with the tubulin and, therefore, the microtubule function. Decreased tubulin activity (as measured by tubulin GTPase activity) showed correlation with the modification of methionine and cysteine in tubulin and a change in the tubulin conformational state as indicated by fluorescence and ultraviolet spectroscopic measurements. As no effect on electric conductivity was observed, indicating that modulation of ionic binding was not involved, the interaction mechanism may be a hydrophobic one.

Amino Acids↗

The synergistic effects of hyperthermia and anticancer drugs on induction of apoptosis.

We studied the synergistic effects of hyperthermia and anticancer drugs on induction of apoptosis in lung cancer cells (LK-2 and LU-65A) using in situ end-labeling of DNA, the DNA fragmentation assay, and transmission electron microscopy. A few apoptotic cells were detected only when both cell lines were heated at relatively high temperature (44 degrees C). Moderate numbers of apoptotic cells were observed when both cell lines were incubated with high concentrations (30 or 40 microM) of anticancer drug. Compared with hyperthermia or anticancer drug alone, the combined treatment induced many apoptotic cells in both cell lines, even in the cells treated with lower concentrations (6 or 8 microM) of anticancer drugs following mild hyperthermia (43 degrees C). In regard to kinetics of apoptotic cells induced by treatment, the maximum induction of apoptosis by the combined treatment was higher than that of hyperthermia or anticancer drug alone in both cell lines, although the time of the peak of apoptotic index differed among the three treatments. Therefore, "hyperthermo-chemotherapy" may reduce the required dosage of anticancer drug and decrease the temperature of hyperthermia on induction of apoptosis.

Antineoplastic Agents↗

Measuring vibration characteristics at large amplitude region of materials for high power ultrasonic vibration system

This study proposes a method of estimating the mechanical quality factor of materials for high-power ultrasonic vibration systems under large vibration amplitude conditions. The quality factors of several metals as well as some polymers are measured by this method. In this method, the quality factor is calculated as the ratio of the reactive energy stored in a specimen to the dissipated energy. The dissipated energy is estimated from the input/output mechanical energy to the specimen by measurement of the vibration intensity, while the reactive energy is measured as the kinetic energy of the vibration. Then, the quality factor for the specified part can be extracted using this method. In this report, quality factors for torsional vibration were measured at about 30 kHz as functions of the vibration strain.

Journal Article↗

Cisternal irrigation therapy with urokinase and ascorbic acid for prevention of vasospasm after aneurysmal subarachnoid hemorrhage. Outcome in 217 patients.

BACKGROUND: Cisternal irrigation therapy with urokinase and ascorbic acid was introduced to prevent symptomatic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). To dissolve and wash out the subarachnoid clot, cisternal irrigation with urokinase is used. Ascorbic acid is added to degenerate oxy-hemoglobin, one of the strongest spasmogenic substances, into verdohemelike products, which are nonspasmogenic. The efficacy and safety of this therapy were evaluated. METHODS: This therapy was performed consecutively in 217 patients. The degree of SAH of the patients was classified as Fisher CT Group 3, and the highest CT number (Hounsfield number) exceeded 60 in the SAH, which suggested a significant risk for symptomatic vasospasm. All patients underwent surgery within 72 hours from the onset of SAH. After clipping the aneurysm, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally or bilaterally and in the prepontine or chiasmal cistern (outlet). Lactated Ringer's solution with urokinase (120 IU/mL) and ascorbic acid (4 mg/mL) was infused at a rate of 30 mL/hour/side for approximately 10 days. RESULTS: Of the 217 patients studied, symptomatic vasospasm was observed in 6 cases (2.8%), and two of these six cases (0.9%) demonstrated sequelae. The average total blood volume calculated from the drainage fluid was approximately 114 mL. Analysis of the absorption spectrum of the drainage fluid revealed disappearance of the oxy-hemoglobin-specific 576-nm peak. Complications occurred in eight patients during irrigation therapy; two patients experienced seizures, two patients developed meningitis, and four patients had an intracranial hemorrhage. However, all of these patients recovered without neurological deficits. CONCLUSIONS: These results suggest that cisternal irrigation therapy with urokinase and ascorbic acid is effective in preventing symptomatic vasospasm after aneurysmal SAH.

Adult↗

Is emergency open chest cardiopulmonary resuscitation accepted by patients' families?

Emergency open chest cardiopulmonary resuscitation (OCCPR) is sometimes performed on patients with cardiopulmonary arrest (CPA), especially those resulting from trauma. Since OCCPR is frequently carried out without the permission of patients' families, we surveyed the opinions of the families. A total of 1058 CPA patients were transferred to our department during the last 15 years. We sent questionnaires individually to the families of these patients to ask their opinions about OCCPR. The questionnaire provided the six questions allowing multiple answers; (1) Do you unconditionally agree with OCCPR? (2) Do you agree with OCCPR in children? (3) Do you agree with OCCPR in elderly patients? (4) Do you agree with OCCPR without permission from patient's families? (5) Do you entrust OCCPR to the doctors in charge? and (6) others. The questionnaire reached 846 families, of which 277 (32.7%) responded. The percentage response to each question was (1) 70.2, (2) 5.8, (3) 21.8, (4) 7.1, (5) 4.2 and (6) 5.0%. The younger the age of the responders the more they agreed with OCCPR. All the responders less than 30 years old agreed with the procedure. Of the 277 families, 95 had CPA patients treated with OCCPR. This group of families responded to six questions at the following rates: (1) 79.5, (2) 6.0, (3) 13.3, (4) 2. 4, (5) 4.8 and (6) 4.8%, suggesting that families with OCCPR patients are more cooperative to our treatment than those with non-OCCPR patients. The results of this study suggest that OCCPR in CPA patients is generally accepted by the patients' families, especially by young generations, although post-OCCPR careful explanation to patients' families is still indispensable.

Adult↗

Effects of nonionic surfactants on electrochemical behavior of ubiquinone and menaquinone incorporated in a carbon paste electrode.

A carbon paste electrode, in which the carbon particles were coated with a thin layer of a nonionic surfactant (NIS), was constructed with a pasting liquid containing ubiquinone (UQ) or menaquinone (MQ). It has revealed that the layer acts not only as a diffusion barrier but also as a matrix for the redox reaction of quinones at electrode surface, and its effects on the electrochemical behavior of quinones depend on both the physico-chemical structure of a surfactant and the kind of quinones. Further, such a modification was applied to the preparation of an enzyme electrode in which the quinone molecule act as a redox mediator and the influences on the sensitivity of the glucose biosensor was demonstrated.

Carbon↗