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Biomedical subjects

K Kawakami

Publications and source records attributed to K Kawakami.

At least 127 records · Page 7Linked to original sources
PubMed2000

Whole-bladder irradiation and doxorubicin-containing chemotherapy as successful treatment for a primary mucosa-associated lymphoid tissue lymphoma of the bladder.

Primary bladder lymphoma, a rare disease, is usually of the low-grade mucosa-associated lymphoid tissue (MALT) type. The best treatment approach for this disease remains unknown. We encountered a case of localized MALT lymphoma with a partial high-grade component in a 27-year-old Japanese man. Taking therapeutic efficacy and the quality of life of the patient into consideration, we treated him with a combination of doxorubicin-containing chemotherapy and 30-Gy whole-bladder irradiation. The patient had a complete remission and has been disease-free without serious adverse effects or sequelae for a year and a half since completion of the treatment. These observations suggest that a combination of systemic chemotherapy and relatively low-dose irradiation without a total cystectomy is effective for a MALT lymphoma of the bladder, even with a high-grade component.

Adult↗
PubMed2000

[Pneumonia and influenza].

Pneumonia is more frequent in the elderly and results in higher mortality. Primary viral pneumonia is not so common but important in severe cases. Chest X-ray shows grand-glass appearance or linear shadow in pure viral pneumonia cases. That is sometimes specific and clearly different from consolidation or infiltration with bacterial pneumonia. We can try to decrease pneumonia and influenza mortality, if we prevent influenza infections by vaccination and treat by anti-influenza drugs. Secondary bacterial pneumonias are more common, caused by such as Streptococcus pneumonia, Hemophilus influenzae, Branhamella catarrhalis. Gram staining and the culture of purulent sputum was useful for treatment by antibiotics.

Humans↗
PubMed2000

[Therapeutic effect of interleukin-12 on murine infection with Mycobacterium tuberculosis through modulating Th1 and Th2 cytokine balance].

OBJECTIVE: To study the effect of IL-12 on cytokines of murine infection with Mycobacterium tuberculosis. METHODS: 42 BALB/c mice infected with Mycobacterium tuberculosis were randomized into normal control (PBS) and IL-12 (n = 21) groups, treated with PBS or IL-12 respectively. Blood level of IFN-gamma, IL-4, and IL-10 were detected with ELISA method. The numbers of viable bacteria in organs were counted. Survival rate after treatment was investigated. RESULTS: In IL-12 group, none was dead. The numbers of viable bacteria in lung, liver and spleen were (227 +/- 107) x 10(5) cfu/ml, (4 +/- 3) x 10(5) cfu/ml and (1.5 +/- 0.5) x 10(5) cfu/ml respectively. INF-gamma (1,090 +/- 406) pg/ml. In PBS group, 8 mice were dead. The numbers of viable bacteria in lung, liver and spleen were (659 +/- 405) x 10(5) cfu/ml, (23 +/- 19) x 10(5) cfu/ml and (10.8 +/- 3.5) x 10(5) cfu/ml respectively. IFN-gamma (548 +/- 214) pg/ml. There was significant difference between those two groups. No change of the level of IL-4 in two groups. CONCLUSIONS: IL-12 induced IFN-gamma production, promoted development of Th1 cell responses, modulated Th1 and Th2 cytokine balance, suggesting that IL-12 enhance the host defense against the infection.

Animals↗
PubMed1999

Identification of the Tol2 transposase of the medaka fish Oryzias latipes that catalyzes excision of a nonautonomous Tol2 element in zebrafish Danio rerio.

The Tol2 element is found in the genome of the medaka fish, Oryzias latipes, and contains DNA sequences similar to those of transposons of the hAT family. Previously, we have developed a transient embryonic excision assay in zebrafish, in which zebrafish embryos were injected with a plasmid DNA harboring the Tol2 element, and have shown that the Tol2 element is excisable from the injected plasmid DNA (Kawakami, K., Koga, A., Hori, H., Shima, A., 1998. Excision of the Tol2 transposable element of the medaka fish, Oryzias latipes, in zebrafish, Danio rerio. Gene 225, 17-22). Although the Tol2 element is thought to be autonomous, an active transposase encoded by the Tol2 element has not been identified. Here we report the identification and analysis of mRNA transcribed from the Tol2 element in zebrafish embryos. The Tol2 transcript has the capacity to encode a protein of 649 amino acids, whose amino acid sequence is similar to those of transposases of the hAT family. To determine whether the transcript encodes an active enzyme, we developed a novel transient embryonic excision assay in which zebrafish fertilized eggs were co-injected with RNA transcribed in vitro using the Tol2 cDNA as a template and a plasmid DNA harboring a nonautonomous Tol2 element, which has a deletion in the transposase coding region. The nonautonomous Tol2 element could be efficiently excised in the zebrafish only when co-injected with the Tol2 RNA. This result indicates that the Tol2 transcript encodes an active enzyme, a probable transposase, that can catalyze the excision reaction in trans. Further, by the co-injection analysis, we found that the Tol2 sequence lacking the first intron sequence of the transposase gene could not be excised, suggesting that it may contain essential cis-elements.

Amino Acid Sequence↗
PubMed1999

Interleukin-4 weakens host resistance to pulmonary and disseminated cryptococcal infection caused by combined treatment with interferon-gamma-inducing cytokines.

We examined the role of interleukin (IL)-4 in host resistance against infection with Cryptococcus neoformans. First, we examined the effects of a neutralizing anti-IL-4 monoclonal antibody (mAb) on survival of mice infected intratracheally with this fungal pathogen. We also compared the number of live C. neoformans in lungs and brains of treated and untreated mice. Treatment with anti-IL-4 mAb significantly prolonged survival of infected mice and reduced the lung and brain burdens of C. neoformans, which was associated with increased production of IFN-gamma in lungs. In the next experiments, infected mice were treated with two IFN-gamma-inducing cytokines, IL-12 and IL-18, known to enhance protection against infection. We then evaluated the effect of such treatment on the number of live microorganisms and concentration of IL-4 in lungs. These two parameters showed a statistically significant relationship, suggesting a negative regulation of host protection by IL-4. Finally, we examined the effects of IL-4 treatment and administration of neutralizing anti-IL-4 mAbs on host protection against C. neoformans and local production of IFN-gamma in lungs induced by treatment with IL-12/IL-18. The former treatment suppressed host protection and reduced IFN-gamma production, while the latter produced the opposite effects. Our results indicated that IL-4 suppressed the host defense mechanisms against infection with C. neoformans potentiated by IFN-gamma-inducing cytokines probably through the suppression of local production of IFN-gamma.

Animals↗
PubMed1999

Stereoselective synthesis of a new muscarinic M3 receptor antagonist, J-104129.

A diastereoselective synthesis of J-104129 (1) was developed. A key step of this synthesis was Michael addition of enolate generated from cis-chiral dioxolane 2 to cyclopentenone, followed by hydrogenolysis of the resultant enol triflate 4. A mixture of cyclopentyldioxolane (5, 6) was hydrolyzed with sodium hydroxide to yield carboxylic acid 7 in 86% ee.

Alkenes↗
PubMed1999

Differential effect of Cryptococcus neoformans on the production of IL-12p40 and IL-10 by murine macrophages stimulated with lipopolysaccharide and gamma interferon.

In the present study, we examined the in vitro effect of Cryptococcus neoformans on the production of interleukin-12 (IL-12) and IL-10 by murine macrophages. At a dose of 1 x 10(5), 1 x 10(6) or 1 x 10(7) ml-1, a highly virulent strain of C. neoformans (strain YC-11) suppressed the production of IL-12p40 by a murine macrophage cell line, J774.1 stimulated with lipopolysaccharide (LPS) and interferon (IFN)-gamma, while the production of IL-10 was not inhibited, but rather slightly augmented. The suppression of IL-12p40 production did not change by neutralizing anti-IL-10 mAb. A direct contact of C. neoformans with macrophages was largely involved in this inhibitory effect, since placement of a 0.45 micron pore membrane between the organism and macrophages prevented such effect. On the other hand, the culture supernatant of YC-11 did not inhibit macrophage IL-12p40 production when used at a lower dose, which contained an equivalent amount of capsular polysaccharide to that in the supernatant of YC-11 cultured at 1 x 10(5) or 1 x 10(6) ml-1, although it showed a small suppression at higher doses. Our results suggest that C. neoformans may suppress the induction of Th1 responses by inhibiting macrophage IL-12 production predominantly through a direct contact-dependent mechanism and to a lesser extent by a certain soluble factor(s) released from this microorganism.

Animals↗
PubMed1999

CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression.

The molecular basis of aberrant hypermethylation of CpG islands observed in a subset of human colorectal tumors is unknown. One potential mechanism is the up-regulation of DNA (cytosine-5)-methyltransferases. Recently, two new mammalian DNA methyltransferase genes have been identified, which are referred to as DNMT3A and DNMT3B. The encoded proteins differ from the predominant mammalian DNA methyltransferase DNMT1 in that they have a substantially higher ratio of de novo to maintenance methyltransferase activity. We have used a highly quantitative 5' nuclease fluorogenic reverse transcription-PCR method (TaqMan) to analyze the expression of all three DNA methyltransferase genes in 25 individual colorectal adenocarcinoma specimens and matched normal mucosa samples. In addition, we examined the methylation patterns of four CpG islands [APC, ESR1 (estrogen receptor), CDKN2A (p16), and MLH1] to determine whether individual tumors show a positive correlation between the level of DNA methyltransferase expression and the frequency of CpG island hypermethylation. All three methyltransferases appear to be up-regulated in tumors when RNA levels are normalized using either ACTB (beta-actin) or POLR2A (RNA pol II large subunit), but not when RNA levels are normalized with proliferation-associated genes, such as H4F2 (histone H4) or PCNA. The frequency or extent of CpG island hypermethylation in individual tumors did not correlate with the expression of any of the three DNA methyltransferases. Our results suggest that deregulation of DNA methyltransferase gene expression does not play a role in establishing tumor-specific abnormal DNA methylation patterns in human colorectal cancer.

Adenocarcinoma↗
PubMed1999

Determination of the entrapped volume of liposomes: dilution method.

A novel method was developed for the determination of the entrapped volume of liposomes. The obtained values of the entrapped volume by our "dilution method" agreed very well with those of the conventional "quenching method." The dilution method also offered the great advantages of simple procedure and high reproducibility. The principle and validity of our method are discussed.

Chemistry Techniques, Analytical↗
PubMed1999

Role of TNF-alpha in the induction of fungicidal activity of mouse peritoneal exudate cells against Cryptococcus neoformans by IL-12 and IL-18.

We have recently demonstrated that two IFN-gamma-inducing cytokines, interleukin (IL)-12 and IL-18, synergistically induced the fungicidal activity of mouse peritoneal exudate cells (PEC) against Cryptococcus neoformans through NK cell production of interferon (IFN)-gamma and nitric oxide (NO) synthesis. In the present study, we further dissected these effects by examining the involvement of tumor necrosis factor (TNF)-alpha in the induction of IL-12/IL-18-stimulated PEC fungicidal activity. The addition of neutralizing anti-TNF-alpha mAb significantly suppressed IL-12/IL-18-stimulated PEC anticryptococcal activity. This effect was ascribed to the inhibition of macrophage NO synthesis, but not of IFN-gamma production by NK cells, because the same treatment inhibited the former response, but not the latter one. On the other hand, combined treatment with IL-12 and IL-18 synergistically induced the production of TNF-alpha by PEC and this effect was almost completely abrogated by neutralizing anti-IFN-gamma mAb. The cell type producing TNF-alpha among PEC was mostly macrophage. TNF-alpha significantly promoted macrophage NO production and anticryptococcal activity induced by IFN-gamma, and furthermore anti-TNF-alpha mAb partially inhibited these responses. Considered together, our results indicated that TNF-alpha contributed to the potentiation of IL-12/IL-18-induced PEC fungicidal activity against C. neoformans through enhancement of IFN-gamma-induced production of NO by macrophages, but not through increased production of IFN-gamma by NK cells.

Animals↗
PubMed1999

Combined effects of IL-12 and IL-18 on the clinical course and local cytokine production in murine pulmonary infection with Cryptococcus neoformans.

We reported recently that interleukin (IL)-12 and IL-18 synergistically increased the fungicidal activity of mouse peritoneal exudate cells against Cryptococcus neoformans by inducing the production of interferon (IFN)-gamma by natural killer (NK) cells. To confirm these findings in vivo, we examined the effect of combined treatment using these two cytokines on the course of experimentally induced pulmonary and disseminated cryptococcosis in mice. IL-12 and IL-18 were used at subtherapeutic doses (0.005 and 2 microg/mouse/day, respectively). A single administration of either cytokine was not effective in protecting mice against the infection, while combined treatment significantly prolonged survival time of infected mice and reduced the lung and brain loads of organisms. These protective effects were associated with elevated IFN-gamma and reduced IL-4 levels in bronchoalveolar lavage fluid. Finally, depletion of NK and gammadelta T cells, but not of CD4+ T cells, by administration of specific antibodies, significantly reduced the production of IFN-gamma in lungs by IL-12/IL-18 treatment during the 7 days of infection. Our results demonstrated that IL-12 and IL-18 protected mice against cryptococcal infection in a synergistic manner by enhancing the local production of IFN-gamma by NK and gammadelta T cells in the early phase of infection and by suppressing the production of IL-4 in lungs.

Animals↗
PubMed1999

Myocardial ischemia due to vasospasm of small coronary arteries detected by methylergometrine maleate stress myocardial scintigraphy.

BACKGROUND: Recently, several case reports have implicated vasospasm of small coronary arteries in vasospastic angina pectoris. Vasospasm of small coronary arteries was also considered from angiographic findings in patients with atypical chest pain. In Syrian hamster, vasospasm in small coronary arteries was considered to be the cause of dilated cardiomyopathy. HYPOTHESIS: This study was undertaken to determine whether vasospasm in small coronary arteries can be induced by methylergometrine maleate stress thallium-201 (201Tl) myocardial scintigraphy. METHODS: Twenty-five patients with chest pain, all of whom had intact coronary arteries, were studied. After intracoronary methylergometrine maleate injection, coronary arteriograms also looked normal in all cases. Thallium-201 myocardial scintigraphy was carried out immediately after intracoronary methylergometrine maleate injection in four patients with chest pain. In the remaining 21 patients with chest pain, methylergometrine maleate was given intravenously within up to 2 weeks before 201Tl myocardial scintigraphy. RESULTS: In the intracoronary injection study, one patient had chest discomfort after methylergometrine maleate injection, and ST-segment elevation was observed on electrocardiogram (ECG). Of the 21 patients with chest pain, 11 patients felt angina-like chest pain after intravenous injection of methylergometrine maleate, but their ECGs showed no ischemic changes. Stress 201Tl myocardial scintigrams showed methylergometrine maleate-induced perfusion defects with complete redistribution in 3 of 4 patients in the intracoronary injection study and in 12 of 21 patients in the intravenous injection study. These findings suggest that vasospasm in small coronary arteries caused myocardial ischemia in 15 of 25 patients (60%) with chest pain. CONCLUSION: Vasospasm in small coronary arteries may be involved in the myocardial ischemia of some patients with chest pain who do not show any large coronary artery vasospasm.

Adult↗
PubMed1999

How secure are the arteries occluded by a newly developed ultrasonically activated device?

BACKGROUND: We developed a new ultrasonically activated device (USAD) for endoscopic surgery. The current investigation was conducted to evaluate the security of the arteries occluded and divided by this USAD. METHODS: The intraperitoneal arteries of anesthetized living pigs were individually occluded by the USAD at power levels of 70% or 100%. The burst pressures of the harvested arteries were measured in vitro. For comparison, arteries occluded by laparoscopic clips or silk ligatures were evaluated in the same manner. RESULTS: The pressures to burst the occluded artery ranged from 353 to 2,148 mmHg with an average of 1,204 mmHg in the USAD group at 70% power level; from 324 to 2,207 mmHg with an average of 1,193 mmHg in the USAD group at 100% power level; from 794 to 1,868 mmHg with an average of 1,421 mmHg in the clip group; and from 618 to 3,207 mmHg with an average of 1,586 mmHg in the silk ligature group. CONCLUSION: The data suggest the improbability that small- to medium-size arteries appropriately occluded and divided by the USAD can burst when exposed to intravascular pressures commonly found in living animals.

Animals↗
PubMed1999

Experimental study on heat production by a 23.5-kHz ultrasonically activated device for endoscopic surgery.

An experimental study was carried out to evaluate heat production by an ultrasonically activated device (USAD) using an animal model. In an anesthetized living pig, the gastroepiploic and mesenteric vessels were coagulated and cut by an USAD at a power level of 70% (n = 8) or 100% (n = 8). During the division, the time-discrete temperature change on the surface of the animal tissue adjacent to the blade was measured by thermography. To compare the USAD with conventional electrocautery (EC), a full-thickness incision of the gastric wall was performed by each device, and the temperature change was measured. With the USAD, the temperature increased gradually and remained below 150 degrees C during the entire activating time at both power levels. By contrast, with EC at 30 W, the temperature increased rapidly and exceeded 350 degrees C within only a few seconds. The area above 60 degrees C reached a final width of 10 mm for the USAD, as compared with 22 mm for EC. Microscopically, thermal alterations such as carbonization and vaporization were much more severe and extensive in the adjacent tissue when using EC rather than the USAD. With the USAD, heat production is much slower and more limited than with conventional EC; thus, the USAD causes fewer thermal alterations in adjacent tissue. USAD should be preferred for tissue coagulation and cutting during endscopic surgery.

Animals↗
PubMed1999

Multiple minimally invasive direct coronary artery bypass grafting for the complete revascularization of the left ventricle.

BACKGROUND: Single-vessel coronary artery bypass grafting of the left internal mammary artery to the left anterior descending coronary artery using a minithoracotomy has been shown to produce excellent results with a very low mortality rate. However, this procedure cannot be used in patients with double- or triple-vessel disease. Our goal was to develop a minimally invasive direct coronary artery bypass grafting without cardiopulmonary bypass for total revascularization of the left ventricle using multiple arterial grafts. METHODS: Limited lateral thoracotomy was performed in the fourth or fifth intercostal spaces, exposing the left anterior descending coronary artery and left circumflex coronary artery. Two or three arterial grafts were harvested. Revascularization of the left anterior descending coronary artery and the left circumflex coronary artery were performed in 20 patients without cardiopulmonary bypass through the limited lateral thoracotomy using complex performed arterial grafts. In 4 patients, triple- and quadruple-vessel grafting was performed. RESULTS: The mean coronary cross-clamp time was 14.5+/-4.0 minutes for the left anterior descending coronary artery and 16.8+/-5.1 minutes for the left circumflex coronary artery. No early deaths or postoperative complications occurred. There were no late deaths or angina during the mean follow-up of 7.0 months (range, 2 to 22 months). Postoperative coronary angiography demonstrated widely patent grafts in all patients. CONCLUSIONS: Minimally invasive approach through a limited thoracotomy in multiple coronary artery bypass graftings are technically feasible and may be an alternative approach in the complete revascularization of the left ventricle. Mechanical immobilization of the coronary artery enhances early graft patency and is an essential part of this procedure.

Aged↗
PubMed1999

Relationship between the apolipoprotein E and angiotensin-converting enzyme genotypes and LDL particle size in Japanese subjects.

We investigated whether the apolipoprotein E (apoE) and the angiotensin-converting enzyme (ACE) genotypes contribute to the variance in low-density lipoprotein (LDL) particle size in Japanese subjects (n = 136; M/F= 106/30). ACE polymorphism was associated with neither LDL size nor individual lipid levels. In contrast, the subjects with the epsilon2 allele of the apoE genotype had significantly lower levels of total cholesterol (P = 0.002) and LDL cholesterol (P = 0.004) compared with those without the epsilon2 allele. The subjects with the epsilon4 allele had a significantly smaller LDL particle size than those without the epsilon4 allele (P = 0.012). Separate analyses of the male subjects showed similar associations. A stepwise regression analysis revealed the epsilon4 allele to be an independent contributing variable that could affect LDL particle size. Our results suggest that the apoE genotype is associated with the development of atherosclerotic disease, since the epsilon2 and epsilon4 alleles relate to a decrease in LDL cholesterol levels and a decrease in LDL particle size, respectively.

Adult↗
PubMed1999

J-104129, a novel muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors.

A new class of 4-acetamidopiperidine derivatives has been synthesized and investigated for human muscarinic receptor subtype selectivity. Introduction of a hydrocarbon chain of appropriate length into the piperidine nitrogen of the racemic N-(piperidin-4-yl)-2-cyclobutyl-2-hydroxy-2-phenylacetamide platform conferred up to 70-fold selectivity for human muscarinic M3 receptors over M2 receptors. Subsequent synthetic derivatizations resulted in highly potent M3 receptor antagonists with selectivity greater than two orders of magnitude for M3 over M2 receptors, from which the analogue 4r was selected. Preparation of both enantiomers of 4r led to the identification of (2R)-N-[1-(4-methyl-3-pentenyl)piperidin-4-yl]-2-cyclopentyl-2-hyd roxy-2-phenylacetamide (J-104129, (R)-4r), which exhibited 120-fold selectivity for M3 receptors (Ki = 4.2 nM) over M2 receptors (Ki = 490 nM). In isolated rat trachea, (R)-4r potently and specifically antagonized acetylcholine (ACh)-induced responses with a K(B) value of 3.3 nM. The highly subtype-selective profile was also seen in isolated rat tissue assays (50-fold) and in anesthetized rats (> 250-fold). Oral administration of J-104129 ((R)-4r) antagonized ACh-induced bronchoconstriction with an ED50 value of 0.58 mg/kg in rats. Thus, J-104129 ((R)-4r) may effectively facilitate bronchodilation in the treatment of obstructive airway disease.

Alkenes↗