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Biomedical subjects

K Kawakami

Publications and source records attributed to K Kawakami.

At least 217 records · Page 12Linked to original sources

[A case of pulmonary sarcoidosis with multiple cavitation and pneumothorax].

We describe a rare case of pulmonary sarcoidosis with multiple cavitation and pneumothorax. A 32-year-old woman was admitted to our hospital with a dry cough and an interstitial shadow with dense infiltrates in both upper lungs and cavitation in the right upper lung on chest roentgenogram and CT. Laboratory tests revealed an elevated level of serum lysozyme. BAL fluid demonstrated a high proportion of lymphocytes with an increased CD4/CD8 ratio, compatible with sarcoidosis. Transbronchial lung and skin biopsies showed evidence of noncaseating epithelioid-cell granuloma, and a diagnosis of sarcoidosis was made. Although pneumothorax appeared in the left lung on chest roentgenogram during clinical observation conservative treatment without corticosteroids or any other therapy for a follow-up period of 3 years resulted in improvement of her clinical condition and abnormal X-ray findings.

Adult↗

[Midazolam for anesthetic induction in neonates].

The purpose of this study is to evaluate the effects of midazolam on circulation, respiration, sedation, and liver function of the neonates. The study subjects are 27 neonates (body weight 2.1 to 3.8 kg, gestational age at birth 34 to 41 weeks) who underwent surgery in neonatal period. Of 27, 13 patients received lidocaine (1.5 mg.kg-1) immediately before tracheal intubation (group L), and 14 had midazolam (0.1 mg.kg-1) with lidocaine (group ML). We compared the effects of midazolam in the presence of lidocaine on the following parameters: (1) the incidence of hypotension (systolic blood pressure < 50 mmHg) and bradycardia (heart rate < 100 beats.min-1), (2) the incidence of apnea and desaturation of oxygen (< 80%), (3) the degree of sedation, and (4) the serum levels of bilirubin and unbound bilirubin after surgery. In group L, there were hypotension (1/13) and desaturation (1/13). In group ML, there were desaturation (1/14) and post-operative apnea (1/14). None in both groups developed bradycardia or intracranial hemorrhage. A single-dose of lidocaine induced sedation only in 4 neonates, while combination of midazolam and lidocaine in 11. None had elevation of either total or unbound bilirubin after surgery. In conclusion, the titrated dose of midazolam with lidocaine is useful for anesthetic induction of neonates, although cares should be taken on its adverse effects such as hypotension, desaturation, and post-operative apnea.

Anesthesia, Intravenous↗

[Thymidylate synthase expression in patients with hypopharyngeal carcinoma].

We analyzed the relationship between clinical response to neo-adjuvant chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS expression was evaluated with immunohistochemical staining techniques on biopsy specimens from HPC patients. TS immunostaining was divided into four levels (TS0-TS3) according to its level and pattern. The relationship between prognosis, tumor size, nodal status, differentiation of tumor cells and TS expression were also investigated. There was a statistically significant association between the level of TS expression and tumor size (p < 0.01). In terms of the effectiveness of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical difference was not found in TS expression. These results suggest that the level of TS expression may show the degree of tumor proliferation, but may not necessarily be useful to obtain a response to chemotherapy including other drugs, e.g., cisplatin and other derivatives of platinum.

Aged↗

Cryopreserved ascending aortic homograft for Stanford B dissecting aneurysm.

A 68 year-old woman underwent replacement of the descending thoracic aorta with a cryopreserved aortic homograft for the treatment of a Stanford B dissecting aneurysm. After surgery, the patient made an uneventful recovery without recurrent infection. In such cases, the use of aortic homografts to replace aortic segments is a promising and effective therapeutic option.

Aged↗

[Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children's Cancer and Leukemia Study group (CCLSG)].

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Synergism of the ATF/CRE site and GC box in the housekeeping Na,K-ATPase alpha1 subunit gene is essential for constitutive expression.

Na,K-ATPase alpha1 subunit gene is constitutively expressed in a wide variety of tissues. Our previous studies revealed that the promoter region between -77 and +17 of the transcription initiation site of the rat Na,K-ATPase alpha1 subunit gene (Atp1a1) is sufficient for the promoter activity. In this region, an ATF/CRE site with an adjacent GC box exists. To elucidate how these sites are involved in the promoter activity, we analyzed effects of point mutations at these sites on transcription by in vitro transcription assays using nuclear extracts prepared from various rat tissues. Mutation at either site resulted in dramatic reduction of the promoter activity in all nuclear extracts, while mutation at both sites did not lead to further reduction. These results indicate that the ATF/CRE site and GC box are both essential for promoter activity and show synergistic activation. Electrophoretic mobility shift assay indicated that Sp1 and/or Sp3 bind to the GC box, and ATF1-CREB heterodimer binds to the ATF/CRE site. Since an element, ATF/CRE site-GC box, is conserved in mammalian Na,K-ATPase alpha1 subunit genes and in other constitutive promoters, we propose that this element is a critical unit for constitutive expression.

Activating Transcription Factors↗

IL-18 protects mice against pulmonary and disseminated infection with Cryptococcus neoformans by inducing IFN-gamma production.

We examined the effects of a newly identified cytokine, IL-18, originally designated as IFN-gamma-inducing factor, in a mouse model of pulmonary and disseminated infection with a highly virulent strain of Cryptococcus neoformans. Administration of murine rIL-18 enhanced elimination of live micro-organisms from the lungs, prevented fungal dissemination to the brain, reduced the level of serum cryptococcal capsular polysaccharide Ags, and increased the survival rate of infected mice. Histologic examination of lung sections of infected and PBS-treated mice showed a poor cellular inflammatory reaction and a large number of multiplying C. neoformans yeast cells in alveolar spaces. In contrast, massive infiltration of inflammatory cells, consisting mainly of mononuclear cells, characterized sections of lungs of infected animals treated with IL-18. Treatment with IL-18 also increased the level of serum IFN-gamma. In addition, the protective effect of IL-18 on cryptococcal infection was abrogated by administration of neutralizing anti-IFN-gamma mAb. Finally, we examined the effect of neutralizing anti-IL-18 Ab on cryptococcal infection to define the physiologic role of this cytokine in host defense using another weakly virulent strain of C. neoformans, which induced the expression of IL-18 mRNA in the infected lungs. Administration of this Ab exacerbated the infection, as shown by the increased lung burden. Our results indicate that IL-18 plays an important role in host defense against infection with C. neoformans.

Animals↗

Cryptococcus neoformans inhibits nitric oxide production by murine peritoneal macrophages stimulated with interferon-gamma and lipopolysaccharide.

We examined the effect of Cryptococcus neoformans on nitric oxide (NO) production by activated cultured macrophages. C. neoformans suppressed NO production by murine peritoneal macrophages stimulated with bacterial lipopolysaccharide (LPS) and interferon (IFN)-gamma, while it did not influence the production of IL-1 beta. This effect was observed when 1 x 10(6) or 10(7) of C. neoformans was added to macrophage cultures. A direct contact of C. neoformans with macrophages was essential for this inhibitory effect, since placement of a 0.45-micron-pore membrane between the organism and macrophages prevented such effect. In addition, C. neoformans killed by heat or paraformaldehyde did not show this inhibitory activity. Capsular polysaccharide did not mediate the inhibitory effect, since two nonencapsulated mutant strains of C. neoformans showed an inhibitory activity similar to that of encapsulated wild strains, and culture supernatants of C. neoformans, rich in polysaccharide antigens, did not inhibit macrophage NO production compared with control culture medium. The inhibitory effect was also not mediated by interleukin (IL)-10 and transforming growth factor (TGF)-beta since neutralizing specific antibodies to these cytokines did not influence C. neoformans-induced reductions in macrophage NO production. Our results suggest that C. neoformans may cause a direct suppression of NO-mediated fungicidal activity of macrophages, and the effect is independent of the capsular polysaccharide and production of IL-10 and TGF-beta.

Animals↗

Different element ratios of red cosmetics excavated from ancient burials of Japan.

Marker elements of red cosmetics, collected from ancient burials of Matsuyama, Tokushima and Nara Japan, were determined by emission spectrometry (ICP/AES). The mass ratios of Hg, Fe, Cu, and Zn were different between samples. Element levels were compared with reference to relative amounts of sulfur. Of the possible contaminants from the bone and sand of burials, the relative amounts of Hg and Fe to S were most commonly available to evaluate the difference between the cosmetics. The cosmetics were divided into four groups; type I (high Hg with less Fe), type II (both moderate Hg and Fe), type III (moderate Hg with high Fe) and type IV (less Hg with high Fe). The main constituents of cosmetics are mercury sulfide (cinnabar) or ferric oxide mixed with trace metals. Zinc contents differ between the Fe and Hg amounts for the three areas. Cosmetic compositions varied with each burial site, suggesting that they were derived from different mines of ancient Japan.

Anthropology↗

Promoter of the Na,K-ATPase alpha3 subunit gene is composed of cis elements to which NF-Y and Sp1/Sp3 bind in rat cardiocytes.

Na,K-ATPase alpha subunit has three isoforms whose expression is regulated developmentally and hormonally. Na,K-ATPase alpha3 subunit gene (Atpla3) is expressed only in brain and neonatal heart in a rat. The purpose of this study is to analyze cis-acting elements and trans-acting factors regulating the transcription of Atpla3 in cultured neonatal rat cardiocytes. Transient transfection assays with Atpla3-luciferase chimeric construct and a series of 5' sequential deletion mutations revealed the existence of positive regulatory elements from -74 to -59 and from -59 to -39. A factor was identified to bind across -59 by gel retardation assay. Methylation interference and DNase I footprinting analyses revealed the binding region from -74 to -53 (positive regulatory element (PRE) 1). The binding factor was identified to be NF-Y by gel retardation assay using specific antibody. Gel retardation and methylation interference analyses revealed that factors bind to two other elements from -54 to -43 (PRE2) and from -25 to -13 (PRE3). The binding factors were identified to be Sp1/Sp3 using specific antibodies. The functions of above-mentioned three elements were examined by transient transfection assay with various combinations of mutations. They all regulated the transcription positively and a synergistic enhancement of it was observed. Roles of NF-Y in the transcriptional activation and synergy are discussed.

Animals↗

Impairment of T cell development in deltaEF1 mutant mice.

Using the method of gene targeting in mouse embryonic stem cells, regulatory function of deltaEF1, a zinc finger and homeodomain-containing transcription factor, was investigated in vivo by generating the deltaEF1 mutant mice. The mutated allele of deltaEF1 produced a truncated form of the deltaEF1 protein lacking a zinc finger cluster proximal to COOH terminus. The homozygous deltaEF1 mutant mice had poorly developed thymi with no distinction of cortex and medulla. Analysis of the mutant thymocyte showed reduction of the total cell number by two orders of magnitude accompanying the impaired thymocyte development. The early stage intrathymic c-kit+ T precursor cells were largely depleted. The following thymocyte development also seemed to be affected as assessed by the distorted composition of CD4- or CD8-expressing cells. The mutant thymocyte showed elevated alpha4 integrin expression, which might be related to the T cell defect in the mutant mice. In the peripheral lymph node tissue of the mutant mice, the CD4-CD8+ single positive cells were significantly reduced relative to CD4+CD8-single positive cells. In contrast to T cells, other hematopoietic lineages appeared to be normal. The data indicated that deltaEF1 is involved in regulation of T cell development at multiple stages.

Animals↗

Phosphorylation of ATF-1 enhances its DNA binding and transcription of the Na,K-ATPase alpha 1 subunit gene promoter.

Transcriptional activity of both ATF-1 and CREB is enhanced by protein phosphorylation. While enhancement has been attributed to an increase in binding affinity for a co-activator (CBP), induction of the DNA binding activity by phosphorylation is an open question. Using the Na,K-ATPase alpha1 subunit gene promoter, which has an asymmetrical ATF/CRE site, we analyzed the effect of phosphorylation on DNA binding activity of the ATF-1-CREB heterodimer. Dephosphorylation of the heterodimer in nuclear extracts reduced binding to the ATF/CRE site. Phosphorylation of ATF-1 at Ser63 enhanced its binding to the ATF/CRE site in both the homodimeric and heterodimeric forms. Transcription of the Na,K-ATPase alpha 1 subunit gene promoter was also stimulated by phosphorylated ATF-1 in vitro.

Activating Transcription Factor 1↗

Functional role of endogenous CD14 in lipopolysaccharide-stimulated bone resorption.

Lipopolysaccharide (LPS) is a bacterial cell component that plays multifunctional roles in inflammatory reactions, and one of these roles is that of a powerful stimulator of bone resorption. However, the mechanism by which LPS stimulates bone resorption is not yet understood. In the present study, we show, by using mouse embryonic calvarial cells, that endogenous CD14 and interleukin-1 beta (IL-1 beta) play an important role in the LPS-mediated bone resorption and that interferon-gamma (IFN-gamma) functions as a strong inhibitor of this resorption by suppressing LPS-stimulated expression of CD14 and IL-1 beta genes in the calvarial cells. We observed that LPS-stimulated differentiation of osteoclastic cells and bone resorption were markedly neutralized by anti-mouse CD14 antibody and were clearly inhibited by anti-sense CD14 oligonucleotide treatment. In addition, because LPS stimulated CD14 gene expression in the calvarial cells, these observations demonstrate the precise role of endogenous CD14 in LPS-stimulated differentiation of osteoclastic cells and bone resorption. However, the stimulation of the differentiation of osteoclastic cells and bone resorption was also inhibited by anti-mouse IL-1 beta antibody. Interestingly, anti-sense CD14 oligonucleotide inhibited LPS-stimulated expression of the IL-1 beta gene in the calvarial cells. These observations suggest a functional role of endogenous CD14 in LPS-stimulated expression of the IL-1 beta gene in the cells. Because IFN-gamma is a potent inhibitor of bone resorption stimulated by IL-1, in additional experiments, we examined whether IFN-gamma is able to inhibit LPS-stimulated differentiation of osteoclastic cells and bone resorption. We found that IFN-gamma inhibited these stimulations by suppressing CD14 and IL-1 beta genes in the calvarial cells. The present study thus clearly demonstrates a functional role of endogenous CD14 in LPS-stimulated bone resorption.

Acid Phosphatase↗

Synergistic cytotoxic effect of quercetin and heat treatment in a lymphoid cell line (OZ) with low HSP70 expression.

Heat shock protein 70 (HSP70) protects cells from various injurious stimuli and is important in cell growth and differentiation. However, its expression in leukemia cells has not been analyzed systematically. We, therefore, investigated the expression of HSP70 in various types of leukemia cells and hematopoietic cell lines. Immunoblot analysis revealed that HSP72/73 were expressed at low levels in the acute lymphocytic leukemia cells and lymphoid cell lines examined. However, heat (43 C for 2 h) preferentially augmented HSP72/73 expression in lymphoid cells. This induction was partially blocked by the treatment with quercetin (10 microM for 24 h). Finally, heat shock following quercetin treatment synergistically induced apoptosis in a lymphoid cell line (OZ). These observations suggest the possibility of selective purging of lymphocytic leukemia cells by combination with quercetin and heat.

Apoptosis↗

GM-CSF- and IL-3-dependent CD34 expressing myeloid cell line (SAS-1) established from CD7 and CD34 expressing acute myeloblastic leukemic cells.

A novel factor-dependent human myeloid leukemia cell line (SAS-1) was established from a 69-year-old Japanese male suffering from CD7 and CD34 expressing acute myeloblastic leukemia (AML M2 in FAB classification). Morphological and cytochemical staining showed that SAS-1 cells were round with basophilic cytoplasm which is positive for peroxidase. Analysis of surface markers revealed that SAS-1 cells were myeloblasts derived from an immature progenitor origin, which express CD34. The consensus karyotype of the cell line was 41 XY 5q-, -7, 11p-, 12p+, -13, -14, -16, -17, -19, -22, with two markers. The proliferation of SAS-1 cells was dependent on the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and GM-CSF- and IL-3-induced proliferation was dose dependent. Neither, stem cell factor (SCF) nor granulocyte colony-stimulating factor (G-CSF) alone supported the growth of SAS-1 cells, but supported their viability for more than 4 days and arrested them in the G0/G1 phase. SCF also enhanced GM-CSF- or IL-3-induced growth, but other cytokines did not have this synergistic effect. Clonogenic assays revealed that SAS-1 cells formed 36.0 +/- 5.7 or 41.5 +/- 0.7 colonies/1000 cells in the presence of GM-CSF or IL-3, respectively. SCF also increased the number of colonies formed by GM-CSF or IL-3 treatment, while SAS-1 cells did not form colonies in the presence of SCF alone. SAS-1 cells may prove to be a useful tool for studying the regulation of the cell cycle, myeloid proliferation, and differentiation.

Aged↗

Intraoperative ultrasonography versus cholangiography during laparoscopic cholecystectomy: a prospective comparative study.

BACKGROUND: The purpose of this study was to compare the functional utility of intraoperative ultrasonography (IOUS) and cholangiography (IOC) during a laparoscopic cholecystectomy for the treatment of gallstone disease. STUDY DESIGN: A prospective study comparing IOUS and IOC was carried out in 65 patients. Intraoperative ultrasonography was conducted first using a 7.5-MHz linear array probe. After IOUS, IOC was then conducted in all patients. The respective usefulness of IOUS and IOC in the identification of gallstones, detection of hepatobiliary structures, and demonstration of congenital anomalies was then compared. RESULTS: Intraoperative ultrasonography was successful in all 65 patients, and IOC was successful only in 54. The time required for IOUS was significantly shorter (p < 0.0001) than for IOC. Intraoperative ultrasonography imaged the hepatic ducts and their confluence, the common hepatic duct, the common bile duct, and the ampulla of Vater in 97, 100, 97, and 51% of cases, respectively. Intraoperative cholangiography, on the other hand, depicted these structures in 85, 89, 100, and 94% of cases, respectively. Intraoperative ultrasonography demonstrated the cystic duct and its confluence in 94% of cases. Biliary anomalies were identified by IOUS in 12 patients and by IOC in 13. Intraoperative ultrasonography could detect the hilar vascular structures in most patients and visualized anomalies of the hepatic arteries in 5 patients. In this series, 5 patients had choledocholithiasis. The sensitivities, specificities, positive and negative predictive values, and accuracies in identifying these bile duct stones were 80, 98, 80, 98, and 97% by IOUS, and 80, 97, 67, 98, and 95% by IOC, respectively. CONCLUSIONS: Intraoperative ultrasonography is superior to cholangiography with respect to its safety, shorter examination period, and ease of administration in all patients. In addition, IOUS is also better for identifying subtle anatomic detail. Intraoperative ultrasonography compares favorably with IOC in terms of utility in exploring bile ducts for stones. Intraoperative ultrasonography is an effective procedure for biliary exploration during a laparoscopic cholecystectomy.

Cholangiography↗