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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 469 records · Page 26Linked to original sources

Chronic neutrophilic leukemia with dysplastic features mimicking myelodysplastic syndromes.

A 52-year-old male patient with chronic neutrophilic leukemia (CNL) with dysplastic features is described. He had a 2-year history of anemia followed by marked leukocytosis up to 57.5 x 10(9)/l with 88% segmented neutrophils. Bone marrow aspiration and biopsy showed hypercellular marrow with myeloid hyperplasia and 16% myeloblasts. There were also significant morphological abnormalities which included neutrophils with few granules, hypersegmented nucleus or Pelger-Heut anomaly, and micromegakaryocytes. Cytogenetic analysis disclosed a deletion of the long arm of chromosome 7 (7q-). He was diagnosed as having CNL with dysplastic features and was treated conservatively. However, leukemic transformation to acute myelogenous leukemia occurred within a year and he died 16 months after diagnosis. Neutrophilia is a feature not of myelodysplastic syndromes (MDS) but rather of myeloproliferative disorders such as CNL. However, this patient was considered to have MDS with increased proliferation and differentiation of neutrophilic lineage, because of marked myelodysplasia and poor prognosis.

Diagnosis, Differential↗

N-arachidonoylethanolamine (anandamide), an endogenous cannabinoid receptor ligand, and related lipid molecules in the nervous tissues.

The effects of N-arachidonoylethanolamine (anandamide) and related compounds on the binding of [3H]CP55940 to rat brain synaptosomes were examined. Anandamide was shown to inhibit competitively the specific binding of [3H]CP55940 to synaptosomal membranes. The Ki value was 89 nM. In contrast, N-acylethanolamines containing saturated or monoenoic fatty acids did not exhibit high binding affinity. Several structural analogues of anandamide showed some binding activity. Among them, 2-arachidonoylglycerol is noteworthy because of its occurrence in mammalian tissues. A biosynthetic study indicated that anandamide can be synthesized via two separate synthetic pathways. The first is synthesis from free arachidonic acid and ethanolamine, and the second is the formation of N-arachidonoyl phosphatidylethanolamine (PE) from diarachidonoyl phospholipids and PE and the subsequent enzymatic release of N-arachidonoylethanolamine. The latter pathway appears to explain very well the fatty acid composition of N-acylethanolamines present in mammalian tissues.

Animals↗

Extended thymectomy for myasthenia gravis patients: a 20-year review.

BACKGROUND: Since 1973 we have performed extended thymectomy for myasthenia gravis because of the presence of thymic tissue in the anterior mediastinal fatty tissue. Follow-up results were reviewed and influencing factors were investigated. METHODS: Three hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point. RESULTS: Remission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome. CONCLUSIONS: Extended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.

Adult↗

Esophageal tracheobronchoplasty for diseases of the central airway.

Three infants with congenital tracheal stenosis and three adults with various diseases of the central airway underwent esophageal tracheobronchoplasty to repair long-segment stenoses and defects. The primary operative goal was enlargement of the stenosis (n = 4), repair of the defect (n = 1), or both (n = 1). Cardiopulmonary support was required in two cases. All three infants were operated on for generalized congenital tracheal stenoses. There was one postoperative death on the fifth day. Another infant died of pneumonia 3 months after operation. Tracheal patency was excellent in two infants. One infant is well without symptoms 6 years after the operation, although balloon dilation was required three times during the first postoperative year. In the three adult patients, the primary diseases were congenital tracheal stenosis, iatrogenic injury associated with relapsing polychondritis, and malignant mediastinal tumor involving the trachea. All lesions involved both the trachea and main stem bronchi. Postoperative airway patency was excellent in all three adults, although expandable metallic stents had to be inserted in one patient. Postoperative pulmonary function was improved, particularly forced expiratory volume in 1 second and peak expiratory flow rate. Although the postoperative mortality rate was still high, especially among the infants, and prolonged postoperative ventilatory support was required for five of the six patients, long-term patency and postoperative pulmonary functional improvement are encouraging.

Adult↗

Preoperative intrahepatic segmental cholangitis in patients with advanced carcinoma involving the hepatic hilus.

BACKGROUND: Major hepatic resection for biliary tract carcinoma continues to be a risky operation. In this study we examined the influence of preoperative intrahepatic segmental cholangitis on posthepatectomy mortality. METHODS: We analyzed retrospectively the clinical features of 118 patients who underwent liver resection including more than two segments for biliary tract carcinoma involving the hepatic hilus. RESULTS: Intrahepatic segmental cholangitis was encountered before operation in 22 cases. The morbidity and mortality rates for these patients were significantly higher than those of patients without preoperative cholangitis. Selective percutaneous transhepatic biliary drainage was performed before operation in 11 patients for segmental cholangitis. The morbidity rate of patients after hepatectomy was significantly lower than that of patients treated without percutaneous transhepatic biliary drainage. CONCLUSIONS: The presence of preoperative intrahepatic segmental cholangitis is a major prognostic factor in the outcome of major hepatic resection for biliary carcinoma. Selective percutaneous transhepatic biliary drainage for preoperative intrahepatic segmental cholangitis plays an important role in reducing complications after major hepatic resection.

Adult↗

Identification of K1/K10 and K5/K14 keratin pairs in human melanoma cell lines.

Keratin expression in cultured malignant melanoma cells has been studied only rarely. Moreover, no studies have reported of universality of keratin expression in human malignant melanoma cells. In this study, therefore, we analyzed keratin expression in eight cell lines. Using a low-salt aqueous solution without high salt and Triton X-100, as a washing buffer for keratin extraction, followed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and immunological analysis, we demonstrated keratin expression in all eight human malignant melanoma cell lines. The keratin polypeptide expressions common to all melanoma cells were K1, K5, K10 and K14. In addition, K8, K13, K17 and K18, respectively, were detected in individual cells. A measure of keratin expression universality in malignant melanoma cells may have implications regarding their invasive and metastatic behaviors, co-expressed with vimentin.

Electrophoresis, Gel, Two-Dimensional↗

Cyclic AMP-regulated GABA release at inhibitory synapses in rat cerebellar slices.

We have investigated the effects of agents interfering with the cAMP pathway on the rate of miniature IPSCs in cerebellar slices. Noradrenaline and group II glutamate metabotropic receptor agonists respectively enhance and reduce the rate of miniature IPSCs, presumably because they respectively increase and decrease the presynaptic concentration of cAMP.

Adenine↗

Pediatric and adult tracheobronchomalacia.

Twelve cases of tracheobronchomalacia (TBM) cases were reviewed: five were pediatric, and seven were adult, two of which were due to relapsing polychondritis (RPC). In pediatric TBM, the malacic segments were short. Resection of the malacic segment in one case and laryngotracheoplasty with autologous costal cartilage in one case were unsuccessful. However, aortopexy gained good results. Two cases managed conservatively experienced gradual improvement of their symptoms. In adult TBM, plication of pars membranacea was not effective in one case. The insertion of a stent was minimally effective in one case, and distinctly in one polychondritic case. The other four cases managed conservatively have deteriorated gradually. From these findings, a new classification system is proposed.

Adult↗

Pulmonary delivery of salmon calcitonin dry powders containing absorption enhancers in rats.

PURPOSE: To evaluate the effects of absorption enhancers in dry powders and in liquids, pulmonary absorption of salmon calcitonin (sCT) in various formulations was measured. METHODS: The dry powder of sCT was prepared by a freeze-drying method with a jet mill. After intratracheal administration of sCT dry powder and liquid (solution) preparations to rats, plasma sCT levels and calcium levels were measured. RESULTS: After intratracheal administration without absorption enhancers, sCT in the dry powder and in the liquid were absorbed nearly to the same degree. Absorption enhancers (oleic acid, lecithin, citric acid, taurocholic acid, dimethyl-beta-cyclodextrin, octyl-beta-D-glucoside) were much more effective in the dry powder than in the solution. The reason may be that the enhancers added to the dry powder dissolved at high concentrations in a trace volume of the fluid lining the alveolar epithelium. CONCLUSIONS: The present results suggest that the pulmonary absorption of peptides and proteins can be greatly improved by formulating them into dry powders with smaller amounts of enhancers than in liquid dosage forms.

Absorption↗

mdm2 gene mediates the expression of mdr1 gene and P-glycoprotein in a human glioblastoma cell line.

The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumours. The mechanism by which mdr1 gene and P-gp are overexpressed in human tumours, however, is not yet clear. In this report, we show that the mdm2 (murine double minute 2) gene induced the expression of the mdr1 gene and P-gp in human glioblastoma U87-MG cells, which did not express the MDM2 protein or P-gp. The mdm2 gene, in addition, conferred the resistance of U87-MG cells to the apoptotic cell death induced by etoposide (VP-16) or doxorubicin. Furthermore, treatment with mdm2 antisense oligonucleotides inhibited the expression of P-gp in MDM2-expressing U87-MG cells. These findings suggest that the mdm2 gene may play an important role in the development of MDR phenotype in human tumours.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

p53-dependent apoptosis suppresses radiation-induced teratogenesis.

About half of human conceptions are estimated not to be implanted in the uterus, resulting in unrecognizable spontaneous abortions, and about 5% of human births have a recognizable malformation. In order to find clues to the mechanisms of malformation and abortion, we compared the incidences of radiation-induced malformations and abortions in p53 null (p53-/-) and wild-type (p53+/+) mice. After X-irradiation with 2 Gy on day 9.5 of gestation, p53-/- mice showed a 70% incidence of anomalies and a 7% incidence of deaths, whereas p53+/+ mice had a 20% incidence of anomalies and a 60% incidence of deaths. Similar results were obtained after irradiation on day 3.5 of gestation. This reciprocal relationship of radiosensitivity to anomalies and to embryonic or fetal lethality supports the notion that embryonic or fetal tissues have a p53-dependent "guardian" of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of cells with apoptotic DNA fragments was greatly increased in tissues of the p53+/+ fetuses but not in those of the p53-/- fetuses.

Animals↗

The role of CD4 molecules in the induction phase of contact hypersensitivity cytokine profiles in the skin and lymph nodes.

We have previously demonstrated that CD4 gene-targeted mutant mice (CD4- mice) demonstrate hyporesposiveness in contact hypersensitivity (CHS) suggesting that CD4 molecules are required for optimal induction of CHS. In the present study, we wished to examine the mechanisms of this hyporesponsiveness, in particular, we examined whether cytokines were altered in the skin and lymph nodes of CD4- mice following exposure to the contact allergen dinitrofluorobenzene (DNFB). Cytokine mRNA in the ear skin and draining lymph nodes (DLN) were examined by reverse transcription-polymerase chain reaction (RT-PCR) at various times after sensitization. Skin cytokine patterns revealed that in normal mice, interleukin (IL)-2, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha mRNA levels increased at 12 hr sensitization, whereas these cytokines were below the level of detection in CD4- mice. In the DLN of normal mice following the hapten application, sequential upregulation of cytokine mRNA including IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-10, IFN-gamma and TNF-alpha was found. No change was seen for IL-1 alpha, IL-1 beta, IL-10 and TNF-alpha and IL-2, IL-4 and IFN-gamma mRNA levels were below the level of detection in DLN from CD4- mice following the hapten application. However, IL-1 beta, IL-2 and TNF-alpha mRNA levels of lymph node cells from CD4- mice could be upregulated by phorbol myristate acetate in vitro. Flow cytometry study has revealed that the number of Langerhans' cells (LC) in DLN of CD4- mice was similar to that of normal mice, thus, inferring that the alterations of cytokine milieu in the ear skin did not have a significant effect on LC migration to DLN. These results suggest that CD4 molecules are crucial for the induction of certain cytokines in the skin and in inducing sequential cytokine signals in DLN required for optimal development of CHS, but that these changes in cytokines do not effect LC migration.

Animals↗

Enzymatic synthesis of oleamide (cis-9, 10-octadecenoamide), an endogenous sleep-inducing lipid, by rat brain microsomes.

The enzymatic synthesis of a novel sleep-inducing lipid, oleamide (cis-9,10-octadecenoamide), was studied using rat brain subcellular fractions as enzyme sources. We found that oleamide was formed from oleic acid and ammonia on incubation with a brain homogenate. The enzyme activity catalyzing the formation of oleamide from oleic acid and ammonia was highest in the microsomal fraction among the subcellular fractions. Boiled microsomes did not exhibit appreciable enzyme activity. These results strongly suggest that oleamide can be synthesized enzymatically in the brains of stimulated animals.

Adenosine Triphosphate↗

Effect of a novel topical immunomodulator, S-28463, on keratinocyte cytokine gene expression and production.

A new immunomodulating agent, imiquimod, has been reported to have antiviral and antitumor activities in animal models. S-28463 (4-amino-2-ethoxymethyl-alpha, alpha-dimethyl-1H-imidazo[4, 5-c]quinoline-1-ethanol), an analog of imiquimod, has more potent antiviral activity in animals than imiquimod. It has also been shown to be more potent at inducing cytokines in human blood in vitro. However, its precise role as an immunomodulator in the skin has not been determined. We investigated the effect of S-28463 on human keratinocyte (KC) production of interferon-alpha (IFN-alpha) and other proinflammatory cytokines, including interleukin (IL)-1alpha, IL-8, and tumor necrosis factor-alpha (TNF-alpha). Human KC were incubated with S-28463 at two concentrations (1 microgram/ml and 10 micrograms/ml) for 6 h. Cytokine gene expression was analyzed by reverse-transcriptase PCR. In human KC, S-28463 stimulated significant increases in IFN-alpha mRNA at both concentrations. IL-1alpha mRNA increased 1.4-fold at 10 micrograms/ml. IL-8 mRNA was upregulated 2.5-fold at 10 micrograms/ml. Twenty-four hours after treatment, IL-1 alpha, IL-8, and TNF-alpha protein were increased, but IFN-alpha was below the level of detection. These results suggest that in the skin, S-28463-induced-IL-1 alpha, IL-8, and TNF-alpha production may be involved in the immunomodulating action of S-28463.

Adjuvants, Immunologic↗

High frequency class switching of an IgM+ B lymphoma clone CH12F3 to IgA+ cells.

We have developed an efficient in vitro class switching system using a subclone (CH12F3) of the IgM+ CH12.LX lymphoma cell line. CH12F3 cells switched from surface IgM+ cells to surface IgA+ cells at a high frequency (50%) after 72 h stimulation with IL-4, transforming growth factor (TGF)-beta and CD40L. No other class isotype-producing cells were detected, indicating that the CH12F3 clone is exclusively committed to IgA isotype switching. To understand the molecular basis of the isotype commitment, we studied the methylation profiles of I region promoters and I region transcription of CH12F3 cells. No germline transcripts other than those from the I alpha region were detected and only the I alpha promoter was demethylated in uninduced CH12F3 cells. TGF-beta, CD40L and IL-4 synergistically induced efficient switch recombination in CH12F3 cells, suggesting that the three stimulations up-regulate different steps of switch recombination in isotype-committed B cells such as CH12F3 cells. Stimulation of CH12F3 cells by IL-4 or TGF-beta, but not by CD40L, induced transient but complete methylation of the I alpha region. TGF-beta and CD40L, but not IL-4, increased the amounts of germline alpha transcripts. We found that the extents of methylation and the amounts of germline transcripts do not necessarily correlate with the efficiency of recombination in induced CH12F3 cells. These results led to the proposal that switch recombination can be separated into at least two phases, i.e. commitment and recombination. The roles of IL-4, TGF-beta and CD40L in the two phases are discussed.

Animals↗

The in-vitro activity of an antifungal antibiotic benanomicin A in comparison with amphotericin B.

Benanomicin A showed a broad antifungal spectrum, inhibiting the growth of all test strains of 41 yeasts, 23 dimorphic fungi, 23 dematiaceous fungi, 16 aspergilli, and 19 dermatophytes, with the exception of 12 zygomycetic strains. The MIC values of benanomicin A were comparable to those of amphotericin B against Cryptococcus. Rhodotorula, Trichosporon, Geotrichum, Sporothrix, and some dermatophytes, but were two to eightfold higher than those of amphotericin B against other fungal pathogens tested. The action of benanomicin A was fungicidal.

Amphotericin B↗

Microinfusion method using barium sulfate for visualization of embryonic blood vessels with light and scanning electron microscopy.

An X-ray contrast medium commonly used for clinical examination of the gastrointestinal tract was purified and applied as an injectant for the observation of the blood vasculature maturing in an early embryonic stage of the mouse. The embryos were perfused with the injectant through the umbilical cord and were processed for light and scanning electron microscope (LM and SEM) observations. When infused, the vessels turned white, the color of barium sulfate, thereby the adequate injection pressure and the amount of the injectant were readily controlled. The whole vasculature of the embryo was elucidated with an SEM in great detail at 9.5 days of the embryonic stage, four days earlier than previously achieved with a resin injection. The back scattered electron image of the lung alveolar capillaries containing barium sulfate was successfully obtained with an SEM in the 17.5 day embryo. The backscattering image and the secondary electron image of the identical area were compared to elucidate the spatial relationship between the capillaries and their circumferential cells such as type I and type II alveolar cells. The vascular injection with barium sulfate introduced may facilitate the systemic study of the blood vasculature and may provide useful information as to the relationship vascular formation and organogenesis occurring in an early embryonic stage.

Animals↗