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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 397 records · Page 22Linked to original sources

Experimental acute glomerulonephritis induced in the rabbit with a specific streptococcal antigen.

FITC-labelled IgG obtained from patients convalescing from acute poststreptococcal glomerulonephritis (APSGN) stains glomeruli of patients with early APSGN. We previously reported a streptococcal antigen (preabsorbing antigen (PA-Ag)) that preabsorbed the stain out of sera from the convalescent patients and thus prevented glomerular staining. To confirm the nephritogenicity of PA-Ag, we administered up to 40 mg of this antigen to rabbits for 8 days and observed them for up to 9 weeks. Immunohistological analysis showed diffuse and global glomerular staining for C3 without notable staining for gamma-globulin. Light microscopic examinations revealed slight to moderate proliferative glomerulonephritis with exudative change. Control rabbits, which received similar doses of bovine serum albumin, did not show significant staining for C3. A transient and significant decrease in CH50 was observed from weeks 3 to 7 (9.7 +/- 0.3 U/ml at week 3; normal range 12.9 +/- 0.6 U/ml). This experimental model showed a resemblance to immunological and immunohistological features of APSGN in humans. Although the precise mechanisms are yet to be determined, complement activation by PA-Ag seems to hold a key position in this model and in the human disease.

Acute Disease↗

Human hepatocyte growth factor in bile: an indicator of posthepatectomy liver function in patients with biliary tract carcinoma.

We measured the concentration of hepatocyte growth factor (HGF) in bile obtained from patients after hepatectomy. The HGF concentrations in the bile samples were quantified using an enzyme-linked immunosorbent assay (ELISA). By immunoblotting, using a monoclonal antibody raised against the HGF alpha-subunit, the bile HGF, which was purified on a Heparin-Sepharose column, showed a band of the same size as the recombinant HGF alpha-subunit (69 kd). Bile samples were obtained from 24 patients with biliary tract disease before and after hepatectomy by means of biliary drainage. Before surgery, the bile HGF concentrations were minimal (0.8 +/- 0.1 ng/mL); however, after hepatectomy on postoperative day 1 in patients without posthepatectomy liver failure (20 of 24), they increased severalfold (4.1 +/- 0.4 ng/mL, P < .05). The patients with posthepatectomy liver failure (4 of 24) showed no significant increase in bile HGF after hepatectomy (less than 2 ng/mL on postoperative day 1). The volume of the remnant liver correlated positively with the bile HGF concentration. The bile HGF concentration on postoperative day 1 exhibited a significant negative correlation with the maximum concentration of serum total bilirubin after hepatectomy. The concentration of bile HGF was generally higher than that in serum (2.1-fold). Thus, the bile HGF concentration after hepatectomy may be useful for the early assessment of posthepatectomy liver function.

Adult↗

Costimulation with ultraviolet B and interleukin-1 alpha dramatically increase tumor necrosis factor-alpha production in human dermal fibroblasts.

Ultraviolet light, particularly in wavelengths of 290-320 nm (UVB), is known to induce cytokine synthesis in the skin. Cytokines act in a cascade fashion and can have synergistic or antagonistic actions on regulation of other cytokines. In this study, we sought to determine whether cotreatment with UVB and interleukin-1 alpha (IL-1 alpha) induces tumor necrosis factor-alpha (TNF-alpha) production synergistically by human dermal fibroblasts. UVB irradiation (200 J/m2) or IL-1 alpha (10 ng/ml) independently induced small amount of TNF-alpha (< 25 pg/ml) from human dermal fibroblasts. However, combined treatments with UBV and IL-1 alpha induced 30-40-fold higher levels of TNF-alpha (750 pg/ml) than with either UVB of IL-1 alpha treatment alone. This synergy was also seen with mRNA expression. Maximum synergistic effect was observed when IL-1 alpha was added immediately after irradiation. Considering the fact that UVB is capable of causing release of IL-1 alpha from human keratinocytes and approximately 10% of incident UVB penetrates to the level of dermal fibroblasts, our results suggest that UVB may act in a cascade fashion to induce inflammation by initial release of keratinocyte IL-1 alpha, which then synergizes with UVB on human dermal fibroblasts to significantly increase TNF-alpha production.

Cells, Cultured↗

Effects of interferons on the production of interleukin-6 and interleukin-8 in human keratinocytes.

Interferons (IFNs) originally described for antiviral activity have been reported to have pleiotropic effects, including the ability to induce interleukin-6 (IL-6) and IL-8 production in several cell types. IL-6 and IL-8 are proinflammatory cytokines and are known to be produced by a wide variety of cells, including human keratinocytes. In the present study, we sought to examine the effects of IFNs on IL-6 and IL-8 production from human keratinocytes. IFN-gamma (10-50 ng/ml) induced IL-6 and IL-8 production dose dependently, but no induction of IL-6 or IL-8 was observed with either IFN-alpha or IFN-beta. Because cytokines often work in a cascade fashion and keratinocytes are a source of primary cytokines, IL-1 alpha, and tumor necrosis factor-alpha (TNF-alpha), we examined whether combined treatment with IFN-gamma and these primary cytokines, IL-1 alpha and TNF-alpha, had a synergistic effect on the production of IL-6 and IL-8. Combined treatment with IFN-gamma and IL-1 alpha induced 6-fold to 7-fold higher levels of IL-6 than IL-1 alpha alone. Combined treatment with IFN-gamma and TNF-alpha induced 11-fold to 12-fold higher levels of IL-6 than TNF-alpha alone. The same treatment induced 3-fold to 4-fold higher levels of IL-8 in both cases. These results suggest that IFN-gamma is a positive regulator for the production of IL-6 and IL-8 from human keratinocytes and likely has an augmentative effect on skin inflammation.

Cells, Cultured↗

The expression and modulation of IFN-alpha and IFN-beta in human keratinocytes.

In addition to leukocytes and fibroblasts, the classic sources of human interferons (IFN), many other human cells are now known to be capable of producing IFN. Keratinocytes (KC) are abundant in the skin and provide the first line of defense against viruses and other noxious agents. Human KC are a potent source of cytokines and were implicated as forming IFN-like protein(s). We have investigated whether KC form IFN. We found that culture supernatants from unstimulated human KC did not contain detectable amounts of IFN-alpha or IFN-beta. However, those from KC activated with the potent IFN inducer, polyriboinosinic:polriboycytidylic acid (poly rI:rC), had appreciable antiviral activity, which studies with neutralizing sera showed to be caused by IFN-beta. In ELISA tests, we detected IFN-beta protein in the supernatants but not IFN-alpha protein. Nevertheless, reverse transcription PCR showed that both IFN-alpha and IFN-beta mRNA were upregulated in poly rI:rC-treated KC. The levels of these mRNA were also increased in KC exposed to ultraviolet B (UVB) irradiation, interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), or lipopolysaccharide (LPS). These results show that IFN-beta is among the cytokines secreted from human KC and, together with IFN-alpha, may have a role in host defense mechanisms in the skin.

Antiviral Agents↗

Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice.

The non-obese diabetic (NOD) mouse is an excellent animal model of autoimmune diabetes associated with insulitis. The progression of insulitis causes the destruction of pancreatic beta cells, resulting in the development of hyperglycemia. Although it has been well documented that T cells are required for the development of insulitis and diabetes in NOD mice, the importance of B cells remains unclear. To clarify the role of B cells in the pathogenesis of NOD mice, we therefore generated B cell-deficient NOD (B-NOD) mice. Surprisingly, none (of 13) of the B-NOD mice developed diabetes by 40 weeks of age, while the control littermates with B cells (B+NOD) suffered from a high proportion (43 of 49) of diabetes. The insulin reactivity of B+NOD mice was significantly impaired, while the B-NOD mice showed a good insulin response, thus suggesting the pancreatic beta cell function to be well preserved in B-NOD mice. Although B-NOD mice did develop insulitis, the extent of insulitis was significantly suppressed. These data thus provide the direct evidence that B cells are essential for the progression of insulitis and the development of diabetes in NOD mice.

Animals↗

The in-vivo activity of an antifungal antibiotic, benanomicin A, in comparison with amphotericin B and fluconazole.

The in-vivo antifungal activity of benanomicin A administered intravenously or subcutaneously was compared with that of amphotericin B and fluconazole using animal models of systemic infections with Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The efficacy of benanomicin A in C. albicans infection was more pronounced when administered in multiple doses than in a single dose. This was also true of fluconazole, but not of amphotericin B, which showed no difference between single and multiple dosings. Benanomcin A eradicated C. albicans cells from the kidneys of infected mice in a manner comparable to that of amphotericin B, but more effectively than fluconazole. The histopathological findings obtained from the kidneys of the C. albicans-infected mice confirmed the therapeutic efficacy of benanomicin A. The subcutaneous ED50 values of benanomicin A were 1.30 mg/kg/day (C. albicans) and 19.0 mg/kg/day (A. fumigatus) which were intermediate between those of amphotericin B and fluconazole in the two models. The subcutaneous ED50 value of benanomicin A for C. neoformans was 21.5 mg/kg/day, which was higher than that of amphotericin B.

Amphotericin B↗

Induction of Bip mRNA upon programmed cell death of differentiated PC12 cells as well as rat sympathetic neurons.

We have found that expression of the Bip (immunoglobulin heavy chain binding protein)/GRP78 (glucose regulated protein 78) gene is markedly enhanced specifically among the heat shock protein (HSP) 70 gene family during the neuronal cell death of PC12 (22a) cells, that is induced by removal of nerve growth factor (NGF) and blocked by a transcription inhibitor, actinomycin D. The Bip mRNA induction is suppressed when the NGF-deprivation-dependent cell death of PC12 (22a) cells is inhibited by cAMP, cycloheximide or high K+. The Ca2+ ionophore, A23187, caused neuronal cell death accompanied by up-regulation of Bip, HSP90, and HSP70 mRNAs. In addition, a chelator of intracellular Ca2+ (BAPTA) elevated Bip mRNA and induced cell death in a low Ca2+ medium. Alterations of intracellular calcium homeostasis thus appear to induce Bip mRNA expression as well as apoptosis in PC12 (22a) cells. However, release of Ca2+ from intracellular stores by thapsigargin induced Bip mRNA expression but not cell death, indicating that Bip mRNA induction is not sufficient for neuronal death. Induction of Bip mRNA in association with apoptosis was also observed for NGF-deprived sympathetic ganglion cells in primary culture. These lines of evidence suggest that selective induction of Bip mRNA may play an important role in the programmed cell death of neurons deprived of neurotrophic factors and could be a landmark of the neuronal programmed cell death.

Actins↗

Purification and characterization of polyamine aminotransferase of Arthrobacter sp. TMP-1.

Polyamine aminotransferase of Arthrobacter sp. TMP-1 was induced by 1,3-diaminopropane (DAP), N-3-aminopropyl-1,3-diaminopropane (norspermidine), spermidine, and spermine, but not by putrescine. The enzyme was purified to homogeneity. Its molecular weight and subunit size were 129,000 and 64,000, respectively. Its absorption spectrum had maxima at 280 and 420 nm and a shoulder at about 350 nm, and changes were observed upon the addition of DAP, putrescine, and sodium borohydride. The spectrum and its changes indicated that the enzyme contained pyridoxal-5'-phosphate as the coenzyme. The coenzyme content was found to be 1 mol per mol of subunit. DAP, putrescine, norspermidine, spermidine, and spermine were active amino donors and gave relative rates of 100, 73, 24, 30, and 23%, respectively. Pyruvate was the most active amino acceptor, while 2-ketoglutarate and oxaloacetate were inert. The equilibrium constant of the DAP-pyruvate transamination was 0.34. DAP was suggested to be a minor product of the norspermidine-pyruvate reaction.

Arthrobacter↗

Action of polyamine aminotransferase on norspermidine.

The norspermidine-pyruvate reaction catalyzed by polyamine aminotransferase from Arthrobacter sp. TMP-1 formed N-3-aminopropyl-3-aminopropionaldehyde (APAPAL), L-alanine, 1,3-diaminopropane (DAP), allylamine, and acrolein, and the relative rates of formation of the latter four products were 24, 3.3, 2.3, and 1.2%, respectively, of the rate of the DAP-pyruvate transamination. The identification of APAPAL was done by 13C-NMR after it had been enzymatically oxidized to N-3-aminopropyl-beta-alanine followed by isolation of the oxidized product. The DAP was also isolated and identified by 13C-NMR. The allylamine and acrolein were identified by HPLC and a specific color reaction with m-aminophenol, respectively. In the absence of pyruvate, the enzyme catalyzed the elimination of DAP from norspermidine to yield allylamine, and the addition of DAP to allylamine to yield norspermidine with relative rates of 0.007 and 0.095%, respectively. When allylamine was incubated with the enzyme as the sole substrate, it was converted to N-allyl-1,3-diaminopropane and an unidentified product.

Acrolein↗

Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor? Structural requirements for triggering a Ca2+ transient in NG108-15 cells.

The effects of delta9-tetrahydrocannabinol and 2-arachidonoylglycerol on the intracellular free Ca2+ concentration ([Ca2+]i) in NG108-15 cells were examined in detail. We found that delta9-tetrahydrocannabinol induces a rapid, modest increase in [Ca2+]i. The response was detectable with 3 nM delta9-tetrahydrocannabinol. We also found that very low concentrations of 2-arachidonoylglycerol elicit a rapid, more prominent increase in [Ca2+]i. Such a response was observed not only in NG108-15 cells but also in N18TG2 cells. The response induced by 2-arachidonoylglycerol in either NG108-15 cells or N18TG2 cells was abolished by pretreatment of the cells with a cannabinoid CB1 receptor specific antagonist, SR141716A, suggesting that 2-arachidonoylglycerol interacts with the CB1 receptor to induce the response. The results of an experiment involving a phospholipase C inhibitor suggested that phospholipase C is involved in the rapid increase in [Ca2+]i induced by 2-arachidonoylglycerol. We also found that 1(3)-arachidonoylglycerol exhibits similar activity to that of 2-arachidonoylglycerol, although its activity at low concentrations was somewhat weak compared with that of 2-arachidonoylglycerol. We further confirmed that several structural analogues of 2-arachidonoylglycerol were less active compared with 2-arachidonoylglycerol. These results suggest that the structure of 2-arachidonoylglycerol is strictly recognized by the CB1 receptor, which raises the possibility that the CB1 receptor is originally a 2-arachidonoylglycerol receptor.

Calcium↗

Reduction malarplasty.

One of the most frequently requested facial contour improvement procedures in the Orient is reduction malarplasty. However, until recently, osteotomies in the malar region have been performed by means of a coronal incision that required a larger incision and more invasive procedure than many patients are comfortable with when considering an elective cosmetic surgical procedure. We have developed a reduction malarplasty method to improve facial contours that circumvents the drawbacks inherent in the conventional method. In our method, the protrusion in the cheekbone area is corrected by performing an osteotomy of the zygoma through an intraoral incision and an osteotomy of the zygomatic arch through a small preauricular incision.

Adult↗

CD45 molecule in gammadelta T-cell generation: disruption of CD45 exon 6 does not affect Vgamma3 dendritic epidermal T-cell development.

There are two distinct lineages of T cells: T-cell receptor (TCR) alphabeta-bearing cells (alphabeta T cells) and TCR gammadelta-bearing cells (gammadelta T cells). All of the alphabeta T cells and most subsets of gammadelta T cells develop in the thymus. It has been demonstrated that the protein tyrosine phosphatase CD45 plays a pivotal role in the intrathymic development of alphabeta T cells. Thymocyte maturation is arrested at the transitional stage from immature CD4+ CD8+ double-positive to mature CD4+ or CD8+ single-positive cells after CD45 exon 6 gene disruption. In this study, we examined whether Vgamma3 dendritic epidermal T cells (DETC), a subset of thymus-dependent gammadelta T cells uniquely residing in the murine epidermis, are altered in the CD45 exon 6-deficient mice. In situ immunolabeling on epidermal sheets demonstrated that the CD45-deficient mice had a normal density and immunophenotype of Vgamma3 DETC compared with the wild-type control mice. Reverse transcriptase polymerase chain reaction revealed that similar levels of Vgamma3 TCR mRNA were present in the epidermis of CD45-deficient mice and wild-type controls. Flow cytometry demonstrated no significant difference in the proportion of Vgamma3 T cells in the epidermis between the genotypes. In addition, Vgamma2 T cells, another subset of gammadelta T cells, were also examined by flow cytometry. The frequency of Vgamma2 T cells in lymph nodes was normal in the CD45-deficient mice. Our results indicate that although CD45 is crucial for the development of alphabeta T cells, this molecule is not necessary for the thymic maturation of gammadelta T cells, including Vgamma3 DETC and Vgamma2 T cells.

Animals↗

Toxic epidermal necrolysis possibly linked to hyperacute graft-versus-host disease after allogeneic bone marrow transplantation.

Toxic epidermal necrolysis (TEN) is a severe blistering skin disease of high mortality. TEN may occur after bone marrow transplantation (BMT). In such cases, TEN have been attributed to graft-versus-host disease (GVHD) or an adverse drug reaction. It is very difficult to distinguish the causes of TEN after BMT. We report a 21-year-old Japanese man who developed TEN eight days after BMT, evaluate the differential diagnosis of hyperacute GVHD and an adverse drug reaction, and deduce that hyperacute GVHD was the more likely pathogenesis of TEN in this patient.

Acute Disease↗

Sister Joseph's nodule: a case report and review of the Japanese literature.

We report a case of metastatic carcinoma on the umbilicus, which is known as Sister Joseph's nodule. A 65-year-old man with the chief complaint of a painful nodule on the umbilicus was referred to our hospital. Histopathological examination revealed moderately differentiated tubular adenocarcinoma in the dermis. Endoscopic examination found gastric cancer of Borrmann type IV. The umbilical lesion represented a metastasis from the gastric cancer. We reviewed 80 cases of metastatic carcinomas to the umbilicus that have been reported in the Japanese literature.

Adenocarcinoma↗

A case of triple extramammary Paget's disease.

We report a 74-year-old Japanese man with triple extramammary Paget's disease; the genital and both of the axillar regions were simultaneously involved. Literature review revealed that 27 cases of triple extramammary Paget's disease have been reported in Japan, but there are no reports of triple extramammary Paget's disease from countries other than Japan, although 2 cases of double extramammary Paget's disease are reported. In all 28 cases, including our case, the genital lesion preceded the axillary lesions. All cases except one were male and only the exceptional female case was reported to have an the invasive tumor in the dermis. We speculate that extramammary Paget's disease may appear multi-centrically.

Aged↗