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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 559 records · Page 31Linked to original sources
PubMed1995

Interleukin-1 receptor antagonist suppresses contact hypersensitivity.

Interleukin-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of interleukin-1 (IL-1), blocks IL-1 binding to its receptors but has no agonistic activity. IL-1 is thought to play an important role in contact hypersensitivity (CHS), although the effects of exogenously administered IL-1 in CHS have been somewhat controversial. To clarify the role of IL-1 in CHS, we studied the effect of IL-1 receptor blockade using exogenous IL-1ra and evaluated these effects on CHS. We examined the in vivo effects of local administration of recombinant human IL-1ra in the murine CHS model. Local injection of IL-1ra to sensitized BALB/c mice just before challenge with dinitrofluorobenzene resulted in a significant reduction in the intensity of CHS responses, assessed by ear swelling. A dose-response study revealed that maximal inhibition of ear swelling (36% to 43%) was observed after intradermal injection of IL-1ra at doses of 10 to 100 micrograms/ear. This reduction in ear swelling in IL-1ra-injected ears consisted of less inflammatory cell infiltration and decreased edema in the dermis compared with controls. Suppression of CHS was observed when IL-1ra was applied in the 24-h interval preceding challenge with dinitrofluorobenzene, whereas no suppressive effect was observed when IL-1ra was applied 48 h before or after the challenge. Local administration of IL-1ra to naive mice 5 h before sensitization also suppressed CHS responses. However, IL-1ra injection did not suppress phenol-induced inflammation. These results suggest that IL-1ra is an effective inhibitor of both the sensitization and elicitation phases of CHS expression in mice, thus emphasizing the role of IL-1 as an immunologic potentiator of responses associated with CHS.

Animals↗
PubMed1995

Failure to detect interleukin (IL)-3 mRNA or protein in human keratinocytes: antibodies to granulocyte macrophage-colony-stimulating factor or IL-6 (but not IL-3) neutralize "IL-3" bioactivity.

Interleukin (IL)-3-like bioactivity has been found in culture supernatants from human and murine keratinocytes. However, there is controversy as to the presence of IL-3 mRNA in human keratinocytes. Using highly sensitive reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay techniques, we examined human keratinocytes from four different donors (neonatal foreskins) and were unable to detect IL-3 mRNA or IL-3 protein. Despite successful amplification of DNA from an IL-3 cDNA, no product could be obtained by amplification of keratinocyte RNA treated with reverse transcription-polymerase chain reaction. Analysis of concentrated (up to 50-fold) supernatants failed to detect IL-3 protein by enzyme-linked immunosorbent assay. Because ultraviolet radiation up-regulates many cytokines, we irradiated human keratinocytes with 300 J/m2 ultraviolet B and collected supernatants 24 h post-irradiation. Supernatants concentrated 50-fold were also negative for IL-3 protein by enzyme-linked immunosorbent assay. When assayed on the IL-3-responsive M-07e cell line, unirradiated supernatants stimulated M-07e proliferation 22-fold over background levels. Irradiated supernatants stimulated M-07e proliferation 128-fold. Neither the unirradiated nor the irradiated supernatant activity could be neutralized with antibody to human IL-3. However, incubation of irradiated supernatants with antibody to granulocyte macrophage-colony-stimulating factor (GM-CSF) reduced the M-07e proliferation by 90%. Antibodies against GM-CSF and IL-6 completely abrogated proliferation. Reverse transcription-polymerase chain reaction confirmed a concomitant elevation of IL-6 (2.6- to 5.6-fold) and of GM-CSF mRNA (2.7- to 4.3-fold) at 6 and 24 h after ultraviolet B irradiation in keratinocytes, but no IL-3 amplification products could be detected. IL-3 mRNA was also not detected in adult keratinocytes. Even after stimulation by IL-1 alpha, tumor necrosis factor-alpha, or phobol myristate acetate, IL-3 mRNA was not detected in either neonatal or adult human keratinocytes. We have been unable to detect IL-3 mRNA or IL-3 protein in human keratinocytes. The IL-3-like activity in human keratinocytes is mainly due to GM-CSF, with a small contribution from IL-6.

Antibodies↗
PubMed1995

Relative amounts of keratin 17 are higher than those of keratin 16 in hair-follicle-derived tumors in comparison with nonfollicular epithelial skin tumors.

Specimens of trichilemmal cyst, malignant trichilemmoma, keratoacanthoma, and epidermal cyst were examined to characterize keratin peptides in hair-follicle-derived tumors. Keratins were extracted from the specimens and analyzed by two-dimensional gel electrophoresis and densitometry; the results were then compared with those for normal epidermis, the outer root sheath of hair follicles, psoriatic epidermis, and various nonfollicular cutaneous epithelial tumors. The specific nonfollicular tumors examined were squamous cell carcinoma, Bowen disease, actinic keratosis, eccrine porocarcinoma, and sebaceous carcinoma. Immunohistochemistry also was performed with a few anti-keratin monoclonal antibodies. As a general rule, K6 and K16 were expressed in hyperproliferative conditions, such as epidermal tumors, and K17 was coexpressed in the same lesions. The ratio of K16 to K17 in many epithelial skin tumors has been unclear until now. K17 content exceeded K16 content in most follicular tumors, whereas in almost all the nonfollicular tumors and the psoriatic epidermis, K17 levels were less than or about equal to K16 levels. There was a significant difference in the ratio of K16 to K17 between follicular and nonfollicular skin tumors. These results indicate that alterations in the content of these keratins may be associated with follicular differentiation.

Epidermis↗
PubMed1995

Assessment of cellular proliferation of sebaceous neoplasms by AgNOR counts and immunohistochemical demonstrations of PCNA and Ki-67.

We assessed cellular proliferation of sebaceous neoplasms by AgNOR counts and the immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and Ki-67, using formalin-fixed and paraffin-embedded tissue specimens. We used three categories of sebaceous neoplasms: four cases of sebaceoma, three cases of basal cell carcinoma with sebaceous differentiation (BCSD), and seven cases of sebaceous carcinoma (SC). Significant differences were noted between SC and non-SC tumors (sebaceoma and BCSD) in AgNOR counts and semi-quantitative grading of PCNA and Ki-67 labelling indices (P < 0.01). When a cut-off value of 6 was chosen, the AgNOR value discriminated SC from non-SC tumors with high specificity and sensitivity. When a cut-off value of 25% was chosen, PCNA and Ki-67 labelling indices also discriminated between these tumors. Significant differences were not observed between sebaceoma and BCSD with PCNA and Ki-67 labelling indices. AgNOR counts of BCSD were a little higher than those of sebaceoma, but the number of cases was too small to perform statistical assessment. We consider AgNOR counts and semi-quantitative grading of PCNA and Ki-67 labelling indices to be useful in differentiating SC from BCSD and sebaceoma.

Cell Division↗
PubMed1995

Keratinocyte-derived cytokines and UVB-induced immunosuppression.

Ultraviolet radiation (UVB) in sunlight is known to have multiple effects on the immune system. Evidence suggests that UVB-induced immunosuppression is mediated in part by immunosuppressive and immunoregulatory cytokines. Our studies have utilized gene-targeted mutant mice to determine key molecular requirements essential for the development of UVB-induced immunosuppression. Preliminary results from our laboratory suggest that TNF-alpha plays a regulatory role in contact hypersensitivity, but is not a crucial factor for UVB-induced immunosuppression, and that multiple factors are involved in the induction of UVB mediated immunosuppression.

Animals↗
PubMed1995

Identification of biclonal (duplex) leukaemic cells expressing either CD4+/CD8- or CD4-/CD8+ from a patient with adult T-cell leukaemia/lymphoma.

A 24-year-old Japanese woman was admitted to our hospital in 1987 with a chief complaint of skin eruptions, and was diagnosed as having chronic ATLL. In 1993 the leucocyte count increased gradually to 126.0 x 10(9)/l with 91.5% abnormal lymphocytes expressing two different types of antigenicity, either CD+/CD8- or CD4-/CD8+. Monoclonal integration of human T-cell lymphotropic virus type-I proviral DNA was detected at different sites of the genomic DNA in each cell type. These studies clearly indicate that CD4+/CD8- and CD4-/CD8+ leukaemic cells originated from two independent clones.

Adult↗
PubMed1995

Assessment of cellular proliferation of eccrine acrospiromas and eccrine sweat gland carcinomas by AgNOR counting and immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and Ki-67.

Argyrophil nucleolar organizer regions (AgNORs) were counted and immunostaining using antibodies raised against proliferating cell nuclear antigen (PCNA) and Ki-67 was carried out on eccrine acrospiroma and eccrine sweat gland carcinoma, to determine the malignant potential and prognosis of these tumours. Formalin-fixed and paraffin-embedded tissue specimens surgically excised from 25 patients with eccrine sweat gland carcinoma (20 cases of eccrine porocarcinoma, four cases of ductal sweat gland carcinoma and one case of malignant clear cell hidradenoma) and 25 patients with eccrine acrospiroma (16 cases of eccrine poroma, four cases of poroid hidradenoma and five cases of clear cell hidradenoma) were used. PCNA and Ki-67 labelling indices were categorized semiquantitatively into four grades. Significant differences were noted between eccrine sweat gland carcinoma and eccrine acrospiroma with these three methods (P < 0.01). When a cut-off of 5 was chosen, the AgNOR value distinguished eccrine sweat gland carcinoma from eccrine acrospiroma with high specificity and sensitivity. Moreover, we compared the results of these three methods between stages 1 or 2 (17 cases) and stage 3 (eight cases) eccrine sweat gland carcinomas, and no significant differences were observed. From these findings, these three methods are useful in discriminating malignant from benign lesions of eccrine tumours, but have no value in estimating the aggressiveness of eccrine sweat gland carcinomas.

Acrospiroma↗
PubMed1995

Motor disturbance during REM sleep in group A xeroderma pigmentosum.

We investigated motor phenomena during rapid eye movement (REM) sleep in 13 patients with group A xeroderma pigmentosum aged from 11 to 39 months, and compared them with those obtained from 12 age-matched controls. At the time of sleep study, they had no abnormality on routine electrophysiological examinations. The amount of REM sleep and the incidence of motor phenomena during REM sleep in patients were similar to those in age-matched controls. However using the newly designated indices, we demonstrated disturbance on both the tonic motor inhibition occurring during the whole REM sleep period and the phasic one acting simultaneously with horizontal rapid eye movements in these patients. Since the motor inhibition during REM sleep is mediated by the subcortical structures, our study indicate that these structures are functionally impaired in group A xeroderma pigmentosum even during the early stage of the illness.

Brain Stem↗
PubMed1995

Successful treatment of Pneumocystis carinii Pneumonia in mice with benanomicin A (ME1451).

Benanomicin A (BNM-A) has antimycotic activities via binding to mannan in the cell walls of fungi. Anti-Pneumocystis carinii activity of the agent was examined in the P. carinii-infected BALB/c nu/nu female mouse model because P. carinii also possesses mannan in the membranes. The infected mice were treated with intraperitoneal injections of six doses of BNM-A (1, 2.5, 5, 10, 30, and 100 mg/kg of body weight), 4 mg of pentamidine isethionate per kg, 100 mg of sulfamethoxazole per kg combined with 20 mg of trimethoprim per kg (co-trimoxazole), or saline for 21 days. Each dosage group consisted of 10 mice. During treatment, five mice in the control group (saline) died, whereas 8 to 10 mice in all treatment groups survived. Almost the same efficacies were obtained for the groups treated with 5 mg or more and 10 mg or more of BNM-A per kg regarding the weight and number, respectively, of cysts found in the lungs as were obtained for the groups treated with pentamidine isethionate and co-trimoxazole. Overall, a dose of 10 mg of BNM-A per kg was effective against P. carinii pneumonia infection in the mice. Thus, BNM-A is a good candidate for a novel treatment for P. carinii pneumonia as a compound with a new mechanism of action against P. carinii.

Animals↗
PubMed1995

Reactive oxidants mediate TNF-alpha-induced leukocyte adhesion to rat mesenteric venular endothelium.

We investigated the role of reactive oxygen metabolites (ROMs) as potential mediators of tumor necrosis factor-alpha (TNF-alpha)-stimulated neutrophil adhesion to rat mesenteric venules in vivo, using intravital microscopy and fixed whole mount preparations of mesentery. Intraperitoneal injection of TNF-alpha significantly increased leukocyte rolling, adhesion, and emigration in a dose- and time-dependent manner. Leukocyte adhesion and emigration, but not rolling, were significantly attenuated by prior intravenous administration of monoclonal anti-intercellular adhesion molecule-1 (ICAM-1). Rolling leukocyte flux was significantly attenuated by intravenous preadministration of superoxide dismutase (SOD), catalase, or both. Only catalase or SOD plus catalase significantly inhibited leukocyte adhesion. Catalase alone inhibited emigration. Moreover, postadhesive treatment with catalase but not SOD, 4 h after TNF-alpha administration reduced the flux of rolling (but not adherent) leukocytes that had previously increased in response to TNF-alpha. Intragastric allopurinol (50 mg/kg at 3 and 18 h before TNF-alpha administration) or 3 wk of a tungsten-enriched diet substantially inhibited xanthine oxidase activity but had no significant effects on the above parameters of neutrophil dynamics. In parallel experiments using fixed whole mount preparations of the mesoappendix stained specifically for neutrophil esterase, neutrophil adhesion 2 h after TNF-alpha administration was also inhibited by continuous intravenous administration of catalase but not by SOD, intragastric allopurinol, or tungsten diet. These findings suggest that ROMs, apparently not from xanthine oxidase, are important mediators of TNF-alpha-induced upregulation of neutrophil adhesion in rat mesenteric venules.

Allopurinol↗
PubMed1995

Inhibition of cytokine gene expression in mouse skin by subcutaneous injection of cyclosporine.

Cyclosporine A (CsA) has been shown to be an effective therapeutic agent for a wide variety of cutaneous diseases yet its exact mechanism of action is still unclear, although one well-defined effect of CsA is the inhibition of T-cell-derived cytokine expression. We recently demonstrated in vitro that CsA inhibits cell proliferation and suppresses cytokine gene expression in keratinocytes. In this study, we report the in vivo effects of CsA on skin cytokine gene expression as determined by reverse-transcriptase polymerase chain reaction. C57BL6 mice (female, 8-10 weeks old) were subcutaneously injected with CsA in olive oil (0, 5 and 10 mg/kg) every other day for 3 weeks. Treatment with 5 mg/kg CsA inhibited both interleukin (IL)-1 alpha and tumor necrosis factor alpha gene expression by about 70 and 90%, respectively, relative to vehicle control levels. However, IL-6 gene expression did not significantly change. Injection of 10 mg/kg CsA inhibited expression of all three genes by 80-90% relative to control levels. These data show that CsA can inhibit constitutive cytokine gene expression in mouse skin.

Animals↗
PubMed1995

Muscarinic cholinergic receptor subtypes in human detrusor muscle studied by labeled and nonlabeled pirenzepine, AFDX-116 and 4DAMP.

The densities of M1, M2 and M3 muscarinic receptors in human detrusor muscle were measured using 3H-pirenzepine (3H-PZP), 3H-AFDX-116 (3H-AFDX) and 3H-4-diphenyl-acetoxy-N-methyl-piperidine methidide (3H-4DAMP). The affinities of PZP, AFDX and 4DAMP for human detrusor were determined in inhibition experiments with 3H-quinuclidinyl benzilate (3H-QNB). Saturation experiments with 3H-PZP, 3H-AFDX and 3H-4DAMP revealed the presence of M1, M2 and M3 receptors in human detrusor. The KD values (nM) and the Bmax values (fmol/mg protein) (mean +/- SD, n = 6) were 0.84 +/- 0.15 and 13.04 +/- 1.54 for 3H-PZP, 0.68 +/- 0.21 and 9.30 +/- 1.10 for 3H-AFDX, and 0.25 +/- 0.13 and 102.1 +/- 7.40 for 3H-4DAMP. These data indicate that the bladder muscarinic receptors consist mainly of the M3 subtype. Nonlabeled PZP, AFDX and 4DAMP inhibited the 3H-QNB binding to human detrusor with Ki values (nM) (mean +/- SD, n = 6) of 243 +/- 62.5, 59.7 +/- 15.3, 2.69 +/- 0.96, respectively. Human detrusor was found to have a high affinity for 4DAMP. These data suggest that M3 muscarinic receptors are biochemically predominant in human detrusor muscle.

Aged↗
PubMed1995

Benign prostatic hypertrophy affects the endothelin receptor density in the human urinary bladder and prostate.

The effects of benign prostatic hypertrophy (BPH) on the endothelin (ET) receptor density in the lower urinary tract tissues were studied using radioligand binding techniques. Saturation experiments revealed that there were significant amounts of the binding sites for the ET isoforms (ET-1, -2, -3) in the human bladder and prostate in both prostate hypertrophy (PH) and nonhypertrophy (NPH) patients. Autoradiograms of hypertrophic adenoma showed that ET-1 receptors were localized in both the stromal and glandular tissue. In the bladder and the prostate, the KD values were not significantly different between the PH and NPH groups. In the bladder dome, the Bmax values of 125I-ET-1, -2 and -3 decreased significantly in the PH groups, while, in the adenoma, they increased significantly in the PH group. BPH was found to affect the ET receptor density in both the bladder and the prostate. These data suggest that ETs are involved in the pathophysiology of BPH.

Autoradiography↗
PubMed1995

Tumor necrosis factor-alpha induces p53-dependent apoptosis in rat glioma cells.

In this study, we demonstrated that tumor necrosis factor (TNF)-alpha inhibited the viability of rat glioma (C6) cells and induced apoptosis but did not affect the viability of rat newborn brain, mainly astroglial cells. The antitumor activity of TNF-alpha against C6 cells was partially inhibited by actinomycin D and cycloheximide, suggesting that it is possibly dependent upon new ribonucleic acid and protein synthesis. The results of immunoblotting assay demonstrated that TNF-alpha decreased the expression of mutant p53 protein but induced the expression of wild-type p53 in C6 cells during apoptosis. We suggest that TNF-alpha may activate the function of wild-type p53 protein by the suppression of mutant p53, at least indirectly, and induce p53-dependent apoptosis in glioma cells.

Animals↗
PubMed1995

Apoptosis by antitumor agents and other factors in relation to cell cycle checkpoints.

More than a dozen cancer patients died in 1993 after treatment with antineoplastic derivatives of 5-fluorouracil and the antiherpes drug Sorivudine. This paper gives a short review of previous reports showing that killing of cells by 5-fluorouracil and other antitumor agents, including radiation at high doses, results from activation of apoptosis in the G2 phase. On the other hand, apoptosis of lymphocytes by radiation at low doses and treatment with other agents is known to occur in the G1 phase. The cells dying in the G1 or G2 phase could share the same final self-killing steps. For these common steps, I assume a mitotic catastrophe model, in which commitment to self-killing results from premature activation of the mitosis machinery, and propose a concept of a 'G1/G2 death circuit' for cells dying in the G1/G2 phase by short circuit to the M phase. Based on this model, reported modes of cell death, spontaneously occurring or after treatment with various agents, are classified by the phase of dying cells. The associations of incomplete apoptosis with production of chromosomal aberrations and prevention of tumorigenesis by complete apoptosis of carcinogen-treated cells are discussed. A presumptive rule for differentiation of G1 apoptosis and G2 apoptosis is proposed.

Antineoplastic Agents↗
PubMed1995

Juvenile parkinsonism treated with bilateral pallidotomies--case report.

A 47-year-old female diagnosed as having juvenile parkinsonism at age 38 years developed progressive motor fluctuation while receiving levodopa medication. She underwent right posteroventral pallidotomy which achieved only a transient effect on the wearing-off. An additional procedure on the left pallidum resulted in long-lasting relief of the parkinsonian symptoms.

Female↗
PubMed1995

Combination therapy with cisplatin and nifedipine inducing apoptosis in multidrug-resistant human glioblastoma cells.

The authors found that multidrug-resistant human glioblastoma GB-1 cells demonstrated significantly more resistance to cisplatin than did nondrug-resistant human glioblastoma U87-MG cells (p < 0.1). They therefore attempted to determine whether calcium channel blockers enhance the antitumor activity of cisplatin against GB-1 cells. Nifedipine, a dihydropyridine calcium channel blocker, significantly enhanced the antitumor effect of cisplatin on GB-1 cells (p < 0.05). In the absence of normal extracellular Ca++, nifedipine enhanced the cytotoxicity of cisplatin. In addition, the antitumor activity of combined cisplatin and nifedipine was inhibited both by actinomycin D and cycloheximide, suggesting that such activity is dependent upon new RNA and protein synthesis. Surprisingly, DNA fragmentation assay demonstrated that synergism between cisplatin and nifedipine resulted in apoptosis (programmed cell death) at a relatively low concentration of cisplatin, which when tested alone did not induce apoptosis. In addition, it was demonstrated that nuclei from GB-1 cells lacked a Ca(++)-dependent endonuclease that degrades chromatin into nucleosomes and that calcium ionophore A 23187 did not decrease the viability of GB-1 cells. The above findings suggest the hypothesis that the noncytotoxic agent nifedipine synergistically enhances the antitumor effect of cisplatin on multidrug-resistant GB-1 cells lacking Ca(++)-dependent endonuclease, and subsequently induces apoptosis via its interaction with an as yet uncharacterized functional site other than the calcium channel on GB-1 cells.

Apoptosis↗