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Biomedical subjects

F Sakamoto

Publications and source records attributed to F Sakamoto.

At least 37 records · Page 2Linked to original sources
PubMed1995

CD26 (dipeptidyl peptidase IV/DPP IV) as a novel molecular marker for differentiated thyroid carcinoma.

In this report we show that CD26 (dipeptidyl peptidase IV/DPP IV) is a novel molecular marker for differentiated thyroid carcinoma. Northern-blot analysis of 22 various thyroid tissues revealed that CD26 is a more specific marker of differentiated thyroid carcinoma than 3 proto-oncogenes previously reported to increase mRNA expression in thyroid carcinomas: c-met, c-erbB-2 and EGF-R. A comparative study of 3 CD26 assays, Northern blotting, immunohistochemical staining and activity staining clearly showed that CD26 enzyme activity staining is the most specific assay for differentiated thyroid carcinoma, yet the easiest to perform. Activity staining of 216 thyroid tissues detected CD26 in all 52 papillary carcinomas and all 5 follicular carcinomas, while all 58 cases of Graves' disease were CD26-negative. Among benign neoplasms, 54 of 55 adenomatous goiters and 29 of 33 follicular adenomas were CD26 negative. Staining intensity of the enzyme activity was relative to the degree of CD26 mRNA expression. Southern-blot study showed no gene amplification or major translocation of the CD26 gene in 7 papillary carcinomas examined. Based on this study, ectopic expression of CD26 in differentiated thyroid carcinomas is thought to be mainly caused by increased CD26 mRNA expression. In conclusion, CD26 activity staining is a simple, specific assay which should be added to the usual pathological examinations in order to distinguish differentiated thyroid carcinomas from benign thyroid diseases.

Adolescent↗
PubMed1995

Expression of tenascin in hamster buccal pouch mucosa during experimental carcinogenesis.

Experimental carcinogenesis by topical application of 7,12-dimethylbenz(a)anthracene (DMBA) in hamster buccal pouch mucosa was evaluated for expression of tenascin, an extracellular matrix glycoprotein expressed at the epithelial-mesenchymal interface during embryonic and fetal development, wound healing and in the stroma of various neoplastic lesions, by using immunohistochemical methods. The buccal pouch mucosa in normal hamsters showed immunoreactive tenascin either as a linear delicate band or without reactivity at the immediate vicinity of the basement membrane. During carcinogenesis, in the second to fourth week of application of DMBA, the hyalinous changes in the submucosal connective tissue had a weak but diffuse immunoreactivity for tenascin. The hyperkeratinised and hyperplastic mucosa following 5 weeks of application of DMBA showed focal areas of enhanced expression in the vicinity of the basement membrane. Subsequently, specimens showing hyperplasia, dysplasia, carcinoma in situ and invasive carcinomas had comparatively more widespread stromal immunoreactivity where the extent of enhanced reactivity positively correlated with the advancing lesion. These results compared with the results of expression in human normal mucosa, leukoplakia and squamous cell carcinoma of the oral cavity (Shrestha et al., Oral Oncol, Eur J Cancer 1994, 30, 132-137) suggest that the expression of tenascin in experimental carcinogenesis of hamster buccal pouch mucosa, as a model, faithfully mimics the same in human oral mucosa.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Human parvovirus B19 infection: immunohistochemical and electron microscopic studies of skin lesions.

Erythema infectiosum is known to be caused by human parvovirus B19 and shows characteristic clinical skin manifestations in children, although adult cases of human parvovirus B19 infection do not always show such characteristic features. Recently, we experienced an epidemic adult cases of human parvovirus B19 infection and examined the erythematous skin lesion by immunohistochemistry and electron microscopy to clarify the pathogenesis of the skin manifestations. Light microscopic examination showed slightly irregular-shaped vessels in the dermis. By immunohistochemistry, using anti-human parvovirus B19 monoclonal antibody, positive reactions were found in endothelial cells. No immunoglobulins were found, but C3 deposits were present in the perivascular areas. By electron microscopy, virus particles were found in the cytoplasm of endothelial cells. An inflammatory reaction due to the direct human parvovirus B19 infection in dermal vessels seems to be an important factor in the pathogenesis of the skin manifestations.

Adult↗
PubMed1995

c-Kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor.

Although c-kit proto-oncogene product is known to be weakly expressed on normal thyrocytes, its function is unclear. In order to investigate the significance of thyroid c-kit, c-kit gene expression in 37 various thyroid tissues was analyzed by comparing c-kit gene expression with the mRNA expression of three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor, c-kit mRNA was hardly detected by the usual northern blot method in 2 of 7 follicular carcinomas, 11 of 12 papillary carcinomas, and a medullary carcinoma. On the other hand, a high level of c-kit mRNA expression was found in all 17 benign thyroid tissues (4 normal thyroid tissues, 4 Graves' disease, 2 adenomatous goiters, and 7 follicular adenomas). This study found that c-kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than any thyroid-specific gene. Decreased c-kit gene expression may serve as an indicator for the de-differentiation of thyrocytes.

Blotting, Northern↗
PubMed1995

Proliferating cell nuclear antigen (PCNA) expression in oral squamous cell carcinoma - an aid to conventional histological grading?

Proliferating cell nuclear antigen (PCNA) is a well known marker for cell proliferation. It tends to accumulate in the late G1 and S-phase of the cell cycle. A monoclonal antibody (MoAb) against PCNA is now available and it can react with paraffin-embedded specimens. In the present study, PCNA immunohistochemical staining of 36 cases of oral cancer specimens obtained from surgery were investigated. The results showed differing nuclear staining patterns for PCNA in normal, hyperplastic and dysplastic epithelium, early cancer and 3 levels of differentiation for squamous cell carcinoma of the oral cavity. It appears that PCNA can be a useful marker in delineating normal epithelium and hyperplastic epithelium from dysplasia in the oral cavity. The use of PCNA staining may further emphasize the conventional histopathological grading of well-differentiated, moderately-differentiated and poorly-differentiated oral squamous cell carcinoma but is still dependent on basic criteria as observed without immunostaining. PCNA expression for all grades of squamous cell carcinoma are present at the deep, infiltrative margins.

Biomarkers, Tumor↗
PubMed1994

Synthesis and antibacterial activity of thiazolopyrazine-incorporated tetracyclic quinolone antibacterial agents. 2.

A novel series of 8-(2-substituted morpholino)-9,1-[(N-methylimino) methano]-7-fluoro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids, designated 8a-j, with a unique tetracyclic structure were synthesized, and the in vitro and in vivo antibacterial activities against Gram-positive strains, including methicillin-resistant Staphylococcus aureus isolates (MRSA), and Gram-negative strains were evaluated. These morpholino derivatives, 8a-j, showed excellent in vitro antibacterial activities against Gram-positive bacteria. The substitutions at the C-2 position of the 8-morpholino moiety of compound 8 play an important role in the enhancement of in vivo antibacterial activity. The unsubstituted morpholino derivative 8a, the 2,6-dimethyl derivative 8c, and the 2-ethylmorpholino derivative 8d showed poor in vivo antibacterial activity, while 8b, 8f-h, and 8j exhibited good activities. The 2-(methoxymethyl)morpholino derivative, 8h, showed the most potent activity in vivo. The therapeutic effects of 8h on systemic infection against S. aureus IID 803 were over 10-fold more potent than that of ofloxacin. Compound 8h, which showed superior oral bioavailability, has a chiral center. The enantiomers of 8h were synthesized, and the in vitro and in vivo antibacterial activities were evaluated. Both enantiomers, (S)-8h and (R)-8h, and the racemic compound 8 exhibited similar activities in vitro and in vivo. Compounds 8b and 8f-h also showed good levels of antibacterial activity against MRSA strains. The morpholino derivatives with unique tetracyclic structures are characterized by strong antibacterial activities against MRSA strains.

4-Quinolones↗
PubMed1994

Synthesis and antibacterial activity of thiazolopyrazine-incorporated tetracyclic quinolone antibacterials.

A novel series of 8-substituted-9,1-[(N-methylimino)methano]- 7-fluoro-5-oxo-5H-thiazolo[3,2-alpha]-quinoline-4-carboxylic acids 5a-q having a unique thiazolopyrazine-incorporated tetracyclic structure were synthesized, and the in vitro and in vivo activities were determined against Gram-positive and Gram-negative bacteria. All compounds 5a-q had more potent activity than ofloxacin (6), which is one of the most popular quinolones, against Gram-positive and Gram-negative bacteria. The 8-pyrrolidinyl, 5a-e, and 8-morpholino, 5p, derivatives showed the most potent activity against Gram-positive bacteria. It is also significant that these compounds, 5a-q, showed more potent antibacterial activity against methicillin-resistant Staphylococcus aureus isolates (MRSA) than ofloxacin (6). The combination of the morpholino group and this unique tetracyclic thiazolopyrazine skeleton contributes to the enhancement of the antibacterial activity against MRSA isolates. The in vivo antibacterial activities of these compounds, 5a-q, were limited and depended on the structure of the 8-substituent. The 8-(4-alkyl-1-piperazinyl) derivatives 5g, 5h, 5j, and 5n provided good oral efficacy and exhibited more potent activity than ofloxacin (6) against the systematic infection with S. aureus IID 803 in mice.

Animals↗
PubMed1994

Histogenesis and possible mechanism of chondroid changes in mixed tumour of the skin: immunohistochemical evaluation of bone morphogenetic protein, glycosaminoglycans, keratin, vimentin and neuronal markers.

The distribution of immunoreactivity of bone morphogenetic protein (BMP), the glycosaminoglycans chondroitin 4-sulphate (C4SPG), chondroitin 6-sulphate (C6SPG), dermatan sulphate (DSPG) and keratan sulphate proteoglycans (KSPG), cytokeratin (K8.12), vimentin, glial fibrillary acidic protein (GFAP), actin, desmin, S-100 protein and neuron-specific enolase (NSE) in mixed tumour of the skin was investigated using immunohistochemical methods using monoclonal (MoAb) and polyclonal antibodies (PoAb). A strong BMP immunoreactivity was found characteristically in outer tumour cells of tubuloductal structures and modified myoepithelial cells. Modified myoepithelial cells and chondroidally changed cells showed positive immunoreactivity for C4SPG, C6SPG and DSPG; and KSPG was more pronounced in the modified myoepithelial cells. Vimentin, S-100 protein, GFAP and NSE, but not actin and desmin, were distribute in the outer tumour cells and modified myoepithelial cells in chondroidally changed tissue. Two factors show that chondrogenesis in mixed tumour of the skin is associated with the modified myoepithelial cells through the activity of BMP and biosynthesis of glycosaminoglycans as matrix substance. First, outer or basal tumour cells in mixed tumour of the skin is characterized by the presence of positive immunoreactivity for BMP, KSPG, vimentin, cytokeratin K8.12, S-100 protein, GFAP and NSE, and second, there is a matrix of chondroidally changed tissue containing the reaction products of C4SPG, C6SPG, DSPF and KSPG.

Actins↗
PubMed1994

Enhanced tenascin immunoreactivity in leukoplakia and squamous cell carcinoma of the oral cavity: an immunohistochemical study.

Tenascin is an extracellular matrix glycoprotein that shows a site restricted expression especially in areas of cell proliferation, cell motility, and tissue modeling at the epithelial-mesenchymal junction during embryogenesis. Tissue specimens obtained from surgery and/or biopsy for oral leukoplakia (n = 22) and squamous cells carcinoma (n = 36) were examined for the presence of tenascin by using monoclonal antibody. In normal tissue specimens (n = 5), tenascin immunoreaction appeared as a linear continuous lining at the immediate vicinity of basement membrane (n = 3). Hyperplastic epithelia in leuoplakia showed a distinct increase in tenascin immunoreactivity in the submucosa correlating with the degree of hyperplasis and/or dysplasia. In squamous cell carcinoma (SCC), the reactivity was most intense extending deeply into the underlying stroma with marked reaction around large tumour cell nests and the infiltrating tumour margin. The connective tissue stroma, however, in undifferentiated carcinoma showed traces of immunoreactivity. Positive immunoreactivity was seen around metastatic squamous cell carcinoma masses in regional lymph nodes. The stromal tissues infiltrated by inflammatory cells were usually unreactive while those with desmoplastic changes were positive for tenascin. The authors conclude that an enhanced expression of tenascin may play an important role during active phases of tumour cell proliferation and stromal changes in the premalignant and malignant lesions of the oral mucosa.

Carcinoma, Squamous Cell↗
PubMed1993

Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids.

A novel tetracyclic pyridone carboxylic acid with a thiazolidine ring, 1,2-dihydro-9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo -5H- thiazolo[3,2-a]quinoline-4-carboxylic acid (4a), and variants with a nitrogen atom (4b) or carbonyl group (4c) in the place of the 10-position oxygen atom of 4a were prepared and tested for antibacterial activity and inhibitory activity on DNA gyrase from Escherichia coli KL-16. The in vitro antibacterial potency with regard to the 10-position atom was found to be of the following order; O > NCH3 = C = O. The IC50 values for DNA gyrase inhibition activity for the 4a, 4b, and 4c compounds were 0.33, 0.53, and 0.67 g/mL, respectively. The activity of 4a, in which the C-3 methyl group and C-5 of ofloxacin (2a) were connected with a sulfur atom to restrict the conformation of 2a, was more potent than that of 2a against both Gram-positive and -negative bacteria, except for Pseudomonas aeruginosa. Compared to the tetracyclic pyridone carboxylic acid 1a, which has a flat thiazole ring, compound 4a showed comparable or slightly more potent activity against both Gram-positive and -negative bacteria, except for P. aeruginosa.

Anti-Infective Agents↗
PubMed1993

Synthesis of antimicrobial agents. 5. In vivo metabolism of 7-(4-hydroxypiperazin-1-yl)quinolones.

A series of novel pyridone carboxylic acids having a 4-hydroxypiperazin-1-yl, a 4-hydroxy-3-methylpiperazin-1-yl, and a 4-hydroxy-3,5-dimethylpiperazin-1-yl group was prepared, and their metabolism to corresponding piperazinyl derivatives after oral administration to mice and rats was studied. This reductive metabolism appeared to be more extensive in mice than in rats. Moreover, the introduction of a methyl group into the alpha-position of the 4-hydroxy group depressed the metabolism in both species.

4-Quinolones↗
PubMed1993

Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids.

A series of novel tetracyclic pyridone carboxylic acids replacing the 10-position oxygen atom of 9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo [3,2-alpha]quinoline-4-carboxylic acid by imino groups (NR; R = Me, Et, c-Pr, allyl, Ph, benzyl), a sulfur atom, or a carbonyl group was prepared and evaluated for antibacterial activity and inhibitory activity on DNA gyrase isolated from E. coli KL-16. The in vitro antibacterial potency and DNA gyrase inhibitory activity were found to be in the following order: NMe > or = O > S >> C = O. Moreover, a methyl group was the optimal alkyl substituent at the 10-position nitrogen atom for antibacterial activity and for DNA gyrase inhibitory activity. 7-Fluoro-9,1-[(N-methylimino)methano]-8- (4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo[3,2-alpha]quinoline-4-carboxy lic acid (10-NCH3) showed potent in vivo antibacterial activity.

Animals↗
PubMed1993

Chronotoxicological effect of methyl mercury in rat submandibular gland. Immunohistochemical changes of r-EGF, S-100 protein and keratin.

The effect of toxicity of methyl mercury was investigated in the submandibular gland (SMG) of adult male rats subjected to 12 h light dark cycle (6 a.m. to 6 p.m. light/resting phase; 6 a.m. to 6 p.m. dark/active phase). Two groups of rats received a defined dose of methyl mercury hydroxide at seven different time points during the active (dark) and resting (light) phase over a 24 h period. After 10 d, the rats were killed at 9 a.m. and 9 p.m. in the resting and active phase, respectively. The immunohistochemical distribution pattern of epidermal growth factor (r-EGF), S-100 protein and K8.12 keratin were studied in granular convoluted tubules (GCT). Those rats which received injections during the active phase (6 p.m. to 6 a.m.), showed stronger reactivity for r-EGF; however, the reactivity for S-100 protein was unchanged. On the contrary, in both groups, GCT cells showed intense staining for K8.12 keratin. It is concluded that the detoxification mechanism of mercury appears to be dependent on the chronobiological oscillation pattern of the GCT and their substructures.

Animals↗
PubMed1993

Chronoimmunohistochemical localization of epidermal growth factor in the submandibular gland of male rats.

Chronobiological oscillation was established for epidermal growth factor (r-EGF) in granular convoluted tubule (GCT) cells of the male rat submandibular gland (SMG) using immunohistochemistry. The high amplitude oscillation with a peak at 9 p.m. and low amplitude oscillation during the day time was noted. The distribution pattern of the r-EGF in the GCT segment was time-dependent, as it was seen at 3 p.m. when many cells with r-EGF staining were detectable. The higher reactivity during the activity phase of the rats may correlate with the intracellular biosynthesis of r-EGF required for cell proliferation and maintenance of ductal integrity. The chronobiological oscillation pattern of r-EGF seems to be important for the maintenance of ductal integrity and wound healing.

Animals↗
PubMed1992

Vimentin expression in sweat gland tumours.

Immunohistochemical localization of vimentin was studied in 93 cases of sweat gland tumours using a monoclonal anti-vimentin antibody. A strong immunoreactivity of vimentin was observed in modified myoepithelial or neoplastic myoepithelial cells of mixed tumour of the skin, syringoma, and sweat gland adenoma. Tumour cells in outer layers of tubular, ductal, and duct-like structures usually showed positive staining for vimentin, which coincided with modified myoepithelial cells. All tumour cells of clear cell hydroadenoma showed positive vimentin staining. Tumour cells of the luminal border of tubulo-ductal structures of mixed tumours were rarely immunoreactive for vimentin. Positive vimentin staining of tumour cells in the outer zone of tubulo-ductal structures in sweat gland tumours may be related to reactive proliferation of modified myoepithelial cells and simultaneous growth of luminal tumour cells.

Adenoma↗
PubMed1992

Synthesis and antibacterial activity of new tetracyclic quinolone antibacterials.

A series of 8-substituted-9,1-(epoxymethano)-7-fluoro-5-oxo-5H- thiazolo[3,2-a]quinoline-4-carboxylic acids having a novel tetracyclic structure was synthesized and tested for antibacterial activity. The nature of the heteroatom (N, O, or S) substituted at the 8-position had little influence on the antibacterial activity. Among the six pyrrolidinyl derivatives and the five piperazinyl derivatives, the 8-(3-hydroxy-1-pyrrolidinyl) derivative 6h and the hydrochloride of the 8-(4-methyl-1-piperazinyl) derivative 6l showed the most potent activity against both Gram-positive and Gram-negative bacteria. Against nalidixic acid resistant strains, isolated from Escherichia coli KC-14, compound 6h was less potent than 6l. Replacement of the piperazinyl nitrogen atom by a carbon atom, an oxygen atom, or a sulfur atom (corresponding to the piperidino, morpholino, or thiomorpholino group, respectively) enhanced the activity against Gram-positive bacteria, but reduced the activity against Gram-negative bacteria. Compound 6l also showed potent in vivo antibacterial activity against Gram-positive and Gram-negative bacteria, and did not cause convulsions in mice with the concomitant administration of fenbufen. Replacement of the carboxy group by a sulfonic acid group in 6l resulted in a complete loss of antibacterial activity.

Animals↗
PubMed1992

[A case of penile necrosis in a patient with diabetes mellitus].

The patient was a 63-year-old male who was with having diabetes mellitus since 1967. Hemodialysis was carried out from June 1983 for diabetic nephropathy. Neuropathy and retinopathy were already present at that time. He complained pain in penile glans from the middle of June 1990. Three month later, partial penectomy was performed because of the development of black-mummy-shaped necrosis on the whole glans. Histopathological examination widely revealed luminal obstruction and formation of thrombus due mainly to vascular lesions as a result of diabetes mellitus. As far as we know, case reports of diabetes mellitus complicated with penile necrosis are extremely rare, and this present case seems to be the 2nd one in Japan and the 5th one in the world, including those reported previously in the West.

Diabetes Complications↗