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Biomedical subjects

F Sakamoto

Publications and source records attributed to F Sakamoto.

At least 55 records · Page 3Linked to original sources

Ultrastructural study of a mucinous carcinoid of the skin.

A tumor of 60 years' duration overlying the sternum of an 87-year-old woman is described. Histologically, the tumor was composed of lobules and cords of epithelial cells with finely granular, eosinophilic cytoplasm. The epithelial nests were floating in large pools of mucinous stroma, separated by thin fibrovascular septa. Cytoplasmic argyrophilia was seen by Grimelius silver stain. Positive reactions of the tumor cells were also found for chromogranin and neuron-specific enolase. Ultrastructural study revealed that the cytoplasm of the tumor cells contained two types of granules: neurosecretory and mucinous. From these findings, the present tumor is considered to be a carcinoid tumor with amphicrine cells, and the term "mucinous carcinoid" of the skin seems to be appropriate for the diagnosis of the present case.

Aged↗

Proliferating trichilemmal cyst with apocrine-acrosyringeal and sebaceous differentiation.

An adnexal tumor on the scalp of a 74-year-old woman is described. Histologically, the tumor was composed of cystic structures showing typical trichilemmal keratinization. The tumor cells in the cyst walls often formed duct-like or squamous eddy-like structures and occasionally showed vacuolation or poroma-like change. Ultrastructurally, some tumor cells showed differentiation either toward the acrosyringium or sebaceous cells. From these findings, the present tumor is considered to differentiate toward various parts of the hair follicle including infundibulo-isthmus epithelium, apocrine acrosyringium, and sebaceous cells.

Adenoma↗

2-Oxo-1,3-dioxoles as specific substrates for measurement of arylesterase activity.

Various 4-arylthiomethyl-2-oxo-1,3-dioxole derivatives IIIa-o were synthesized. Their hydrolysis rates by arylesterase (EC 3.1.1.2) and cholinesterase (EC 3.1.1.8) in human serum were evaluated. Some of them were not hydrolyzed by cholinesterase, but were hydrolyzed easily by arylesterase. Among the substrates, sodium 4-((5-methyl-2-oxo-1,3-dioxol-4-yl)methylthio)benzenesulfonate (IIIg) was selected for its substrate reactivity toward arylesterase and its good water solubility. In addition, neither aliesterase (EC 3.1.1.1), acetylesterase (EC 3.1.1.6) nor cholesterol esterase (EC 3.1.1.13) hydrolyzed the compound. IIIg is thus concluded to be a specific substrate for arylesterase. Our assay system for serum arylesterase using IIIg can be readily applied to an automatic analyzer in the diagnosis of liver cirrhosis.

Carboxylic Ester Hydrolases↗

Cytofluorometric study of lectin binding to the keratinocytes of epidermolysis bullosa simplex.

Epidermolysis bullosa (EB) simplex is a congenital disease that has blister formation following minor mechanical trauma to the skin. The least amount of information concerning the pathogenesis is known in this disease. One possibility is that there are structural abnormalities in keratinocytes. In the present study, we report the binding of lectin (Ricinus communis agglutinin, Peanut agglutinin, and Soybean agglutinin) to keratinocytes using cytofluorometry. Biopsy skin specimens were taken from patients with simplex, junctional, and dystrophic forms of EB, and normal volunteers. Free keratinocytes were obtained by the treatment of EDTA and trypsin, and fractionated by centrifugation on a continuous colloidal silica (Percoll) density gradient. Fractionated basal cells were stained with biotinyl lectins and avidin-FITC, and measured by cytofluorometry. In all lectins examined, the intensity was low in the basal cells of EB simplex, as compared with normal controls. However, there were no differences among the other forms of EB and normal controls. This results suggest the presence of structural abnormalities in epidermis of EB simplex.

Avidin↗

Synthesis and antibacterial activity of thiazolo-, oxazolo-, and imidazolo[3,2-a][1,8]naphthyridinecarboxylic acids.

It is known that thiazolo[3,2-a][1,8]naphthyridine derivatives (3a) exhibit good antibacterial activity. Accordingly, several analogues of 3a, viz. oxazolo- and imidazolo[3,2-a][1,8]naphthyridine derivatives 3b and 3c, were synthesized and evaluated for antibacterial activity in vitro and for inhibitory activity against DNA gyrase of Escherichia coli K-12 C600. Compound 3a exhibited antibacterial activity comparable to that of ofloxacin and enoxacin against Gram-positive and Gram-negative bacteria and displayed antibacterial activity superior to that of 3b and 3c. The antibacterial activities of 3b and 3c decreased in that order. DNA gyrase inhibitory activities of 3a-c in E. coli K-12 C600 paralleled their in vitro antibacterial activity. It was found that enhancement of the DNA gyrase inhibitory activity of 3a was dependent on a certain feature of the sulfur atom of the thiazole ring.

Anti-Bacterial Agents↗

Ultrastructural study of nuclear inclusions in spindle and epithelioid cell nevus cells.

The nuclei of spindle and epithelioid cell nevus (SECN) cells often contain inclusions. To determine the origin and pathogenesis of the nuclear inclusions, 12 cases of SECN were electron microscopically examined. True inclusions, pseudoinclusions, and electron-lucent areas were frequently found in the nuclei of SECN cells in all cases. The true inclusions were composed of various structures including vesicles and electron-dense homogenous substance. The pseudoinclusions were a cytoplasmic structure engulfed by nucleus; they were surrounded by a nuclear membrane and rich in cytoplasmic vesicles and electron-dense materials. Occasionally, a partial dissolution of the covering membrane of the pseudoinclusions was seen, leaving their contents in the nuclear matrix. It was concluded that a sequential process from the pseudoinclusions to the true inclusions in nuclei was morphologically present in SECN cells.

Cell Nucleus↗

[Adenosquamous carcinoma of the skin--ultrastructural and immunohistochemical studies].

Adenosquamous carcinoma, which arose on the face of a 83-year-old woman was studied ultrastructurally and immunohistochemically. The tumor was composed of squamoid cells and mucinous cells including signet-ring cells. Electron microscopically, the tumor cells developed numerous microvilli on the cell surface, and had tonofilaments, well-developed rough endoplasmic reticulum and secretory granules of a mucinous type in the cytoplasm. The signet-ring cells had a large intracytoplasmic cavity containing fine fibrillar, mucin-like substance. Occasionally observed were intercellular masses, around which the tumor cells formed hemidesmosome-like and basal lamina-like structures. Immunohistochemical staining revealed foci of positive reaction for laminin surrounding the tumor cells. The tumor cells displayed positive stainings for stratified-epithelial keratins, but not for simple-epithelial keratins. From these findings, it was concluded that the present tumor might be a carcinoma of squamous cell origin, showing a mucinous metaplasia.

Adenocarcinoma↗

Studies on prodrugs. 11. Synthesis and antimicrobial activity of N-[(4-methyl-5-methylene-2-oxo-1,3-dioxolan-4-yl)oxy]norfloxacin .

The chemical oxidation of N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] norfloxacin (2) was carried out to afford N-[(4-methyl-5-methylene-2-oxo-1,3-dioxolan-4-yl)oxy]norfloxacin (4). In vitro, 4 exhibited lower activity than that of norfloxacin (NFLX, 1) for both Gram-positive and Gram-negative bacteria. However, in vivo the activity of 4 was higher than that of NFLX. Bioavailability studies in mice showed that 4 liberated a higher concentration of NFLX in plasma than NFLX itself when administered orally. From these data, 4 obtained by the chemical oxidation of 2 functioned as a prodrug of NFLX as well as did 2. The mechanism of the formation of 4 is interpreted in terms of [2,3]-sigmatropic rearrangement.

Animals↗

Studies on prodrugs. 10. Possible mechanism of N-dealkylation of N-masked norfloxacins having several active methylene groups.

As a prodrug approach to norfloxacin (NFLX, 2), we have prepared several N-masked NFLXs (1a-f) and studied the cleavage mechanism of the C-N bond of N-masked NFLXs utilizing the following experiments: (1) the oxidation of N-masked NFLXs (1a-f) with m-chloroperbenzoic acid (MCPBA) and their subsequent cleavage to 2 in chloroform at room temperature or at 50 degrees C; (2) the liberation of NFLX from N-masked NFLXs after oral administration in mice. It was found that the chemical oxidative dealkylation of N-masked NFLXs proceeded when anion-stabilizing groups (e.g., CN, COR, COOR) are present on the alpha carbon of the nitrogen atom. In in vivo experiments, N-masked NFLXs having acidic hydrogens on the alpha carbon to the nitrogen atom also liberated NFLX (2) after oral administration.

Animals↗

Production and characterization of recombinant human neutrophil chemotactic factor.

A putative mature human neutrophil chemotactic factor (NCF) corresponding to the C-terminal 72 amino acids of its precursor was directly produced in Escherichia coli by recombinant DNA technology. Human NCF was present in both the soluble and insoluble protein fractions of the homogenate of host cells, and it was partially purified as a water-soluble polypeptide from both fractions, separately. The partially purified NCF preparation was highly purified to an endotoxin-free homogeneous polypeptide by means of CM-Sepharose CL-6B column chromatography and gel filtration on Toyopearl HW-55. No difference between the human NCF preparations purified from both starting materials could be found concerning purity, primary structure, solubility, molecular weight, and chemotactic activity for human neutrophils. The amino acid sequence of recombinant human NCF was identical to the sequence deduced from the cDNA sequence. A methionine residue due to the translation initiation codon was removed. Recombinant human NCF was found to be biologically active and to exhibit chemotactic activity for human neutrophils in vitro and cause a neutrophil infiltration in vivo in mice.

Amino Acid Sequence↗

Pathogenesis of pili annulati.

Plucked scalp hairs and hair roots of pili annulati were examined to understand their pathogenesis. Stereoscopic examinations of hairs in transmitted light and/or reflected light and light microscopic surveys of the cross-sections of hairs confirmed that the cortical empty spaces appeared to be responsible to the unique dotted shiny appearance of the hairs seen by the unaided eyes under a refracted light. By transmission electron microscope, small vacuoles and dense bodies were observed in the cytoplasm of the differentiating cortical cells; subsequently, with increasing number of tono-filaments, an uneven distribution of free ribosomes occurred and abnormal spaces containing fine granular substances were formed in the cytoplasm of the cortical cells. Occasionally, extremely large cortical trichohyaline granules were found. In the keratinized hair, irregular empty spaces were present in the cortex of the abnormal hair segments. Histochemically, the keratinized cortex of the affected hairs always had more residual SH groups than the controls. Pili annulati may be a disorder of protein metabolism involving a partial dysfunction of cytoplasmic ribosomes, resulting in a lack of cortical keratin formation.

Hair↗

Effect of antianaphylactic agents on substance-P induced histamine release from rat peritoneal mast cells.

Substance P is known to be a potent histamine liberator for mast cells. The influence of antianaphylactic agents, disodium cromoglycate (DSCG), ketotifen, and tranilast was studied on substance-P and compound 48/80-induced histamine release from rat peritoneal mast cells. Substance-P induced histamine release was inhibited by these agents, while compound 48/80-induced histamine release was not inhibited by tranilast. Our findings suggest that these antianaphylactic agents are assumed to be effective for cutaneous diseases which might be concerned with substance P and histamine.

Animals↗

Quantification of urinary glucose and protein with test-strips through reflectometric analysis.

Reflectometric measurement of urine test-strips, using the Urotron RL9, was employed to quantify urinary glucose and protein. Although the test-strips (Combur-9-Test) are designed for qualitative use, the reflectance intensities determined by the Urotron RL9 are applicable to quantitative analysis. Reflectance quantitation and conventional colorimetric methods were closely correlated for glucose (r = 0.953) and protein (r = 0.906). Intra-assay coefficients of variation of reflectance value were less than 5%. The negative influence of ascorbic acid on glucose determination was defined quantitatively. A significant positive interference from hemoglobin on protein determination was also demonstrated, but effectively eliminated after compensating for urine color.

Ascorbic Acid↗

Abnormal binding of lectin to the epidermal cell membranes in the skin of epidermolysis bullosa simplex.

Epidermolysis bullosa (EB) simplex is a congenital disease that has blister formation following minor mechanical trauma to the skin. However, the least amount of information concerning the pathogenesis is known in this condition. One possibility is that there are structural abnormalities in epidermal cell membranes. In the present study, we examined the binding of lectins to epidermal cell membranes by ABC method. Biopsy skin specimens were obtained from patients with simplex, junctional and dystrophic forms of EB, and normal volunteers. In the case of EB simplex, the cell membranes of keratinocytes in the basal and spinous cell layers did not bind to soybean agglutinin in specimens from blister edges or mechanical traumatized areas. No differences were found in binding pattern between the other forms of EB and normal controls. This results suggest the presence of structural abnormalities in epidermis of EB simplex.

Cell Membrane↗

Immunohistochemical observation of S-100 protein and neuron specific enolase in the tumour cells of granular cell tumour.

An immunohistochemical technique for the detection of S-100 protein, neuron specific enolase (NSE), carcinoembryonic antigen (CEA) and muramidase (lysozyme) was applied to a case of the granular cell tumour. S-100 protein was detected both in the nuclei and cytoplasma of the granular cells, and NSE was weakly positive in their cytoplasms. CEA and lysozyme were negative in the tumour cells. Our results supports the concept that granular cell tumours are derived from Schwann cells.

Adult↗

Studies on prodrugs. 7. Synthesis and antimicrobial activity of 3-formylquinolone derivatives.

Several 3-formylquinolone derivatives (8a-c) were synthesized to assay the antibacterial activity both in vitro and in vivo. In vitro, all of the compounds 8a-c showed lower activity than that of the corresponding 3-carboxyl compounds 1a-c, and in vivo, they showed higher activity than that of compounds 1a-c. After oral administration of 3-formyl compounds 8a-c to mice, the compounds were rapidly metabolized into 3-carboxyl compounds 1a-c. In particular, the 3-formyl derivative (8a) of norfloxacin (NFLX, 1a) gave a 2-fold higher serum level than that of NFLX and functioned as a prodrug of NFLX.

Animals↗