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Biomedical subjects

O Mori

Publications and source records attributed to O Mori.

At least 37 records · Page 2Linked to original sources

Value of magnetization transfer contrast as a sensitive technique to reflect histopathological changes in the white matter adjacent to the frontal horns of lateral ventricles.

The purpose of this study is to evaluate the usefulness of magnetization transfer contrast (MTC) as a technique to reflect histopathological changes in the white matter adjacent to the frontal horns of the lateral ventricles. Radiological-pathological correlation was performed in six patients who underwent Magnetic Resonance (MR) examination prior to death and in whom postmortem examinations of the brain were obtained. The extent and the severity of degeneration in the white matter adjacent to the frontal horns were evaluated histopathologically, and compared with those observed on the conventional proton density (PD) weighted MR images (Group 1). Changes in the white matter of another 35 patients were classified into three types according to the pattern of high signals adjacent to the frontal horns on conventional PD weighted MR images, and magnetization transfer ratio (MTR) in the white matter adjacent to the frontal horns was calculated from multi-slice and single-slice FSE images (Group 2). The relationship between signal intensities and MTR in the white matter adjacent to the frontal horns was evaluated. The extent of degeneration in the white matter adjacent to the frontal horns was classified into mild, moderate and severe types on the basis of stainin for myelins, axons and astrocytes. In Group 1, histopathological findings indicated a difference in severity of degeneration in the white matter adjacent to the frontal horns among the three types, while no significant differences were noted in the signals on PD weighted MR images. In Group 2, MTR showed significant differences in the signal intensities in the white matter adjacent to the frontal horns (p < 0.01) between the three types, while conventional PD weighted MR images failed to differentiate between them. In conclusion, MT imaging is a sensitive technique to evaluate the histopathological changes in the white matter adjacent to the frontal horns that cannot be detected by conventional MR imaging.

Adult↗

Emergence of immunoreactivities for phosphorylated tau and amyloid-beta protein in chronic stage of fluid percussion injury in rat brain.

Head injury is one of the potential environmental factors in Alzheimer's disease (AD). To study the chronic stage of concussive brain injury, histological analyses were performed 2-6 months after right lateral fluid percussion (FP) brain injury (3.6-4.8 atm) in rats. Six months after injury, numerous normal-looking neurons in the telencephalon and brain stem were immunoreactive with either antibody to phosphorylated tau or with four antibodies to beta-amyloid protein. Neuronal counts in the cortices were gradually decreased after injury, up to 42% loss at 6 months after injury. These neuropathological changes suggest that this animal model could serve as a good animal model of neurodegenerative diseases such as AD.

Amyloid beta-Peptides↗

Apoptosis in murine hair follicles during catagen regression.

Catagen hair follicle involution has been reported to involve apoptosis, although the precise mechanism has not been satisfactorily resolved. Previous studies have involved solely morphological or electron microscopical methods. We report here studies on murine hair follicles during the first postnatal hair cycle conducted using the terminal deoxy-nucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method. Electrophoresis of DNA isolated from the hair follicles of the same animals was carried out in order to confirm the systematic fragmentation of DNA that typifies apoptosis. On day 10, when all the follicles were growing, there was no evidence of staining with TUNEL in the hair bulbs. Electrophoresis similarly did not show characteristic DNA ladders. By day 15, a few positive cells were observed in the hair bulbs and the numbers had increased by day 17 when many positive cells were seen, especially in the lower portions of the follicles. Electrophoresis demonstrated DNA ladders on days 15, 16 and 17, although the DNA ladder on day 15 was less prominent than that on day 17. These studies confirmed that apoptosis, as identified by techniques that measure DNA fragmentation, occurs in the lower regions of hair follicles towards the end of catagen.

Age Factors↗

Novel non-radioisotope immunoprecipitation studies indicate involvement of pemphigus vulgaris antigen in paraneoplastic pemphigus.

We have developed two different novel immunoprecipitation assays in which radioisotopes are not used, and have examined antigens for four cases of paraneoplastic pemphigus (PNP) including three new patients. The PNP sera showed a clear reactivity with transitional epithelia of rat urinary bladder by immunofluorescence, and reacted with a characteristic doublet of the 210 and 190 kD proteins by immunoblotting of normal human epidermal extract, confirming the diagnosis of PNP. In addition, by immunoprecipitation using silver-stain to detect immunoprecipitated proteins, the PNP sera detected the 250, 210 and 190 kD proteins, while control bullous pemphigoid sera detected only the 230 kD bullous pemphigoid antigen. Furthermore, with another immunoprecipitation using cell surface biotinylation, three of the four PNP sera specifically reacted with the 130 kD pemphigus vulgaris antigen (Dsg3), indicating that pemphigus vulgaris antigen may be involved in PNP. This reactivity was further suggested by the immunoblot analysis using recombinant pemphigus vulgaris antigen. In future, these non-radioisotope immunoprecipitation assays should become a useful tool not only to unravel the complex situation for the PNP antigens, but also to study antigens in other autoimmune bullous skin diseases.

Animals↗

Bullous pemphigoid showing unusual ocular changes.

We describe a 68-year-old Japanese woman with erythematous and bullous skin lesions. Antibasement membrane zone antibodies of IgG class were detected in the serum, which reacted with the 230 kDa and 180 kDa bullous pemphigoid antigens on immunoblot analysis. The patient later developed corneal opacity in both eyes and a detachment of the epithelium in the centre of the cornea. However, no change was seen in the conjunctiva. These ocular lesions are different from those of cicatricial pemphigoid. The ocular lesions could be reproduced by injection of IgG from this patient into the stroma of the corneas of rabbits. Both the cutaneous and ocular lesions responded well to oral corticosteroid therapy. We diagnosed this patient as having bullous pemphigoid associated with a unique ocular lesion.

Aged↗

Immunobead and density gradient purification of Paget cells: in vitro studies of proliferation.

Previous studies using primary monolayer cultures of epithelial cells from the involved epidermis of patients with mammary and extramamary Paget's disease investigated whether Paget cells proliferate as other malignant cells do. Although epithelial monolayers from the involved skin were maintained for approximately 45 days, no permanent cell lines were established. The proportion of carcinoembryonic antigen (CEA)-positive cells did not increase in the long-term cultures. Herein, we report studies of whether there is a real reduction of Paget cell numbers or if this is merely a decrease in the expression of CEA by the cells. Furthermore, we investigated whether Paget cells survive longer when cultured free from any potential inhibitory keratinocytes or other epidermal cells. Skin samples were obtained from one patient with mammary Paget's disease and three with extramammary Paget's disease; epidermal cells were cultured in vitro. An enrichment of Paget cells was carried out from the cultured epidermal cells by combining an antiepithelial membrane antigen monoclonal antibody, binding to immunobeads, and density gradient centrifugation in Nycodenz. The separated cells were re-cultured in Keratinocyte-SFM serum-free media. The proportion of CEA-positive cells did not increase in the culture, and the purified cells did not show any increase in survival times compared to the non-purified cultured cells. These results suggest that the decrease of CEA-positive cells noted during culture results from a decline in expression of CEA in the Paget cells. Paget cells in the involved epidermis do not proliferate significantly and thus differ from many other malignant cells.

Aged↗

A case report of renal cell tumor in a 45-year-old female mimicking lower portion nephrogenesis.

This report describes a renal tumor with an unusual histology in a 45-year-old woman. The tumor was white in color, different from usual renal cell carcinoma, and mainly consisted of variously shaped tubules formed by flat or cuboid cells within marked edematous stroma. Elaborated branching or tubules arranged in a papillary pattern with focal spindle-shaped cell proliferation were characteristic features. Immunohistochemical staining expressed diffusely positive for vimentin and S-100 protein, partially positive for cytokeratin and epithelial membrane antigen and negative for Leu-M1, Leu-7, CD34 and markers for muscle cells. Ultrastructural studies of the tumor cells showed adenocarcinoma-like characteristics. According to these histological, immunohistochemical and electron microscopy findings, it is suggested that this tumor be designated as unclassified renal cell carcinoma with histology mimicking lower-nephron nephrogenesis.

Biomarkers, Tumor↗

Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus.

IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human Dsc. To determine the antigen for IgA pemphigus, we focused on conformation-dependent epitopes of Dsc, because sera of patients with classical pemphigus recognize conformation-sensitive epitopes of desmogleins. We constructed mammalian expression vectors containing the entire coding sequences of human Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3. In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells transfected with any Dscs. These results convincingly indicate that human Dsc1 is an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an important role for Dsc1 in the pathogenesis of this disease. This study shows that a Dsc can be an autoimmune target in human skin disease.

Animals↗

Epidermal cell cultures from involved skin of patients with mammary and extramammary Paget's disease.

In involved epidermis, Paget cells are completely enclosed by the surrounding keratinocytes, which appear to be intact and unaltered. It is possible that the surrounding keratinocytes inhibit Paget cell proliferation. Accordingly, Paget cells might proliferate differently when cultured as an epidermal cell suspension. In this study, primary monolayer cultures of epithelial cells from involved epidermis of patients with mammary and extramammary Paget's disease were carried out to investigate whether Paget cells proliferate in the same manner as other malignant cells. Skin samples were obtained from one patient with mammary Paget's disease, and from 2 patients with extramammary Paget's disease. The epidermis was separated from the dermis with dispase, and epidermal cell suspensions were obtained with ethylenediamine tetraacetate and trypsin. A commercially available serum-free media, Keratinocyte-SFM, was used. Epithelial monolayers from the involved skin could be maintained for approximately 45 days, while keratinocytes from normal skin were maintained for approximately 35 days. The mechanism for the longer survival of the mixed cell culture of keratinocytes and Paget cells is not known. Permanent cell lines were not developed from these primary cultures. Paget cells could not be distinguished from keratinocytes by phase-contrast microscopy. The proportion of carcinoembryonic antigen (CEA) positive cells in the culture did not increase, but instead decreased. In certain areas of the dish, the CEA positive cells proliferated and accumulated like mushrooms. However, at the periphery of the dish, the Paget cells identified by immunostaining for CEA were dispersed and not clustered. These findings indicate that the influence of keratinocytes on Paget cells also occurs in cultured cells, which may explain why Paget cells survive longer than keratinocytes. In conclusion, the Paget cells in the involved epidermis do not proliferate like other malignant cells.

Aged↗

Expression of desmogleins in Paget cells of mammary and extramammary Paget's disease.

Sagebiel (1969) electronmicroscopically observed that desmosomes are present between adjacent Paget cells, as well as between Paget cells and adjacent keratinizing epidermal cells. Desmosomes contain the proteins desmoglein (Dsg) and desmocollin as their transmembrane components, and Dsg has three isotypes. Among the three isotypes of Dsg, Dsg1 and Dsg3 are autoantigens for pemphigus foliaceus and pemphigus vulgaris (PV), respectively. We examined the expression of Dsgs in Paget cells of mammary and extramammary Paget's disease. Skin samples were obtained from one patient with mammary Paget's disease, and from 2 with extramammary Paget's disease. One part of the samples was cut into small pieces and epidermal sheets were separated with dispase, then treated with a mixture of EDTA and trypsin. The resulting cell suspensions were cultured in low Ca++ medium, then the cells were incubated in high Ca++ medium. Paget cells identified with anti-epithelial membrane antigen (EMA) antibody were positive for serum from a PV patient which was confirmed to react with both Dsg1 and Dsg3. However, the intensity of fluorescence of Paget cells was weaker than that of EMA-negative keratinocytes. In the cryostat sections, Paget cells identified with anti-EMA antibody showed the same staining pattern as cultured cells in high Ca++ medium. The data presented in this study confirm that Paget cells express Dsgs, and are consistent with the electronmicroscopical data by Sagebiel (1969). However, our data do not support the hypothesis that Paget cells are of keratinocyte origin, because sweat ducts or sweat glands could be positive for sera from PV patients. It is necessary to confirm whether or not sweat ducts or sweat glands express Dsgs, because sera from PV patients exhibit high background in the dermis.

Aged↗

[Proteoglycans in senile dementia of Alzheimer's type].

Levels of the proteoglycans hyaluronic acid, heparan sulfate, dermatan sulfate and chondroitin sulfate in brains were measured. The samples were from 25 brains obtained at autopsy from patients who had senile dementia of Alzheimer's type (SDAT) (60 to 97 years old) and 10 brains from non-demented elderly subjects (75 to 101 years old). Proteoglycan levels in the brains of patients with SDAT were twice as high in the hippocampus and four times higher in the superior frontal gyrus than the levels in brains of non-demented elderly subjects. The content of heparan sulfate proteoglycan was greatest nine times higher in the hippocampus and seven times higher in the superior frontal gyrus. By immuno-electronmicroscopic examination, heparan sulfate proteoglycan was found in the basement membranes of capillaries, and in a portion of the cores of the senile plaques.

Aged↗

[Bone metabolism and phosphorus metabolism in patients with prostate cancer: paracrine and endocrine effects produced by prostate neoplasm].

We examined whether paracrine factors produced by prostate cancer cells can modulate bone metabolism in proportion to the volume of cancer cells in bone metastasis. Endocrine factors produced by prostate cancer cells affect both phosphate and 1,25-dihydroxyvitamin D metabolisms. Levels of urine pyridinoline (U-Pyr) excretion and serum carboxy-terminal propeptide of type 1 procollagen (P1CP) in patients with bone metastasis were significantly higher than those in patients without bone metastasis (P < 0.05). In patients with bone metastasis (n = 17), serum prostate-specific antigen (PSA) levels were significantly correlated with the levels of U-Pyr and urine deoxypyridinoline (U-dPyr) excretion, serum cross-linked carboxyterminal telopeptide of type 1 collagen (1CTP), and P1CP levels (p < 0.05). However, serum PSA levels were not correlated with U-Pyr, U-dPyr excretions, serum 1CTP and P1CP levels in patients without bone metastasis. Therefore, prostate cancer cells appear to have some paracrine effects on bone cells. In controls (n = 15), serum 1,25-dihydroxyvitamin D levels (1,25-(OH)2D) were inversely correlated with serum phosphorus levels (P < 0.01). In prostate cancer patients with bone metastasis, the ability to regulate the serum 1,25-(OH)2D levels in response to serum phosphorus levels is lost. These results suggest that endocrine factors produced by prostate cancer cells disturb the regulation of serum 1,25-(OH)2D in response to serum phosphorus levels.

Aged↗

Microfluorometric study of nuclear DNA in normal human epidermis.

Quantitative and qualitative changes of nuclear DNA were analyzed by microfluorometry in normal human epidermis during terminal differentiation. Normal human epidermis from five healthy volunteers was separated by an EDTA-trypsin method and fractionated by Percoll density gradient. Staining was carried out with either Feulgen reaction, Acridine Orange or 4'-6-diamidino-2-phenylindole (DAPI). When the cells with lower density (granular layer cells) were stained with Acridine Orange or DAPI, the greatest population was found at lower value of DNA than that in the cells stained with Feulgen reaction. After thermal denaturation procedure, a ratio of double-stranded DNA to single-stranded DNA was highest in the cells with lower density. These results seem to suggest the qualitative and quantitative changes of nuclear DNA during terminal differentiation of human epidermal keratinocytes.

Acridine Orange↗