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Biomedical subjects

K Hara

Publications and source records attributed to K Hara.

At least 415 records · Page 23Linked to original sources
PubMed1995

Lichen planus pemphigoides: identification of 180 kd hemidesmosome antigen.

We describe a man with lichen planus pemphigoides. Direct immunofluorescence studies of peribullous skin showed linear deposition of IgG and C3 in the basement membrane zone. Indirect immunofluorescence studies disclosed circulating anti-basement membrane zone antibodies. Immunoelectron microscopy demonstrated binding of antibodies to the hemidesmosomes and lamina lucida. The patient's serum defined only the minor bullous pemphigoid antigen with a molecular weight of 180 kd. These findings suggest the coexistence of lichen planus and bullous pemphigoid in lichen planus pemphigoides.

Aged↗
PubMed1995

Splenic metastasis from lung cancer.

Splenic metastasis from lung cancer is a rare clinical event, most often diagnosed at the time of autopsy. We report 2 cases of splenic metastasis with a primary lung cancer. The first case was a 76-year-old man presenting with a recurrent solitary splenic metastasis 14 months after surgical removal of a squamous cell carcinoma of the lung. The second patient was a 72-year-old woman who had a poorly differentiated carcinoma of the lung and multiple abdominal metastasis. We also investigated 267 autopsy cases of lung cancer from 1975 to 1992. Histologically, there were 73 cases of squamous cell carcinoma, 123 adenocarcinoma, 29 large cell carcinoma, 36 small cell carcinoma, and 7 other miscellaneous tumours. The number of splenic metastasis from lung cancer in these cases was 15 (5.6%). Splenic metastasis from a primary cancer of the left lung was more frequent than that from the right lung. Nine of 15 splenic metastases were smaller than 1 cm in size. Splenic metastasis was associated with liver and pancreas metastasis. All 15 autopsy cases with splenic metastasis from lung cancer had other abdominal organ metastasis. Our analysis indicates that a solitary splenic metastasis is rare. Selection of a suitable therapeutic approach is important.

Aged↗
PubMed1995

Rat epidermal cathepsin B: purification and characterization of proteolytic properties toward filaggrin and synthetic substrates.

The aim of this study was to purify epidermal cathepsin B from rat skin and investigate its proteolytic activities on filaggrin and several synthetic substrates. The molecular weight of purified monomeric cathepsin B was estimated to be 30 kDa by SDS-polyacrylamide gel electrophoresis. The amino acid composition, similar to that of liver cathepsin B, indicated the enzyme to be an acidic protease. The enzyme had strong hydrolytic activity toward N-benzyloxy-carbonyl-L-arginyl-L-arginine-7-amido-4-methylcoumarin (Z-Arg-Arg-MCA) (152 mU/mg) and N-benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido-4-methylcoumarin (424 mU/mg), but had no proteolytic activity toward L-arginine-7-amido-4-methylcoumarin. The Km value for Z-Arg-Arg MCA was 0.34 mM and pH optimum was 5.5. Cathepsin B degraded rat epidermal filaggrin into small fragments at pH 4.0 and 5.5., and was inhibited by a specific cysteine proteinase inhibitor, N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)L-leucyl]- agmatin. This study demonstrated that filaggrin was susceptible to degradation by cathepsin B. Such an action may have relevance to skin differentiation in which acid proteases are thought to participate.

Animals↗
PubMed1995

The inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain.

Although the effects of vitamin K2 and vitamin K1 on bone metabolism have been reported, the difference between them has not been investigated. We now show the effects of menatetrenone, one of the vitamin K2 homologues, and vitamin K1 on bone resorption. Menatetrenone at greater than 3 x 10(-6) M significantly inhibited the calcium release from mouse calvaria induced by 3 x 10(-10) M of 1,25(OH)2D3 or 10(-7) M of prostaglandin E2, and it also inhibited osteoclast-like multinucleated cell (MNC) formation induced by 10(-8) M of 1,25(OH)2D3 in co-culture of spleen cells and stromal cells at the same concentrations. In contrast, the same doses of vitamin K1 had no effects on bone resorption and MNC formation in these in vitro systems. The inhibitory effect of menatetrenone on the calcium release from calvaria was not affected by the addition of 3 x 10(-5) M of warfarin, an inhibitor of vitamin K cycle. The same concentration of geranylgeraniol, the side-chain component of menatetrenone at the 3-position of the naphthoquinone, inhibited tartrate-resistant acid phosphatase (TRACP) activity and MNC formation to the same degree as menatetrenone. Phytol, the side-chain component of vitamin K1, did not affect TRACP activity at all doses tested, but weakly inhibited MNC formation. Moreover, multi-isoprenyl alcohols of two to seven units, except geranylgeraniol which contains four units, did not effect MNC formation. These findings suggest that the inhibitory effect of menatetrenone on bone resorption is not due to gamma-carboxylation and that the side chain of menatetrenone may play an important role in this inhibitory effect.

Acid Phosphatase↗
PubMed1995

Adult T-cell leukemia with multiple lymphomatous polyposis of the gastrointestinal tract.

A rare case of adult T-cell leukemia (ATL) in which multiple lymphomatous polyposis (MLP) was revealed throughout the entire gastrointestinal tract is reported here. The polypectomy specimens taken from the rectum revealed infiltration of neoplastic T-cells, the integration of HTLV-1 proviral DNA, and increased CD4 (OKT4) and CD25 (IL-2R) cells. The analysis of surface markers of the lymphocytes from polypoid lesions may be useful for elucidating cell tropism and homing properties in the gastrointestinal tract. Although MLP has always been associated with B-cell lymphoma in the Western world, it is important for clinicians and pathologists to be aware that MLP may be caused by the infiltration of ATL cells.

Adult↗
PubMed1995

Rat epidermal cathepsin L-like proteinase: purification and some hydrolytic properties toward filaggrin and synthetic substrates.

We have purified cathepsin L-like proteinase from rat epidermis, determined its NH2-terminal amino acid sequence, and investigated its proteolytic activities on an intermediate filament-associated protein filaggrin and several synthetic substrates. The amino acid sequence of its NH2-terminus was determined to be Val-Pro-Asn-Ser-Leu-Asp-Trp-Arg-Glu-Lys-Gly-Tyr-Val-Thr-Pro-, which differed from that of rat cathepsin L and was not found in the amino acid sequence data bank. The enzyme consisted of a single-chain form with M(r) 30,000. Its hydrolytic properties toward synthetic substrates were similar to those of cathepsin L in other tissues. The enzyme effectively proteolyzed rat epidermal filaggrin into small fragments at pH 4.0-6.0 and was inhibited by a specific cysteine proteinase inhibitor, N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)L-leucyl]-agmatin. However, cathepsins D and E from rat epidermis did not hydrolyze filaggrin. This study demonstrated that filaggrin was susceptible to degradation by rat epidermal cathepsin L-like proteinase, suggesting that this proteolytic activity may have relevance to skin differentiation, in which acid proteases are thought to participate.

Amino Acid Sequence↗
PubMed1995

Pemphigoid nodularis: a case with 230 kDa hemidesmosomes antigen associated with bullous pemphigoid antigen.

We report a 73-year-old woman with typical clinical, histological and immunofluorescence features of pemphigoid nodularis. Direct immunofluorescence studies of prurigo nodularis-like lesions and peribullous skin showed the linear deposition of IgG and C3 at the basement membrane zone. Circulating IgG against the basement membrane was also detected by indirect immunofluorescence. The serum from the patient was shown to contain the autoantibody against 230 kDa hemidesmosomal antigen associated with bullous pemphigoid antigen.

Aged↗
PubMed1995

"Malignant Spitz nevus" in a 2-year-old Japanese child.

Smith et al. (1989) have reported a variant of Spitz's nevus with histological atypical features. Despite local lymph node metastases, further metastases were not observed. They proposed the name "malignant Spitz nevus" for this variant. A 2-year-old Japanese girl had a large nodule (27 x 17 mm) surrounded by an indurated erythema over the Achilles tendon. Histologically, it proved to be a melanocytic lesion resembling spindle cell and epithelioid cell nevus (Spitz's nevus) with unusual features; the tumor extended deep into the subcutis, and the mitotic figures deep into the tumor, together with prominent lymphatic vessel invasion by melanocytes. Thus the tumor was aptly termed "malignant Spitz nevus". Flow cytometric analysis of the DNA content revealed a diploid pattern. The child is well 5 years after a wide resection of the tumor. The diploid pattern of the DNA content as well as the good prognosis could support the idea that "malignant Spitz nevus" fits within the spectrum of Spitz's nevus.

Child, Preschool↗
PubMed1995

T cell-dependent activation of macrophages and enhancement of their phagocytic activity in the lungs of mice inoculated with heat-killed Cryptococcus neoformans: involvement of IFN-gamma and its protective effect against cryptococcal infection.

Previous investigations have demonstrated that macrophages play a critical role in the first-line cellular defense mechanism against infection with Cryptococcus neoformans. In the present study, to elucidate the way in which anticryptococcal activity of macrophages is regulated at the site of infection, pulmonary intraparenchymal macrophages were directly analyzed for expression of their surface molecules and their phagocytic activities against the organism, and the effects of depletion of T cells and endogenous IFN-gamma in vivo on these parameters were examined. In the lungs of mice intratracheally inoculated with heat-killed C. neoformans, macrophages were activated, as indicated by augmented expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1) and Fc receptor (FcR), and about two-thirds of macrophages were found to have ingested an average of 3.77 +/- 0.12 yeast cells per macrophage. In mice depleted of both CD4+ and CD8+ T cells by injecting the specific monoclonal antibodies (mAbs) or anti-IFN-gamma mAb, not only augmentation of the expression of macrophage activation markers but also phagocytosis of C. neoformans was significantly reduced. These results suggest that anticryptococcal activity of macrophages is regulated by IFN-gamma endogenously produced by T cells. Additionally, treatment with IFN-gamma were shown to significantly prolong the survival time of mice infected with viable C. neoformans. Additionally, preimmunization with heat-killed C. neoformans significantly prolonged the survival time of mice which received the following infection.

Animals↗
PubMed1995

Pharmacokinetic and pharmacodynamic analysis of a novel leukotriene biosynthesis inhibitor, MK-0591, in healthy volunteers.

1. The pharmacokinetic and pharmacodynamic properties of a novel 2-indolealkanoic acid derivative (MK-0591), a potent inhibitor of leukotriene biosynthesis, were investigated in healthy male Japanese volunteers. Single oral doses of 50, 125, 250 and 500 mg and multiple oral doses of 125 mg twice daily for 9.5 days and 250 mg once daily for 10 days were administered. 2. After the single-dose administration following overnight fasting, Cmax and AUC of MK-0591 in plasma increased in a dose-dependent manner, while elimination half-life remained constant (11.2-13.2 h) irrespective of dose. Food intake decreased Cmax and AUC by 71% and 68%, respectively, at a dose of 250 mg. With respect to multiple-dose administration before meals, there were no significant differences in the pharmacokinetic parameters between the first and last days, indicating a lack of significant accumulation of MK-0591 in plasma. Urinary recovery as the unchanged form was negligible throughout the study. 3. Ionophore-stimulated production of leukotriene B4 (LTB4) in blood ex vivo was inhibited significantly from 1 h until 12 to 48 h after single-dose administration as compared with predose value. In parallel, the urinary excretion of endogenous leukotriene E4 (LTE4) was significantly decreased from 4 to 8 h until 48 to 72 h after drug administration. Reduction of ionophore-stimulated LTB4 biosynthesis and urinary excretion of LTE4 following single administration of MK-0591 was statistically significant as compared with placebo group, and the duration of inhibition of LTB4 biosynthesis was dose-related.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Immunohistological analysis of T cell functional subsets in chronic inflammatory periodontal disease.

IL-2, interferon-gamma (IFN-gamma), IL-4 and IL-6 producing T cells in periodontitis and gingivitis-affected human tissues were investigated by immunohistochemistry to clarify the relationship between T cell functional subsets and disease entity. Using alkaline-phosphatase anti-alkaline-phosphatase technique, the relative proportions of each cytokine-producing T cell were calculated in the crevicular 1/3, middle 1/3 and oral 1/3 areas selected in the connective tissue of sections. CD19:CD3 and CD4:CD8 ratios were determined on the serial sections. Compared with gingivitis tissues, the proportion of cytokine-producing cells in periodontitis-affected samples was higher overall in the crevicular 1/3 (P < 0.02). The middle 1/3 exhibited a higher percentage of cytokine-producing cells, except for IL-6-producing cells. Frequencies of cytokine-producing cells in the oral 1/3 did not differ. IL-4 was the prominent cytokine in periodontitis-affected tissues, with the highest proportion detected in the crevicular 1/3. The CD19:CD3 ratio was higher in periodontitis tissues irrespective of the location, indicating a B cell dominance in periodontitis lesions. Furthermore, a significant positive correlation between the proportion of IL-4-producing cells and the CD19:CD3 ratio was noted. The CD4:CD8 ratio consistently exceeded 2.0 in both periodontitis and gingivitis. These results suggest that immunoregulation of both periodontitis and gingivitis are T cell-dependent, but in periodontitis type 2 helper T cells predominate and thereby control B cell activation.

Adult↗
PubMed1995

Mixed tumours of the skin: a histopathological, enzyme-histochemical and immunohistochemical study.

Twenty-eight cases of mixed tumour of the skin were studied and subclassified into three types: eccrine (1 case), indeterminate (7), and apocrine type (20). The indeterminate type was defined as mixed tumours having tubuloalveolar patterns with two layers of epithelium, ut without apocrine secretion or pilosebaceous differentiation. Enzyme-histochemical studies were performed on four cases (one indeterminate, three apocrine): in the indeterminate type the tubular epithelial cells showed eccrine differentiation while in the apocrine type tubules were found showing the direction of differentiation to be toward the apocrine gland, but tubules with eccrine differentiation were intermingled in all three. Immunohistochemically, no differences were observed between the indeterminate and the apocrine type: hints of eccrine features were observed in both groups. Thus, the indeterminate type could be an eccrine tumour and the apocrine type showed direction of differentiation toward both eccrine and apocrine glands. It is concluded that mixed tumours of the skin are fundamentally eccrine neoplasmas, and that the apocrine features may represent apocrine metaplasia.

Acetylesterase↗
PubMed1995

Changes in gnathosonic and tooth contact characteristics induced by experimental occlusal interferences created using a full-cast double crown.

Occlusal sounds, contact timings and time moments were measured and analysed on 10 subjects onto whom an occlusal interference was created experimentally. A full-cast double crown was unilaterally set on the upper first molar of each subject, then gradually elevated for 0.06, 0.10, 0.20 and 0.30 mm by inserting a pre-calibrated metal folio. Occlusal sound was measured with an analyser designed for the purpose. Timings and time moments were analysed with a T-scan system. All measurements were performed at least 10 times per subject. The results showed that prolonged occlusal sound duration, changes in acoustic signal waveform and increased shift of the centre of effort were observed concomitantly with crown elevation. Differences in these values at 0.06 mm as compared with those at baseline were not statistically significant. This could be explained through a physiological compensation by the periodontal ligament. The differences with baseline were statistically significant from 0.10 mm ongoing. The distribution of occlusal conacts was determined by the use of a newly developed parameter. Referred to as 'Tap Score', the parameter consists of converting contact timings occurring in seven ranges into least-square-based weighted scores. Analysis of the tap score disclosed evident imbalance between the crowned and the non-crowned side starting from 0.10 mm elevation, whereby a forward shift of the major contact point was observed on the non-crowned side. Our study demonstrated that evident changes in gnathosonic and T-scan parameters are likely to occur at a crown elevation within a 0.06-0.10 mm range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Interleukin 4 (IL-4) and IL-6-producing memory T-cells in peripheral blood and gingival tissue in periodontitis patients with high serum antibody titers to Porphyromonas gingivalis.

We assessed cytokine production and proliferation of memory T-cells that were isolated from peripheral blood of adult periodontitis patients with high anti-Porphyromonas gingivalis titer. Memory T-cells were stimulated with P. gingivalis lipopolysaccharide, sonicates and formalin-killed whole cells. Interleukin 4(IL-4)- and IL-6-producing cells were stained by immunocytochemistry on peripheral blood smears and compared with cryostat sections of autologous gingival biopsies. Memory T-cells in the peripheral blood of patients rated significantly higher than in healthy subjects (32.3 + or - 7.1 vs 25.3 + or - 3.0%). Stimulation of patient-derived memory T-cells with P. gingivalis whole cells induced higher IL-4 production than in healthy subjects (4.4 + or - 4.1% vs 0.7 + or - 0.6%). Induction of IL-4 producing memory T-cells by P. gingivalis lipopolysaccharide and whole cells was respectively 1.37 and 1.56 times that induced by medium alone. IL-6 production did not differ between the groups. Proliferation of memory T-cells in healthy subjects tended to be more inhibited by P. gingivalis antigens than that in patients. In some patients, induction of IL-4- and IL-6-producing memory T-cells in peripheral blood and in autologous gingival biopsies tended to coincide. Memory T-cells with functional characteristics of Th2 could be a crucial cell population capable of reflecting individual susceptibility to periodontitis.

Adult↗
PubMed1995

In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar bone resorption in rats.

The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on alveolar bone resorptive activity in rats were examined. Continuous administration of rhIL-1 beta or phosphate-buffered saline (PBS) was given via osmotic pumps for 3, 7 and 14 days to rats with silk ligatures around second maxillary molars. Other animals without ligatures received insertion of pumps containing rhIL-1 beta or remained untreated. Sections were subject to three different stains:--hematoxylin and eosin (H-E) for histology, acid phosphatase (ACPase) activity for osteoclast detection, and immunohistochemistry using anti-rat monocyte/macrophage monoclonal antibody (ED 1). In addition, body weight, plasma calcium and phosphorus levels were monitored. The mean body weight of rats receiving rhIL-1 beta was significantly lower (P < 0.05 to P < 0.01) compared with untreated rats throughout the experimental period. On Day 7, plasma calcium and phosphorus levels were significantly lower in rats receiving rhIL-1 beta than in rats receiving PBS only (P < 0.05). Sections revealed a moderate inflammatory cell infiltrate reaching near the alveolar crest in both groups with ligatures on Day 3. Only rats receiving rhIL-1 beta exhibited enhancement of inflammatory cell invasion on Days 7 and 14. In rats receiving rhIL-1 beta with ligatures, numerous resorption lacunae containing ACPase-positive multinucleated giant cells (MNGCs), coinciding with ED1-positive cells, were located on the mesial side of the septum where extensive bone resorption had occurred throughout the experimental period. In animals receiving rhIL-1 beta without ligatures, compared with untreated rats, increased ACPase-positive cells were observed on the mesial side of the septum on Day 3. In animals receiving PBS only, a few ACPase-positive cells were observed confined to the mesial regions where slight bone resorption occurred on Days 7 and 14. These results indicate that the administration of rhIL-1 beta accelerated alveolar bone destruction in ligature-induced periodontal tissue inflammation over a two-week period.

Acid Phosphatase↗
PubMed1995

Presence of activated eosinophils, high IgE and sCD23 titers in gingival crevicular fluid of patients with adult periodontitis.

Our previous studies showed that the expression of CD23 on polymorphonuclear leukocytes (PMNLs) in gingival crevicular fluid (GCF) from adult periodontitis (AP) patients was higher than in autologous peripheral blood (PB). Percentages of eosinophils in GCF PMNLs ranged between 6 and 14%. The purpose of the present studies was to increase understanding of the potential role of eosinophils and their products, including CD23, in periodontal disease. We analysed the eosinophil fraction in GCF and PB by flow cytometry using monoclonal antibodies to CD23b (BB10), eosinophil cationic protein (ECP) in stored and secretory forms (EG1 and EG2), and CD67 (80H3). Simultaneously, we measured IgE and soluble CD23 titer and GCF and serum by ELISA. Flow cytometric analysis of BB10, EG2 and 80H3 binding showed that GCF eosinophils from AP were activated. A large BB10+ EG2+ cellular fraction was detected in GCF from AP whereas it was very low in autologous serum (9.30 +/- 2.460 vs 0.16 +/- 0.10, p < 0.001). GCF from gingivitis patients exhibited no flow cytometric evidence for the presence of BB10+ EG2+ cells. BB10+ EG1+ cells, or inactivated eosinophils rated lower in GCF than in PB both in gingivitis and periodontitis patients (0.45 +/- 0.63 vs 1.83 +/- 0.96 and 0.15 +/- 0.30 vs 1.30 +/- 0.20, p < 0.05, respectively). IgE titer in AP patients reached 1208.1 +/- 421.2 IU/ml in GCF while only 49.1 +/- 50.4 in sera. Soluble CD23 in GCF reached 236.1 +/- 81.3 ng/ml in GCF and 5.6 +/- 1.8 ng/ml in sera. GCF of gingivitis patients, however, contained no detectable sCD23.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

ICAM-1-expressing pocket epithelium, LFA-1-expressing T cells in gingival tissue and gingival crevicular fluid as features characterizing inflammatory cell invasion and exudation in adult periodontitis.

Activated T lymphocytes constitute a major component of inflammatory cells in the early periodontal lesion, and also appear in the gingival crevicular fluid. In an attempt to clarify the relationship between the ICAM-1 (CD54) expression of pocket epithelium in gingiva and the infiltrating lymphocyte population, we carried out an analysis of CD11a+(LFA-1 alpha), CD25+(IL-2R alpha) and CD4+(Th) cells subjacent to ICAM-1-expressing pocket epithelia and CD11a+CD25+CD4+ cells in gingival crevicular fluid (GCF). GCF was collected by crevicular washing from 16 patients with periodontitis (P group) and 3 subjects with healthy gingiva (H group). Peripheral blood (PB) was collected at the same time. Mononuclear cells were isolated by Ficoll-paque gradient centrifugation from GCF and PB. Monoclonal antibodies (mAb) to CD11a, CD25, and CD4 were used for three-color flow cytometry. Gingival biopsies were obtained from 7 patients in P group and 3 subjects in H group. Serial cryostat sections (6 microns in thickness) were prepared from each biopsy, on which a double staining was performed. The number of CD11a+CD25+CD4+ cells and the fluorescence intensity of FITC conjugated anti-CD11a were significantly higher in GCF than in PB (p < 0.001 to p < 0.01). CD11a+CD25+CD4+ cells were not detected in GCF in H group. The pocket epithelia expressed CD54 in P group, but not in H group. The number of CD11a+, CD25+ and CD4+ cells infiltrating the connective tissue subjacent to the upper, middle and lower parts of the CD54 positive pocket epithelium (n = 16) was 141 +/- 26, 38 +/- 13, 144 +/- 29 (cells/0.04 mm2), respectively, whereas in the CD54 negative pocket epithelium, it was (n = 5) 9 +/- 2, 3 +/- 1, 8 +/- 3. In P group, the CD11a+CD25+CD4+ cell number in GCF correlated with CD25+, CD11a+ cells in the connective tissue subjacent to the CD54+ pocket epithelium. These results indicate that expression of ICAM-1 in pocket epithelium is relevant to the migration of CD11a, CD25, CD4 positive cells in connective tissue subjacent to the pocket epithelium into the periodontal pocket. Assessing the relationship of our findings and other adhesion molecules would offer important clues to the understanding of T cell migration in affected gingiva.

Adult↗