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Biomedical subjects

K Hosokawa

Publications and source records attributed to K Hosokawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dominant expression and distribution of oestrogen receptor beta over oestrogen receptor alpha in the human corpus luteum.

To investigate the potential importance of oestrogen as a local regulator of human corpus luteum function, the mRNA expression pattern and cellular localization of oestrogen receptors (ERs), ER-alpha and ER-beta, were studied in corpora lutea grouped according to age, where days 2-5 post-LH rise were designated as the early luteal phase, days 6-10 as mid-luteal and days 11-14 as the late luteal phase respectively. Northern blot analysis using an ER-beta probe in samples from whole ovarian tissue and isolated corpora lutea, revealed a major band at 7.5 kb and several minor bands between 4-10 kb, while no signals for ER-alpha mRNA were obtained. However, using a semi-quantitative reverse transcription-polymerase chain reaction followed by Southern blotting, ER-beta mRNA levels were found to be 63% lower (P: < 0.05, n = 39) in the mid-luteal phase compared with the early luteal phase, while ER-alpha mRNA expression showed no statistical differences between the different age groups. Using in-situ hybridization, ER-beta mRNA expression was localized to the steroidogenic luteal cells as well as perivascular cells and fibroblasts in the corpus luteum. Immunohistochemistry confirmed the localization of ER-beta protein, but no clear staining of luteal cells was found using antibodies against ER-alpha. Collectively, the findings of low to moderate expression of ER-beta mRNA and protein in the steroidogenic cells, and also in vascular endothelial cells of the corpus luteum, as opposed to diminutive amounts of ER-alpha mRNA, suggest that oestrogen activity is primarily transduced via ER-beta in the human corpus luteum.

Adult↗
PubMed2001

Endoscopic mucosal resection for treatment of early gastric cancer.

BACKGROUND: In Japan, endoscopic mucosal resection (EMR) is accepted as a treatment option for cases of early gastric cancer (EGC) where the probability of lymph node metastasis is low. The results of EMR for EGC at the National Cancer Center Hospital, Tokyo, over a 11 year period are presented. METHODS: EMR was applied to patients with early cancers up to 30 mm in diameter that were of a well or moderately histologically differentiated type, and were superficially elevated and/or depressed (types I, IIa, and IIc) but without ulceration or definite signs of submucosal invasion. The resected specimens were carefully examined by serial sections at 2 mm intervals, and if histopathology revealed submucosal invasion and/or vessel involvement or if the resection margin was not clear, surgery was recommended. RESULTS: Four hundred and seventy nine cancers in 445 patients were treated by EMR from 1987 to 1998 but submucosal invasion was found on subsequent pathological examination in 74 tumours. Sixty nine percent of intramucosal cancers (278/405) were resected with a clear margin. Of 127 cancers without "complete resection", 14 underwent an additional operation and nine were treated endoscopically; the remainder had intensive follow up. Local recurrence in the stomach occurred in 17 lesions followed conservatively, in one lesion treated endoscopically, and in five lesions with complete resection. All tumours were diagnosed by follow up endoscopy and subsequently treated by surgery. There were no gastric cancer related deaths during a median follow up period of 38 months (3-120 months). Bleeding and perforation (5%) were two major complications of EMR but there were no treatment related deaths. CONCLUSION: In our experience, EMR allows us to perform less invasive treatment without sacrificing the possibility of cure.

Adult↗
PubMed2001

Role of laminin in ovarian cancer tumor growth and metastasis via regulation of Mdm2 and Bcl-2 expression.

Ovarian cancer is among the most lethal cancers in women because of its high metastatic potential and lack of response to therapy. An experimental model to study this disease was developed using a transformed granulosa cell line expressing a mutant p53 and Ha-ras. When injected into the ovary of nude mice in the presence of laminin-1, tumors develop in the ovary and peritoneum and metastasize to various organs, leading to death within 21 days. In contrast, when cells were injected in the presence of gelatin, development of tumors was slower and no metastases were observed by day 21. Here we investigated the possible mechanism by which laminin-1 exerts its promotion of tumorigenesis and metastasis. Cells were co-injected with laminin-1 and active laminin peptides from the alpha1; (A13: RQVFQVAYIIIKA, A12: WVTVTLDL RQVFQ, AG73: LQVQLSIR, IKVAV) and beta1 (YIGSR) chains. Ovarian tumor growth and metastasis were increased in the presence of laminin-1 plus either AG73 peptide, IKVAV, or A13, and were significantly reduced in the presence of A12 or YIGSR. Expression of Bcl-2 and Mdm2 was higher by 3.5- and about 100-fold, respectively, in ovarian tumors grown in the presence of laminin compared to tumors grown in the presence of gelatin. Moreover, peptides A13 and AG73 further elevated Bcl-2 expression by 6- and 7-fold respectively, while IKVAV yielded expression similar to laminin-1. YIGSR and A12 reduced the expression of Bcl-2 by 7- and 3-fold, respectively, compared to treatment with laminin-1. A13 and AG73 increased Mdm2 expression by 1.8- and 1.3-fold, respectively, while IKVAV, A12, and YIGSR were without effect. Thus, laminin-1 exerts its proliferative effect on the development of ovarian tumors via upregulation of survival genes such as Bcl-2 and Mdm2. Peptides A13 and AG73 (which increased tumor growth and spread) enhance the expression of these genes and A12 and YIGSR (which decrease tumor growth and spread) attenuate their expression. IKVAV probably enhances tumor growth and metastasis by another mechanism.

Animals↗
PubMed2001

Epithelial-mesenchymal interactions in wounds: treatment of palmoplantar wounds by nonpalmoplantar pure epidermal sheet grafts.

BACKGROUND: Palms and soles differ from other body sites in terms of clinical and histologic appearance and response to mechanical stress. We previously reported that palmoplantar fibroblasts regulate keratin 9, which is a marker of palms and soles. OBJECTIVE: To treat palmoplantar wounds by using nonpalmoplantar pure epidermal sheets as a graft. DESIGN: Nonrandomized controlled trials. SETTING: University dermatology and plastic surgery services. PATIENTS: Forty-eight patients with palmoplantar wounds caused by burns, trauma, chronic ulcers, and the resection of malignant tumors, such as squamous cell carcinoma and acral lentiginous melanoma. INTERVENTIONS: The patients received nonpalmoplantar pure epidermal sheet grafts (n = 14), nonpalmoplantar donor site skin grafts (n = 17), or palmoplantar donor site skin grafts (n = 17). MAIN OUTCOME MEASURES: Clinical and histologic findings. RESULTS: The pure epidermal sheets were successfully grafted and gradually demonstrated the adoption of a palmoplantar phenotype when reticular dermis of the recipient site remained. The epidermis showed hyperkeratosis and acanthosis by histologic studies and stained positively for keratin 9 in all of the suprabasal keratinocyte layers like palmoplantar-type skin. Pure epidermal sheets were placed on deeper wounds after the wounds had an artificial dermis applied and adopted the palmoplantar phenotype without erosions and ulcerations. Neither nonpalmoplantar split-thickness nor full-thickness skin grafts resulted in a palmoplantar phenotype. CONCLUSIONS: Pure epidermal sheet grafting would be useful for the treatment of palmoplantar wounds as nonpalmoplantar epidermis is much easier to obtain clinically. In addition, secondary procedures are not required to repair the donor site, since this wound is superficial.

Adolescent↗
PubMed2000

Factor VIII C2 domain contains the thrombin-binding site responsible for thrombin-catalyzed cleavage at Arg1689.

Thrombin-catalyzed factor VIII activation is an essential positive feedback mechanism regulating intrinsic blood coagulation. A factor VIII human antibody, A-FF, with C2 epitope, exclusively inhibited factor VIII activation and cleavage at Arg(1689) by thrombin. The results suggested that A-FF prevented the interaction of thrombin with factor VIII and that the C2 domain was involved in the interaction with thrombin. We performed direct binding assays using anhydro-thrombin, a catalytically inactive derivative of thrombin in which the active-site serine is converted to dehydroalanine. Intact factor VIII, 80-kDa light chain, 72-kDa light chain, and heavy chain fragments bound dose-dependently to anhydro-thrombin, and the K(d) values were 48, 150, 106, and 180 nm, respectively. The C2 and A2 domains also dose-dependently bound to anhydro-thrombin, and the K(d) values were 440 and 488 nm, respectively. The A1 domain did not bind to anhydro-thrombin. A-FF completely inhibited C2 domain binding to anhydro-thrombin (IC(50), 18 nm), whereas it did not inhibit A2 domain binding. Furthermore, C2-specific affinity purified F(ab)'(2) of A-FF, and the recombinant C2 domain inhibited thrombin cleavage at Arg(1689). Our results indicate that the C2 domain contains the thrombin-binding site responsible for the cleavage at Arg(1689).

Antibodies, Monoclonal↗
PubMed2000

Effects on Rb(+)(K+) uptake of HeLa cells in a high K(+) medium of exposure to a switched 1.7 Tesla magnetic field.

Effects of a switched, time-varying 1.7 T magnetic field on Rb(+)(K+) uptake by HeLa S3 cells incubated in an isosmotic high K(+) medium were examined. The magnetic flux density was varied intermittently from 0.07-1.7 T at an interval of 3 s. K(+) uptake was activated by replacement of normal medium by high K(+) medium. A membrane-permeable Ca(2+) chelating agent (BAPTA-AM) and Ca(2+)-dependent K(+) channel inhibitors (quinine, charibdotoxin, and iberiotoxin) were found to reduce the Rb(+)(K+) uptake by about 30-40%. Uptake of K(+) that is sensitive to these drugs is possibly mediated by Ca(2+)-dependent K(+) channels. The intermittent magnetic field partly suppress ed the drug-sensitive K(+) uptake by about 30-40% (P < 0.05). To test the mechanism of inhibition by the magnetic fields, intracellular Ca(2+) concentration ([Ca(2+)]c) was measured using Fura 2-AM. When cells were placed in the high K(&plus;) medium, [Ca(2+)]c increased to about 1.4 times the original level, but exposure to the magnetic fields completely suppressed the increase (P < 0.01). Addition of a Ca(2+) ionophore (ionomycin) to the high K(+) medium increased [Ca(2+)]c to the level of control cells, regardless of exposure to the magnetic field. But the inhibition of K(+) uptake by the magnetic fields was not restored by addition of ionomycin. Based on our previous results on magnetic field-induced changes in properties of the cell membrane, these results indicate that exposure to the magnetic fields partly suppresses K(+) influx, which may be mediated by Ca(2+)-dependent K(+) channels. The suppress ion of K(+) fluxes could relate to a change in electric properties of cell surface and an inhibition of Ca(2+) influx mediated by Ca(2+) channels of either the cell plasma membrane or the inner vesicular membrane of intracellular Ca(2+) stores.

Calcium↗
PubMed2000

Proteome analysis of mouse brain: two-dimensional electrophoresis profiles of tissue proteins during the course of aging.

Mouse brain proteins were isolated from five regions (cerebellum, cerebral cortex, hippocampus, striatum, and cervical spinal cord) at five ages from the 10th week to the 24th month, and separated by two-dimensional gel electrophoresis (2-DE). 2-DE was carried out with an immobilized pH gradient bar in the first dimension, and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. Over one thousand protein spots were visualized by silver staining and quantified by image processing. In the analyses, 58 protein spots were distinguishable among the above five brain regions, and 17 proteins were shown to be varied in quantity in the course of aging. Partial amino-terminal sequences and/or internal sequences for a total of 301 protein spots were analyzed. One hundred and eighty proteins appeared to have blocked N-termini and 122 proteins were identified. Twenty-seven new proteins were identified by sequence homology search. A mouse brain proteome database was constructed, which consists of the 2-DE map images and the respective spot data files with 15 related references.

Acrylic Resins↗
PubMed2000

Ichthyosis follicularis with alopecia and photophobia in a mother and daughter.

A mother and daughter having ichthyosis follicularis with alopecia and photophobia (IFAP) are reported, with histopathological and electron microscopic findings. We have followed the clinical course of the mother for 26 years since she was 5 years old, and the daughter since birth. They have had almost all the classical and some of the minor symptoms of IFAP, including severe photophobia, extensive non-inflammatory follicular hyperkeratosis, generalized non-scarring alopecia, hyperkeratosis of the extensor aspect of the four extremities, nail deformity and recurrent cheilitis. In addition, their facial appearance greatly resembles that of previously reported patients. A consistent feature in the mother was florid keratotic inflammatory eruptions on the genital region during each of her pregnancies, which rapidly improved after the delivery. Skin biopsy of the genital lesion showed marked acanthosis with dyskeratosis and spongiotic changes. The electron microscopic examination of diseased skin showed damaged desmosomes with spongiosis. No obvious changes were found in normal appearing skin.

Adult↗
PubMed2000

Larynx preservation in surgical treatment of cervical esophageal cancer--combined procedure of laryngeal suspension and cricopharyngeal myotomy.

From July 1994 to July 1998, a larynx-preserving procedure was performed on 10 out of 22 (45%) patients in the surgical treatment of hypopharyngeal and cervical esophageal cancer. At first, all 10 patients were treated with concurrent radiochemotherapy with cisplatin (10 mg/m2/day), 5-fluorouracil (500 mg/m2/day) and radiation (2 Gy/day) five times per week for 4 weeks. After preoperative radiochemotherapy, the larynx-preserving procedure, combining laryngeal suspension and cricopharyngeal myotomy, was performed. The operative and hospital mortality rate was 0%. The incidence of post-operative morbidity with minor complications was 70% in the present study. Laryngeal speech and oral food intake were preserved in all patients after this procedure. The new larynx-preserving procedure combining laryngeal suspension and cricopharyngeal myotomy for cervical esophageal cancer is a favorable operative method for retaining intelligible laryngeal speech and good food intake.

Adult↗
PubMed2000

Involvement of keratinocyte activation phase in cutaneous graft healing: comparison of full-thickness and split-thickness skin grafts.

BACKGROUND: Little is known about keratinocytic activation in the graft take and healing process. OBJECTIVE: To investigate the clinical and molecular differences between pure epidermal sheet graft (PESG), split-thickness skin graft (STSG), and full-thickness skin graft (FTSG). METHODS: Three different thickness skin grafts (PESG, STSG, and FTSG) were performed onto three kinds of porcine wounds: shallow, deep, and full. Graft take, contraction, and Ki-67 and beta1 integrin expression in epidermis were studied. RESULTS: All grafts took well. As expected, full wounds covered by PESG and STSG contracted more than those covered by FTSG, whereas shallow wounds covered by FTSG contracted more than those covered by STSG. No difference in contracture was observed among deep wounds covered by PESG, STSG, and FTSG. Up-regulation of Ki-67 and beta1 integrin expression was greater in PESG and STSG, compared with little expression in FTSG. CONCLUSION: The keratinocytic activation phase may occur both in the STSG and PESG healing process, as well as serum imbibition, inosculatory, and revascularization phases.

Animals↗
PubMed2000

Discrimination among three species of medicinal Scutellaria plants using RAPD markers.

An analysis of random amplified polymorphic DNA (RAPD) was performed using nine accessions of three species of medicinal plants in the genus Scutellaria (S. galericulata, S. lateriflora and S. baicalensis; known collectively as skullcap) in an effort to distinguish between members of these three species. Dried aerial parts of the two species S. galericulata and S. lateriflora are difficult to distinguish morphologically. Ten arbitrary primers produced 92 fragments, and eight of the primers yielded 23 species-specific fragments among the three species. Six fragments were specific for S. galericulata, seven for S. lateriflora and ten for S. baicalensis. When primers A02 and A06 were used in the polymerase chain reaction, RAPD fragments that were specific for each of the three species were generated simultaneously. Primer A02 produced five species-specific fragments: one was specific for S. galericulata; two for S. lateriflora; and two for S. baicalensis. Primer A06 produced three species-specific fragments: one for S. galericulata; one for S. lateriflora; and one for S. baicalensis. The RAPD markers that were generated with these two primers should rapidly identify members of the three species of Scutellaria. The consistency of the identifications made with these species-specific RAPD markers was demonstrated by the observation that each respective marker was generated from three accessions of each species, all with different origins. Furthermore, cluster analysis using the 92 RAPD fragments produced a dendrogram of genetic relatedness that was in good agreement with the taxonomic designations of the three species. Thus, the RAPD markers should be useful for the future identification of members of the three species of medicinal Scutellaria plants.

Plants, Medicinal↗
PubMed2000

A case of inoperable esophageal carcinoma with hepatic and nodal metastases which showed a long-term survival after chemoradiotherapy including nedaplatin.

We report a case of metastatic esophageal carcinoma successfully treated with chemoradiotherapy. A 61-year-old man, diagnosed as suffering from advanced esophageal carcinoma with liver and lymph node metastases, was treated with a combination of nedaplatin (90 mg/m2/day, 1 h drip infusion, day 1), 5-fluorouracil (800 mg/m2/day, continuous infusion, days 1-5), and radiotherapy (2 Gy/day, days 1-5, 8-12 and 15-19). The cycle was repeated twice every 5 weeks from July 2, 1997. He achieved a complete response 1 month after finishing two courses of chemoradiotherapy followed by an additional three courses of chemotherapy without radiation. Seven months after the completion of radiotherapy, pericardial effusion with negative cytology was recognized. The effusion was treated by pericardiocentesis and drainage for several days. After drainage, the effusion could be easily managed with diuretics. This patient is still alive with no evidence of disease more than 2.5 years after the initiation of the treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

A putative stimulatory role of progesterone acting via progesterone receptors in the steroidogenic cells of the human corpus luteum.

To further explore the proposed auto-regulatory role of progesterone action in the human corpus luteum (CL), the expression and functional roles of progesterone receptor (PR) isoforms A and B during the luteal phase (LP) of the menstrual cycle were investigated. A total of 27 otherwise healthy patients previously scheduled for surgery were recruited after informed consent. An LH rise was detected, and CL were grouped according to age (Days 2-5 post-LH-rise, early LP; Days 6-10, mid LP; Days 11-14, late LP). Using a semiquantitative reverse transcription-polymerase chain reaction assay, the PR-B mRNA levels, which were 100- to 1000-fold lower than PR-A/B mRNA, were 46% lower (P < 0.05, n = 24) in mid LP, compared to early and late LP. CL tissue levels of progesterone and PR-A/B protein levels were inversely correlated to increasing CL age; i.e., significantly reduced levels were observed in the late LP (r(2) = 0.34, P < 0.01, n = 23). Expression of PR-A/B mRNA as well as PR-A/B protein were detected by in situ hybridization and immunohistochemistry, respectively. Both methods revealed a clear and distinct localization to cells in the steroidogenic layer of the CL. Freshly obtained mid-luteal CL cells were cultured in vitro, and media were analyzed for progesterone concentrations after treatment by incremental doses of hCG and the stable PR antagonist mifepristone, alone or in combination. Mifepristone did not per se alter progesterone synthesis, but when it was added in conjunction with hCG, a dose-related inhibitory response was seen, with a maximal 47% reduction in progesterone output at a 10 microM addition (P < 0.05, n = 3). Collectively, these data implicate a stimulatory role of progesterone receptor-mediated action in the steroidogenic cells of the human CL, which may serve as an important pathway for maintaining functional homeostasis during early pregnancy.

Adult↗
PubMed2000

A new technique for the treatment of syndactyly with osseous fusion of the distal phalanges.

In treating complex syndactyly of the hand, including bony union of varying degrees, how to cover the exposed bone surface is still disputable. The authors adopted a homemade device for the treatment of a case of syndactyly with terminal bony union. External tissue expander theory was applied to their device, and expansion of the cutaneous bridge was followed by division of the fused distal phalanges. Two months later the raw bone could be covered simply with the expanded local skin, and no skin graft was needed except for at the base of the affected fingers. This technique produces good cosmetic results of the fingertips and nail grooves without secondary deformities.

Humans↗
PubMed2000

Philtral construction by composite skin-muscle rotation and orbicularis oris muscle advancement in secondary cleft lip deformity.

The authors describe a method of philtral construction in a secondary cleft lip deformity to achieve better philtral definition and natural lip animation. The operation begins with a skin incision based on the usual design of secondary revision. Subcutaneous undermining is then performed laterally, and medially up to the line of the new philtral ridge, where the lip is divided vertically to the mucosa. A wedge-shaped flap is developed in the medial lip by dissecting from the posterior mucosal wound edge toward the cutaneous midline up to the dermis. The composite skin-muscle flap is thus elevated and rotated 90 deg on the axis of the cutaneous midline to form the philtral ridge. The orbicularis oris muscle is reapproximated in the midline by advancing the lateral orbicularis segment. The wedge-shaped flap is placed over the advanced orbicularis, and the skin is closed. Ten consecutive patients, followed for more than 6 months, were evaluated. In all patients the lip showed a well-defined philtrum with sufficient thickness and smooth continuity. Natural lip animation was also reproduced. Purportedly, the composite skin-muscle rotation provides a well-defined philtrum, and the midline approximation of the orbicularis muscle provides natural lip animation.

Adolescent↗