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Biomedical subjects

M Kawashima

Publications and source records attributed to M Kawashima.

At least 55 records · Page 3Linked to original sources

Human papillomavirus type 58 in Bowen's disease of the elbow.

Human papillomavirus (HPV) can be detected in skin lesions of Bowen's disease, particularly on the fingers, and its genotype is associated with mucosal/genital types of HPV. We report herein an 85-year-old woman who had HPV-associated Bowen's disease on her elbow. HPV-58 DNA was detected in the lesion by polymerase chain reaction with restriction fragment length polymorphism and by Southern blot hybridization. In situ hybridization revealed numerous hybrid cells in the nuclei of the upper epidermis and stratum corneum of Bowen's disease. A high-risk type of mucosal HPV-58 DNA is associated with Bowen's disease in this case, suggesting that HPV-related Bowen's disease is not always restricted to genital or finger lesions.

Aged↗

The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1alpha and TNF-alpha, which stimulate secretion of endothelin 1.

BACKGROUND: Seborrhoeic keratosis (SK) is a benign epidermal tumour with increased pigmentation. We have recently demonstrated that increased secretion of endothelin (ET)-1, a strong keratinocyte-derived mitogen and melanogen for human melanocytes, is intrinsically involved in the hyperpigmentation mechanism of SK. OBJECTIVES: To examine whether the increased ET secretion results from cytokines that induce ET production and/or from differences in the processing of ET that lead to its final active, secreted form. METHODS: We used immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine whether ET-inducing enzymes and/or cytokines are also highly expressed in SK. RESULTS: RT-PCR of mRNAs encoding interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and endothelin-converting enzyme (ECE)-1alpha demonstrated that there is an increased expression of TNF-alpha and ECE-1alpha mRNAs in SK, whereas the IL-1alpha transcript is rather downregulated in SK compared with that in perilesional normal epidermis. In parallel, immunohistochemical analysis of SK revealed marked immunostaining for TNF-alpha in basaloid cells at lower levels of the epidermis and in basal cells, and for ECE-1alpha in most basaloid and basal cells in comparison with their weak staining throughout the epidermis in perilesional normal controls. In contrast, immunostaining for IL-1alpha was almost negative in SK relative to distinctive staining throughout the epidermis in the perilesional normal controls. CONCLUSIONS: These findings suggest that the increased secretion of ET-1 leading to enhanced pigmentation in SK results from the co-ordinated increased expression of TNF-alpha and ECE-1alpha.

Cell Culture Techniques↗

The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis.

Little is known about the mechanism(s) underlying hyperpigmentation in lentigo senilis. We have previously reported that keratinocyte-derived endothelins are intrinsic paracrine mitogens and melanogens for human melanocytes and that they play an essential role in stimulating ultraviolet-B-induced melanogenesis. In this study, we have used immunohistochemistry and reverse transcriptase polymerase chain reaction analysis to clarify the role of the endothelin cascade, including endothelin production, processing by endothelin-converting enzyme, and expression of the endothelin B receptor, in the hyperpigmentary mechanism(s) involved in lentigo senilis. The number of tyrosinase immunopositive melanocytes in lentigo senilis lesional skin was increased 2-fold over the perilesional epidermis. Immunohistochemistry using antibodies to endothelin-1 demonstrated relatively stronger staining in the lesional epidermis than in the perilesional epidermis. Reverse transcriptase polymerase chain reaction analysis concomitantly demonstrated accentuated expression of transcripts for endothelin-1 and for the endothelin B receptor in lentigo senilis lesional skin, which was accompanied by a similar accentuated expression of tyrosinase mRNA compared with the perilesional control. The endothelin-1-inducible cytokine, tumor necrosis factor alpha, was consistently upregulated in the lentigo senilis lesional epidermis as determined at the transcriptional level and by immunostaining, whereas interleukin-1alpha was downregulated. In contrast, endothelin-converting enzyme 1alpha mRNA was not substantially increased in the lesional epidermis. These findings suggest that an accentuation of the epidermal endothelin cascade, especially with respect to expression of endothelin and the endothelin B receptor, plays an important role in the mechanism involved in the hyperpigmentation of lentigo senilis.

Aspartic Acid Endopeptidases↗

Effectiveness of laparoscopic gonadectomy using abdominal wall lift method on Turner's syndrome patients with 45, X/46, XY mosaicism.

We present a Turner's syndrome patient with a 45, X/46, XY mosaicism who underwent a prophylactic laparoscopic gonadectomy using the abdominal wall lift method. The patient was a 14-year-old phenotypic girl who was referred for an examination of primary amenorrhea. She had already been found to have Turner's syndrome with 45, X/46, XY mosaicism. After an extensive discussion with the patient and her family regarding her high risk for developing a gonadoblastoma, a laparoscopic bilateral salpingo-oophorectomy using the abdominal wall-life method was performed. Laparoscopy using the abdominal wall lift method has an advantage over CO2 pneumoperitoneum method for patients with Turner's syndrome when it is difficult to intubate because of a webbed neck or a shortened trachea.

Adolescent↗

Influence of postsurgical residual tumor volume on local control in radiotherapy for maxillary sinus cancer.

BACKGROUND: The aim was to study the influence of postsurgical gross residual tumor volume on local control of maxillary sinus cancer treated with radiotherapy combined with debulking surgery. METHODS: Forty-three patients who underwent combined surgery and radiotherapy (50-72 Gy, median 60 Gy) for squamous cell carcinoma of the maxillary sinus were reviewed. Gross residual tumor volume (GRTV) after surgery was measured on computed tomograms obtained during the radiotherapy planning. Patients were classified according to GRTV as follows: group AA, GRTV = 0 (microscopic residual, n = 2); group A, GRTV < 10 cm3 (n = 24); group B, 10-40 cm3 (n = 9); and group C, > or = 40 cm3 (n = 8). The relationship between local control and GRTV was analyzed using univariate and multivariate analysis. RESULTS: The 2-year local control rate for all patients was 62%. The differences in local control rates between groups AA, A and B were not significant (P > 0.05), but the rate was significantly lower in group C than in the other groups (69% at 2 years vs 31% at 1 year, P < 0.001). Multivariate analysis showed that GRTV (P = 0.002) and histological differentiation (poorly differentiated histology was favorable, P = 0.035) were independent prognostic factors and that intra-arterial chemotherapy and administered total dose were not. Local control in groups A and B significantly depended on the total dose of radiotherapy, with 2-year control rates of patients receiving 50 Gy (n = 6) and > or = 60 Gy (n = 27) of 17% vs 79%, respectively (P < 0.001). CONCLUSIONS: Our data suggest that adequate, not complete, debulking associated with a total radiotherapy dose of > or = 60 Gy can provide satisfactory local control for patients with squamous cell carcinoma of the maxillary sinus.

Carcinoma, Squamous Cell↗

Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors.

Oxidative DNA damage generated by an attack of reactive oxygen species causes mutation or cell death that may lead to various diseases and may be related to initiation or progression of carcinogenesis. 8-Oxo-2'-deoxyguanosine (8-oxo-dG) is a major oxidative DNA damage product that can result in mutation, and hMTH1, human MutT homolog protein 1, has been identified as an enzyme that hydrolyzes 8-oxo-dGTP to the monophosphate, thus preventing accumulation of 8-oxo-dG in DNA. With immunohistochemical approaches, we investigated accumulation of 8-oxo-dG and expression of hMTH1 in brain tumor tissues obtained from surgical and autopsy cases, including 42 neuroepithelial tumors, 5 meningiomas, 2 metastatic brain tumors, and 1 schwannoma. 8-Oxo-dG accumulation and hMTH1 expression were increased in various brain tumors. Nuclei of brain tumor cells were immunoreactive for 8-oxo-dG in all cases. In most cases, both nuclei and cytoplasm of the tumor cells were immunoreactive for hMTH1. Both 8-oxo-dG accumulation and hMTH1 expression were most evident in high-grade gliomas, indicating that oxidative stress was high in these gliomas. Thus, the defense mechanism against such oxidative stress may be enhanced as well. These results suggest that oxidative stress may play a role in tumor progression.

8-Hydroxy-2'-Deoxyguanosine↗

Developmental changes of parathyroid hormone/parathyroid hormone-related peptide and calcitonin receptor binding properties in the chicken calvaria and kidney.

The equilibrium dissociation constant (Kd) and the maximum binding capacity (Bmax) of receptors for parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) and calcitonin (CT) in the membrane fraction of the calvaria and the kidney of chickens were examined from 1 d after the hatch up to 24 wk of age by the use of radioligand binding assays. The Kd values of the PTH/PTHrP receptor in both tissues were decreased at 10 and 24 wk in female birds, whereas the values were increased at 24 wk in male birds. The Bmax values of the PTH/PTHrP receptor in both tissues were decreased at 10 wk and returned to baseline at 24 wk in female birds. The values were increased at 24 wk in male birds. The Kd and Bmax values of CT receptors in the both tissues were constant during the experimental period in female and male birds. The results suggest that the binding properties of PTH/PTHrP receptor and of CT receptor may be influenced by gonadal hormones relating to sexual maturation.

Age Factors↗

Increased interleukin-5 levels in bronchoalveolar lavage fluid is a major factor for eosinophil accumulation in acute eosinophilic pneumonia.

BACKGROUND: Increased interleukin-5 (IL-5) levels have been reported in bronchoalveolar lavage fluid (BALF) from patients with acute eosinophilic pneumonia (AEP); however, it still remains to be determined whether IL-5 is responsible for the eosinophil accumulation in the lung. OBJECTIVE: We examined the effect of antibodies against cytokines on eosinophil chemotaxis induced by BALF from AEP patients to identify factors responsible for eosinophil accumulation. METHODS: We measured a series of specific cytokines, including IL-3, IL-4, IL-5, IL-6, IL-8, GM-CSF, RANTES, MCP-1, MIP-1alpha and eotaxin, in the BALF from 4 patients with AEP. BALF from 4 patients with chronic eosinophilic pneumonia (CEP) and 13 patients with non-eosinophilic interstitial lung diseases (ILD) were examined as controls. The eosinophil chemotactic activity in the BALF was examined using tissue culture insert furnished with a polycarbonate membrane. RESULTS: The total protein content in BALF from patients with AEP was extremely elevated. Even after standardization with protein concentration, IL-5 levels in AEP patients were significantly higher than those in CEP and ILD. IL-3 and chemokines were rather lower in the AEP group than in the CEP and ILD groups. In AEP BALF, anti-IL-5 neutralizing antibody significantly inhibited eosinophil chemotaxis. Antibodies against IL-3, GM-CSF, and IL-8 did not affect the eosinophil migration. CONCLUSION: These findings suggest that locally produced IL-5 plays an important role in eosinophil accumulation of AEP.

Acute Disease↗

Granzyme-B-containing lymphocyte involvement in epidermal injury in graft-versus-host disease.

BACKGROUND: Skin lesions from graft-versus-host disease (GVHD) show histological features of epidermal cell death with lymphocyte infiltration. Perforin and granzyme B are involved in the process of apoptosis induced by cytotoxic T lymphocytes (CTL). OBJECTIVE: To elucidate the role of CTL in the mechanism of epidermal injury in GVHD. METHODS: We studied immunohistochemical staining for granzyme B and perforin in the skin lesions of 8 patients who developed GVHD after bone marrow transplantation. RESULTS: Granzyme-B-positive lymphocytes were CD8 positive and were observed in the epidermis of 3 out of 6 specimens in acute GVHD, and of 5 specimens of chronic GVHD except for 1 sclerotic type in which it was negative. Perforin-positive lymphocytes were observed in the epidermis of the specimens from 1 acute and 1 chronic GVHD. CONCLUSIONS: Granzyme B derived from CTL may be involved in the mechanisms of epidermal injury in GVHD.

Acute Disease↗

A patient with severe palindromic rheumatism and frequent episodes of pain.

A 44-year-old man began to experience episodes of joint pain with erythema in his knees, elbows, shoulders, and hands in April 1996. He was diagnosed as having palindromic rheumatism. Due to the increasing frequency and severity of these episodes, he was admitted to our hospital in May 1999. Heat therapy to the affected area produced a rapid improvement in symptoms. In addition, the continued use of physical therapy during symptom-free periods tended to reduce the frequency and severity of pain attacks. We present this case and discuss treatment options in patients with palindromic rheumatism.

Adult↗

Microvessel density predicts the radiosensitivity of metastatic head and neck squamous cell carcinoma in cervical lymph nodes.

Cervical lymph node metastasis is the most common recurrence pattern of head and neck squamous cell carcinoma (HNSCC), and it is usually treated with radiation therapy and/or neck dissection. There has long been a desire for markers useful in predicting radiosensitivity to enable assignment of patients with recurrent head and neck cancer to clinical trials to improve their survival rates and quality of life. A total of 43 cases of HNSCC treated with whole or elective neck irradiation (total dose, 26-70 Gy; median, 60 Gy) for recurrent metastatic SCC in neck lymph nodes after neck dissection between 1992 and 1999 were the subject of this study. The relationship between radiosensitivity and clinicopathological and histopathological factors, including the Ki-67-labeling index for cell proliferation, p53 immunoreactivity and microvessel density (MVD), in surgical neck lymph node specimens were investigated by univariate and multivariate analysis. Of the 43 patients, 31 had recurrent tumors in neck lymph nodes after radiotherapy. Univariate analysis revealed significant associations between radiosensitivity and both high grade of keratinization (p=0.033) and low MVD (p=0.004), and marginally significant associations between radiosensitivity and grade of differentiation of the cancer in the lymph nodes (p=0.070). Multivariate analysis showed that only MVD had predictive value (p=0.016). Tumors with a high MVD possessed a significantly better neck control rate than tumors with a low MVD (p=0.004) by Kaplan-Meier analysis. MVD can be used as a good predictive marker for radiosensitivity of metastatic HNSCCs in cervical lymph nodes after neck dissection.

Aged↗

[A case of micronodular pneumocyte hyperplasia, lymphangiomyomatosis associated with tuberous sclerosis].

We report a case of tuberous sclerosis (TS) associated with renal angiolipomas, subungual fibroma, adenoma sebaceum, pulmonary lymphangiomyomatosis (LAM), and micronodular pneumocyte hyperplasia (MNPH). A CT scan of the chest demonstrated multiple minute nodules present throughout both lung fields. Histologically, the nodules were well demarcated, and were composed of thickened, fibrotic, alveolar septa lined by pleomorphic, type II pneumocytes. This type of MNPH is extremely rare, and appears to be a hamartomatous proliferation occurring in patients with TS.

Adult↗

[A case of desmoplastic malignant pleural mesothelioma].

A 71-year-old woman with no history of asbestos exposure was referred to our hospital for evaluation of mediastinal soft tissue density. Six months prior to the admission, she had developed back pain and had been diagnosed as having intercostal neuralgia. Since the symptoms progressed, she was referred to another hospital. While chest radiography revealed no abnormality, chest computed tomography showed the prominence of mediastinal soft tissue, extending to the left hilum and partially destroying the nearby vertebrae. However, no pleural effusion was noted. After admission, a thoracoscopic examination was performed, and a whitish mass was found on the pleural surface partially adhering to the chest wall. Histological examination of the biopsied material showed dense areas of collagenous tissue with small foci of slightly atypical spindle cells. These findings led to the diagnosis of desmoplastic malignant pleural mesothelioma. The patient was treated with combined chemo-radiotherapy, but the response to this treatment was unclear. To date, reports for this subgroup of malignant mesothelioma are still rare.

Aged↗

Sphingosylphosphorylcholine is an activator of transglutaminase activity in human keratinocytes.

We characterize functional roles of a newly discovered chemical, sphingosylphosphorylcholine (SPC), in the epidermis by elucidating the biological effect of SPC on human keratinocytes in culture. The intracellular calcium level of human keratinocytes was increased by incubation with SPC, but not with sphingosine (SS) or sphingomyelin (SM). The addition of SPC, sphingosine 1-phosphate (SSP), or SS to human keratinocytes at 10 microM concentrations also significantly suppressed DNA synthesis, and SPC, but not SSP, or SS increased the activities of membrane-bound and soluble transglutaminases (TGases). Reverse transcription polymerase chain reaction (RT-PCR) of TGase transcripts revealed that SPC treatment at 10 microM concentrations increased the expression of TGase 1 mRNA. The increased activity of soluble TGase was accompanied by the concomitant activation of cathepsin D as revealed by the increased ratio of mature active form to inactive intermediate form of the protease. Pretreatment of human keratinocytes with pepstatin, a protease inhibitor, blocked the increase in soluble TGase activity induced by treatment with SPC. Consistently, SPC treatment at 1-10 microM concentrations stimulated the cornified envelope formation. These findings suggest that SPC plays an important role in the altered keratinization process of epidermis in skin diseases with high expression of sphingomyelin deacylase, such as atopic dermatitis.

Calcium↗

Cross-sectional survey on risk factors for insomnia in Japanese female hospital nurses working rapidly rotating shift systems.

A cross-sectional survey was carried out for the purpose of examining the association of work stress with insomnia among nurses working rotating shift systems. A self-administered questionnaire on sleep and mental health was distributed to 875 nurses at five hospitals in Japan. Out of the data from 785 (89.7%) respondents, those from 555 women engaged in rapidly and irregularly rotating shift systems as full-time nurses were examined. The prevalence of insomnia (29.2%) was three to four times higher than that in the general population. Among the insomniacs, 23% were current users of medically prescribed hypnotics. Multiple logistic analysis revealed that being 24 or less years old, working three or less night shifts per month, having six or less non-working days per month, receiving less support from colleagues and superiors, and taking care of severely ill patients were independent risk factors for insomnia. The number of hours of a night shift was found not associated with insomnia, taking the above variables into account. These results suggest that at least three factors, i.e., 1) young nurses not adapted to shiftwork, 2) the nurses requiring to remedy sleep deficits on non-working days, and 3) the work stress partly characteristic of nurses, have an adverse influence on their sleep.

Adult↗

The skin of atopic dermatitis patients contains a novel enzyme, glucosylceramide sphingomyelin deacylase, which cleaves the N-acyl linkage of sphingomyelin and glucosylceramide.

We have demonstrated previously that there is an abnormal expression of sphingomyelin (SM) deacylase in the epidermis of patients with atopic dermatitis (ADe). In the present study, we have prepared N-[palmitic acid-1-(14)C]SM and N-[palmitic acid-1-(14)C]glucosylceramide (GCer) to use as substrates and have quantified SM deacylase activity by detecting the release of [(14)C]palmitic acid in extracts of the stratum corneum or the epidermis of ADe patients. In studies using [palmitic acid-1-(14)C]SM as a substrate, a pH dependency of catalytic activity with a peak at pH 5.0 was found. Preparative SDS/PAGE using an extract of ADe epidermis revealed that the molecular mass of SM deacylase is 40000 Da, which is consistent with its apparent molecular mass of 42000 Da estimated by gel-filtration analysis of stratum corneum extracts. Analytical isoelectric focusing (IEF) chromatography demonstrated that the pI values of SM deacylase, beta-glucocerebrosidase (GlcCDase), sphingomyelinase (SMase) and acid ceramidase were 4.2, 7.4, 7.0 and 5.7, respectively. In enzymic analysis using pI-4.2 SM deacylase partially purified by IEF, which had no detectable contamination with acid ceramidase, GlcCDase or SMase, radio-TLC analysis revealed that radiolabelled sphingosylphosphocholine or [1-(14)C]palmitic acid was enzymically liberated from [choline-methyl-(14)C]SM or N-[palmitoyl-1-(14)C]GCer, respectively, used as substrates. Further the pI-4.2 protein purified from extracts of the stratum corneum of ADe patients was able to hydrolyse N-[palmitoyl-1-(14)C]SM and GCer, but not N-[palmitoyl-1-(14)C]ceramide. These results indicate that a hitherto undiscovered epidermal enzyme, termed here glucosylceramide sphingomyelin deacylase, is expressed in the skin of ADe patients, which plays an important role in ceramide deficiency (including acylceramides) in the stratum corneum.

Carboxylic Ester Hydrolases↗