Biomedical subjects

Y Hozumi

Publications and source records attributed to Y Hozumi.

At least 19 recordsLinked to original sources

PubMed2006

A case of Coffin-Lowry syndrome with premature exfoliation of primary teeth.

We present a case of a 5-year-old boy with premature exfoliation of primary teeth. All eight primary incisors had exfoliated by the age of 3 years, and three canines and one primary first molar were subsequently lost when he was 4 years old. None of the exfoliated teeth exhibited caries. The boy also showed characteristic facial changes, tapering of the fingers, and mental and motor retardation. Based on these findings, he was diagnosed as having Coffin-Lowry syndrome. Premature exfoliation of primary teeth in Coffin-Lowry syndrome has been described in a few reports. This manifestation of the disease would be helpful for diagnosis at an early stage as those previous reports suggested.

Child, Preschool↗

PubMed2005

Direct evidence for mutual interactions between perineuronal astrocytes and interneurons in the CA1 region of the rat hippocampus.

Recent studies have demonstrated that astrocytes express a variety of ion channels and neurotransmitter receptors and can modulate the activity of neurons. Since a single astrocyte makes tight contacts with many neighboring neuronal cells, they can provide efficient and wide modulation of neuronal networks. Here, we provide direct evidence for mutual interactions between perineuronal astrocytes and interneurons in the stratum radiatum of the rat hippocampus. Direct depolarization of a perineuronal astrocyte suppressed the excitatory postsynaptic currents in an adjacent interneuron and increased the paired-pulse ratio, indicating that perineuronal astrocytes have a suppressive effect on presynaptic elements. Moreover, perineuronal astrocyte activation modulated the directly induced firing pattern of the interneuron, with initial facilitation and subsequent suppression. Conversely, direct firing of the interneuron depolarized the membrane potential and reduced the input resistance of the perineuronal astrocyte. These results directly demonstrate the existence of bidirectional interactions between neurons and perineuronal astrocytes.

4-Aminopyridine↗

PubMed2005

Influence of prostaglandin F2alpha and its analogues on hair regrowth and follicular melanogenesis in a murine model.

Latanoprost and isopropyl unoprostone, which are analogues of prostaglandin F2alpha (PGF2alpha), are promising drugs for the reduction of intra-ocular pressure. However, they have been reported to have side effects, including hypertrichosis and hyperpigmentation of the eyelashes and periocular skin, and occasionally poliosis. In order to investigate these effects further, PGF2alpha, latanoprost and isopropyl unoprostone were applied to the dorsal skin of 7-week-old C57BL/6 mice, and hair length was measured during the treatment. The three molecules all showed stimulatory effects on the murine hair follicles and the follicular melanocytes in both the telogen and anagen stages, and stimulated conversion from the telogen to the anagen phase. PGE2 is known to act synergistically with PGF2alpha, and hence the influence of PGE2 was also examined. PGE2 did not induce distinct telogen-to-anagen conversion, but showed moderate growth stimulatory effects on early anagen hair follicles. In addition, we observed a case of hypertrichosis and trichomegaly with an excess of melanogenesis, leading to the emergence of white hair, suggesting that poliosis can occur as a side effect of eye treatment with solutions of PGF2alpha analogues. The stimulatory effects of PGF2alpha and PGE2 on hair growth have been discussed with regard to the role of protein kinase C and mast cells.

Animals↗

PubMed2002

Genotype-phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1.

We report a 42-year-old Japanese man with an unusual autosomal recessive genodermatosis. The clinical features comprised normal skin at birth, loss of scalp hair at 3-months of age after a febrile illness, progressive nail dystrophy during infancy, palmoplantar keratoderma starting around the age of 18 years and trauma-induced skin fragility and blisters noted from the age of 20 years. Skin biopsy of rubbed non-lesional skin revealed widening of spaces between adjacent keratinocytes from the suprabasal layer upwards. Electron microscopy demonstrated a reduced number of hypoplastic desmosomes. Immunohistochemical labeling showed a reduction in intercellular staining for the desmosome component plakophilin 1. Mutation analysis revealed a homozygous intron 11 donor splice site mutation in the plakophilin 1 gene, 2021+1 G>A (GenBank no. Z34974). RT-PCR, using RNA extracted from the skin biopsy, provided evidence for residual low levels of the full-length wild-type transcript (approximately 8%) as well as multiple other near full-length transcripts, one of which was in frame leading to deletion of 17 amino acids from the 9th arm-repeat unit of the plakophilin 1 tail domain. Thus, the molecular findings help explain the clinical features in the patient, who has a similar but milder phenotype to previously reported patients with skin fragility-ectodermal dysplasia syndrome associated with complete ablation of plakophilin 1 (OMIM 604536). This new 'mitis' phenotype provides further clinicopathological evidence for the role of plakophilin 1 in keratinocyte cell-cell adhesion and ectodermal development.

Adult↗

PubMed2000

Comparative inhibitory effects of vitamin D3 and an analogue on normal and psoriatic epidermis in organ culture.

Recently, there have been many vitamin D3 analogues synthesized and tried in the treatment of psoriasis. In the experiments reported here we observed and compared their effects on normal and psoriatic epidermis in organ culture in vitro. We employed a new vitamin D3 analogue, 22-oxa-calcitriol (OCT), the effect of which was compared with that of calcitriol (1,25-D3). Both caused suppression of proliferation of normal and psoriatic epidermis, dependent upon concentration and culture time. Histologically, in the presence of the agents, degeneration started from the top of the epidermis downwards. This is the first report of cell degeneration as a direct effect of vitamin D. The nature of the degeneration was evaluated by electron microscopy (EM) and by the in situ nick end labeling technique (TUNEL), and these studies revealed that the degeneration involved necrosis rather than apoptosis. This in vitro method may be useful to assess the effectiveness of newly synthesized vitamin D3 analogues in the treatment of psoriasis.

Apoptosis↗

PubMed2000

C2-ceramide induces apoptosis in a human squamous cell carcinoma cell line.

BACKGROUND: Previous studies have demonstrated that synthetic cell-permeable analogues of ceramide promote differentiation and inhibit proliferation of keratinocytes, and that the vitamin D3 inducible sphingomyelin cycle generates ceramide in keratinocytes. Although it has been suggested that exogenous ceramide induces apoptosis of keratinocytes, which is similar to their effect on other cell types, such as leukaemia cells, only a few studies have reported ceramide-induced apoptosis of keratinocytes. OBJECTIVE: To determine whether ceramide induces apoptosis of keratinocytes, we used the synthetic ceramide analogue, C2-ceramide (N-acetylsphingosine) and a human squamous cell carcinoma cell line, HSC-I. METHODS: We treated HSC-I cells with C2-ceramide, followed by a viability assay, morphological observations, nick end-labelling (TUNEL), DNA electrophoresis, and electron microscopy. RESULTS: In the viability assay, C2-ceramide was toxic to HSC-I cells in a dose-dependent manner. Manifestations of apoptotic morphology occurred in the ceramide-treated cells, whereas these morphological changes did not occur in cells treated with dihydroceramide (N-acetylsphinganine). TUNEL revealed that many of the ceramide-treated cells showed positive reactivity. DNA electrophoresis demonstrated that C2-ceramide caused internucleosomal fragmentation in a dose- and time-dependent manner. Electron microscopy revealed that the ceramide-treated cells manifested morphological characteristics typical of apoptosis. CONCLUSIONS: The present results demonstrate that C2-ceramide induces apoptosis of transformed human keratinocytes, whereas C2-dihydroceramide does not have such an effect. The fact that ceramide induces apoptosis of keratinocyctes raises the possibility that intracellular ceramide, which is increased with differentiation of the epidermis, might be involved in terminal differentiation, a specialized form of apoptosis of keratinocytes.

Apoptosis↗

PubMed2000

E-cadherin expression in skin tumors using an AMeX immunohistostaining method.

The AMeX (acetone-methylbenzoate-xylene) method results in good preservation of tissue and morphological details, almost equivalent to that of routinely processed formalin-fixed and paraffin-embedded tissue specimens, and of antigenicity equivalent to that of fresh frozen tissue specimens. It has been reported that the expression of the cell-cell adhesion molecule E-cadherin is often decreased in some types of carcinomas. A decrease in E-cadherin expression is associated with the invasive or metastatic potential of tumor cells. We immunohistochemically examined the expression of E-cadherin with anti-E-cadherin monoclonal antibody in various skin tumors (25 basal cell carcinomas, 11 squamous cell carcinomas, 9 keratoacanthomas, and 11 Bowen's disease) using the AMeX method and found that this method preserved antigenicity well without pretreatment. E-cadherin expression was decreased in 18.2% of squamous cell carcinomas and 33.3% of keratoacanthomas. On the other hand, it was preserved in almost all Bowen's disease and basal cell carcinomas. From the results of our study, we suggest that Bowen's disease and basal cell carcinoma do not have much metastatic potential due to retention of high levels of E-cadherin expression. We hope to apply the AMeX method to other immunohistochemical examinations because this is a very useful staining method.

Acetone↗

PubMed2000

Tamoxifen inhibits lipoprotein activity: in vivo and in vitro studies.

Tamoxifen, a nonsteroidal antiestrogenic antitumor agent, has weak estrogen-like effects on lipid metabolism, however, the mechanism remains unknown. We previously reported that tamoxifen decreases the activity of lipoprotein lipase (LPL), a key enzyme in triglyceride metabolism, in patients with breast cancer. This study evaluated the effect of tamoxifen on LPL activity in vitro and in vivo. In experiment 1, total cholesterol, triglyceride, adipose tissue weight, and LPL activity of post-heparin plasma were measured in ovariectomized female rats with and without tamoxifen treatment. In experiment 2, purified very-low-density lipoprotein (VLDL) and purified LPL were incubated with and without tamoxifen or estrogen, and the triglycerides in VLDL were measured using an enzymatic method. In experiment 1, total cholesterol and adipose tissue weight decreased significantly in tamoxifen-treated rats (p < 0.001 and p < 0.01, respectively). Triglyceride measurements were not significantly different between the two groups, however, the LPL activity was lower in tamoxifen-treated rats (p < 0.005). In experiment 2, triglycerides in VLDL were significantly higher after VLDL and LPL were incubated with tamoxifen and estrogen (p < 0.005). We concluded that tamoxifen inhibits the hydrolytic activity of LPL in vivo and in vitro. This mechanism may explain the elevated serum triglyceride levels in some patients treated with tamoxifen.

Animals↗

PubMed2000

In vitro study of the effect of raloxifene on lipid metabolism compared with tamoxifen.

OBJECTIVE: Tamoxifen and raloxifene, selective estrogen receptor modulators, decrease serum concentrations of total cholesterol; however, the effect of these drugs on triglyceride metabolism is unclear. In the present study, we investigated the in vitro effect of raloxifene on lipid metabolism and compared it with that of tamoxifen. DESIGN AND METHODS: Intracellular concentrations of total cholesterol and triglyceride in HepG2 cells were measured by an enzymatic method after tamoxifen or raloxifene treatment with or without oleic acid and with or without very low density lipoprotein. RESULTS: Intracellular concentrations of total cholesterol and triglyceride without oleic acid or very low density lipoprotein were not significantly different after treatment with tamoxifen or raloxifene. In contrast, although raloxifene with oleic acid did not increase the intracellular concentrations of triglyceride, tamoxifen treatment in the presence of oleic acid or very low density lipoprotein significantly increased (P<0.05) the triglyceride concentrations. CONCLUSION: The present study suggests that raloxifene does not increase intracellular triglyceride in the presence of oleic acid or very low density lipoprotein, in contrast to tamoxifen. Therefore, raloxifene might be safer than tamoxifen for treating patients with unstable triglyceride levels or a history of hypertriglyceridemia.

Antineoplastic Agents, Hormonal↗

PubMed1999

Immunotherapy for experimental rat autoimmune thyroiditis using a novel immunosuppressant, FTY720.

While autoimmune disease needs to be continuously treated via long term, administration of immunosuppressants conventional immunotherapy using drugs such as cyclosporin and tacrolimus may cause adverse effects. Recently, a novel agent, FTY720, which was structurally modified from a natural product, has been shown to have a moderate and different immunosuppressive effect from conventional drugs. In this study, we examined the effect of FTY720 on experimental autoimmune thyroiditis (EAT), which was induced in rats by neonatal thymectomy, followed by subsequent sublethal irradiation. Thyroid stimulating hormone (TSH) was measured before and at the end of drug therapy. Histological and hematological examinations were performed using the samples from sacrificed animals. High TSH levels in the animals returned to the normal range following treatment with FTY720. The severity of the thyroiditis was lower in the FTY720 group than in the control group. FTY720 markedly decreased the number of circulatory lymphocytes, and no infections episodes were observed under this treatment. Thus, FTY720 treatment might be preferred for continuous immunotherapy for autoimmune disease without adverse effects.

Animals↗

PubMed1999

An immunohistochemical study of E-cadherin expression in human squamous cell carcinoma of the skin: relationship between decreased expression of E-cadherin in the primary lesion and regional lymph node metastasis.

E-cadherin is a Ca(2+)-dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and is essential for maintaining intercellular connections. It has been reported that E-cadherin expression of tumor cells is often decreased in some types of metastasizing carcinomas as compared with those without metastasis. We immunohistochemically examined the expression of E-cadherin with anti-E-cadherin monoclonal antibody and compared primary lesions of human squamous cell carcinoma of the skin (SCC) with regional lymph node metastasis to those without regional lymph node metastasis. Tumor samples from fifty-five cases of SCC (32 cases of SCC without metastasis and 23 cases with metastasis) were formalin-fixed, paraffin-embedded, and examined. E-cadherin was reduced or absent in 39 (70.9%) out of 55 cases of SCC, and in 21 (91.3%) of 23 cases with regional lymph node metastasis. Our results suggest that the decreased expression of E-cadherin in the primary lesion is correlated with regional lymph node metastasis in SCC and that it is more frequently correlated with well-differentiated than with poorly differentiated SCC. E-cadherin may be useful as a marker for metastatic potential in well-differentiated SCC.

3,3'-Diaminobenzidine↗

PubMed1998

Changes in immune-endocrine response after surgery.

The authors evaluated the relationship between hormonal and cytokine responses after surgery. Patients who underwent thoracic oesophagectomy (O group; n = 7), pulmonary lobectomy (P group; n = 5), modified mastectomy (M group; n = 5) and laparoscopic cholecystectomy (LC group; n = 7), were randomly selected. Circulating neutrophil and lymphocyte numbers were assayed. Changes in the concentration of the hormones [adrenocorticotrophic hormone (ACTH), cortisol, and antidiuretic hormone (ADH)] and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, and IL-10] were analysed. In O and P groups, neutrophils were still seen on post-operative day (POD) 3, while the leukocyte counts of M and LC groups returned to normal. The number of lymphocytes significantly decreased on POD1 and POD3 only after oesophagectomy. The pattern of hormonal levels was consistent in all groups. While TNF-alpha and IL-1 beta were undetectable in the peripheral blood, the concentration of IL-6 and IL-10 increased in O and P groups, but not in M and LC groups. The degree of lymphocytepenia and neutrophilia correlated well with the extent of surgical trauma.

Adrenocorticotropic Hormone↗

PubMed1998

1alpha,24-dihydroxyvitamin D3 (tacalcitol) is effective against Hailey-Hailey disease both in vivo and in vitro.

We report a case of Hailey-Hailey disease (HHD) in which 1alpha, 24-dihydroxyvitamin D3 (tacalcitol) was effective both clinically (in vivo) and in explant cultures (in vitro) of a skin lesion. The patient was a 65-year-old man with HHD lesions in the axillary and inguinal areas bilaterally. We applied ointment containing 1alpha, 24-dihydroxyvitamin D3 (tacalcitol), an analogue of active vitamin D3, to the lesions and assessed its clinical effectiveness. The HHD lesions in both groins disappeared after treatment with the 1alpha, 24-dihydroxyvitamin D3 ointment, and the remission has continued to the present. A punch biopsy specimen of the lesion that had remitted showed no acantholysis. In addition, dissociation of migrating keratinocytes was observed when biopsy specimens of the HHD skin lesion were cultured in medium without 1alpha,24-dihydroxyvitamin D3, but inhibition of keratinocyte dissociation was observed in medium containing it. These results suggest the effectiveness of 1alpha, 24-dihydroxyvitamin D3 against HHD both in vivo and in vitro.

Aged↗

PubMed1998

A case of infantile digital fibromatosis with spontaneous regression.

We reported a fourteen-month-old boy with infantile digital fibromatosis. At the age of seven months, a nodule appeared on the back of the left third toe, and developed into a slight red tumor divided into five hemispherical nodules. Histopathologically, spindle-shaped tumor cells with an eosinophilic inclusion body in the cytoplasm were seen in the dermis. Electron microscopy showed a dense body in the cytoplasm of the tumor cells. One year and two months after the first visit, the tumor regressed without any aggressive treatment. Japanese cases of infantile digital fibromatosis were reviewed. The literature review and our case suggest that the tumor should be observed without any aggressive treatment unless it causes mobile dysfunction of the affected finger or toe.

Diagnosis, Differential↗

PubMed1998

Effect of tamoxifen on serum lipid metabolism.

The effect of tamoxifen, an antiestrogenic agent, on lipid metabolism was studied in postmenopausal patients with breast cancer who received the drug for postoperative adjuvant treatment following mastectomy. To measure total cholesterol and triglyceride concentrations, fasting blood samples were collected before and 2 months after the initiation of tamoxifen therapy from 16 patients who satisfied the study criteria. All patients were normolipidemic before tamoxifen was administered. Control samples were obtained from hypertriglyceridemia patients who were free from breast cancer. Marked hypertriglyceridemia was observed in 3 of 16 patients after tamoxifen treatment. The activity of lipoprotein lipase and hepatic triglyceride lipase, the key enzymes of triglyceride metabolism, decreased significantly in all of 16 patients as a result of tamoxifen treatment (P = 0.008 and P = 0.007, respectively). However, the mean mass of lipoprotein lipase significantly increased (P = 0.011) after tamoxifen treatment. We therefore conclude that tamoxifen might increase inactive lipoprotein lipase. Because marked hyperlipidemia is a potent risk factor for life-threatening acute pancreatitis and arteriosclerosis, plasma lipid levels should be tested periodically during tamoxifen treatment, even if the patients are normolipidemic during the pretreatment stage.

Breast Neoplasms↗

PubMed1998

Relation between apolipoprotein e phenotype and the changes in lipids during tamoxifen treatment.

We recently reported three cases of severe hypertriglyceridemia caused by tamoxifen-treatment after breast cancer surgery. In that report we showed that one of the three patients had apo E3/3 and another had E4/2 phenotype. There are few data about the relationship between apoprotein E phenotype, one of modifiers of lipoprotein metabolism, and tamoxifen induced lipemia. In the present study, we studied apo E phenotype to clarify the relationship between apo E phenotype and the changes in lipids during tamoxifen treatment. Plasma triglyceride levels in apo E3/3 and apo E4/3 were 114 +/- 9 mg/dl and 87 +/- 12 mg/dl, respectively, before tamoxifen treatment, and increased significantly to 191 +/- 35 mg/dl in apo E3/3 and 167 +/- 35 mg/dl in apo E4/3 during tamoxifen treatment. There was no significant difference between apo E3/3 and apo E4/3 in triglyceride levels before and during tamoxifen treatment. Plasma levels of total cholesterol during tamoxifen treatment in both apo E3/3 and apo E4/3 were similar to those before treatment. Our data suggest that the increase in triglyceride during tamoxifen treatment may occur in every type of apo E phenotype.

Aged↗

PubMed1997

Severe hypertriglyceridemia caused by tamoxifen-treatment after breast cancer surgery.

Tamoxifen, a nonsteroidal estrogen antagonist, has been widely used in a hormonal treatment for breast cancer. The side effects of tamoxifen are generally recognized to be mild. However, we experienced three cases of severe hypertriglyceridemia and/or hyperglycemia induced by tamoxifen. For normalization of their hypertriglyceridemia we need to stop giving tamoxifen. In one of three cases we analyzed her lipoprotein profile in detail with lipoprotein lipase activities and apolipoprotein E phenotype. The case was a 49 year-old woman. After 15 months of tamoxifen administration, she was diagnosed as severe hypertriglyceridemia. Consecutively, severe hyperglycemia was occurred to need insulin therapy. After tamoxifen withdrawal, her triglyceride and glucose levels improved. Her lipolytic enzyme was reduced during tamoxifen treatment. Apolipoprotein E phenotype was uncommon E4/2. Although hypertriglyceridemia was not considered to be a risk factor for coronary heart disease, a marked hypertriglyceridemia might occasionally produce severe lethal pancreatitis. We recommend that a periodic plasma lipid analysis is needed for patients treated with tamoxifen, especially for diabetic and hypertriglyceridemic patients, to avoid such complications.

Antineoplastic Agents, Hormonal↗

PubMed1996

Identification of K1/K10 and K5/K14 keratin pairs in human melanoma cell lines.

Keratin expression in cultured malignant melanoma cells has been studied only rarely. Moreover, no studies have reported of universality of keratin expression in human malignant melanoma cells. In this study, therefore, we analyzed keratin expression in eight cell lines. Using a low-salt aqueous solution without high salt and Triton X-100, as a washing buffer for keratin extraction, followed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and immunological analysis, we demonstrated keratin expression in all eight human malignant melanoma cell lines. The keratin polypeptide expressions common to all melanoma cells were K1, K5, K10 and K14. In addition, K8, K13, K17 and K18, respectively, were detected in individual cells. A measure of keratin expression universality in malignant melanoma cells may have implications regarding their invasive and metastatic behaviors, co-expressed with vimentin.

Electrophoresis, Gel, Two-Dimensional↗