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Biomedical subjects

S Iizuka

Publications and source records attributed to S Iizuka.

At least 19 recordsLinked to original sources

Effects of endogenous and exogenous prostaglandin E2 on the proliferation and differentiation of a mouse cementoblast cell line (OCCM-30).

BACKGROUND: Cementum formation is considered to be a critical event for successful regeneration of periodontal tissues. Cementoblasts share many characteristics with osteoblasts. Prostaglandin E(2) (PGE(2)) is an important local factor in bone metabolism. Although the effects of PGE(2) on osteoblasts are well known, its effects on cementoblasts have not yet been established. We examined the effects of PGE(2) on proliferation and differentiation in a mouse cementoblast cell line, OCCM-30 cells. METHODS: OCCM-30 cells were treated with three concentrations of PGE(2) (10, 100, and 1,000 ng/ml). Cell number, alkaline phosphatase (ALP) activity, and expression for mineralization-related genes were determined. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL) expression were also examined by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The addition of PGE(2) at the highest dose used in this study suppressed cell proliferation of OCCM-30 cells. The expression of mineralization-related marker mRNA, such as type 1 collagen, ALP, bone sialoprotein (BSP), and osteocalcin (OCN), was constitutively detected in OCCM-30 cells. PGE(2) dose dependently stimulated ALP activity and BSP-mRNA expression in OCCM-30 cells at day 3. Transcripts for OPG and RANKL and the protein level of OPG in culture media were upregulated with PGE(2) stimulation. CONCLUSION: These results demonstrate that PGE(2) suppressed cementoblast proliferation but stimulated ALP activity and the BSP-mRNA level, suggesting a role of PGE(2) in controlling cementoblast differentiation, and further indicate that PGE(2) modulates RANKL and OPG expression in cementoblasts; the increase of OPG secreted from cementoblasts with PGE(2) stimulation may be essential to protect the root surface from resorption.

Alkaline Phosphatase↗

Brain transplantation of genetically modified bone marrow stromal cells corrects CNS pathology and cognitive function in MPS VII mice.

Current therapies for lysosomal storage diseases (LSDs), enzyme replacement therapy and bone marrow transplantation are effective for visceral organ pathology of LSD, but their effectiveness for brain involvement in LSDs is still a subject of controversy. As an alternative approach, we transplanted genetically modified bone marrow stromal (BMS) cells to lateral ventricle of newborn mucopolysaccharidosis VII (MPS VII) mice. MPS VII is one of LSDs and caused by deficiency of beta-glucuronidase (GUSB), resulting in accumulation of glycosaminoglycans (GAGs) in brain. At 2 weeks after transplantation, the GUSB enzyme-positive cells were identified in olfactory bulb, striatum and cerebral cortex, and the enzymatic activities in various brain areas increased. The GAGs contents in brain were reduced to near normal level at 4 weeks after transplantation. Although GUSB activity declined to homozygous level after 8 weeks, the reduction of GAGs persisted for 16 weeks. Microscopic examination indicated that the lysosomal distention was not found in treated animal brain. Cognitive function in MPS VII animals as evaluated by Morris Water Maze test in treated mice showed a marked improvement over nontreated animals. Brain transplantation of genetically modified BMS cells appears to be a promising approach to treat diffuse CNS involvement of LSDs.

Animals↗

A Case of Tuberculous Uveitis Complicated by Myelodysplastic Syndrome.

Background: Recently, the incidence of tuberculosis in compromised hosts has increased.Case: A 52-year-old man suffering from myelodysplastic syndrome (MDS) had pulmonary tuberculosis. On June 22, 1996, we found a disc-sized choroidal lesion with milky appearance on the paramacular in his right eye. After 1 month, a similar choroidal lesion was found near the disc in the same eye. In spite of chemotherapy for MDS and antituberculosis medications, those choroidal lesions gradually enlarged. In November, satellite lesions were found around them. Some retinal exudates and hemorrhage were also detected in both eyes. He died on April 6, 1997. We found Langhan's giant cells in the choroid on the specimen of his eyes. So we judged the choroidal lesions to be tuberculous uveitis.Conclusion: This case showed choroidal tuberculosis and choroidal miliary tuberculosis in the same eye that were resistant to medications. We thought resistance to medication was due to destruction of the immune system by MDS.

Journal Article↗

Possible mechanisms underlying mammary carcinogenesis in female Wistar rats by nitrofurazone.

Mechanisms underlying mammary carcinogenesis in female rat given nitrofurazone (NF) were examined. Experiment I: female Wistar rats were divided into three groups, and given diets containing 0, 500 or 1000 ppm NF for 5 weeks. At terminal sacrifice, body and uterus weights were the same in all groups, although ovary weights in NF-treated animals were significantly higher than in control animals, the increase being dose-dependent. Serum prolactin (PRL) concentrations in NF-treated groups at 17:00 h on the day of proestrus were also dose-dependently higher than that in control group. Experiment II: a two-stage rat mammary carcinogenesis protocol was performed. Rats were divided into four groups, Groups 2 and 4 being treated by 9,10-dimethyl-1,2-benzanthracene (DMBA) at 7-weeks-old. Groups 3 and 4 were given diets containing 1000 ppm of NF between 8 and 27 weeks of age, when all surviving rats were autopsied. DMBA-treated animals demonstrated mammary tumors at high incidences, 91.1 and 90.5%, respectively, in Groups 2 and 4, no tumor development being observed without the initial carcinogen exposure (Groups 1 and 3). The mean tumor weights and the mean numbers of tumors per tumor-bearing rats in Group 4 were increased as compared with Group 2, albeit not significantly. Serum PRL (proestrus day at 17:00 h) and progesterone (PG) (diestrus day at 10:00 h) concentrations in NF-treated animals (Groups 3 and 4) were significantly higher than those in untreated rats (Groups 1 and 2). These results suggest that increases of serum PRL and PG concentrations by NF may be the most important factors regarding its promotion of mammary tumor growth and/or enhancement of mammary carcinogenesis in female rats.

9,10-Dimethyl-1,2-benzanthracene↗

Reduction of lysosomal storage in murine mucopolysaccharidosis type VII by transplantation of normal and genetically modified macrophages.

This study examined the ability of macrophages to serve as target cells of gene therapy for mucopolysaccharidosis (MPS) type VII using a murine model. Bone marrow cells were harvested from syngeneic normal mice and differentiated to macrophages. These cells were given to nonmyeloablated MPS VII mice. After transplantation, donor cells populated the liver and spleen. The pathologic improvement at day 38 after transplantation was significant and glycosaminoglycan storage was reduced. To develop gene therapy using this system, a retroviral vector expressing human beta-glucuronidase (HBG) was used to infect macrophages cultivated from MPS VII mice and given to nonmyeloablated MPS VII mice. At 38 days after transplantation, HBG-positive cells were still observed histochemically and pathologic improvement was significant. These observations suggest that macrophage transplantation is a promising method for treatment of murine MPS VII without myeloablation, and macrophages may be good target cells for ex vivo gene therapy for MPS VII.

Animals↗

Hemophagocytosis by leukemic blasts in 7 acute myeloid leukemia cases with t(16;21)(p11;q22): common morphologic characteristics for this type of leukemia.

BACKGROUND: In a previous study of a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22), which displayed hemophagocytosis by leukemic blasts, the authors mentioned that the same type of morphology had been cited in the literature for 4 other cases of acute myeloid leukemia (AML) with the same translocation. This observation prompted the authors to examine more cases of AML with t(16;21)(p11;q22) for this morphology. METHODS: The authors reviewed bone marrow smears for the presence of hemophagocytosis in 7 patients with AML identified as having t(16;21)(p11;q22). RESULTS: The leukemias belonged to the FAB-M1/M7 (n = 5), M5b (n = 2), and contained phagocytic blasts in various percentages (< 0.2-36.7%). The blasts contained either single or multiple cytoplasmic vacuoles, in some of which the phagosomes were visible. The engulfed hemopoietic cells (red cells, erythroblasts, lymphocytes, and thrombocytes) were also noted in their cytoplasm. These observations confirmed that hemophagocytosis by leukemic blasts is a common and characteristic feature of this type of leukemia. CONCLUSIONS: The study of 12 cases (the 7 cases described here and the previous 5 cases) strongly supports the hypothesis that hemophagocytosis by leukemic blasts is common and characteristic in this type of leukemia, which may be related to the specific chromosome aberration of t(16;21)(p11;q22).

Adolescent↗

[A case of tuberculous uveitis complicated by myelodysplastic syndrome].

BACKGROUND: Recently, the incidence of tuberculosis in compromised hosts has increased. CASE: A 52-year-old man suffering from myelodysplastic syndrome (MDS) had pulmonary tuberculosis. On June 22, 1996, we found a disc-sized choroidal lesion with milky appearance on the paramacular in his right eye. After 1 month, a similar choroidal lesion was found near the disc in the same eye. In spite of chemotherapy for MDS and antituberculosis medications, those choroidal lesions gradually enlarged. In November, satellite lesions were found around them. Some retinal exudates and hemorrhage were also detected in both eyes. He died on April 6, 1997. We found Langhans' giant cells in the choroid on the specimen of his eyes. So we judged the choroidal lesions to be tuberculous uveitis. CONCLUSION: This case showed choroidal tuberculosis and choroidal miliary tuberculosis in the same eye that were resistant to medications. We thought resistance to medication was due to destruction of the immune system by MDS.

Choroid Diseases↗

Reminiscence therapy using odor in alcohol-dependent patients--psychophysiological evaluation and psychological evaluation; power spectral analysis of heart rate variability.

OBJECTIVE: This research was based on the hypothesis that when alcohol-dependent patients describe themselves, awakening of emotion by affirmative odor stimulation may facilitate memory reframing focusing on more affirmative emotion and memories. To prove the hypothesis, physiological changes accompanied by emotional awakening were evaluated by measuring the autonomic activity. In addition, subjective evaluation by a self-report manner was examined to investigate the effectiveness of Reminiscence Therapy (RT) using odor in alcohol-dependent patients. SUBJECTS: Thirty-four patients who met the DSM-IV criteria of alcohol-related disorders and were hospitalized in a ward specialized to alcohol dependence therapy. METHODS: Each patient underwent a one-to-one interview twice. For counterbalance, one interview was performed with odor stimulation using an odor with a relaxing effect that recall pleasant emotion, and the other was without odor stimulation. As the evaluation indices of physiological changes accompanied by emotional awakening, index of autonomic function (HRV; Heart rate variability) for objective evaluation and psychological indices (STAI; State-Trait Anxiety Inventory VAS; Visual Analog Scale) for subjective evaluation were measured. RESULTS: 1) Objective evaluation: Regarding the evaluation index of the autonomic function, the sympathetic nervous system activity (LF/HF; low frequency component/high frequency component ratio) was significantly inhibited by odor stimulation (p < 0.05). 2) Subjective evaluation: Compared to the state prior to interview, state anxiety judged by STAI was significantly decreased after interview (p < 0.01). The VAS score was significantly decreased after interview regardless of the presence or absence of odor stimulation (p < 0.0001). CONCLUSIONS: A reduction in state anxiety was observed. The effect of odor was not significant on the subjective evaluation, but the objective evaluation suggested that the odor inhibited the sympathetic nervous system. Thus, it was suggested that odor can be used in RT, that is, emotional changes due to stimulation of odor may be applicable in RT.

Adult↗

Effects of humid heat exposure on human sleep stages and body temperature.

The objective of this study was to confirm the effect of humid heat exposure on sleep stages and body temperature. Seven healthy male volunteers with a mean age of 22.7+/-1.63, served as the subjects. The experiments were carried out under four different conditions of room temperature and relative humidity: 29 degrees C RH 50% (29/50), 29 degrees C RH 75% (29/75), 35 degrees C RH 50% (35/50), and 35 degrees C RH 75% (35/75). The subjects wearing only shorts slept from 23:00 to 7:00 on a bed, which was covered with a 100% cotton sheet. EEG, EOG, and mental EMG were recorded through the night. Rectal temperature (Tr) and skin temperature were measured continuously. The 35/75 condition caused more wake and a lower sleep efficiency index (SEI) and stage S3+S4 than 29/50 and 29/75. Stage REM and stage 3 were significantly decreased at 35/75 than at 29/50 and 35/50. Tr was maintained at a higher level at 35/75 than under the other conditions. Mean skin temperature was higher at 35/50 and 35/75 than at 29/50 and 29/75. These results suggest that humid heat exposure during night sleep increases the thermal load to supress the sleep-evoked Tr decrease, stage 3, SWS, and REM, and increase wakefulness.

Adult↗

Release of zinc from the brain of El (epilepsy) mice during seizure induction.

Brain distribution after i.v. injection of 65ZnCl2 into El mice, an animal model of genetically determined epilepsy, was studied by autoradiography to study the utilization of zinc in the brain. The distribution of 65Zn in the brain of El mice 6 days after injection was almost the same as that of ddY (normal) mice, suggesting that the uptake of zinc by the brain of El mice is normal. To study the movement of zinc in the brain in the course of seizure induction, the concentrations of 65Zn in the brain of seizure-afflicted and untreated control El mice were compared 20 days after 65Zn injection. The concentration of 65Zn in the brain of seized El mice was overall lower than that of control El mice; the concentration of 65Zn was decreased notably in the piriform cortex and amygdaloid nuclei complex during convulsion. These results suggest that the release of zinc from the El mouse brain is enhanced during convulsion. The decrease in actively functioning zinc in the brain may be associated with the increase in susceptibility to seizure in the El mouse.

Animals↗

Pigmented squamous cell carcinoma with dendritic melanocyte colonization in the external auditory canal.

A case of pigmented squamous cell carcinoma (SCC) with dendritic melanocyte colonization in the external auditory canal is reported and the previous cases are reviewed. A 65-year-old Japanese female was referred with a 7-year history of otitis. The patient also had a darkly pigmented 9 x 8 mm nodule in the external auditory canal. Microscopically, the tumor was SCC, but in some areas melanin pigments were found in the cytoplasm of the tumor cells. The tumor was thus diagnosed as pigmented SCC. As well as the tumor cells, dendritic-shaped cells colonized the tumor parenchyma and were immunohistochemically defined as melanocytes. The authors believe this is the first case of pigmented SCC with dendritic melanocyte colonization in the external auditory canal.

Aged↗

A new mouse model of spontaneous diabetes derived from ddY strain.

By the selective breeding of obese male mice of the ddY strain and using indices of the heavy body weight and appearance of urinary glucose, we established two inbred strains in 1992: one with obesity and urinary glucose (Tsumura, Suzuki, Obese Diabetes: TSOD) and the other without them (Tsumura, Suzuki, Non Obesity: TSNO). The male TSOD mice constantly showed signs of obesity and urinary glucose with increases in food and water intake, body weight and some fat weight. The body mass index (BMI) clearly showed moderate obesity. Increases in the levels of diabetic blood parameters (glucose, insulin and lipids) were also found in males, in which the levels of blood glucose and insulin were high to the ages past the growth peak. In the histological studies, pancreatic islets of the TSOD males were found hypertrophic without any signs of insulitis or fibrous formation. Among these diabetic characteristics, some of which were similar to the reported models of non-insulin-dependent diabetes mellitus (NIDDM), the stable appearances of the hyperglycemia, the hyperinsulinemia and the hypertrophy of pancreatic islets to the ages past the growth peak were the prominent features. In these respect the TSOD mouse may be a useful model for researching the mechanisms of human diabetes and its complications.

Animals↗

Short-term longitudinal changes in subcutaneous fat distribution and body size among Japanese women in the third decade of life.

This research clarified the changes in body shape among Japanese women aged in their 20's, by measuring the subcutaneous fat distribution over the whole body and its circumference at certain points. The subjects, 13 healthy women, were measured twice, once in their early 20's and 5 years later in their late 20's. Subcutaneous fat thickness was measured at 14 points on the body using the B-mode ultrasound method and the body size was measured directly at 8 points on the body using a steel measure. Subcutaneous fat thickness tends to increase with age, except at the cheek, neck, bust and leg. Significant increases were detected especially at lower parts of the trunk such as the waist and infragluteal region. Meanwhile, despite the significant change in subcutaneous fat thickness, the circumferences measured did not change, and also weight tended to decrease with age. Based on this finding, except for fat, body mass, such as muscle and bone, decreases with age due to decreased exercise and changes in calorie intake. Cluster analysis of the accumulation patterns of subcutaneous fat indicated that there were the following 3 patterns of subcutaneous fat accumulation from the early 20's to the late 20's. I. Accumulation on the whole trunk (bust, abdomen, waist and back) and upper arm--trunk/upper arm accumulation pattern. II. Significant accumulation around waist--waist accumulation pattern. III. Even accumulation at abdomen, side abdomen, hip and lower hip--abdomen/hip accumulation pattern.

Adipose Tissue↗

Analysis of thoracic duct flow waves using fast Fourier transform in sheep.

We measured the lymph flow of the thoracic duct using an ultrasound transit-time flowmeter and then analyzed the obtained flow signals by fast Fourier transform. We found that the wave form included a low frequency component (approximately 0.1 Hz) as well as high frequency components which represented cordiac pulsation and respiratory movement. The low frequency component signified an intrinsic thoracic duct pulsation. When venous outflow pressure was increased, the frequency of the thoracic duct pulsation increased, whereas the frequencies of cardiac pulsation and respiratory movement were unchanged. These findings suggest that thoracic duct pulsation is independent of cardiac pulsation and respiratory movement.

Animals↗

Efficient and persistent expression of beta-glucuronidase gene in CD34+ cells from human umbilical cord blood by retroviral vector.

We succeeded in efficiently transferring the beta-glucuronidase gene in a retroviral vector to human hematopoietic progenitor cells using a centrifugation enhancement protocol. The transduction efficiency in CFU-GM was highly variable (23-100%) with an average of 66.8%. In the case of BFU-E, efficiency was 83% and 76% in 2 separate experiments. In LTCIC (long-term culture-initiating cell), transduction efficiency were 20% and 50% in 2 experiments. The enzymatic activity of beta-glucuronidase in transduced cells were increased above the control level up to 5 wk. Considering that correction of the enzyme deficiency in a small number of hematopoietic cells can be therapeutic for the Sly disease mouse, our data provide encouragement that human trials of gene therapy based on transferring beta-glucuronidase gene to hematopoietic cells may be efficacious.

Animals↗