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Biomedical subjects

M Ito

Publications and source records attributed to M Ito.

At least 523 records · Page 29Linked to original sources

Histologic and cell kinetic studies of hair loss and subsequent recovery process of human scalp hair follicles grafted onto severe combined immunodeficient mice.

To establish a model for studying human scalp hair, individually isolated hair follicles were grafted onto back skin of severe combined immunodeficient mice. Histologic changes and cell kinetics in the hair loss and subsequent recovery process were investigated. In the dystrophic stage (from day 7 to 30), all the hair shafts became dystrophic and were shed. Thickening and corrugation of vitreous membrane, apoptosis, and regression of the lower part were observed in the grafted hair follicles. 5-bromo-2'-deoxy-uridine-labeled cells were not detected in the lower end of the follicles, and keratin 19-positive cells appeared there. At the end of this stage their lower part was maximally retracted, secondary germ remained beneath the bulge, and the vitreous membrane disappeared. In the regeneration stage (from day 30 to 50), the same histologic findings as those at the end of the dystrophic stage were observed. The keratin 19-positive cells in the secondary germ, however, were replaced with keratin 19-negative and 5-bromo-2'-deoxy-uridine-labeled cells. Then, differentiation into an inner root sheath and a hair shaft began, and apoptosis was terminated. In the stable growth stage (from day 40 to at least 150), the grafted follicles were immunohistochemically and light microscopically identical with the normal anagen hair follicles except for the presence of melanin incontinence. These findings suggest that the grafted hair follicles entered into dystrophic catagen, subsequently dystrophic telogen, then returned to normal anagen follicles, and that stem cells or their close progeny in the secondary germ play an important part in the recovery process.

Animals↗

mu-Crystallin, thyroid hormone-binding protein, is expressed abundantly in the murine inner root sheath cells.

In an attempt to investigate the genes expressed during the development of mouse hair follicles, we employed RNA differential display and identified a cDNA encoding micro-crystallin, that is a major component of kangaroo lens and a cytosolic NADP-regulated thyroid hormone-binding protein in human kidney. In northern blot study, mu-crystallin transcripts were detected in skin at the highest level among the mouse tissues, whereas lower but detectable in the eye, brain, kidney, heart, lung, and liver. Furthermore, in mouse skin, the gene expression of mu-crystallin followed hair cycle fundamentally, increased significantly during mid- and late anagen phases and decreased during the catagen, telogen, and early anagen phases. In situ hybridization revealed that mu-crystallin gene starts to be activated in hair cone of anagen III, and that in anagen VI, its expression is detected predominantly in the cuticle layer of the inner root sheath from the upper hair bulb to the middle portion of the keratogenous zone and in the Huxley's layer through the keratogenous zone. The expression was not detected in catagen, telogen, and early anagen hair follicles, and any other skin components. These results suggest the possible involvement of mu-crystallin in the development of mouse hair follicles during the anagen phase.

Animals↗

A novel mouse gene, Sh3yl1, is expressed in the anagen hair follicle.

In an attempt to investigate the genes expressed in the anagen hair follicle, we differentially screened a mouse anagen skin cDNA library, and identified a cDNA encoding a novel protein containing one Src homology 3 domain at the carboxyl terminus. The predicted amino acid sequence revealed a significant homology with YHRO 16c/Ysc 84, the yeast Src homology 3 domain-containing protein, for which transcripts are expressed at high levels during meiosis. The sequence identity was remarkable at the amino terminus as well as the carboxyl-terminal Src homology 3 domain, suggesting that the novel protein is a mouse homolog of the yeast protein, and we have termed this protein Sh3yl1. In northern blot study, the transcripts were detected not only in the skin but also in other tissues, especially the kidney, stomach, small intestine, and colon. Furthermore, in mouse skin, the expression of these transcripts basically followed the hair-growth cycle, increasing significantly during mid and late anagen phases, and decreasing during catagen, telogen, and early anagen phases. An in situ hybridization experiment showed that the Sh3yl1 transcripts are expressed predominantly in the hair bulb, the hair shaft, inner root sheath, and outer root sheath in the lower half of the follicle during mid and late anagen phases. These transcripts were not detected in catagen, telogen, and early anagen hair follicles, or in other skin components. Thus, these data suggest the possible involvement of Sh3yl1 in the development of hair follicles during the anagen phase.

Amino Acid Sequence↗

Small diameter vascular prosthesis with a nonthrombogenic phospholipid polymer surface: preliminary study of a new concept for functioning in the absence of pseudo- or neointima formation.

The purpose of this study was to prepare a small diameter vascular prosthesis functioning without pseudointima formation. A nonthrombogenic phospholipid polymer, the 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, has a cell membrane-like structure and has demonstrated strong nonthrombogenicity. We have recently prepared 2 kinds of vascular prostheses, 2 mm in diameter, composed of the MPC polymer and segmented polyurethane (SPU). One includes 7.5 wt% MPC polymer (SPU/MPC[7.5] prosthesis), and the other includes 10.0 wt% (SPU/MPC[10] prosthesis). These prostheses were placed in rabbit carotid arteries and were retrieved at 1 and 4 weeks after implantation. A pseudointima was observed at 4 weeks on the SPU/MPC(7.5). For the SPU/MPC(10), the surface was macroscopically clear without a pseudointima even after a 4 week implantation. It appears that the SPU/MPC(10) prosthesis, functioning without a pseudointima, possesses a stronger nonthrombogenicity and would be more applicable for clinical use.

Anastomosis, Surgical↗

Hepatocyte transplantation in rats with decompensated cirrhosis.

Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver-based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL(4)) and animals were studied only when evidence of liver failure did not improve when CCL(4) was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2-G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P <.01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P <. 01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P <.01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans.

Animals↗

Survivin promotes cell proliferation in human hepatocellular carcinoma.

Survivin is a recently described inhibitor of apoptosis. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression and function of survivin in human hepatocellular carcinomas (HCCs). We have shown that 4 HCC cell lines and 7 out of 8 human HCC tissues expressed survivin messenger RNA (mRNA), whereas expression of survivin mRNA was not detected in normal liver and nontumor areas of these tissues using the reverse transcription polymerase chain reaction. Survivin was detected primarily in the nucleus by immunofluorescence staining of HCC cells. In addition, 14 of 20 (70%) HCC tissues showed positive nuclear staining for survivin, whereas nontumor tissues showed little detectable staining by immunohistochemistry. Survivin expression strongly correlated with the proliferation index but not significantly with the apoptosis index in HCC tissues. Therefore, we performed cell cycle analysis after survivin transfection and showed that overexpression of survivin resulted in a decrease in the G(0)/G(1) phase and an increase in the S phase in all 4 HCC cell lines. Furthermore, we have found that survivin interacted with cyclin-dependent kinase 4 (Cdk4) and overexpression of survivin released p21(WAF1/Cip1) (p21) from Cdk4. From these results, we conclude that survivin promotes cell proliferation by interacting with Cdk4 and releasing p21 from Cdk4. This may play an important role in carcinogenesis and progression of human HCCs.

Apoptosis↗

Chemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular carcinoma cell lines.

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in various transformed cell lines but not in almost-normal tissues. It is regulated by 2 death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, and 2 decoy receptors, TRAIL-R3 and TRAIL-R4. We investigated the expression of TRAIL-R- and TRAIL-induced apoptosis in human hepatocellular carcinomas (HCCs). TRAIL-R1, -R2, and -R4 were expressed in 6 HCC cell lines examined, but TRAIL-R3 was expressed in only 2 of the 6 cell lines. In addition, immunohistochemical results revealed a high and prevalent expression of TRAIL-R1 and -R2 in human HCC tissues. Despite the expression of TRAIL-R1 and -R2, all 6 HCC cell lines showed resistance to TRAIL-induced apoptosis with no relation to nuclear factor kappa B (NF-kappaB) levels induced by TRAIL. TRAIL-induced death signal was inhibited with both decreased caspase-8 and caspase-3 activity. However, TRAIL induced significant apoptosis in the presence of a subtoxic level of actinomycin D, indicating that the TRAIL-induced apoptotic pathway is in place in these cell lines. In addition, we found that treatment with conventional chemotherapeutic agents, doxorubicin and camptothecin, dramatically augmented TRAIL-induced cytotoxicity in most of the HCC cell lines. Actinomycin D and camptothecin almost completely suppressed NF-kappaB induction by TRAIL, whereas doxorubicin had little effect. These results indicate that TRAIL, in combination with chemotherapeutic agents, may have therapeutic potential in the treatment of human HCC.

Antibiotics, Antineoplastic↗

Placental aminopeptidase A as a possible barrier of angiotensin II between mother and fetus.

Aminopeptidase A (AP-A EC 3.4.11.7), which is a membrane-bound zinc metalloprotease, is present in the placenta. AP-A selectively hydrolyzes N-terminal glutamyl and aspartyl residues and cleaves angiotensin II to form angiotensin III. To determine the role of placental aminopeptidase A under physiological and pathological conditions, we evaluated its immunolocalization and enzymatic activities in the placenta. AP-A was localized in the basal zone of the syncytiotrophoblast, in the membranes of the cytotrophoblast, and in fetal arterioles and venules within the stem villi. AP-A activity in the microsomal fraction of placental villi seemed to be remained essentially constant throughout gestation. The renin-angiotensin system is considered to be accelerated in pre-eclampsia. This AP-A activity was higher in pre-eclampsia (2.86+/-0.30 nmol beta NA/mg protein/h) than in uncomplicated pregnancy from 28 to 41 weeks of gestation (2.08+/-0.18 nmol beta NA/mg protein/h). Angiotensin II evoked AP-A activity in first trimester trophoblast, and Losartan and PD 123177 in combination significantly inhibited this induction of AP-A activity. The results of immunohistochemical evaluation and enzymatic activity suggested that placental aminopeptidase A may play a role as a component of the barrier of angiotensin II between mother and fetus.

Adult↗

Symptomatic generalized epilepsy associated with an inverted duplication of chromosome 15.

An inverted duplication of chromosome 15 (inv dup[15] chromosome) is the most common supernumerary marker chromosome in humans. Inv dup(15) chromosomes are commonly associated with mental retardation, epilepsy, behavioral problems and structural malformations. Though epilepsies associated with inv dup(15) chromosomes are often intractable, there have been very few reports regarding the seizure manifestations or types. We report a patient with severe mental retardation and intractable epilepsy, associated with an inv dup(15) chromosome. The seizures recorded with EEG-VTR monitoring were axial and generalized tonic seizures, and our case was diagnosed as symptomatic generalized epilepsy. Molecular and cytogenetic analysis showed an inv dup(15) chromosome containing the Prader-Willi syndrome/Angelman syndrome region mapped within bands 15q 11-q13.

Adult↗

Ictal brain hemodynamics in the epileptic focus caused by a brain tumor using functional magnetic resonance imaging (fMRI).

Using functional magnetic resonance imaging (fMRI) we were able to observe, in detail, ictal brain hemodynamics during epileptic seizure caused by a brain tumor. A 53-year-old man was experencing partial motor seizures of the left side of his face and neck. In a brain MR image a mass lesion was found in the subcortical area of the right frontal lobe. We found focal spikes in his right hemisphere, though dominantly in C4 and T4 regions. fMRI investigations were carried out at 1.5 T (GE Signa Horizon) using gradient-echo echo-planar neuroimaging. We were able to perform the ictal examination twice. The activated regions were focalized and clearly found only on the lateral side of the tumor base. The region was in agreement with the epileptic focus examined using an electrocorticogram (ECOG). The signal intensity in the seizure focus rapidly increased 30 seconds before the convulsion was observed. After the end of the convulsion it also took 30 seconds to restore the signal intensity to the baseline value. fMRI is a very useful tool for various studies such as the identification of the epileptic focus, the mechanism of epileptic seizure, and so on.

Brain Mapping↗

Association of remnant-like particle cholesterol with coronary artery disease in patients with normal total cholesterol levels.

BACKGROUND: Limited information is available as to whether there is a difference in the association of lipid and fibrinolytic variables with coronary artery disease according to the presence or absence of elevated serum total cholesterol. We examined the levels of various lipid and fibrinolytic variables including remnant-like particle cholesterol (RLP-C). RLP-C is a recently established simple assay method for the estimation of triglyceride-rich lipoprotein remnants. METHODS AND RESULTS: Levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride, lipoprotein(a), RLP-C, uric acid, blood glucose, tissue plasminogen activator, tissue plasminogen activator inhibitor type 1, antithrombin III, and protein C were measured in 208 patients who underwent diagnostic coronary angiograms. Of these 208 patients, 57 were hypercholesterolemic (> or =220 mg/dL) and 151 were normocholesterolemic. HDL-C showed significant differences between patients with and those without angiographically determined coronary artery stenosis in both hypercholesterolemic and normocholesterolemic patients (P =.0025 and P =.0003, respectively). Both RLP-C and uric acid showed significant differences only in the normocholesterolemic subgroup (P =.0006 and P =.0060, respectively). This difference in uric acid was not significant by multivariable analysis. The ratio of RLP-C/HDL-C was demonstrated to be highly significantly (P <.0001) associated with coronary artery stenosis in patients with normal total cholesterol, whereas there was no statistically significant association in the hypercholesterolemic patient subgroup. CONCLUSIONS: Our current study disclosed that RLP-C levels are strongly associated with coronary artery disease, especially in patients with normal total cholesterol levels. Moreover, RLP-C/HDL-C ratio may be even more significantly associated with the presence of coronary artery stenosis in normocholesterolemic patients.

Adult↗

Keratinocyte growth factor in the promotion of human chorionic gonadotropin production in human choriocarcinoma cells.

OBJECTIVE: Several growth factors and cytokines appear to participate in the proliferation or differentiation of trophoblast cells. The purpose of this study was to investigate the extent to which keratinocyte growth factor participates in the development of human embryonic and trophoblast cells at the maternal-fetal interface. STUDY DESIGN: The reverse transcriptase-polymerase chain reaction method was used to determine the gene expression of keratinocyte growth factor and keratinocyte growth factor receptor in human choriocarcinoma cells (BeWo), human teratocarcinoma cells (PA-1), and human endometrial stromal cells. We also examined the effects of keratinocyte growth factor on cell proliferation and production of human chorionic gonadotropin in BeWo and PA-1 cells. RESULTS: Keratinocyte growth factor gene was expressed in all cell types. The expression was pronounced in stromal cells of the endometrium collected during the secretory phase and early pregnancy. The keratinocyte growth factor expression was also enhanced in the differentiated BeWo cells. The expression of keratinocyte growth factor receptor gene was observed only in the BeWo cells. The addition of keratinocyte growth factor to the medium did not affect cell proliferation of the BeWo and PA-1 cells. On the other hand, keratinocyte growth factor (100 ng/mL) significantly enhanced human chorionic gonadotropin production in the BeWo cells. Stimulatory action of keratinocyte growth factor on human chorionic gonadotropin production in the BeWo cells was markedly enhanced after forskolin-induced differentiation. CONCLUSIONS: We conclude that keratinocyte growth factor may play an important role in promotion of human chorionic gonadotropin production in the trophoblast cells.

Cell Division↗

Gastric metaplasia in the duodenal bulb shows increased mucosal interleukin-8 activity in Helicobacter pylori-positive duodenal ulcer patients.

BACKGROUND: Although increased levels of interleukin (IL)-8 are known to be associated with infiltration of neutrophils in the gastric mucosa with Helicobacter pylori infection, no study has investigated the relationship between local IL-8 levels and neutrophil infiltration in the duodenal mucosa of patients with duodenal ulcer (DU). METHODS: Duodenal mucosal biopsy specimens with and without gastric metaplasia (GM) were obtained from patients with DU and controls with an endoscopic methylene blue (MB) staining method. Levels of IL-8 secreted in the organ cultures of biopsy specimens were measured with an enzyme-linked immunosorbent assay. The number of myeloperoxidase-positive neutrophils infiltrating the lamina propria was determined in immunohistochemically stained tissue sections. RESULTS: Histologic assessment showed that there was a strong correlation between the absence of endoscopic MB staining and the extent of GM. The levels of IL-8 in both duodenal and antral mucosal tissues were significantly higher in patients with H. pylori infection than in those without infection. In patients with DU the duodenal mucosal tissues with GM (MB-unstained mucosa) showed significantly higher levels of IL-8 than those without GM (MB-stained mucosa) or the antral mucosa. The number of neutrophils showed similar variations among DU and control patients with a positive correlation with IL-8 activity. The levels of IL-8 and the number of neutrophils decreased after H. pylori eradication in both duodenal and antral mucosal tissues, and these changes were more remarkable in the duodenal mucosal tissues with GM. CONCLUSIONS: Increased IL-8 activity in the duodenal mucosa with GM may be important for ulcerogenesis in H. pylori-positive DU patients.

Adult↗

Helicobacter pylori infection is a major risk factor for gastric carcinoma in young patients.

BACKGROUND: Helicobacter pylori has been established as a risk factor for gastric carcinoma (GCa). Since before the discovery of H. pylori, atrophic gastritis and intestinal metaplasia have been linked to GCa, especially the intestinal-type tumor. The prevalence of H. pylori infection and atrophic gastritis increase with age. Thus, analysis of H. pylori infection in young patients with GCa could help clarify the role of this bacterium in the development of GCa. Accordingly, we investigated the relationship between H. pylori infection, GCa, and histologic gastritis in patients less than 30 years old. METHODS: Fifty GCa patients less than 30 years (mean, 26.4 years) and 100 sex- and age-matched controls (mean, 26.8 years) were examined for the presence of H. pylori infection and histologic gastritis. RESULTS: The prevalence of H. pylori infection was significantly higher in GCa patients than in controls (94% versus 40%, P < 0.01). Its prevalence was not associated with tumor location, tumor stage, or histologic type. Gastritis, atrophy, and intestinal metaplasia significantly increased the risk of GCa. By means of multiple logistic regression analysis, the odds ratio for the risk of GCa in H. pylori-positive subjects was found to be 23.5 (95% confidence interval, 6.84-80.7). CONCLUSIONS: We confirmed a strong association between H. pylori infection and GCa in young patients. Along with H. pylori infection, histologic gastritis might play an important role in the pathogenesis of GCa in these patients.

Adult↗

Caries-preventive effect of Er:YAG laser irradiation with or without water mist.

OBJECTIVE: This investigation was performed to evaluate the effect of Er:YAG laser irradiation on the acquired acid resistance of sound dental hard tissues to artificial caries formation by spectrophotometry, and the ultrastructure of lased areas was investigated by scanning electron microscopy (SEM) in vitro. BACKGROUND DATA: Although an Er:YAG laser has shown the most promise for hard tissue ablation, there have not been any dissolution studies to determine if this laser is suitable for caries preventive treatments. METHODS: An Er:YAG laser was used to irradiate the enamel and dentin samples from 20 extracted human molars at 400 mJ pulse energy with or without water mist. Samples were subjected to 2 microL of 0.1 M lactic acid solution (pH 4.8) for 24 hours at 36 degrees C. The parts per million (ppm) of calcium ion (Ca2+) dissolved in each solution was determined by atomic absorption spectrophotometry and the morphological changes were investigated by SEM. RESULTS: The lowest mean Ca2+ ppm was recorded in the samples irradiated without water mist, in those by irradiated with water mist, and in the unlased samples. SEM observation showed that the lased areas had melted and seemed to be thermally degenerated when irradiated without water mist. After acid demineralization, the thermally degenerated enamel or dentin surfaces were almost unchanged. CONCLUSIONS: The results of this study suggest that Er:YAG laser irradition with and without water mist appears to be more effective for caries prevention.

Dental Caries↗

Calcium phosphate-containing precipitate and the carcinogenicity of sodium salts in rats.

Sodium saccharin, ascorbate and other sodium salts fed at high doses to rats produce urinary bladder urothelial cytotoxicity with consequent regenerative hyperplasia. For sodium salts that have been tested, tumor activity is enhanced when administered either alone or after a brief exposure to a known genotoxic bladder carcinogen. These sodium salts alter urinary composition of rats resulting in formation of an amorphous precipitate. We examined the precipitate to ascertain its composition and further delineate the basis for its formation in rat urine. Using scanning electron microscopy with attached X-ray energy dispersive spectroscopy, the principal elements present were calcium, phosphorus, minor amounts of silicon and sulfur. Smaller elements are not detectable by this method. Infrared analyses demonstrated that calcium phosphate was in the tribasic form and silicon was most likely in the form of silica. Small amounts of saccharin were present in the precipitate from rats fed sodium saccharin (<5%), but ascorbate was not detectable in the precipitate from rats fed similar doses of sodium ascorbate. Large amounts of urea and mucopolysaccharide, apparently chondroitin sulfate, were detected in the precipitate by infrared analysis. Chemical analyses confirmed the presence of large amounts of calcium phosphate with variably small amounts of magnesium, possibly present as magnesium ammonium phosphate crystals, present in urine even in controls. Small amounts of protein, including albumin and alpha(2u)-globulin, were also detected (<5% of the precipitate). Calcium phosphate is an essential ingredient of the medium for tissue culture of epithelial cells, but when present at high concentrations (>5 mM) it precipitates and becomes cytotoxic. The nature of the precipitate reflects the unique composition of rat urine and helps to explain the basis for the species specificity of the cytotoxic and proliferative effects of high doses of these sodium salts.

Animals↗