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Biomedical subjects

T Ito

Publications and source records attributed to T Ito.

At least 235 records · Page 13Linked to original sources
PubMed2001

CD34 expression by murine hematopoietic stem cells. Developmental changes and kinetic alterations.

For more than a decade it was believed that hematopoietic stem cells express CD34. However, this dogma was recently challenged by the observation that stem cells of normal adult mice are CD34-. In order to clarify the controversy, we carried out systematic examination of stem cells by using C57BL/6 mice that are congenic for Ly-5. As reported previously, stem cells in the normal adult mice were CD34-. However, stem cells stimulated in vivo by 5-fluorouracil injection or in vitro by a combination of interleukin-11 and steel factor were CD34+. The activated CD34+ stem cells reverted to CD34- when the recipients' marrow achieved steady state. The majority of G-CSF-mobilized stem cells also were CD34+ and reverted to CD34- under steady-state conditions. Most recently, we examined the developmental changes of stem cell CD34 expression. In order to gain information on the total population of stem cells we prepared CD34+ and CD34- populations of mononuclear cells without prior enrichment and studied their engrafting potentials. All stem cells from perinatal to 5-week-old mice were CD34+. In 7-week-old mice CD34- stem cells began to emerge, and the majority of the stem cells were CD34- in the 10- and 20-week-old mice. An estimated 20% of the adult stem cells expressed CD34. These observations provide insight into the current controversy regarding CD34 expression by adult hematopoietic stem cells.

Animals↗
PubMed2001

Stability of atheromatous plaque affected by lesional composition: study of WHHL rabbits treated with statins.

We examined how lesional composition is related to the stability of coronary plaques. WHHL rabbits (12 months old) were given pravastatin and fluvastatin orally for 52 weeks. Both statins decreased plasma cholesterol levels by about 25%, but the suppressive effects on the degree of coronary plaques were mild. Macrophage (Mphi) contents in fibromuscular cap regions were decreased by pravastatin, and smooth muscle cell (SMC) contents in those were decreased by fluvastatin. The plaque vulnerability index was low in Mphi)-poor plaques, but high in SMC-poor plaques. Our results suggest that reduction in M(phi)s in the fibromuscular cap is related to plaque stabilization and that reduction in SMCs in the fibromuscular cap is related to plaque destabilization.

Animals↗
PubMed2001

[Tsutsugamushi disease (scrub typhus) in Japan: epidemiological aspects].

Epidemiological aspects of tsutsugamushi disease (scrub typhus) in Japan in 1998 were analyzed using questionnaires. Four hundred and sixteen scrub typhus cases were reported in 24 prefectures in 1998. The annual number of the patients in 1998 was similar to those in the preceding three years. There was no sex difference. The patients at the age of 51 or greater accounted for 72% of the total cases. Patients engaged in farming and forestry accounted for 32% and 14% cases, respectively. Fifty-six, 21 and 19% were reported in Kyusyu, Kanto and Tohoku-Hokuriku districts, respectively, 96% of the total cases being reported in these 3 districts. Most cases were reported from April through June with some from October through December in Tohoku-Hokuriku districts, while most cases were reported from October through December in other districts, including Kyusyu and Kanto districts. Thus, there was a difference in epidemic seasons among the districts. Serotypes of scrub typhus rickettsia were analyzed by serum antibody titers in the Kyusyu district. The novel Kawasaki and Kuroki types were major strains; however, no geographical difference was seen within the Kyusyu district. Interestingly, 24 cases were diagnosed only by the new serotypes not by the classical serotypes (Kato, Karp and Gilliam) in serological tests. This result suggests that further investigations are required to determine the prevalent serotypes in each district and to improve the serological tests. This was the first comprehensive report of epidemiology of scrub typus in entire Japan. Information obtained in the present study provides deep insight into prediction, diagnosis, treatment and prevention of scrub typhus in Japan.

Adolescent↗
PubMed2001

[Tsutsugamushi disease (scrub typhus) in Japan: clinical features].

Clinical features of tsutsugamushi disease (scrub typhus) were analyzed, based on 416 cases reported in Japan in 1998. Three major clinical symptoms: eschar, fever and rash were found in 87%, 98% and 92% of the cases, respectively. Elevated levels of CRP, GOT, GPT and LDH were observed in 96%, 85%, 78% and 91%, respectively. These clinical and laboratory findings were observed in the majority of the cases and considered important for diagnosis. Disseminated intravascular coagulation developed in 21 cases, indicating that scrub typhus can be life threatening. Lymphadenopathy was observed in 51% of the cases. Enlarged lymph nodes were limited to the local sites in 75% of these lymphadenopathy cases and most of these sites were adjacent to eschars. Most eschars were scabbed and located in the abdomen and the lower half of the body, especially the feet. This suggests that these parts are frequently exposed to tsutsugamushi mites. Furthermore, the skin is soft in these parts and covered by cloth. These factors may make it possible for mites to keep biting without being noticed for several hours, long enough for rickettsial transmission. Interestingly, eschar and rash were absent in 14% and 8% of the cases, respectively. This result suggests that the cases without the unique symptoms may have been misdiagnosed as common cold or other febrile illnesses. One hundred and fifty-four suspected cases were not scrub typhus cases by the serological tests. The three major clinical symptoms were present in approximately a half of these negative cases, eschar being observed in approximately 70%. This may suggest the presence of new type of scrub typhus can not be diagnosed by the present laboratory tests. Clinical features of scrub typhus in Japan were well revealed, and information obtained in the present study is useful for improving clinical diagnosis. It should, however, be stressed that there were cases that could not be correctly diagnosed only by the clinical symptoms, suggesting that it is important to improve the serological tests.

Diagnosis, Differential↗
PubMed2001

Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus.

The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S. aureus (MRSA) strain. We now report identification of two additional types of mecA-carrying genetic elements found in the MRSA strains isolated in other countries of the world. There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. However, new elements shared the chromosomal integration site with the SCCmec. Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec. The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome. Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome.

Amino Acid Sequence↗
PubMed2001

Genetic organization of the chromosome region surrounding mecA in clinical staphylococcal strains: role of IS431-mediated mecI deletion in expression of resistance in mecA-carrying, low-level methicillin-resistant Staphylococcus haemolyticus.

We report on the structural diversity of mecA gene complexes carried by 38 methicillin-resistant Staphylococcus aureus and 91 methicillin-resistant coagulase-negative Staphylococcus strains of seven different species with a special reference to its correlation with phenotypic expression of methicillin resistance. The most prevalent and widely disseminated mec complex had the structure mecI-mecR1-mecA-IS431R (or IS431mec), designated the class A mecA gene complex. In contrast, in S. haemolyticus, mecA was bracketed by two copies of IS431, forming the structure IS431L-mecA-IS431R. Of the 38 S. haemolyticus strains, 5 had low-level methicillin resistance (MIC, 1 to 4 mg/liter) and characteristic heterogeneous methicillin resistance as judged by population analysis. In these five strains, IS431L was located to the left of an intact mecI gene, forming the structure IS431L-class A mecA-gene complex. In other S. haemolyticus strains, IS431L was associated with the deletion of mecI and mecR1, forming the structure IS431L-DeltamecR1-mecA-IS431mec, designated the class C mecA gene complex. Mutants with the class C mecA gene complex were obtained in vitro by selecting strain SH621, containing the IS431L-class A mecA gene complex with low concentrations of methicillin (1 and 3 mg/liter). The mutants had intermediate level of methicillin resistance (MIC, 16 to 64 mg/liter). The mecA gene transcription was shown to be derepressed in a representative mutant strain, SH621-37. Our study indicated that the mecI-encoded repressor function is responsible for the low-level methicillin resistance of some S. haemolyticus clinical strains and that the IS431-mediated mecI gene deletion causes the expression of methicillin resistance through the derepression of mecA gene transcription.

Bacterial Proteins↗
PubMed2001

First report of methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Thailand.

To investigate whether there are methicillin-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin in Thailand, a total of 155 MRSA strains isolated from patients hospitalized between 1988 and 1999 in university hospitals in Thailand were tested for glycopeptide susceptibility. All the strains were classified as susceptible to vancomycin and teicoplanin when judged by NCCLS criteria for glycopeptide susceptibility using the agar dilution MIC determination. Vancomycin MICs at which 50 and 90% of the isolates tested were inhibited (MIC50 and MIC(90), respectively) were 0.5 and 1 microg/ml, respectively, with a range of 0.25 to 2 microg/ml. For teicoplanin, MIC50 and MIC90 were 2 microg/ml, with a range of 0.5 to 4 microg/ml. However, one-point population analysis identified three MRSA strains, MR135, MR187, and MR209, which contained subpopulations of cells that could grow in 4 microg of vancomycin per ml. The proportions of the subpopulations were 2 x 10(-4), 1.5 x 10(-6), and 4 x 10(-7), respectively. The subsequent performance of a complete population analysis and testing for the emergence of mutants with reduced susceptibility to vancomycin (MIC > or = 8 microg/ml) confirmed that these strains were heterogeneously resistant to vancomycin. Two of these strains caused infection that was refractory to vancomycin therapy. Pulsed-field gel electrophoresis showed that the two strains had identical SmaI macrorestriction patterns and that they were one of the common types of MRSA isolated in the hospital. This is the first report of heterogeneous resistance to vancomycin in Thailand and an early warning for the possible emergence of vancomycin resistance in S. aureus in Southeast Asia.

Adolescent↗
PubMed2001

Generation of a highly pathogenic avian influenza A virus from an avirulent field isolate by passaging in chickens.

Highly virulent avian influenza viruses can arise from avirulent strains maintained in poultry, but evidence to support their generation from viruses in wild birds is lacking. The most likely mechanism for the acquisition of virulence by benign avian viruses is the introduction of mutations by error-prone RNA polymerase, followed by the selection of virulent viruses. To investigate whether this mechanism could apply to wild waterfowl, we studied an avirulent wild-swan virus that replicates poorly in chickens. After 24 consecutive passages by air sac inoculation, followed by five passages in chicken brain, the avirulent virus became highly pathogenic in chickens, producing a 100% mortality rate. Sequence analysis at the hemmaglutinin cleavage site of the original isolate revealed a typical avirulence type of sequence, R-E-T-R, which progressed incrementally to a typical virulence type of sequence, R-R-K-K-R, during repeated passages in chickens. These results demonstrate that avirulent viruses maintained in wild waterfowl in nature and bearing the consensus avirulence type sequence R-E-T-R have the potential to become highly pathogenic while circulating in chickens.

Animals↗
PubMed2001

p300 forms a stable, template-committed complex with chromatin: role for the bromodomain.

The nature of the interaction of coactivator proteins with transcriptionally active promoters in chromatin is a fundamental question in transcriptional regulation by RNA polymerase II. In this study, we used a biochemical approach to examine the functional association of the coactivator p300 with chromatin templates. Using in vitro transcription template competition assays, we observed that p300 forms a stable, template-committed complex with chromatin during the transcription process. The template commitment is dependent on the time of incubation of p300 with the chromatin template and occurs independently of the presence of a transcriptional activator protein. In studies examining interactions between p300 and chromatin, we found that p300 binds directly to chromatin and that the binding requires the p300 bromodomain, a conserved 110-amino-acid sequence found in many chromatin-associated proteins. Furthermore, we observed that the isolated p300 bromodomain binds directly to histones, preferentially to histone H3. However, the isolated p300 bromodomain does not bind to nucleosomal histones under the same assay conditions, suggesting that free histones and nucleosomal histones are not equivalent as binding substrates. Collectively, our results suggest that the stable association of p300 with chromatin is mediated, at least in part, by the bromodomain and is critically important for p300 function. Furthermore, our results suggest a model for p300 function that involves distinct activator-dependent targeting and activator-independent chromatin binding activities.

Animals↗
PubMed2001

Changes in myometrial and junctional zone thickness and signal intensity: demonstration with kinematic T2-weighted MR imaging.

PURPOSE: To demonstrate uterine contractions by evaluating changes during time in the thickness of the myometrium and junctional zone and in signal intensity of the uterus with T2-weighted fast magnetic resonance (MR) images in a kinematic fashion. MATERIALS AND METHODS: Sagittal MR imaging was performed with T2-weighted fast spin-echo (FSE) and multiphase-multisection single-shot FSE (SSFSE) in 60 premenopausal patients during free breathing. SSFSE MR images were evaluated with cine display. The pattern of uterine contractions and changes in signal intensities of the uterine structures were evaluated. Thickness of both myometrium and junctional zone, and their signal intensities, were measured during 15 phases of SSFSE and FSE MR imaging. RESULTS: Slow-massive (mean, 55%), middle-cycle (mean, 80%), and fine (mean, 93%) contractions were observed. Shape of junctional zones dynamically changed during time, showing focal (mean, 58%) and diffuse (mean, 82%) thickening and wavelike motions (mean, 88%). Ratio of thickness of the myometrium to junctional zone with FSE MR imaging was not significantly different from the mean ratio during 15 phases of SSFSE MR imaging, although maximum percentage of change of the ratio during 15 phases was 42.5%-56.8%. The signal intensities of the myometrium (97%) and junctional zone (75%) changed during time. CONCLUSION: Kinematic T2-weighted SSFSE MR images demonstrate uterine contractions related to dynamic changes in thickness and signal intensities of the myometrium and junctional zone, and these findings might affect the diagnosis of uterine disease.

Adolescent↗
PubMed2001

Involvement of iNOS in postischemic heart dysfunction of stroke-prone spontaneously hypertensive rats.

We investigated the possible contribution of inducible nitric oxide synthase (iNOS) to postischemic heart dysfunction and injuries in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP, 13-14 wk of age, had significantly higher systolic blood pressure and greater heart weight than age-matched Wistar-Kyoto rats (WKY). Permanent occlusion of the left anterior descending coronary artery (LAD) caused significant and long-lasting increases in the activity and mRNA expression of myocardial iNOS in SHRSP compared with WKY. However, there was no significant difference in the LAD occlusion-induced expression of interleukin-1beta mRNA between SHRSP and WKY. Hemodynamic deterioration and myocardial fibrosis were also observed in SHRSP at 4 wk after LAD occlusion. Continuous administration of 2-amino-5,6-dihydro-6-methyl-4H-1,2-thiazin (AMT) completely blocked the LAD occlusion-induced increase in the myocardial iNOS activity of SHRSP. Moreover, postischemic heart dysfunction and injuries were also significantly ameliorated by 2-amino-5,6-dihydro-6-methyl-4H-1,2-thiazin (AMT). These results suggest that the increased activity of myocardial iNOS plays a pivotal role in the development of postischemic cardiac dysfunction and injuries in SHRSP with the hypertensive and hypertrophic heart.

Animals↗
PubMed2001

Expression of estrogen receptor (ER-alpha and ER-beta) mRNA in human prostate cancer.

OBJECTIVE: The distribution of the two estrogen receptors (ER-alpha, ER-beta) in human prostate tissue have not been fully clarified, so the present study investigated the mRNA expression of the receptors to explain the broad spectrum of estrogen activity in prostate cancer. MATERIALS AND METHODS: Four human prostate cancer cell lines (LNCap, JCA-1, DU-145 and PC-3) and 24 pairs of untreated prostate cancer tissue and noncancerous tissue from resected prostate glands were subjected to RT-PCR testing. RESULTS: Both LNCap and JCA-1 expressed the mRNA of both receptors, but DU-145 and PC-3 only expressed ER-beta mRNA. In the human prostate tissue samples, 20 of the 24 prostate cancer tissues expressed ER-alpha, and 23 of the 24 expressed ER-beta. Of the 24 noncancer tissues, 14 expressed ER-alpha mRNA and 17 expressed ER-beta mRNA. The incidence of ER-beta mRNA expression between the paired cancer and noncancer tissues was statistically significantly different (p<0.05). CONCLUSIONS: A higher incidence of ER-beta mRNA expression in untreated prostate cancer tissues was observed. Furthermore, the absence of ER-alpha mRNA and the presence of ER-beta mRNA expression in hormone-independent and/or untreated prostate cancer cells leads to a tentative speculation of the mechanism of the hormone refractory feature of prostate cancer.

Estrogen Receptor alpha↗
PubMed2001

Application of bone marrow-derived stem cells in experimental nephrology.

Recent advancement in developmental biology has led to the discovery of immature mesenchymal stem cells in bone marrow and several established organs. The therapeutic potentials of such stem cells for treating serious diseases constitute a major rationale for every research effort, and clinical trials for replacing some damaged tissues such as cartilage are currently under way. Although the feasibility of such stem cell therapies for renal diseases remains unknown, it is worthy of pursuing possibilities. As an experimental tool, we have made chimeric rats that carry the bone marrow of transgenic rats expressing green fluorescent protein (GFP) throughout the body. All marrow lineages can be traced with bright green fluorescence regardless of their terminal phenotypes in chimeric rats. When compared with other conventional strategies for tracking bone marrow-derived cells, our system is highly sensitive and allows us to take advantage of the rat nephrology. Using this system, we have reported that bone marrow provides mesangial cells during repair process. In this manuscript, we briefly summarize our experiences.

Animals↗
PubMed2001

Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas.

p16, cyclin D1 and retinoblastoma protein (pRB) regulate G1 to S transition and are commonly targeted in various cancers. However, few studies have simultaneously examined all components of the p16/cyclin D1/pRB pathway (RB pathway) in hepatocellular carcinoma (HCC). To clarify the role of the disruption of the RB pathway in HCC, we analyzed p16, pRB and cyclin D1 in 47 HCCs. Inactivation of p16 was detected in 30 of 47 HCCs (64%) by Western blot analysis and significantly correlated with hypermethylation of the promoter of this gene. pRB expression was found to be absent in 13 of 47 HCCs (28%) by immunohistochemistry. We found that 38 of 47 HCCs (81%) contained at least one inactivation in either pRB or p16. Furthermore, there was a significant inverse correlation between p16 and pRB inactivation (p = 0.041). Overexpression of cyclin D1 was detected in 5 of 47 HCCs (11%) by immunohistochemistry. The cases with cyclin D1 overexpression exhibited an advanced clinicopathological appearance and also contained inactivation of pRB and/or p16. These findings suggest that inactivation of pRB and/or p16 is a major event in human hepatocarcinogenesis, while cyclin D1 overexpression may confer additional growth advantages to the tumor in addition to pRB and/or p16 inactivation in HCC.

Adult↗
PubMed2001

Gamma knife radiosurgery for growth hormone-secreting pituitary adenomas invading the cavernous sinus.

The authors assessed whether gamma knife radiosurgery is effective for patients with acromegaly where the pituitary tumors invaded the cavernous sinus. Radiosurgery was performed on 9 patients (average of 20 Gy to the tumor margin), 8 of whom had already undergone transsphenoidal surgery and/or craniotomy with occasional medication of octreotide to reduce tumor size as well as hormonal levels. All tumors have been well controlled so far with follow-up periods ranging from 12 to 69 months (mean: 42). No complications occurred. Forty percent of the patients showed hormonal normalization at 2 years, with the median being 31 months. Similarly, 50% of the patients demonstrated normalization of GH and IGF-I at 36 months. We conclude that gamma knife radiosurgery is a safe and effective tool to treat these tumors invading the cavernous sinus.

Adenoma↗
PubMed2001

ABCA1 overexpression leads to hyperalphalipoproteinemia and increased biliary cholesterol excretion in transgenic mice.

The discovery of the ABCA1 lipid transporter has generated interest in modulating human plasma HDL levels and atherogenic risk by enhancing ABCA1 gene expression. To determine if increased ABCA1 expression modulates HDL metabolism in vivo, we generated transgenic mice that overexpress human ABCA1 (hABCA1-Tg). Hepatic and macrophage expression of hABCA1 enhanced macrophage cholesterol efflux to apoA-I; increased plasma cholesterol, cholesteryl esters (CEs), free cholesterol, phospholipids, HDL cholesterol, and apoA-I and apoB levels; and led to the accumulation of apoE-rich HDL1. ABCA1 transgene expression delayed 125I-apoA-I catabolism in both liver and kidney, leading to increased plasma apoA-I levels, but had no effect on apoB secretion after infusion of Triton WR1339. Although the plasma clearance of HDL-CE was not significantly altered in hABCA1-Tg mice, the net hepatic delivery of exogenous 3H-CEt-HDL, which is dependent on the HDL pool size, was increased 1.5-fold. In addition, the cholesterol and phospholipid concentrations in hABCA1-Tg bile were increased 1.8-fold. These studies show that steady-state overexpression of ABCA1 in vivo (a) raises plasma apoB levels without altering apoB secretion and (b) raises plasma HDL-C and apoA-I levels, facilitating hepatic reverse cholesterol transport and biliary cholesterol excretion. Similar metabolic changes may modify atherogenic risk in humans.

ATP Binding Cassette Transporter 1↗
PubMed2001

Evaluation of accumulated mucopolysaccharides in the brain of patients with mucopolysaccharidoses by (1)H-magnetic resonance spectroscopy before and after bone marrow transplantation.

In seven patients with mucopolysaccharidoses (1 Hurler, 1 Hurler-Scheie, 4 Hunter, 1 Sly), cranial (1)H-magnetic resonance spectroscopy was performed to evaluate the accumulation of mucopolysaccharides and biochemical changes in the CNS in vivo before and after bone marrow transplantation (BMT). In two of seven patients, (1)H-magnetic resonance spectroscopy was performed before and after BMT. Nuclear magnetic resonance spectra of dermatan sulfate and chondroitin sulfate-C and magnetic resonance spectroscopy of chondroitin sulfate-C and urine from patients with mucopolysaccharidoses showed resonance higher than the chemical shift of myoinositol in the brain (3.7 ppm). The resonance was considered to contain signals from mucopolysaccharide molecules. The resonance was measured as presumptive mucopolysaccharides (pMPS). In white matter lesions detected by magnetic resonance imaging, pMPS/creatine ratios and choline/creatine ratios were consistently higher than control ratios. In white matter without lesions, choline/creatine ratios were higher than control ratios. Patients with higher developmental quotient or intelligence quotient tended to show higher N:-acetylaspartate/creatine ratios and lower pMPS/creatine ratios in basal ganglia. After BMT, the pMPS/creatine ratio in white matter lesions of patient 3, with Hunter syndrome, was slightly decreased, but in none of the patients was the ratio ever below the control ratios, even 7 y after BMT. In white matter without lesions, the pMPS/creatine ratio in patient 3 was decreased to the control ratios after BMT, but although the choline/creatine ratios were gradually decreased, they remained higher than the control ratio, 2 y after BMT. These results suggest that evaluation of pMPS, choline, and N:-acetylaspartate by (1)H-magnetic resonance spectroscopy is an important technique that may provide useful biochemical information in vivo on the neurologic process and the efficacy of BMT in patients with mucopolysaccharidoses.

Adolescent↗