Search PubMed⌕ Search

Biomedical subjects

T Hamaguchi

Publications and source records attributed to T Hamaguchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

TU-572, a potent and selective CD45 inhibitor, suppresses IgE-mediated anaphylaxis and murine contact hypersensitivity reactions.

BACKGROUND: CD45, receptor-type protein tyrosine phosphatases (PTPases) are essential components of signaling through both the T cell receptor and the B cell antigen receptor. However, the functional significance of CD45 in the signaling pathway through the high-affinity immunoglobulin (Ig) E receptor has not yet been established. In this study, we demonstrate that the potent CD45 inhibitor negatively regulates IgE-dependent anaphylaxis and contact hypersensitivity reactions. METHOD: We have previously found that TU-572, 2-[(4-methylthiopyridin-2-yl)methylsulfinyl]-5-isopropoxybenzimidazole, had a potent and selective inhibitory effect against PTPase activity of CD45. Using a CD45 inhibitor, we examined in vitro and in vivo IgE-mediated responses. RESULTS: TU-572 potently inhibited histamine release from rat peritoneal mast cells and mouse systemic anaphylaxis reaction using monoclonal anti-dinitrophenyl (DNP) IgE and DNP-BSA. TU-572 also suppressed the immediate-type hypersensitivity response induced by repeated epicutaneous application of trinitrochlorobenzene in BALB/c mice. CONCLUSION: These findings revealed that the PTPase activity of CD45 played a critical role in signal transduction of IgE-mediated anaphylaxis in vitro and in vivo. PTPase inhibitors such as TU-572 are useful in the treatment of allergic diseases.

Anaphylaxis↗
PubMed2001

Does post-translational modification influence chaperone-like activity of alpha-crystallin? I. Study on phosphorylation.

It is difficult to isolate derivatives of alpha-crystallin with only one type of post-translational modification, because this protein is subjected to several different types of modification. In the present study using bovine lens proteins, we isolated mono-phosphorylated alphaB-crystallin with no other post-translational modifications. Using this material, we demonstrated that mono-phosphorylation reduced the activity of alphaB-crystallin by approximately 30%. Our results confirmed that investigation of the correlation between chaperone-like activities of alpha-crystallin and post-translational modification is important to understand the mechanism of cataract formation.

Animals↗
PubMed2001

[Relationship between periodontitis and lifestyle and health status].

The purpose of this study is to clarify the relationship between periodontitis and lifestyle and health status. The subjects were 349 male workers aged on 40s and 50s, who had been working on the development and manufacture of computers. Multiple logistic regression analysis showed that the existence of periodontitis was associated positively with age, the Brinkman index, systolic blood pressure, number of white blood cells, feeling of irritation, and negatively with the use of interdental cleaners. It is therefore important to practice more active oral health promotion in cooperation with the medical staff concerned, as a part of THP (Total Health Promotion) in the workplace.

Age Factors↗
PubMed2001

A human case of protothecosis successfully treated with itraconazole.

Cutaneous protothecosis developed in a 63-year-old Japanese female. The patient had a long history of steroid use for bronchial asthma. A tender, swollen, erythematous plaque with white papules covered the dorsal aspect of the patients right hand. Histopathological examination showed typical protothecosis with numerous mulberry-like sporangia positive for periodic acid-Schiff stain. The pathogen was identified as Prototheca wickerhamii. After a 6-week course of 150-200 mg/day itraconazole (ITCZ) therapy, the patients culture was negative for P. wickerhamii. No recurrence was seen after 12 weeks of ITCZ therapy. This case of protothecosis and those of 16 patients are summarized. All the patients had lived in mid- to southern Japan. Only 12 cases of protothecosis treated with ITCZ have been reported in the literature; 8 of these cases were cured with ITCZ therapy alone. In cases treated with ITCZ at no more than 100 mg/day, medication was typically needed for 2 months; most of the cases treated with ITCZ at 200 mg/day were successfully cured within 2 months. A 2-month course of ITCZ at 200 mg/day appears to be adequate treatment for human protothecosis.

Antifungal Agents↗
PubMed2001

[A case of lymphocutaneous sporotrichosis].

We report a case of lymphocutaneous sporotrichosis in a 69-year old man who had nodular-ulcerated lesions on the right hand and forearm. Small nodules remained on the right hand after 8 weeks of 0.5 g daily treatment with potassium iodide. Alternatively, terbinafine therapy (125 mg/day) resulted in healing with atrophic scars after 9 weeks without side effects. We reviewed 67 patients of cutaneous sporotrichosis in Japan from 1993 to 1999. Those cure rates (and mean durations of treatments in parentheses) are 90.9% (8.1 weeks) with potassium iodide, 86.6% (12.6 weeks) with itraconazole (100 mg/day) and 71.4% (12.8 weeks) with terbinafine (125 mg/day) treatments, respectively. These results lead us to consider a daily dose of 250 mg as more appropriate for terbinafine.

Aged↗
PubMed2001

[Enucleation of renal tumor using a microwave tissue coagulator].

We report our clinical findings on 7 tumors in 5 patients who underwent successful enucleation of renal tumor with a microwave tissue coagulator. All patients presented with incidentally-found renal tumor on ultrasonography or computed tomography. One patient had bilateral renal tumors. The mean size of the renal tumor was 2.5 cm (Range 1.0-5.2 cm). One patient had a tumor larger than 5 cm, and was found to have renal insufficiency preoperatively. Four cases were clinically diagnosed as T1aN0M0. In all patients, the renal tumor was enucleated with a microwave tissue coagulator successfully without renal pedicle clamping. The mean operative time and blood loss were 241 minutes and 788 ml, respectively. The pathological diagnosis was renal cell carcinoma in all cases. Although 2 patients had preoperative renal insufficiency, there were no serious postoperative complications and no evidence of loss of renal function as a result of this operation. Our findings suggest that renal tumors can be enucleated with a microwave tissue coagulator safely and successfully without damaging renal function.

Adenocarcinoma↗
PubMed2001

[Spontaneous rupture of renal angiomyolipoma with tuberous sclerosis during long-term follow-up: a case report].

We present a case of spontaneous rupture of bilateral renal angiomyolipoma (AML) with tuberous sclerosis. A 46-year-old woman was admitted with sudden onset of severe left flank pain. She had been diagnosed to have bilateral AML with tuberous sclerosis 15 years earlier. Four years after the initial diagnosis, spontaneous rupture of right renal AML occurred and right renal embolization of the right renal artery was performed. The treatment for the left renal AML was not performed. Eleven years later in 2000, spontaneous rupture of contralateral renal AML occurred and left renal embolization of the left renal artery was performed. We evaluated the efficacy of selective arterial embolization in right AML and the change of the tumor size during a 10-year follow up after embolization. The right AML had decreased 86% in 11 years. Selective arterial embolization is an effective and safe treatment for AML. We evaluated the natural history of left AML and calculated the doubling time to be about 1,370 days for the first period of 4 years and about 2,075 days for the second period of 11 years. Although the growth change was very slow, we should observe the tumors carefully on computed tomography or ultrasound to prevent life-threatening hemorrhage.

Angiomyolipoma↗
PubMed2000

Synthesis and characterization of a potent and selective protein tyrosine phosphatase inhibitor, 2.

The synthesis and biological activity of a series of 2-[(4-methylthiopyridin-2-yl)methylsulfinyl]benzimidazoles are described. These compounds have potent inhibitory effects against the protein tyrosine phosphatase activity of CD45. Enzymatic analysis with several phosphatases revealed that compound 5a had high specificity for CD45 compared with serine/threonine phosphatases (PP1, PP2A), tyrosine phosphatases (LAR, PTP1B and PTP-S2) and dual phosphatase (VHR).

Benzimidazoles↗
PubMed2000

Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N.

CPI-17 is a phosphorylation-dependent inhibitory protein for smooth muscle myosin phosphate. Phosphorylation at Thr(38), in vitro, by protein kinase C or Rho-kinase enhances the inhibitory potency toward myosin phosphatase. Phosphorylation of CPI-17 by protein kinase N (PKN), a fatty acid- and Rho-activated serine/threonine kinase, and its effect on smooth muscle myosin phosphatase activity were investigated. CPI-17 was phosphorylated by GST-PKN-CAT, a constitutively active GST-fusion fragment of PKN, to 1.46 mol of P/mol of CPI-17, in vitro. The K(m) value of CPI-17 for PKN was 0.96 microM. Phosphorylation of PKN dramatically increased the inhibitory effect of CPI-17 on myosin phosphatase activity. The major and inhibitory phosphorylation site was identified as Thr(38) using a point mutant of CPI-17 and a phosphorylation-state specific antibody. Thus, CPI-17 is a substrate of PKN and might be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho and/or arachidonic acid.

Animals↗
PubMed2000

Post-translational modification of alphaB-crystallin of normal human lens.

The current study reports several post-translational modifications of alphaB-crystallin in normal human lenses. The isoforms of post-translational modified alphaB-crystallin were isolated from the normal human lenses of >70-age group by ion exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoform modifications were determined in detail by fast atom bombardment mass spectroscopy and amino acid sequence analysis. As the criterion of non-modified alphaB-crystallin, alphaB-crystallin from 1-d-old infant lenses were used. The modifications found in this study involve oxidation of the N-terminal methionine-1 residue, phosphorylation of the serine-59 residue, and truncation of four amino acids from the C-terminal position of the crystallin. The oxidation of methionine-1 was found in the early stage of human life in 1-d-old lens, although other modification of alphaB-crystallin were usually only found in old lenses (>70-age group).

Amino Acid Sequence↗
PubMed2000

[Dermatophytosis of the external auditory meatus].

Dermatophytosis of the external auditory meatus is believed to be a fairly rare disease. In the past three and a half years we have had seven cases of dermatophytosis in the external auditory meatus. All cases except one were associated with tinea of other lesions. Case 1: A 44-year-old man had tinea of the auricle, tinea pedis and tinea unguium. Case 2: A 14-year-old boy, the son of case 1 had no tinea elsewhere on his body, including the auricle. He scratched the auditory meatus with an earpick which his father had used. Case 3: A 62-year-old man had tinea of the auricle, tinea pedis and tinea unguium. Case 4: A 50-year-old man had tinea of the auricle, tinea pedis and tinea unguium. Case 5: A 36-year-old man had tinea of the auricle, tinea pedis, tinea unguium and tinea cruris. Case 6: A 30-year-old woman had tinea of the auricle. Case 7: A 68-year-old man had tinea of the auricle, tinea pedis, tinea unguium and tinea manuum. Endoscopic examination (except for cases 4 and 7) revealed dry cerumen from cartilaginous to bony region of the external auditory meatus. Direct examination using KOH method of the cerumen in all cases demonstrated numerous fungal elements. Fungal cultures identified Trichophyton rubrum except for cases 3 and 6. All cases were successfully treated with oral itraconazole or terbinafine. We suggest that tinea of the external auditory meatus is frequently associated with that of the auricle.

Adolescent↗
PubMed2000

Characterization of an extracellular keratinase from Microsporum canis.

Extracellular keratinase (Ekase) 48-, 34- and 31.5-kDa polypeptides, which were isolated from Microsporum canis and examined by immunoblotting reacted with a monoclonal antibody against Ekase of M. canis. We analyzed the amino acid and determined the first 17 amino acid NH2-terminal sequences of the 48-, 34- and 31.5-kDa polypeptides. These polypeptides had a high aspartic acid, glycine and alanine content, respectively. The first 17 amino acid residues of the 34-kDa polypeptide were homologous to those of thermomycolin. This indicated that the 34-kDa polypeptide of Ekase is homologous to the thermomycolin produced by Malbranchea pulchella. Furthermore, Ekase was very heat-stable in the presence of 50 mM CaCl2 at 55 degrees C, since 50% of the initial activity remained. In contrast, no activity was detected after heating in the absence of CaCl2. These results indicate a close relationship between dermatophytes and M. pulchella.

Amino Acid Sequence↗
PubMed2000

[Insulin resistance and cytokine, cytokine receptor].

Insulin resistance is associated with many common diseases including diabetes mellitus, hyperlipidemia and hypertension, and plays an important role for determining their clinical courses. Obesity is a multifactorial syndrome characterized by an excessive adipose tissue accumulation, and is associated with acquired insulin resistance. Adipose tissue, acting as one of the endocrine organs, has been revealed to produce and secrete some bioactive molecules, "adipocytokines", which regulate cell growth and/or metabolic pathways. Tumor necrosis factor(TNF)-alpha is also synthesized by adipocytes, and is involved in the expression of peripheral insulin resistance. This review deals with molecular mechanisms of the TNF/TNF receptor system promoting insulin resistance, and its prevention by the insulin-sensitizing drugs, thiazolidinediones.

Adipocytes↗
PubMed1999

Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization.

AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of the type 3 form of maturity-onset diabetes of the young. We examined the clinical features and molecular basis of hepatocyte nuclear factor-1alpha (HNF-1alpha) diabetes. METHODS: Thirty-seven Japanese subjects with early onset Type II (non-insulin-dependent) diabetes mellitus and 45 with Type I (insulin-dependent) diabetes mellitus were screened for mutations in this gene. Functional properties of mutant HNF-1alpha were also investigated. RESULTS: Three new mutations [G415R, R272C and A site of the promoter (+ 102G-to-C)] were found. Insulin secretion was impaired in the three subjects. Insulin and glucagon secretory responses to arginine in the subject with the R272C mutation were also diminished. Molecular biological studies indicated that the G415R mutation generated a protein with about 50% of the activity of wild-type HNF-1alpha. The R272C mutation had no transactivating or DNA binding activity and acted in a dominant negative manner. The + 102 G-to-C mutation in the A site of the promoter activity was associated with an increase in promoter activity and it had 42-75% more activity than the wild-type sequence. CONCLUSION/INTERPRETATION: Mutations in the HNF-1alpha gene may affect the normal islet function by different molecular mechanisms.

Adult↗
PubMed1999

Risk factors for the progression of microalbuminuria in Japanese type 2 diabetic patients--a 10 year follow-up study.

To clarify risk factors for the progression of microalbuminuria in Japanese type 2 diabetic patients, the longitudinal study for 10 years was conducted on 67 outpatients with type 2 diabetes, who had shown no overt proteinuria at baseline. The urinary albumin index (UAI) has been determined based on the mean of at least two random urine samples each year. Categories were defined as normoalbuminuria (UAI < 30.0 mg/g x Cr.), microalbuminuria (30.0 < or = UAI < 300.0), and macroalbuminuria (UAI > or = 300.0). Progression was defined as worsening of the category and/or more than doubling of the baseline UAI value. Multiple logistic regression analysis was performed using age, duration of diabetes, HbA1c, blood pressure, BMI, serum lipids, smoking habits, and alcohol consumption as independent variables and the progression of microalbuminuria as a dependent variable. Age and HbA1c were estimated as significant and independent variables. Furthermore, genetic polymorphisms of angiotensin I-converting enzyme (ACE) and angiotensinogen were analyzed to evaluate the genetic contribution. The D/D genotype of ACE was significantly more common in progressors than in non-progressors. These results suggest that glycemic control and age are important risk factors and the D/D genotype of ACE acts as a risk factor for the progression of microalbuminuria in Japanese type 2 diabetic patients.

Adult↗
PubMed1999

Developmental genetics of the Drosophila gut: specification of primordia, subdivision and overt-differentiation.

The Drosophila gut is composed of three major parts, the foregut, midgut and hindgut, which arise from anterior and posterior invaginations of the early blastoderm. We review the process of the specification of the gut primordia, subsequent subdivision and region-specific cell differentiation in terms of developmental genetics. Graded activities of maternal signals at anterior and posterior terminal domains of the blastoderm, being mediated by activities of two zygotic gap genes, tailless and huckebein, lead to the activation of key genes that determine the gut primordia: serpent (GATA factor gene) for the endodermal midgut; brachyenteron (Brachyury homolog) for the ectodermal hindgut. fork head (HNF-3 homolog) and caudal (Cdx homolog) are also essential for the development of all gut primordia or hindgut primordium, respectively. Subdivision of the midgut epithelium is regulated by inductive signals emanating from the visceral mesoderm, which is under the control of HOM-C genes. In contrast, pattern formation of the ectodermal foregut and hindgut is regulated by secreted signaling molecules, such as Wingless (Wnt homolog), Hedgehog and Decapentaplegic (Bmp-4 homolog), as in the case of segmented structures and imaginal discs. Finally, the gut is subdivided into at least 36 compartments that are recognized asminimum tissue units of regional differentiation. A few genes that are responsible for determining and maintaining the state of overt-differentiation of the compartments have also been reported. A marked feature of the genetic mechanism of the gut development is the unexpectedly wide spectrum of the similarities of relevant genes and regulatory pathways of gene expression between Drosophila and vertebrates, which may imply a prototypic style of body plan common to protostomes and deuterostomes.

Animals↗
PubMed1998

Interaction of myosin phosphatase target subunit 1 with the catalytic subunit of type 1 protein phosphatase.

In the investigation of the sequences of myosin phosphatase target subunit 1 (MYPT1) involved in binding the substrate and catalytic subunit of protein phosphatase type 1 (PP1c), fragments of MYPT1 were prepared and characterized. The shortest fragment capable of full activation of PP1c contained the sequence of residues 1-295. Within this fragment, the N-terminal sequence of residues 1-38 is involved in activation of PP1c (kcat) and the ankyrin repeats (residues 39-295) were involved in substrate binding (Km). The ankyrin repeats alone (residues 39-295) and the C-terminal fragment of residues 667-1004 did not activate PP1c. Using gel filtration, an interaction with PP1c was detected for the sequences of residues 1-295, 17-295, and 1-170. Affinity columns were prepared with various fragments to assess binding of PP1c. Binding to the column with residues 1-295 was strongest, followed by the binding to the column with residues 1-170. A weak interaction was observed with the column with residues 1-38. The column with residues 1-295 was used to isolate PP1c from gizzard. The purified PP1c was activated by MYPT1 and fragments to a greater extent than previous preparations. These results suggest that the N-terminal sequence (residues 1-38) and the ankyrin repeats are involved in binding PP1c. The C-terminal ankyrin repeats appear to be dominant, but there is an interaction of PP1c with the N-terminal ankyrin repeats. The N-terminal peptide has two apparent functions, the binding of PP1c via the consensus binding sequence and activation of PP1c by the sequence of residues 1-16.

Animals↗