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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 307 records · Page 17Linked to original sources

Expression and role of heat-shock protein 65 (HSP65) in macrophages during Trypanosoma cruzi infection: involvement of HSP65 in prevention of apoptosis of macrophages.

The 65-kDa heat-shock protein (HSP65) is thought to play a role in host defense against infections with various microbial pathogens and in autoimmune inflammatory disorders. We investigated the biological function and expression mechanism of HSP65 in macrophages of mice infected with Trypanosoma cruzi. BALB/c mice, which are susceptible to T. cruzi, showed high levels of parasitemia, and 80% of these mice died within 42 days after the infection, whereas resistant C57BL/6 or DBA/2 mice showed low levels of transient parasitemia and all survived. HSP65 expression was correlated with resistance to T. cruzi infection; HSP65 was more strongly expressed in macrophages of resistant C57BL/6 and DBA/2 mice than in macrophages of susceptible BALB/c mice. Immunodeficient BALB/c-nu/nu (nude) and C.B-17 scid/scid (SCID) mice were shown to be highly susceptible to this infection, and they did not express detectable levels of HSP65, suggesting that T cells play essential roles in the expression of HSP65 as well as in protective immunity against the infection. CD4(+) T cells, but not CD8(+) T cells or gammadelta T cells, were the cell population responsible for the induction of HSP65 expression in macrophages. Furthermore, depletion of asialo GM-1(+) NK cells made resistant C57BL/6 mice more susceptible to the infection, and HSP65 expression in their macrophages was abolished. Semiquantitative reverse transcription PCR analyses showed that both interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) mRNA levels in CD4(+) T cells became low when resistant C57BL/6 mice were depleted of NK cells, suggesting that NK cells contribute to functional differentiation of CD4(+) T cells and thereby affect the induction of HSP65 expression. To determine the function of HSP65, macrophages were treated in vitro with antisense oligonucleotide for HSP65 prior to inducing HSP65 with IFN-gamma plus TNF-alpha or T. cruzi infection. This treatment did not affect the production of nitric oxide following activation, but the treated macrophages became susceptible to apoptosis. These results indicate that HSP65 plays a role in preventing the apoptosis of macrophages and thereby contributes to host resistance against T. cruzi infection.

Animals↗

Banding of the pulmonary trunk in preparation for a Fontan operation.

Banding of the pulmonary trunk is an important surgical procedure for patients who have congenital cardiac malformations with unrestricted pulmonary flow. We propose a new concept for determining in such circumstances the most appropriate length of the band used to constrict the pulmonary trunk in preparation for a Fontan operation. We studied 14 patients undergoing banding of the pulmonary trunk and measured the following parameters: diameter of aorta, diameter of pulmonary trunk, length of pulmonary arterial band and maximum flow velocity across the banded segment. We calculated an index from our original parameter based on the formula; length of band/(diameter of aorta diameter of pulmonary trunk). The diameter of aorta was 9.5 +/- 1.4 mm, and that of the pulmonary trunk was 9.6 +/- 2.3 mm. The length of the band was 16.5 +/- 3.4 mm, giving a calculated index of 0.188 +/- 0.038. The maximum flow velocity was 4.02 +/- 0.46 m/s. No correlation was found between the length of the band and body weight, and also no correlation was found between the length of the band and maximum flow velocity. The calculated index had a negative correlation with the maximum velocity of flow across the band (y = -8.13x +/- 5.56, R = 0.74, p < 0.01). We believe that the proposed index is a useful guide in determining the length of a pulmonary band when preparing patients for a Fontan operation.

Cardiac Catheterization↗

A highly polymorphic CA repeat marker at the interleukin-11 locus.

The interleukin-11 (IL-11) stimulates T cell-dependent development of immunoglobulin-producing B cells and collaborates with IL-3 in supporting murine megakaryocyte colony formation. The interleukin-11 (IL-11) also stimulates osteoclast formation and inhibits osteoclast function in vitro and has been implicated in estrogen deficiency-induced bone loss. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the IL-11 gene located at 19q13.3-q13.4. High heterozygosity (0.81) makes this polymorphism a useful marker in genetic study of disorders affecting immune response and bone metabolism.

Base Sequence↗

Pigmented squamous cell carcinoma of the scrotum associated with a lentigo.

Only 13 cases of pigmented squamous cell carcinoma (SCC) have been reported in the English language literature, with most frequent development in the oral cavity and conjunctiva. However, no case of pigmented SCC of the scrotum has been reported. We report here a case of pigmented SCC that arose primarily in the scrotum of a 70-year-old man. Light microscopically, this tumour exhibited the typical features of a pigmented SCC, including not only keratinization and intercellular bridges but also colonization by plump dendritic melanocytes with marked pigmentation. These features were clearly confirmed by immunohistochemistry, including strong positivity of tumour cells for high-molecular-weight cytokeratin and of colonizing melanocytes for HMB-45. The tumour was associated with a lentiginous lesion and partly involved it. Melanocytes entrapped from the lentigo might therefore have been activated during enlargement of this tumour, resulting in melanocyte colonization. Fourteen cases of pigmented SCC, including ours, are clinicopathologically reviewed.

Aged↗

Polyclonal expansion of TCRBV2- and TCRBV6-bearing T cells in patients with Kawasaki disease.

We examined T-cell receptor (TCR) usage, cytokine production and antibody responses to superantigens in patients with Kawasaki disease (KD) to facilitate a better understanding of the immunopathogenesis of KD. The mean percentage of VB2- or VB6. 5-bearing T cells in peripheral blood mononuclear cells (PBMC) of patients with acute-phase KD was significantly higher than that of patients in the convalescent phase of KD or in healthy donors. Expansion of VB2- or VB6.5-bearing T cells was polyclonal because DNA sequences in the complementarity determining region 3 of VB2- and VB6.5-positive cDNA clones were all different from each other. The plasma levels of interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) were elevated in the acute phase of KD. We previously reported that streptococcal pyrogenic exotoxin C (SPEC) was a potent stimulator of VB2- and VB6.5-positive T cells and, furthermore, serum levels of anti-SPEC antibodies were significantly higher in patients with acute and convalescent KD than in age-matched controls. The results of the present study, together with those of our previous report, suggest that SPEC induces activation and polyclonal expansion of VB2- and VB6.5-positive T cells, and that SPEC-induced activation of T cells may lead to the pathogenesis of KD.

Acute Disease↗

Proportions of various endocrine cells in the pancreatic islets of wood mice (Apodemus speciosus).

Using wood mice (Apodemus speciosus) captured in the wild in Niigata, we analysed the proportion of various endocrine cells in pancreatic islets for both immunohistochemical and microscopic characteristics. In both the dorsal and ventral portions of the pancreas, the centre of the pancreatic islets was occupied predominantly by insulin-positive (B) cells, surrounded by glucagon-positive (A), somatostatin-positive (D), and pancreatic-polypeptide-positive (PP) cells. Although the proportions of the various endocrine cells in pancreatic islets varied from one mouse to the next, in most animals B cells accounted for more than half of all endocrine cells. Dorsal and ventral portions of the pancreas differed in the proportions of various endocrine cells, specifically, in the A-to-PP cell ratio: the proportion of PP cells higher in the ventral portion. The same tendency is seen in humans, rats and mice. Microscopic examinations revealed morphologically distinct secretory granules in A, B and D cells. The morphology of these granules was similar that of secretory granules found in rats and mice.

Animals↗

Classification of the sleeping pattern of normal adults.

A questionnaire concerning their sleep-related lifestyle and mental health was mailed to people aged in their twenties to fifties living in the Fukushima (North East), Tokyo (Central, Metropolitan) and Okayama (West) areas of Japan. We classified the sleeping pattern of 3642 people (1702 men, 1940 women; mean age 41.3+/-10.67) by multivariational analyses (factor analysis and cluster analysis). They were classified into six groups and defined as 'poor sleeper group' (30.0%), 'good sleeper group' (28.3%), 'long sleeper group' (8.2%), 'short sleeper group' (18.5%), 'irregular sleeper group' (11.3%), and 'Delayed Sleep Phase Syndrome group' (3.7%) based on their characteristics of the factor pattern.

Adult↗

Estimated nutritional intake based on the reference growth curves for extremely low birthweight infants.

BACKGROUND: Although the optimal goal of extremely low birthweight (ELBW) infants has been debated, it can be argued that the best nutritional strategy for ELBW infants is one which achieves better growth while preventing neurological sequelae due to nutritional inadequacy, even if it does not mimic fetal growth. Our aim is to propose an advisable and practically feasible nutritional intake for ELBW infants. METHODS: We retrospectively investigated the nutritional intake in 16 ELBW infants (gestational age 26.7 weeks, birthweight 879.6 g), who exceeded the standard growth curves for Japanese infants of ELBW. We also analyzed the nutritional composition of human milk from 15 mothers delivering before term (PT milk) until the 12th week of lactation. The nutritional intake was calculated according to the composition of the parenteral and enteral regimen. RESULTS: The infants tolerated more than 100 mL/kg per day of milk until the fourth week of life. An average weight gain of more than 15 g/kg per day was achieved by the sixth week. An advisable nutritional intake capable of sustaining ELBW infants in a stable growing phase was calculated as the sum of the mean plus 1SD of the daily nutritional intake. CONCLUSIONS: To exceed the ordinary growth curves for ELBW Japanese infants, it was suggested that more than 100 mL milk/kg per day could be fed until the fourth week of life, while the advisable daily intake of nutrients after six weeks of life should be as follows: water 160 mL/kg, protein 3.2 g/kg, fat 7.4 g/kg, carbohydrate 12.8 g/kg, energy 544 kJ/kg, the following minerals in mg/kg: sodium 45, chloride 82, potassium 110, calcium 140, phosphorus 70, magnesium 11, zinc 0.5 and copper at 60 micrograms/kg. Further studies will be needed to confirm the safety and effectiveness of this advisable intake for ELBW infants.

Birth Weight↗

A case of pelvic arteriovenous malformation in a male.

BACKGROUND: Congenital pelvic arteriovenous malformation (AVM) is rare especially in males. We present a case of pelvic AVM in a 38-year-old male. He was admitted to our hospital with left flank abdominal pain and painless gross hematuria. METHODS/DISCUSSION: Pelvic computed tomography demonstrated a homogeneous contrast-enhanced mass, 6 cm in diameter. For diagnosis, non-invasive magnetic resonance imaging (MRI) and color Doppler ultrasonography were very useful in our case. Though the treatment is controversial, we decided to monitor his clinical course.

Abdominal Pain↗

Effect of Bcl-2 overexpression in human prostate cancer cells in vitro and in vivo.

BACKGROUND: Cancer cells often develop mechanisms to resist apoptosis and the extent of such anti-apoptotic ability has been shown to parallel tumor progression in various malignancies. Among various molecules implicated in regulating apoptosis pathway, bcl-2 and its family members are best characterized. METHODS: To investigate the effect of bcl-2-mediated anti-apoptotic ability on tumor growth and progression in prostate cancer, a cell line overexpressing bcl-2 (LNCaP/bcl-2) was established by genetically engineering a prostate cancer cell line LNCaP. Tumor growth of LNCaP/bcl-2 was compared with the parental cell line in vitro and in vivo. RESULTS: LNCaP/bcl-2 cells show resistance to apoptosis caused by nutrient deprivation and did not arrest when cultured in serum-free or androgen-free medium, while parental LNCaP cells or LNCaP cells transfected with the vector only (LNCaP/control) underwent extensive apoptosis on nutrient deprivation and sustained growth suppression in serum-free or androgen-free medium. When injected subcutaneously into nude mice, tumors deriving from LNCaP/bcl-2 cells grew faster compared with LNCaP/control for about 3 weeks (P = 0.02), but this effect was not evident after 5 weeks. Upon castration, the control tumors regressed but LNCaP/bcl-2-derived tumors showed resistance, as was previously reported. CONCLUSIONS: These data confirm the notion that anti-apoptotic function of bcl-2 is oncogenic and confers resistance to androgen deprivation and also indicate that it may also play a critical role in earlier stages of tumorigenesis.

Androgens↗

Stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors by serum human chorionic gonadotropin of patients with hydatidiform mole.

We evaluated the stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors (CHO-hTSHR cell) by sera of five patients with hydatidiform mole before and after the evacuation of the mole, and compared the results with serum human chorionic gonadotropin (hCG) concentrations and serum free thyroid hormones in these patients. Significantly increased CHO-hTSHR cell stimulating activities were observed in sera from untreated patients, and the activity decreased promptly after the evacuation of the mole, concomitantly with the decrease in serum hCG and free thyroid hormones. CHO-hTSHR cell stimulating activity of sera of the untreated patients significantly correlated with serum hCG. Moreover, serum hCG stimulated CHO-hTSHR cells in a dose dependent manner similar to the dose-response curve of the stimulation by purified hCG. Sera of the patients and purified hCG did not stimulate nontransfected CHO-K1 cells. However, a significant correlation was not observed between serum-free thyroid hormones and serum hCG or between serum free thyroid hormones and CHO-hTSHR cell stimulating activities in untreated patients. These results indicate that serum hCG from patients with hydatidiform mole stimulates thyroid gland by interacting with TSH receptors, and suggest that the increase in thyroid hormones in patients may depend on both the increased serum hCG and the responsiveness of their thyroid glands to hCG.

Adult↗

A reliable technique of nuclear transplantation for immature mammalian oocytes.

Transplanting a germinal vesicle (GV) to another enucleated oocyte provides a possible way to avoid age-related aneuploidy in metaphase II (MII) oocytes from older women. This study was conducted to examine the efficiency of each step of nuclear transplantation as reflected in the survival and maturation capacity of immature mouse oocytes subjected to this procedure. GV stage oocytes were retrieved from unstimulated ovaries. A GV removed with a small amount of cytoplasm (karyoplast) was transferred subzonally into a previously enucleated oocyte, which was then exposed to direct current to promote fusion. Such reconstituted oocytes were placed in culture to allow maturation, and some that had extruded a first polar body were fixed and processed for chromosome analysis. Each step of nuclear transplantation - survival, enucleation, grafting, and reconstitution - was successful in >90%, with the overall efficiency of reconstitution being 80%. The observation of normal karyotypes confirmed that the procedure did not increase chromosomal aneuploidy. An electrolytic medium, revealed to be superior for the reconstitution procedure, also allowed haploidization of the transplanted nucleus. These findings suggest that this technique can be applied to study the effects of a 'younger' woman's ooplasm on the disjunction of an 'older' woman's chromosomes during meiosis I.

Aneuploidy↗

Induction of CD8+ T cell-mediated protective immunity against Trypanosoma cruzi.

Trypanosoma cruzi was transformed with the Plasmodium yoelii gene encoding the circum-sporozoite (CS) protein, which contains the well-characterized CD8+ T cell epitope, SYVPSAEQI. In vivo and in vitro assays indicated that cells infected with the transformed T. cruzi could process and present this malaria parasite-derived class I MHC-restricted epitope. Immunization of mice with recombinant influenza and vaccinia viruses expressing the SYVPSAEQI epitope induced a large number of specific CD8+ T cells that strongly suppressed parasitemia and conferred complete protection against the acute T. cruzi lethal infection. CD8+ T cells mediated this immunity as indicated by the unrelenting parasitemia and high mortality observed in immunized mice treated with anti-CD8 antibody. This study demonstrated, for the first time, that vaccination of mice with vectors designed to induce CD8+ T cells is effective against T. cruzi infection.

Animals↗

Synovial sarcoma of the prostate with t(X;18)(p11.2;q11.2).

A case of monophasic synovial sarcoma of the prostate in a 37-year-old man is reported. Histologically, the tumor was chiefly composed of uniform spindle and oval cells, which often formed interlacing fascicles resembling those of fibrosarcoma. In some areas, the compact fascicles of tumor cells alternated with hypocellular myxoid tissue bearing a superficial resemblance to peripheral nerve sheath tumors, whereas small portions of the tumor showed a pericytomatous pattern consisting of polygonal cells arranged around dilated, thin-walled blood vessels. By immunohistochemistry, vimentin was detected in most cells, and a focal reactivity for epithelial membrane antigen was also observed. The tumor cells, however, were negative for keratin, S-100 protein, neuron-specific enolase, CD34, desmin, muscle-specific actin, and alpha-smooth muscle actin. Cytogenetic analysis and fluorescence in situ hybridization (FISH) using the cultured tumor cells demonstrated a translocation t(X;18)(p11.2;q11.2), an aberration specific for synovial sarcoma. To the authors' knowledge, this is the first report of a primary prostatic synovial sarcoma confirmed by cytogenetic analysis.

Adult↗

Hodgkin's disease expressing follicular dendritic cell marker CD21 without any other B-cell marker: a clinicopathologic study of nine cases.

Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neoplastic cells in Hodgkin's disease (HD). Although most data suggest their lymphoid origin, the nature of these cells still remains a subject of controversy. Recently, a number of RS cells have been found to express an antigen that is also present on follicular dendritic cells (FDCs), asserting FDCs as the possible progenitor cells of H-RS cells. This prompted us to investigate whether these CD21-positive cases had distinct clinicopathologic characteristics. In a series of 94 examined cases of HD, we identified 9 CD21-positive ones (4 of 37 cases of nodular sclerosis, 1 of 41 mixed cellularity, and 4 of 12 lymphocyte depletion HD) without any other B-cell marker on paraffin sections. The patients varied in age from 16 to 82 years (median, 50 years) and included six men and three women. They had superficial or mesenteric lymphadenopathy without hepatosplenomegaly. Peripheral blood leukocytosis was seen in three patients. The clinical course was indolent, and all patients but one achieved an initial complete response with HD-based treatment regimens, although three of them relapsed. Morphologically, two subgroups could be delineated. Six of the cases were characterized, besides by the classic RS cells, by a varying number of the cells with the distinctive walnutlike or cerebrumlike nuclei and cytologically with cytoplasmic processes. Their fine structural examination also revealed villous processes, but no desmosomes. The other three cases had multinucleated RS cells often with triangular nuclei, but not cytoplasmic processes. The percentage of CD21-positive tumor cells ranged from less than 10% to 60% among the H-RS cells. These RS cells were positive for CD30 (9 of 9), CD15 (7 of 9), CD68 (1 of 8), fascin (8 of 8), S-100 protein (1 of 7), and epithelial membrane antigen (2 of 8) on paraffin sections. Notably, of eight cases examined on frozen sections, two showed immunostaining for DRC1, CD35, R4/23, and Ki-M4p. Only CD35 was also detected in the other two cases. Genotypic investigation showed germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene in all eight cases examined. In situ hybridization showed Epstein-Barr virus sequences in four cases, three of which were examined by the terminal region analysis and showed the Epstein-Barr virus to be monoclonal. We concluded that in a small proportion (9.6%) of HD, H-RS cells might be derived from FDCs and that they appear to represent a distinct pathologic variant based on morphologic and phenotypic traits within the framework of HD.

Adolescent↗

Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients.

The expression of cytotoxic granule-associated proteins has been reported in some T-cell or natural killer (NK)-cell lymphomas of mostly extranodal origin, but rarely of nodal origin except for anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). This study analyzed 66 nodal lymphomas expressing T-cell intracellular antigen-1 (TIA-1) and/or granzyme B to characterize the clinicopathologic spectrum of these neoplasms. Four main groups could be delineated. The first group consisted of p80/anaplastic lymphoma kinase (ALK)-positive ALCL (n = 35). The patients were 2 to 62 years of age (median age, 16 years), and the lymphomas pursued a relatively indolent clinical course. The tumors were phenotypically of either T- or null-cell type with constant expression of CD30, epithelial membrane antigen (EMA), and p80/ALK, but not CD15 or BCL2. None harbored Epstein-Barr virus (EBV). The second group consisted of peripheral T/NK-cell lymphoma, the nodal high-grade cytotoxic type (n = 13). The patients were 29 to 72 years in age (median age, 55 years), and the tumors pursued an aggressive clinical course. The tumors often showed pleomorphic, anaplastic, or centroblastoid morphology, and were featured by either EBV association or CD56 expression. The third group consisted of peripheral T-cell lymphoma, of the nodal low-grade cytotoxic type (n = 8). The patients, three men and five women, were 31 to 75 years old (median age, 61 years). Notably, six of them exhibited lymphoepithelioid (Lennert's) lymphoma. The fourth group consisted of cytotoxic Hodgkin's-like ALCL/HD (n = 10), included seven cases of Hodgkin's-like ALCL and three cases of HD, and was characterized by the presence of Reed-Sternberg cells and often the CD15+ phenotype. The patients were all men except for one woman, and they ranged in age from 24 to 84 years (median age, 62 years). The link among these four groups was reinforced by the presence of a highly characteristic large cell with horseshoelike or reniform nuclei-the frequent expression of CD30 and EMA-and the often lack of T-cell receptor-alphabeta. In this series, the expression of p80/ALK and CD56 was also associated with favorable and poor prognoses respectively (p<0.001, log-rank test).

Adolescent↗