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Biomedical subjects

T Kato

Publications and source records attributed to T Kato.

At least 451 records · Page 25Linked to original sources

Liver transplantation with renoportal anastomosis after distal splenorenal shunt.

BACKGROUND: The distal splenorenal shunt (DSRS) is designed to maintain hepatopetal portal vein flow while decompressing gastroesophageal varices. However, over time, as the underlying liver disease progresses, the DSRS loses its selectivity. The most common method of addressing this issue during orthotopic liver transplantation is shunt ligation with or without splenectomy. Dismantling the shunt increases the complexity of the transplantation, and splenectomy may increase the risk of infection. HYPOTHESIS: Anastomosis of the donor portal vein to the left renal vein without dismantling the shunt is an effective method of portal vein reconstruction for patients with a patent DSRS. DESIGN: Retrospective analysis. SETTING: University-based teaching hospital, Miami, Fla. PATIENTS: Five liver transplant recipients with patent DSRS who received an orthotopic liver transplant between September 1996 and August 1999. INTERVENTIONS: The donor portal vein was anastomosed end-to-end to the left renal vein during liver transplantation. MAIN OUTCOME MEASURES: Perioperatve morbidity, portal vein flow by Doppler study, patient survival, and graft survival. RESULTS: In all patients, the graft liver reperfused promptly via flow through the left renal vein with adequate decompression of the bowel. Normal portal venous flow was demonstrated by intraoperative and postoperative Doppler ultrasound studies. At the mean follow-up of 16 months, 4 patients were alive with well-functioning grafts. CONCLUSIONS: This novel technique has the advantage of decreasing the complexity of the procedure, without requiring splenectomy, while securing adequate portal perfusion. Additionally, it can be applied without modifications in patients with portal vein thrombosis.

Aged↗

Strong inverse correlation between serum TPO level and platelet count in essential thrombocythemia.

Serum thrombopoietin (TPO) levels in 50 essential thrombocythemia (ET) patients were measured using a highly sensitive sandwich ELISA. In nine cases, TPO levels were measured at two points with different platelet counts. ET patients showed significantly higher serum TPO levels (n = 59, 2.70 +/- 2.74 fmol/mL, P < 0.0001) than those of normal individuals (n = 29, 0.83 +/- 0.36 fmol/mL). Twenty-three previously untreated ET patients also showed significantly higher serum TPO levels (1.33 +/- 0.75 fmol/mL, P = 0.0066) than normal individuals. Extremely high serum TPO levels (5.46 +/- 3.68 fmol/mL) were observed in ET patients with normal platelet counts. Furthermore, a strong inverse correlation was found between serum TPO levels and platelet counts in ET patients (R = -0.729, P < 0. 0001). This inverse correlation also held for each of nine cases with two-point TPO measurements. In the clinical course of ET, megakaryocyte mass may parallel the platelet mass before and after chemotherapy. Although it is unknown whether overproduction of TPO exists or not in ET, total platelet and megakaryocyte mass, i.e., the total number of c-Mpl, may play a role to regulate serum TPO levels.

Adult↗

Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord.

Human olfactory ensheathing cells (OECs) were prepared from adult human olfactory nerves, which were removed during surgery for frontal base tumors, and were transplanted into the demyelinated spinal cord of immunosuppressed adult rats. Extensive remyelination was observed in the lesion site: In situ hybridization using a human DNA probe (COT-1) indicated a similar number of COT-1-positive cells and OEC nuclei within the repaired lesion. The myelination was of a peripheral type with large nuclei and cytoplasmic regions surrounding the axons, characteristic of Schwann cell and OEC remyelination. These results provide evidence that adult human OECs are able to produce Schwann cell-like myelin sheaths around demyelinated axons in the adult mammalian CNS in vivo.

Animals↗

Testosterone 5alpha-reductase inhibitor bisnaphthoquinone derivative from Impatiens balsamina.

The 35% EtOH extract of aerial parts of Impatiens balsamina L. has been investigated for activity against testosterone 5alpha-reductase. Activity-guided fractionation led to the identification of the bisnaphthquione derivative named impatienol (1), 3-hydroxy-2-¿[3-hydroxy-1,4-dioxo (2-naphthyl)] ethyl¿ naphthalene-1, 4-dione, which exhibited significant testosterone 5alpha-reductase inhibitory activity. This 5alpha-reductase inhibitory compound has been previously synthesized, but this is the first report of its isolation from a natural source.

5-alpha Reductase Inhibitors↗

Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF-kappaB.

BACKGROUND: Response to neoadjuvant cisplatin-based chemotherapy has been used to predict overall response to chemoradiation therapy and to select patients with head and neck squamous cell carcinoma (HNSCC) for organ preservation therapy in NCI and VA cooperative group trials. However, different molecular determinants have been reported to contribute to sensitivity of cells to cisplatin and radiation, including glutathione (GSH), and activation of nuclear factor-kappaB (NF-kappaB), a transcription factor that regulates cytoprotective genes. We have reported that NF-kappaB is constitutively activated in HNSCC, but the relationship of NF-kappaB to GSH and to cisplatin and radiation sensitivity in HNSCC is unknown. METHODS: We examined human HNSCC lines to define the relationship of cisplatin and radiation sensitivity to intracellular GSH and NF-kappaB and determined whether HNSCC could be sensitized to these modalities by lowering the concentration of glutathione with L-buthionine sulfoximine or inhibiting activation of NF-kappaB by expression of a degradation-resistant mutant inhibitor-kappaBalpha. RESULTS: Cisplatin resistance did not predict radiation resistance in three HNSCC cell lines, UM-SCC-9, 11B, and, 38. Resistance to cisplatin correlated with intracellular GSH, and depletion of GSH by treatment with L-BSO sensitized UM-SCC-9 cells to cisplatin but not radiation. Conversely, radiation resistance was correlated with activation of NF-kappaB. Expression of a mutant Inhibitor-kappaB after gene transfer inhibited NF-kappaB and sensitized UM-SCC-9 cells to radiation but not cisplatin. CONCLUSIONS: GSH and transcription factor NF-alphaB can contribute independently to cisplatin and radiation sensitivity of human HNSCC. These results highlight the need to define molecular determinants of chemotherapy and radiation sensitivity for use in the selection of patients and as novel targets for therapy in future chemoradiation therapy trials for organ preservation in patients with HNSCC.

Base Sequence↗

Reduced expression of DMAHP/SIX5 gene in myotonic dystrophy muscle.

In myotonic dystrophy (DM), the expansion of CTG triplet repeats in the 3'-untranslated region of DM-protein kinase (DMPK) is a causal gene mutation. However, the pathogenic molecular mechanism of CTG repeat expansion for DM phenotypic expression is unclear. To investigate this issue, we examined the influence of CTG repeat expansion on the expression levels of DMPK gene and 3'-flanking DM locus-associated homeodomain protein (DMAHP)/SIX5 gene in the muscles of DM patients. We isolated RNA from muscle tissues of six DM patients and six controls, and performed a competitive reverse transcriptional polymerase chain reaction (RT-PCR) assay. The total mRNA level of DMAHP/SIX5 was significantly lower in DM than in controls, but the DMPK mRNA level was unchanged. Our results suggest that CTG repeat expansion influences the expression of genes other than DMPK to cause the DM phenotype.

Adult↗

Influence of surface modifications to titanium on oral bacterial adhesion in vitro.

The influence of surface modifications to titanium on the initial adherence of Porphyromonas gingivalis ATCC33277 and Actinobacillus actinomycetemcomitans ATCC43718 was evaluated. Surface modifications were performed with dry processes including ion implantation (Ca(+), N(+), F(+)), oxidation (anode oxidation, titania spraying), ion plating (TiN, alumina), and ion beam mixing (Ag, Sn, Zn, Pt) with Ar(+) on polished pure titanium plates. Comparatively large amounts of P. gingivalis and A. actinomycetemcomitans adhered to polished titanium plates. The degree of P. gingivalis adhesion showed a positive correlation with surface energy and the amount of calcium-ion adsorption. Adherence of both P. gingivalis and A. actinomycetemcomitans increased on calcium-implanted surfaces compared with polished titanium surfaces, whereas adherence of P. gingivalis was remarkably decreased on alumina-coated surfaces. These findings indicate that titanium implants exposed to the oral cavity require surface modification to inhibit the adherence of oral bacteria, and that surface modification with a dry process is useful in controlling the adhesion of oral bacteria as well as ensuring resistance against wear.

Aggregatibacter actinomycetemcomitans↗

Positive and negative regulation of IL-12 receptor expression of naive CD4(+) T cells by CD28/CD152 co-stimulation.

IL-12 is a critical cytokine for polarizing naive CD4(+) T cells toward Th1 subset. Therefore, it is important to elucidate the mechanism of IL-12R expression of naive CD4(+) T cells. In this report, we present evidence to show that expression of both IL-12Rbeta1 and beta2 mRNA is regulated by signals mediated through CD28 and CD152. Naive CD4(+) T cells stimulated with anti-CD3 alone neither expressed IL-12Rbeta2 mRNA nor bound detectable level of rIL-12, although they expressed a very low level of IL-12Rbeta1 mRNA when stimulated with a high dose of anti-CD3. Expression of IL-12Rbeta1 and beta2 mRNA was induced by the co-ligation of CD3 and CD28, and it was down-regulated by the ligation of CD152. CD28 ligation induced not only IL-12Rbeta1 and beta2 mRNA expression, but also enhanced IFN-gammaR to mediate up-regulation of IL-12R by IFN-gamma.

Abatacept↗

Differential regulation of Fas-mediated apoptosis of rheumatoid synoviocytes by tumor necrosis factor alpha and basic fibroblast growth factor is associated with the expression of apoptosis-related molecules.

OBJECTIVE: Fas-mediated apoptosis is associated with the pathophysiology of rheumatoid arthritis (RA). However, the molecular mechanisms of this process remain to be elucidated in rheumatoid synovium. We investigated the behavior of intracellular signaling molecules that regulate Fas-mediated apoptosis in RA synoviocytes. METHODS: Anti-Fas monoclonal antibody (mAb) was added to RA synoviocytes after treatment with tumor necrosis factor alpha (TNFalpha) or basic fibroblast growth factor (bFGF) for 5 days. The cytotoxic activity was measured using a lactate dehydrogenase-release assay. The expression of apoptosis-related molecules in RA synoviocytes was examined by immunoblot analysis. The enzymatic activities of caspases 3 and 8 under Fas ligation were examined. Transfer of the FADD (Fas-associated death domain) protein and the FLIP(L) (long form of the FLICE [FADD-like interleukin-1beta-converting enzyme]-inhibitory protein) gene into RA synoviocytes was performed using adenoviral vectors. RESULTS: Following a 5-day treatment with TNFalpha or bFGF, Fas ligation with its agonistic mAb induced apoptosis of almost all TNFalpha-treated RA synoviocytes but only showed a weak apoptotic activity in bFGF-treated synoviocytes. Although there was no correlation between the induction of Fas-mediated apoptosis and the expression of apoptosis-related molecules among these cells, a high enzymatic activity of caspases 3 and 8 was observed only in the TNFalpha-treated RA synoviocytes after Fas ligation. The bFGF-treated RA synoviocytes were relatively resistant to apoptosis induced by FADD gene transfection, as compared with the TNFalpha-treated synoviocytes. In addition, the expression of FLIP(L), an inhibitory molecule of Fas-mediated apoptosis, was reduced in TNFalpha-treated RA synoviocytes, and the expression of FLIP43 was augmented in bFGF-treated RA synoviocytes. Moreover, Fas-mediated apoptosis in TNFalpha-treated RA synoviocytes was partially inhibited by FLIP(L) gene transfection. CONCLUSION: Our results suggest that Fas-mediated apoptosis of RA synoviocytes is differentially regulated by TNFalpha and bFGF. In addition, the regulatory mechanisms of apoptosis involve the formation of the death-inducing signaling complex, especially at the level of caspase 8 activation, and this process may be partly associated with FLIP expression.

Antibodies, Monoclonal↗

Analysis of accumulated T cell clonotypes in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the accumulated T cell clonotypes in peripheral blood (PB) samples obtained at various times, and the accumulated T cell clonotypes in a PB sample and in an affected kidney, from patients with systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained at 2-4 different times from each of 5 SLE patients, with or without flare-up of the disease; in addition, a biopsied kidney tissue sample was obtained from 1 of the patients. RNA was extracted from each sample and complementary DNA was prepared. Genes that encode the variable region of T cell receptor (TCR) B chains (BV) of 3 BV families, 5S1, 8, and 14, were amplified by reverse transcription-polymerase chain reaction (PCR), and the PCR products were cloned for sequencing. RESULTS: A total of 877 cloned TCR genes was detected in the PBMC samples and the kidney sample. Oligoclonal T cell expansion was detected in 34 of the 36 PCR-amplified BV samples from PBMC (amplification of 3 BV families in 2-4 samples from 5 patients). The composition of clonally expanded T cell clonotypes was relatively stable in the patients with inactive SLE. In contrast, the composition of clonotypes in the PB changed drastically after the patient experienced the active phase of the disease. T cell clonotypes that had accumulated in the kidney appeared to be restricted and distinct from those that had accumulated in the PB of the same patient. CONCLUSION: Different T cell clonotypes expand at different times and at different sites in patients with active SLE. The sensitizing antigens may change over the course of the disease and may be different at each site.

Adult↗

Prevention of the formation of mutagenic and/or carcinogenic heterocyclic amines by food factors.

Introduction of phenolic antioxidants, thiol compounds and reductones into the heated model system composed of glucose/glycine/creatinine was effective to scavenge the intermediary pyrazine cation radical and to reduce the mutagenicity due to imidazoquinoxaline heterocyclic amines. Addition of a reductone, ascorbate or erythorbate, at 0.3% to ground beef effectively reduced the mutagenicity of cooked hamburger. Mutagenicity of cooked hamburger was also decreased by addition of glucose at more than 0.7% to ground beef.

Amines↗

Transcriptional regulation of HIV-1 LTR during antigen-dependent activation of primary T cells by dendritic cells.

Numerous factors are known to bind human immunodeficiency virus (HIV) long terminal repeat (LTR) and activate viral transcription, but little is known as to how they function in naturally activated T cells and to what extent their binding is relevant to HIV replication in vivo. To characterize the HIV LTR-binding factors responsible for antigen-dependent activation of HIV, we examined replication of LTR mutant viruses in CD4+ T cells activated by different stimuli. NF-kappaB or Sp1 mutant virus replicated well in CD4+ T cells activated by phorbol ester and calcium ionophore. When they were activated by antigen-pulsed dendritic cells, the replication of the Sp1-deleted virus was severely impaired in CD45RA+, but not in CD45RO+ T cell subsets that dominantly produce interleukin-2 (IL-2). Stimulation via CD3/CD28 induced a high level of IL-2 production in both T cell subsets, but Sp1-deleted virus poorly replicated in CD45RA+ subset. The level of NF-kappaB and Sp1-binding factors did not differ between these subsets. Our results suggest that additional cofactors distinct from IL-2-inducing signaling molecules are important for LTR activation during antigen-dependent T cell activation.

Antigen Presentation↗

Cloning of bullfrog thyroid-stimulating hormone (TSH) beta subunit cDNA: expression of TSHbeta mRNA during metamorphosis.

A thyroid-stimulating hormone beta subunit (TSHbeta) cDNA encoding both signal peptide and mature TSHbeta molecule was cloned from a cDNA library constructed from total RNA of the bullfrog (Rana catesbeiana) adenohypophysis. The bullfrog TSHbeta mRNA was estimated by Northern blot analysis to be approximately 1 kb. The deduced amino acid sequence showed 40-61% homologies with the sequences of TSH beta subunits of other vertebrates. Using the cDNA as a probe, we measured changes in mRNA expression in metamorphosing tadpoles of R. catesbeiana. The TSH beta subunit mRNA level increased progressively throughout prometamorphic stages, reaching its maximum at the end of prometamorphosis. The maximum level was maintained throughout early and mid climax, declining at late climax. These results, together with previously obtained data on plasma prolactin and pituitary prolactin mRNA levels, as well as thyroid hormone levels, are discussed in relation to metamorphic changes occurring in the bullfrog larvae.

Amino Acid Sequence↗

Microsatellite instability is a late event in the carcinogenesis of uterine cervical cancer.

OBJECTIVE: The purpose of this study was to elucidate the role of genetic instability and LOH in the progression of cervical cancer and also to analyze for correlations between these genetic abnormalities and the clinicopathological characteristics of cervical cancers. METHODS: Seventy-two DNA samples were obtained from 29 carcinoma in situ, 8 microinvasive carcinoma, and 35 invasive cancers. Seven highly polymorphic microsatellite markers representing the chromosome 3p, 6p, and 6q arms were examined by PCR amplification. RESULTS: Microsatellite instability was detected in 8 of 35 (22.9%) invasive cancers and in 1 of 37 (2.7%) early stage cancers (microinvasive cancer and carcinoma in situ). The incidence of MI was statistically higher in invasive cancers (P < 0.02). On the other hand, loss of heterozygosity (LOH) of chromosome 3p was identified in 6/41 (14.6%) invasive cancers and in 3/27 (11.1%) carcinomas in situ. There was no statistical difference between the two groups. There were no significant correlations between the presence of MI or 3p LOH and clinicopathological characteristics including the histological type, FIGO stage, depth of myometrial invasion, lymphovascular involvement, lymph node metastasis, and recurrence. CONCLUSION: Our results indicate that genomic instability is a late event during the carcinogenesis of cervical cancer and is associated with the conversion of cervical intraepithelial neoplasia to an invasive phenotype. To the contrary, LOH of chromosome 3p plays an early role in the development of cervical intraepithelial neoplasia. No significant correlation was observed between the presence of MI or LOH and clinicopathological characteristics.

Adult↗

Prolonged effect of leukocytosis on reperfusion injury of rat intestine: real-time ATP change studied using (31)P MRS.

BACKGROUND: The intestine is one of the most sensitive tissues to ischemia and reperfusion (I/R). Polymorphonuclear neutrophils (PMN) may play an important role in ischemic injury. (31)P magnetic resonance spectroscopy (MRS) has been used to continuously monitor the energy metabolism of an animal in situ. We have applied MRS to study the effect of PMN on the I/R injury of rat intestine. MATERIAL AND METHODS: In a rat model of 30 min of intestinal ischemia and reperfusion, the number of PMNs was manipulated: group A, control; group B, leukopenia induced by cyclophosphamide; group C, leukocytosis induced by granulocyte colony-stimulating factor (G-CSF). MRS was employed to measure the level of real-time intestinal ATP and pH in vivo. RESULTS: In group A, ATP rapidly recovered on reperfusion to 61.0 +/- 11.0% of the preischemia level and maintained that level during reperfusion. The other two groups showed similar recovery of ATP at the initial phase of the reperfusion (<10 min). ATP in group B continued to recover, reaching 74.0 +/- 10.0% of the preischemia level. After the initial recovery, ATP in group C deteriorated reaching 46.0 +/- 4.4% of the preischemic level at 150 min of reperfusion. In group A and group B tissue pH decreased on ischemia and recovered on reperfusion in a similar manner. In group C, tissue pH was significantly lower than in other groups during I/R. CONCLUSION: Leukocytosis induced by G-CSF exerts a prolonged effect on ATP during I/R and leukocyte depletion helps protect against the I/R injury.

Adenosine Triphosphate↗

Passive and active recognition of one's own face.

Facial identity recognition has been studied mainly with explicit discrimination requirement and faces of social figures in previous human brain imaging studies. We performed a PET activation study with normal volunteers in facial identity recognition tasks using the subject's own face as visual stimulus. Three tasks were designed so that the activation of the visual representation of the face and the effect of sustained attention to the representation could be separately examined: a control-face recognition task (C), a passive own-face recognition task (no explicit discrimination was required) (P), and an active own-face recognition task (explicit discrimination was required) (A). Increased skin conductance responses during recognition of own face were seen in both task P and task A, suggesting the occurrence of psychophysiological changes during recognition of one's own face. The left fusiform gyrus, the right supramarginal gyrus, the left putamen, and the right hypothalamus were activated in tasks P and A compared with task C. The left fusiform gyrus and the right supramarginal gyrus are considered to be involved in the representation of one's own face. The activation in the right supramarginal gyrus may be associated with the representation of one's own face as a part of one's own body. The prefrontal cortices, the right anterior cingulate, the right presupplementary motor area, and the left insula were specifically activated during task A compared with tasks C and P, indicating that these regions may be involved in the sustained attention to the representation of one's own face.

Adult↗

Extrastriatal mean regional uptake of fluorine-18-FDOPA in the normal aged brain--an approach using MRI-aided spatial normalization.

The aim of this study was to define the mean regional 6-[(18)F]fluoro-l-dopa (FDOPA) uptake rate constant (K(i)) values in the striatal and extrastriatal regions of the brain of normal subjects using magnetic resonance imaging (MRI)-aided spatial normalization of the FDOPA K(i) image and using automatic region of interest (ROI) analysis. Dynamic three-dimensional FDOPA positron emission tomography (PET) and three-dimensional magnetic resonance (MR) images were acquired in 13 aged normal subjects. The FDOPA add image and the K(i) image of each subject were transformed into standard stereotactic space with the aid of individual coregistered MR image. The mean regional K(i) values of the striatal and extrastriatal regions before normalization were compared with the respective values after normalization. Then automatic ROI analysis was performed on the MRI-aided spatially normalized K(i) images of the 13 normal subjects. The K(i) values on original images and those on spatially normalized images were in good agreement, indicating that the spatial normalization technique did not change the regional K(i) values appreciably. Automatic ROI analysis of the spatially normalized FDOPA K(i) images of the normal subjects, showed high K(i) values in ventral and dorsal regions of the midbrain, amygdala, hippocampus, and medial prefrontal cortex, in addition to caudate nucleus and putamen, which correspond to the dopaminergic projections in the brain. Spatial normalization technique helped to establish a database of FDOPA K(i) images of normal subjects and high K(i) values were observed widely besides striatal regions corresponding to the dopaminergic projections in the brain.

Aged↗

Z-shaped skin incision applying Kraissl's lines for an axillary thoracotomy.

A Z-shaped skin incision applying Kraissl's lines for a thoracotomy is presented herein. The center of the Z-shape is located on the intercostal space of the thoracotomy. Parallel Z-shaped lines are described on circular Kraissl's lines in the axillary region. The oblique cross-line of the Z-shape is drawn from the dorsal edge of the cranial line to the anterior edge of the caudal line. The angle of the triangular skin flaps is adjusted to 30 degrees or greater in order to keep good microcirculation. The incision gives good exposure for the operative fields and results in a cosmetically satisfactory scar.

Axilla↗