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Biomedical subjects

T Tsuchida

Publications and source records attributed to T Tsuchida.

At least 181 records · Page 10Linked to original sources

Derivatives of tetrodecamycin.

The derivatives of tetrodecamycin (1), being introduced acyl, carbamoyl and alkyl groups at 14-hydroxyl group and modified at exo-methylene group, were synthesized and evaluated on their antibacterial activities. Although 14-O-substituted tetrodecamycins (3 approximately 19) showed weak activity against Pasteurella piscicida, they were more active against Gram-positive bacteria than 1. Among them, 15 showed approximately 10-fold higher activity than 1. The derivatives (20 approximately 23) modified at 4 or 5 positions had moderate antibacterial activity. The absolute structure of 4(R),5-dibromotetrodecamycin (23) was determined by X-ray crystallographic analysis.

Anti-Bacterial Agents↗

Azicemicins A and B, a new antimicrobial agent produced by Amycolatopsis. I. Taxonomy, fermentation, isolation, characterization and biological activities.

A new structural class of the antibiotic, azicemicins A (1) and B (2) were isolated from the culture broth of the strain MJ126-NF4, which was closely related to Amycolatopsis sulphurea. They were purified by adsorption on Diaion HP-20, silica gel column chromatography and preparative TLC. The molecular formulas of 1 and 2 were determined to be C23H25O9N and C22H23O9N by HRFAB-MS, respectively. Azicemicins A and B have moderate growth inhibiting activity against Gram-positive bacteria and mycobacteria.

Actinobacteria↗

[Reevaluation of precancerous lesions of the skin].

Precancerous skin lesions are categorized into three groups; (1) carcinoma in situ, (2) hereditary precancerous lesions, and (3) non-hereditary precancerous lesions. Carcinoma in situ includes Bowen's disease, actinic keratosis and leukoplakia as squamous cell carcinoma in situ, Paget's disease as adenocarcinoma in situ, and melanoma in situ. Hereditary precancerous lesions include xeroderma pigmentosum, epidermodysplasia verruciformis and porokeratosis. The mechanisms of carcinogenesis in these diseases are investigated intensively. Chronic radiodermatitis and other scars are treated as non-hereditary precancerous lesions.

Humans↗

[Chemosensitivity of cultured meningiomas].

Meningioma is one of the popular benign brain tumors. However, the recurrence of this tumor is not infrequently encountered. In an attempt to establish the useful adjuvant therapy for the recurrent meningioma, in vitro chemosensitivity study for meningioma was conducted. Among various chemotherapeutic agents tested here, cisplatin showed highest cytotoxicity on cultured meningioma cells. In conclusion, cisplatin may be useful in adjuvant chemotherapy for the recurrent meningioma.

Antineoplastic Agents↗

Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes.

Motor neurons located at different positions in the embryonic spinal cord innervate distinct targets in the periphery, establishing a topographic neural map. The topographic organization of motor projections depends on the generation of subclasses of motor neurons that select specific paths to their targets. We have cloned a family of LIM homeobox genes in chick and show here that the combinatorial expression of four of these genes, Islet-1, Islet-2, Lim-1, and Lim-3, defines subclasses of motor neurons that segregate into columns in the spinal cord and select distinct axonal pathways. These genes are expressed prior to the formation of distinct motor axon pathways and before motor columns appear. Our results suggest that LIM homeobox genes contribute to the generation of motor neuron diversity and may confer subclasses of motor neurons with the ability to select specific axon pathways, thereby initiating the topographic organization of motor projections.

Afferent Pathways↗

Autoreactive CD8+ T-cell responses to human myelin protein-derived peptides.

Identification of the targets of autoreactive T cells is important for understanding the pathogenesis of many autoimmune diseases. In multiple sclerosis, myelin proteins are thought to be the targets of autoreactive T-cell responses. To date only major histocompatibility complex class II-restricted CD4+ T-cell responses to myelin proteins have been investigated. In the present study, the ability of self peptides derived from human myelin proteins to induce autoreactive CD8+ T-cell responses has been assessed. Peptide sequences from human myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and myelin oligodendrocyte glycoprotein have been identified that bind to and form stable complexes with HLA-A2. MBP 110-118, PLP 80-88, MAG 287-295, MAG 509-517, and MAG 556-564 were all able to induce peptide-specific HLA-A2-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses in vitro in HLA-A2+ individuals. CTLs specific for MBP 110-118 and MAG 556-564 could recognize endogenously processed antigens presented by HLA-A2. CTL clones reactive to MBP 110-118 and MAG 556-564 produced tumor necrosis factor alpha and a subset of these clones also produced interferon gamma. These results demonstrate that (i) self peptides derived from human myelin proteins can induce autoreactive CD8+ CTLs and (ii) these CD8+ T cells produce cytokines thought to be important in mediating demyelinating disease. These studies provide an experimental approach for the assessment of CD8+ T-cell responses in such autoimmune diseases.

Adult↗

Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1 and HLA-B8.

Distinct amino acid (aa) residue motifs for peptides binding to HLA-A1 and HLA-B8 were identified by sequence analyses of reversed-phase HPLC fractions containing endogenous peptides derived from these HLA molecules. Fifteen different primary sequences were determined for HLA-A1-associated peptides, 12 of which were nine aa in length. Common features among these peptide sequences were Tyr at the COOH-terminus, a negatively charged aa (usually Glu) at position 3 (P3), and Pro at P4. Twenty-seven different primary sequence assignments were made for HLA-B8-associated peptides, most of which were eight aa in length. Lys, and in a few cases Arg, predominated at P3 and P5; Leu and Pro predominated at P2, and Leu was the preferred COOH-terminal residue. Unlike all other human class I molecules whose peptide-binding properties have been studied, both HLA-A1 and HLA-B8 endogenous peptide sequences have a dominant anchor residue at P3, and these aa are opposite in charge to the aa at position 156 of the peptide-binding site. Synthetic peptides corresponding to endogenous peptide sequences bound to their respective HLA molecules in vitro, indicating that they derive from peptides bound to HLA and not from copurifying contaminants. Eight of the HLA-A1 and HLA-B8 endogenous peptide sequences matched intracellularly expressed proteins found in protein sequence data bases. The HLA-A1 peptide-binding motif was then used to identify potential antigenic peptides from influenza A viral proteins that bound to HLA-A1 in vitro.

Amino Acid Sequence↗

Intra-arterial chemotherapy for brain stem glioma: report of four cases.

Four patients with pontine gliomas were treated with radiation and intra-arterial chemotherapy using ACNU, cisplatin, and/or carboplatin. All underwent biopsy and were histologically proven to have gliomas. Even though three were benign histologically, all appeared malignant on neuroimaging. Two patients had complete remissions; the others had partial responses; three patients died, 36, 14, and 15 months after the primary diagnosis. One patient, now in complete remission, has been alive for 24 months. There was no neurotoxicity except for transient nausea and vomiting. Intra-arterial chemotherapy is effective against brain stem gliomas, producing remission with minimum side effects.

Adolescent↗

Optimal dose of injection in activation study with O-15 water and PET.

In activation studies with the bolus method for O-15 water and PET, the radiotracer concentration may reach the limits of the system in terms of dead time correction and accidental coincidence. To obtain the optimal injection dose of O-15 water, we performed a normal volunteer study to evaluate the relationship between the injected dose and the radioactivity concentration in the brain and a phantom study to evaluate the performance of the PET scanner (PCT3600W) under high count rate conditions and the effect of averaging on the signal to noise ratio for the PET images. A linear relationship was noted between the injected dose (normalized for each body weight: x) and the mean radiotracer concentration in the brain measured by PET (y) (y = 2.52 + 30.1 x, n = 64, r = 0.87, p < 0.001). The percent error in the measurement of radioactivity with PET was within +/- 5% in the 100 to 2000 nCi/ml (3.7-74 KBq/ml) range. Below 100 nCi/ml (3.7 KBq/ml), the percent error increased due to the rapid increase in noise in the reconstructed images. Over 1000 nCi/ml (37 KBq/ml), on the other hand, the noise was almost unchanged. With our PET scanner, the optimal range of the radiotracer concentration in the brain is below 1000 nCi/ml (37 KBq/ml), corresponding to an injection dose of 33 mCi (1.22 GBq)/60 kg body weight. With the same total dose, the increment of number of repeated measurements for averaging provided the better signal to noise ratio. In designing a paradigm for an activation PET study, the injection dose and the number of repeated measurements for averaging should be considered.

Adult↗

Bullous systemic lupus erythematosus with cutaneous mucinosis and leukocytoclastic vasculitis.

A 38-year-old man with systemic lupus erythematosus had nodular cutaneous mucinosis, leukocytoclastic vasculitis, and a vesiculobullous eruption. Immunopathologic study of a bullous lesion revealed granular deposits of IgA and IgG along the basement membrane zone. Localization of immune deposits to the lamina and sublamina densa was confirmed by immunoelectron microscopy.

Adult↗

Different sensitivities of the murine melanomas BL-6 and BL-6-beta m to local injections of interleukin-2 (IL-2). Analysis of gangliosides after the treatment.

The murine melanoma cell line BL-6-beta m, which is a stable cell line transfected with a gene coding a unique actin subspecies called beta m to the BL-6 cell line, has low metastatic potentials as compared with those of the parent cell line. BL-6-beta m melanomas were found to be sensitive to in vivo local injection of IL-2, while BL-6 melanomas showed almost no response. Ganglioside analysis of BL-6 and BL-6-beta melanomas revealed that the main ganglioside of both melanomas was GM3, which suggested that different sensitivities between BL-6 and BL-6-beta m melanomas to the injection of IL-2 did not relate to the different compositions of main gangliosides. However, minor components of the gangliosides such as GM2 and GM1 emerged only in BL-6-beta m melanomas after treatment with IL-2. Local injection of IL-2 caused considerable infiltration of anti-asialo GM1-positive cells into the nests as well as the interstitials of BL-6-beta m melanomas. In contrast, in the BL-6 melanomas treated with IL-2, infiltration of the anti-asialo GM1-positive cells was hardly seen, although anti-Thy1,2 and anti-macrophage-positive cells were found to more or less the same extent as observed in BL-6-beta m melanomas. These results suggest that the murine metastatic variant melanoma cell lines BL-6 and BL-6-beta m have different properties in terms of sensitivity to in vivo IL-2 treatment, and a slight enhancement of the ganglioside components GM2 and GM1 expression only in BL-6-beta m after IL-2 treatment may play a role in the IL-2-mediated attraction of immune cells or may explain the different sensitivities of the two lines to treatment with IL-2.

Actins↗

Bilateral periorbital eccrine hidrocystoma.

We saw four patients showing identical features as cystic lesions on the bilateral external canthi. Histological examination showed cystic cavities in the dermis. Histological and enzyme histochemical findings suggest that these cystic tumors are of eccrine origin. Thus we diagnosed these cystic tumors as eccrine hidrocystoma with characteristic clinical feature. The recognition of this feature would help to correctly diagnose these eccrine hidrocystoma.

Adult↗

A host-vector system for a cellulose-producing Acetobacter strain.

An indigenous plasmid, named pAH4, was detected in a cellulose-producing Acetobacter strain. This plasmid, consisting of 4002 bp, contained an AT-rich region and encoded several open reading frames, as deduced by the complete nucleotide sequence. One of the putative open reading frames showed homology with replication proteins of other plasmids. A shuttle vector of Escherichia coli and this strain was constructed by connecting pAH4 to pUC18. Electroporation of the shuttle vector into the strain yielded 1.7 x 10(5) ampicillin resistant transformants per microgram DNA. The shuttle plasmid was very stably maintained in the strain.

Acetobacter↗

Chemoprevention effects on bronchial squamous metaplasia by folate and vitamin B12 in heavy smokers.

The purpose of this study was to observe the effects of folate and vitamin B12 on bronchial squamous metaplasia with cellular atypia, known to be a precancerous change, in heavy smokers. Cases of squamous metaplasia were recognized on sputum cytologic study. The location of bronchial lesions was identified by bronchofiberoscopy in all cases. The grade of cellular atypia was evaluated on the basis of histologic specimens. Thirty-eight patients with squamous metaplasia, including 21 patients receiving folate and vitamin B12 and 17 patients without any medication, were investigated prospectively for 1 year. Consecutive bronchofiberoscopic examinations were performed in each patient in 3 to 4 months after the first examination in order to evaluate the lesions. Grades of cellular atypia were examined by histologic specimens using a scoring system from 0 to 3. There was no significant difference in mean scores at entry in the medication group (1.7) and control group (1.4). The medication group showed significant decrease in mean scores (0.4) while the control group had no change in mean scores (1.2) at termination. Plasma levels in the medication group were significantly increased at termination of the study while those of the control group showed a slight decrease. The results show that the cellular atypia squamous metaplasia in heavy smokers can be reduced by administration of folate and vitamin B12.

Adult↗

Cushing's disease associated with adrenal myelolipoma, adrenal calcification and thyroid cancer.

A 51-year-old woman with Cushing's disease associated with adrenal myelolipoma is reported. A further characteristic feature was the coexistence of bilateral adrenal calcification and thyroid cancer. Previously several cases of adrenal myelolipoma associated with endocrine dysfunction were reported. The combination of Cushing's disease and adrenal myelolipoma has only been described in two cases of recurrent Cushing's disease but never in an initial occurrence of Cushing's disease. Continued stimulation by excessive adrenocorticotropic hormone (ACTH) not only developed adrenal hyperplasia but also might be involved in the pathogenesis of adrenal myelolipoma.

Adrenal Gland Neoplasms↗