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Biomedical subjects

M Akamatsu

Publications and source records attributed to M Akamatsu.

At least 55 records · Page 3Linked to original sources

Angiocentric immunoproliferative lesions of the skin show lobular panniculitis and are mainly disorders of large granular lymphocytes.

Eleven patients with angiocentric immunoproliferative lesion (AIL) of the skin were studied. Histologically, three patients were grouped into AIL grade II (AIL-II), whereas eight showed angiocentric lymphoma (AIL-III). All the patients' specimens exhibited lobular panniculitis. Infiltrating atypical lymphocytes in nine patients possessed electron-dense membrane bound granules in electron microscopy. Phenotypically, the lymphoid cells in the AIL-II patients were positive for CD3 epsilon; two of these showed a positive reaction to CD2, CD7, and CD8, but lacked natural killer-associated (NKa) antigens CD16, CD56, and CD57. In six AIL-III patients, lymphoma cells were positive for CD2 in all patients, CD56 in five, CD3 epsilon in four, CD7 in four, interleukin-2 beta receptor in four, a pore-forming protein in four, and CD30 in three patients. The remaining two AIL-III patients had B-cell lymphoma. By the Southern blot analysis, three patients with AIL-III showed a rearranged T-cell-receptor beta-gene or a deletion of its germline. The preceding results in nine of 11 patients suggest that abnormal or neoplastic large granular lymphocytes with the characteristics of T and NK cells have an important role in producing the angiocentric/angiodestructive features and lobular panniculitis. Clinically, all three patients with AIL-II and four with AIL-III showed liver dysfunction, cytopenia, and abnormal coagulopathy during the clinical course. Five patients with AIL-III died within 8 months. The histological grading of AIL, patients' age, and limited clinical stage of the disease seem to correlate with response to the treatment and prognosis.

Adolescent↗

A comparison of tactile, auditory, and visual feedback in a pointing task using a mouse-type device.

A mouse was modified to add tactile feedback via a solenoid-driven pin projecting through a hole in the left mouse button. An experiment is described using a target selection task under five different sensory feedback conditions ('normal', auditory, colour, tactile, and combined). No differences were found in overall response times, error rates, or bandwidths; however, significant differences were found in the final positioning times (from the cursor entering the target to selecting the target). For the latter, tactile feedback was the quickest, normal feedback was the slowest. An examination of the spatial distributions in responses showed a peaked, narrow distribution for the normal condition, and a flat, wide distribution for the tactile (and combined) conditions. It is argued that tactile feedback allows subjects to use a wider area of the target and to select targets more quickly once the cursor is inside the target. Design considerations for human-computer interfaces are discussed.

Attention↗

CD30 (Ki-1) expression in adult T-cell leukaemia/lymphoma is associated with distinctive immunohistological and clinical characteristics.

Twenty-one patients with CD30 (Ki-1) positive lymphoma were studied from a group of 91 patients with adult T-cell leukaemia/lymphoma. The patients were grouped into three types: diffuse CD30 positive anaplastic large cell lymphoma in 11 patients (group 1); pleomorphic type lymphoma with diffuse CD30 expression in five patients (group 2); and pleomorphic type lymphoma with positive CD30 expression in large cells but negative in medium-sized and small cells in five patients (group 3). The patients with diffuse CD30 positive lymphomas (groups 1, 2) frequently presented with extranodal tumours (68.8%) and lymph node enlargement greater than 2 cm in diameter (50%), and rarely with leukaemic changes, bone marrow involvement and hypercalcaemia (one case of each). Patients in group 3 rarely had extranodal tumours, but had frequent leukaemic changes. Expression of intercellular adhesion molecule (ICAM-1; CD54) by the lymphoma cells in 13 patients (81.3%) with diffuse CD30 positive lymphomas, was significantly higher than that in 33 patients (9.1%) with CD30 negative adult T-cell leukaemia/ lymphomas. No positive reaction for epithelial membrane antigen (EMA) was found in the lymphoma cells of CD30 positive cases. The overall survival in patients with diffuse CD30 positive lymphomas was better than that of CD30 negative adult T-cell leukaemia/lymphoma patients, but showed no significant difference. These findings suggest that diffuse CD30 positive adult T-cell leukaemia/lymphoma has unusual clinical and immunohistological findings. It is also speculated that local tumour formation and leukaemic changes in such diffuse CD30 positive cases are influenced by CD54 (ICAM-1) expression by the lymphoma cells.

Adult↗

Ubiquitinated cytokeratin inclusions in lichen amyloidosus: an immunohistochemical analysis.

Eosinophilic hyaline inclusions were consistently seen in the perinuclear cytoplasm of suprabasal keratinocytes in lichen amyloidosus. The inclusions, negative with amyloid staining, were immunoreactive for ubiquitin and cytokeratin, and ultrastructurally showed aggregations of fine filaments of two sizes (central thin and peripheral thick). The thin filaments were the main component in the upper epidermal layer. Four monoclonal antibodies (AE1, AE3, KL1 and CAM5.2) and one antiserum (WSS) were used for characterizing cytokeratin expression. The AE1 antibody normally stained the basal cells, but in lichen amyloidosus basal staining mostly disappeared. Instead, groups of suprabasal keratinocytes were labeled, with AE1-reactive inclusions distributed therein. In contrast, the KL1 antibody, showing suprabasal staining, failed to react with the inclusions. The inclusions were weakly reactive with the AE3 and WSS antibodies, which stained all keratinocytes. The CAM5.2 antibody was unreactive. The subepidermal amyloid deposits were negative with all the antibodies. The inclusions were ubiquitinated especially in the granular layer. Immunoelectron microscopy disclosed that ubiquitin was more densely localized in the thin filaments than in the thick ones. This indicated that cytokeratin expression and metabolism are altered in the affected epidermis, and that ubiquitin functions in the process of degradation of abnormal cytokeratin filaments.

Adolescent↗

Quantitative analyses of the structure-hydrophobicity relationship for N-acetyl di- and tripeptide amides.

The partition coefficient (P) of neutral species and the apparent partition ratio (P') at pH 7 of the ionized form were measured with the 1-octanol/water system for a number of N-acetyl di- and tripeptide amides having un-ionizable and ionizable side chains. Their log values were studied in terms of free-energy-related substituent and substructural parameters using regression analysis to give correlation equations of high quality physicochemically as well as statistically. The intrinsic hydrophobicity of side-chain substituents and their steric effect on the relative solvation of the backbone CONH groups were significant in determining the log P values of the un-ionizable acetyl peptide amides. For the log P value of peptides with polar side-chain substituents, respective indicator variable terms were required to account for the sum of specific effects of substituents such as intramolecular hydrogen-bond formation and the "polar proximity factor" for augmentation of the hydrophobicity. For the log P'(pH 7) value of basic and acidic peptides, the ability of counterionic species to form ion-pairs, the change in the apparent hydrophobicity of ionizable groups from the intrinsic value for their nonionized forms, the effect of ion-pairing itself, and other effects were additionally considered. From the regression coefficients of the parameter terms in correlation equations an effective hydrophobicity index was defined for each side chain, and the application and its limitation were suggested.

Acetylation↗

Quantitative structure-hydrophobicity and structure-activity relationships of antibacterial gramicidin S analogs.

The structure-hydrophobicity-antibacterial activity relationships of gramicidin S and its analogs retaining a beta-pleated sheet structure were examined quantitatively with physicochemical substituent and molecular parameters using regression analyses. Variations in their apparent hydrophobicity in an octanol/buffer (pH 7) system, log P' (O/W), were analyzed in terms of the "effective" hydrophobicity and steric parameters of side chain substituents of residues at certain positions in the molecule; however, some of the conformational factors have not been fully defined. For the partitioning into liposomes and the growth inhibitory activity against species of Gram-positive bacteria, the log P' (O/W) value simulated the hydrophobic effects of gramicidin S and its analogs better than substituent parameters. The side chain hydrophobicity was assumed to work together with effects attributed to variations in the entire cyclic peptide structure including conformational components undefined in the structure-log P' (O/W) analysis in these activities.

Amino Acid Sequence↗

Analysis of adhesion molecules in Ki-1 anaplastic large-cell lymphoma.

We analysed the expression of adhesion molecules on lymphoma cells in 13 patients with Ki-1 (CD30)-positive anaplastic large-cell lymphoma (Ki-1 ALCL; lymph nodes in 6, extranodal tumours in 6, and both lymph nodes and bone in 1). Very late activation antigen (VLA)-alpha 4 (CD49d) and Hermes lymph node homing receptor (CD44) were constantly expressed in all specimens, and intercellular adhesion molecule-1 (ICAM-1; CD54) was frequently expressed in 10 of the 14 specimens. The expressions of lymphocyte function-associated antigen-1 alpha (LFA-1 alpha; CD11a) and VLA-alpha 5 (CD49e) occurred in 5 of 14 and 4 of 14 specimens, respectively. The expression of VLA-alpha 2 (CD49b), endothelial leukocyte adhesion molecule-1, neural cell adhesion molecule (CD56) and E cadherin were always lacking. VLA-alpha 6 (CD49f) was absent in all but one specimen. The expression of VLA-alpha 5 on Ki-1 ALCL was high in subcutis-cutis but absent in lymph nodes. Furthermore, in one case, LFA-1 alpha was detected in the primary lymph node, but was absent in a metastatic bone lesion. These results suggest that the expression of ICAM-1 is partially responsible for aleukemic behaviour in Ki-1 ALCL and, moreover, that the Ki-1 ALCL cells modify their expression of adhesion molecules at each of the involved organs.

Adolescent↗

The antibiotic susceptibility of Propionibacterium acnes and Staphylococcus epidermidis isolated from acne.

We studied the susceptibility of antimicrobial agents to Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) isolated from acne patients. We measured the minimum inhibitory concentrations (MICs) of the following five drugs: roxithromycin (RXM), erythromycin (EM), clindamycin (CLDM), minocycline (MINO) and ofloxacin (OFLX), which are frequently used to treat acne and skin infections. We found many resistant strains of S. epidermidis and some resistant strains of P. acnes. There was a correlation between the resistance of S. epidermidis and the former therapy for acne, but no distinct correlation between the resistance of P. acnes and the former therapy for acne.

Acne Vulgaris↗

Heterogeneity of Epstein-Barr virus infection in angioimmunoblastic lymphadenopathy type T-cell lymphoma.

To investigate the relationship of Epstein-Barr virus (EBV) and angioimmunoblastic lymphadenopathy with dysproteinemia, we performed DNA analysis using the polymerase chain reaction (PCR), Southern blot, in situ hybridization, and immunohistochemical analysis of lymph nodes in five patients who were followed up and biopsied more than once. In the course of the disease, nodal architecture diminished, cellular atypia worsened, and clear cells increased in number. In the DNA analysis of the receptor genes, the clonal population increased in number. EBV nucleic acid sequences were found by either PCR or in situ hybridization in all examined nodes. The number of EBV-positive cells varied widely among the cases and throughout the course of the disease in the same patients. The analysis of EBV terminal repeats or lymphocyte-determined membrane antigen genes showed polyclonal populations of EB-infected cells. EBV-positive cells possessed intermediate- to large-sized nuclei, and the cells with large nuclei, especially, expressed latent membrane protein of EBV. These large cells varied among the cases. Double-labelling immunohistochemistry/in situ hybridization studies demonstrated that most of the EBV-positive cells expressed B-cell antigen (CD20). The presence of EBV seems to be associated with the selective defects of the immune system, rather than with the direct pathogenesis of angioimmunoblastic lymphadenopathy.

Base Sequence↗

Structure-depolarizing activity relationship for achatin-I, a tetrapeptide with a D-Phe residue, and its derivatives toward the crayfish giant axon.

Achatin-I (Gly-D-Phe-Ala-Asp) is a tetrapeptide isolated from the ganglia of an African giant snail (Achatina fulica Férussac). The compound and its derivatives were synthesized, and their effects on the action potential of the crayfish giant axon elicited by electrical stimulation were examined by an intracellular recording method. The membrane potential after the action potential had fallen was elevated by some compounds at an acidic but not neutral pH level. An analysis of the structure-activity relationship for the activity to elevate the afterpotential at an acidic pH level, suggests that the factors favorable for activity were the beta-turn conformation, a beta- or gamma-carboxyl group in the C-terminal residue, appropriate hydrophobicity and/or bulkiness in the protecting groups for the alpha-amino group at the N-terminus, and the number of negative charges in the entire molecule.

Action Potentials↗

Aberrant alpha 1-->2fucosyltransferases found in human colorectal carcinoma involved in the accumulation of Leb and Y antigens in colorectal tumors.

Evidence indicates that the presence of aberrant alpha 1-->2fucosylation pathways is responsible for the accumulation of large quantities of Le(b) and Y antigens in human colorectal carcinoma. Significantly higher activities of alpha 1-->2 as well as alpha 1-->3 and alpha 1-->4fucosyltransferases were found in most of the tissues from carcinoma than in the adjacent normal tissues and in healthy subjects. alpha 1-->2Fucosyltransferases associated with the synthesis of Le(b) (Fuc alpha 1-->2Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta) and Y (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta) structures from Le(a) (Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta) and X (Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta) ones, respectively, were demonstrated in colorectal carcinomas and in colorectal carcinoma cell lines (COLO201, LS174T and SW1116). The activation of alpha 1-->2fucosyltransferase with such new substrate specificities in colorectal carcinoma might result in the preferential synthesis of Le(b) and Y structures from Le(a) and X rather than from H type 1 and H type 2 structures.

Blood Group Antigens↗

Quantitative structure-activity relationship (QSAR) study of elastase substrates and inhibitors.

One hundred Suc-X-Y-Ala-pNA peptides: (Suc: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, alpha-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (Km, kcat and kcat/Km) were determined. These reaction constants were quantitatively analyzed using the Free-Wilson/Fujita-Ban method. The contribution of amino acid side chains to the reaction constants Km, kcat and kcat/Km, expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF3CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the Ki value of the inhibitor was generally correlated to the Km value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation. log(1/Ki) = 1.271 log(1/Km) + 4.831 This study may serve as a prototypical approach to unraveling structure-activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance.

Amino Acid Sequence↗

Quantitative analyses of hydrophobicity of di- to pentapeptides having un-ionizable side chains with substituent and structural parameters.

With experimental conditions established recently, we measured the partition ratio (P') of 124 di- to pentapeptides composed of amino acids having un-ionizable side chains in a 1-octanol:pH 7.0 aqueous phosphate buffer system as an approximate zwitterionized "molecular" partition coefficient (P). Empirical equations of good quality, correlating the variations in log P' value of peptides with free energy-related physicochemical parameters for the side chain substituents and substructures, were formulated. The significant side chain parameters were those representing the intrinsic hydrophobicity, the steric effect on the relative solvation of functional groups on the backbone, and the conformational potential index derived from the Chou-Fasman beta-turn potential parameters. For polar side chains, specific indicator variables were required for intramolecular hydrogen-bond formations and the "polar proximity effect" for reductions of hydrophilicity observed when polar groups are crowded together. The proline residue was shown to contribute to the log P' value depending not only on its location on the backbone but also on the number of residues in peptides. On the basis of the analyses, we proposed a new "effective" hydrophobicity index for un-ionizable side chains which could predict the secondary structure of oligopeptides.

Algorithms↗

A bovine homolog to the human myogenic determination factor myf-5: sequence conservation and 3' processing of transcripts.

A bovine cDNA library from fetal skeletal muscle myoblasts. was screened with a 274 bp probe to a conserved region of the mouse MyoD1 cDNA. One positive recombinant, designated bmyf, was found to contain a 1931 bp insert with an open reading frame encoding a predicted protein highly related to the human myogenic factor myf-5 Human and bovine factors are 96% homologous in their predicted amino acid sequences. At the nucleotide level, bmyf and myf-5 are 92% identical in the coding region and 74 and 80% homologous in their 5'- and 3'-untranslated regions, respectively. The bmyf cDNA, nevertheless, extends 475 nucleotides beyond a polyadenylation signal common to both cDNAs. Bmyf transcripts are expressed exclusively in skeletal muscle where three transcripts of 1.5, 2 and 3 kb were detected. While the 1.5 kb transcript lacks sequences 3' to the polyadenylation signal at nt 1415 in the bmyf cDNA, both the 2 and 3 kb RNAs contain these sequences suggesting that bmyf transcripts are alternatively polyadenylated. Bmyf cDNA can activate the expression of the myogenic program in C3H10T1/2 fibroblasts as assayed by stable and transient transfection experiments.

Amino Acid Sequence↗