Visit-to-visit blood pressure variability, average BP level and carotid arterial stiffness in the elderly: a prospective study.

In a cross-sectional study, visit-to-visit blood pressure (BP) variability was shown to be associated with artery remodelling. Here, we investigated the impact of visit-to-visit BP variability and average BP on the carotid artery remodelling progression in high-risk elderly according to different classes of antihypertension medication use/non-use. BP measurements and carotid ultrasound were performed in the common carotid artery in 164 subjects (mean age 79.7 years at baseline, 74.7% females) with one or more cardiovascular risk factors. Based on 12 visits (1 × /month for 1 year), we calculated visit-to-visit BP variability expressed as the standard deviation (s.d.), coefficient of variation (CV), maximum BP, minimum BP and delta (maximum-minimum) BP. We measured mean intima-media thickness (IMT) as well as stiffness parameter ß were measured at baseline and at the mean 4.2-year follow-up. In a multiple regression analysis, the maximum, minimum, s.d. and average of systolic BP (SBP) were significantly associated with a change in ß-values between the baseline and follow-up after adjustment for age, smoking, lower high-density lipoprotein level, baseline ß-value and follow-up period. There were no significant associations between the visit-to-visit BP variability measures and the change in mean IMT. Significant associations of maximum, minimum, s.d. and average SBP were found with increased ß-values in the subjects without calcium channel blocker (CCB) use and in the subjects using renin-angiotensin system inhibitors (RASIs). Thus, exaggerated visit-to-visit SBP variability and a high average SBP level were significant predictors of progression in carotid arterial stiffness in high-risk elderly without CCBs use and in those using a RASI.

Structure and possible catalytic residues of Taka-amylase A.

A complete molecular model of Taka-amylase A consisting of 478 amino acid residues was built with the aid of amino acid sequence data. Some typical structural features of the molecule are described. A model fitting of an amylose chain in the catalytic site of the enzyme showed a possible productive binding mode between substrate and enzyme. On the basis of the difference Fourier analysis and the model fitting study, glutamic acid (Glu230) and aspartic acid (Asp297), which are located at the bottom of the cleft, were concluded to be the catalytic residues, serving as the general acid and base, respectively.

Molecular structure of taka-amylase A. I. Backbone chain folding at 3 A resolution.

The crystal structure of Taka-amylase A was studied by an X-ray diffraction method at 3 A resolution. A total of 452 amino acid residues were found from the electron density map at the present stage. The four disulfide bonds and the branched carbohydrate were also located on the map. The difference electron density map of the maltotriose-soaked crystal showed that a maltose unit was bound in the active center left. The binding of iodine atoms to the enzyme was also studied.

How amino acids control the binding of Cu(II) ions to DNA (II): effect of basic amino acid residues and the chirality on the orientation of the complexes.

The binding structures of bis-lysine and bis-arginine complexes of copper(II) on highly oriented DNA fibers have been investigated by ESR spectroscopy. These complexes bind to DNA in two different modes; species A in one mode has a planar coordination structure as in solution, and species B in the other mode has a distorted planar structure on the DNA. The relative amount of A and B changes with the conformation of the DNA, as well as with the type and chirality of the amino acids. Arginine forms A more than lysine. On A-form DNA fibers, A for L-lysine and L-arginine complexes are bound with the angle theta = 45 degrees between the g// axis and the DNA helical axis, while A and B for the D-isomers are almost randomly oriented. L-arginine fixes the orientation of A on A-form DNA fibers more firmly than L-lysine. On B-form DNA fibers, the orientation of the complexes is modulated dynamically, and the g// axes have a tendency to be reoriented along the fiber axis by the conformational change of the DNA from A- to B-form at room temperature. The D-arginine complex on B-form DNA is peculiar in that it rotates ore freely than the other complexes at room temperature and shows only the A at low temperature.

Large vessel arteritis associated with human herpesvirus 6 infections.

A 9-month-old boy presented with chronic arteritis of the aorta and its major branches. The clinical manifestations at onset of his illness were compatible with those of Kawasaki syndrome. However, the febrile period lasted for 2 months despite various immunosuppressive therapies, and the levels of C-reactive protein remain high 18 months after onset. Elevated circulating immune complexes, decreased serum complement levels, hypergammaglobulinaemia and monoclonal gammopathy were observed. Active HHV-6 infection was shown by increased serum levels of antihuman herpesvirus-6 (HHV-6) IgG and IgM antibodies, and positive HHV-6 DNA in sera, peripheral blood mononuclear cells (PBMNC) and lymph nodes. HHV-6 was actively replicating in PBMNC and lymph nodes, as shown by the detection of transcripts for the virus structural antigen. These results suggest that large vessel arteritis can be associated with HHV-6 infection.

[Clinico-pathological studies on Is, Ip polyps and flat elevations in the large intestine].

We histologically compared 3 types of adenoma and cancer of the large intestine using 620 adenoma specimens (509 Is type lesions, 83 Ip type lesions, and 28 flat type lesions) and 113 specimens of early stage cancer (51 Is type lesions, 39 Ip type lesions, and 23 flat type lesions) obtained during the past 5-year period at our department. More than 90% of the Is and Ip type polyps were adenoma or carcinoma in adenoma while 25.5% of the flat elevations were m or sm carcinoma. Flat elevations even less than 10 mm in diameter were frequently carcinomas (26.3%) compared with the other types (both Is and Ip types, 6.7%), and all of those 10 mm or more in size were carcinomas. The distribution of the flat type early cancers in the large intestine was similar to that of advanced cancer with high percentages of carcinoma at each site compared with the other types. These results suggest that the carcinogenesis and progression of flat type early stage cancer differ from those of the other types.

Biclonal expansion of T cells infected with monoclonal Epstein-Barr virus (EBV) in a patient with chronic, active EBV infection.

Recent studies have suggested that a high percentage of Epstein-Barr virus (EBV)-infected lymphocytes in peripheral blood of patients with chronic, active EBV infection (CAEBV) is of T cell origin. Although T cells are expanded oligoclonally in CAEBV, it is not clear whether the restricted diversity of T cells arise from immune reaction against EBV-related antigens or from proliferation of EBV-infected cells. We experienced a patient with CAEBV who had biclonal expansion of peripheral blood T cells. We identified clonotypes of these two T cell clones in detail and purified the T cell clones. EBV infected mainly the two T cell clones, whereas the viral loads in peripheral blood cells other than these T cell clones were low or undetectable. The EBV strains infecting the two T cells clones were indistinguishable from each other by a series of genotype analyses of the virus. These results suggest that the two T cell clones infected with the same monoclonal EBV proliferated in peripheral blood of the patient.

Oligoclonally expanding gammadelta T lymphocytes induce IgA switching in IgA nephropathy.

The aetiology of IgA nephropathy (IgAN) is closely related with abnormality of mucosal immunity. We investigated the roles of gammadelta T cells in the regulation of IgA production by B cells in IgAN patients. The proportion of gammadelta T cells in peripheral blood mononuclear cells (PBMNC) was higher in IgAN patients than in the controls and was found to be correlated with the proportion of surface IgA-positive (sIgA+) B cells, which are precursors of IgA-secreting plasma cells. After in vitro PWM stimulation, sIgA expression on B cells and IgA production were significantly enhanced in PBMNC obtained from IgAN patients, whereas the enhancements were abolished by removal of gammadelta T cells from the PBMNC. Purified gammadelta T cells from IgAN patients induced surface IgA expression on naïve sIgD+ B cells more effectively than did alphabeta T cells. Moreover, stimulated gammadelta T cells from IgAN patients produced a larger amount of TGF-beta1, which is one of the main cytokines that induces IgA class switching on B cells, as compared with alphabeta T cells and control gammadelta T cells. The expanded gammadelta T cells from IgAN patients exclusively expressed Vgamma9, and the nucleotide sequences of junctional regions of Vgamma9 showed very limited TCR diversities. It was therefore concluded that gammadelta T cells, which are expanded in response to specific antigens, enhance IgA class switching on B cells in IgAN patients.

Rapid method for identification of group B streptococci in neonatal blood cultures.

A rapid technique used for the identification of Streptococcus agalactiae, Lancefield group B, from the blood cultures of two neonatal infants is reported. The method utilized the Phadebact Streptococcus Test System (Pharmacia Diagnostics, Piscataway, N.J.) and the supernatant from 13- and 14-h blood cultures. Additional studies with simulated neonatal blood cultures revealed that this method was reproducible. Additional studies also revealed that some non-specific agglutination did occur, which could not be eliminated with dithiothreitol, but was visibly reduced by treatment with soluble staphylococcal protein A.

Development-specific protein S of Myxococcus xanthus: purification and characterization.

Protein S, a development-specific protein of Myxococcus xanthus, was purified from the cells of a late stage of development and crystallized. Its circular dichroism spectra indicated that protein S had a high content of beta-structure in both the presence and absence of calcium ion, which is required for self-assembly of protein S on the myxospore surface. Its amino and carboxyl terminal sequences were determined to be alanine-aspartic acid-isoleucine-glycine-valine-alanine-methionine-asparagine-asparagine-aspartic acid-threonine-serine-serine and isoleucine-arginine (isoleucine, serine), respectively. When protein S (molecular weight, 23,000) was digested with trypsin, a trypsin-resistant core of 10,000 molecular weight was obtained. The core peptide was purified, and its amino acid composition was compared with that of protein S. The core peptide was capable of self-assembly on the spore surface in the presence of calcium ion and competed with protein S for binding on the spore surface. The ratio of affinity to the spore surface for protein S to that for the core peptide was 1.55.

Papillary adenocarcinoma in thyroid hemiagenesis.

Variation in the gross anatomy of the thyroid gland is relatively common. Although thyroid hemiagenesis is felt to be a rare anomaly, its incidence is probably underestimated as the diagnosis is usually incidental. The case of a 41-year-old woman with right thyroid hemiagenesis associated with papillary adenocarcinoma is presented. The diagnosis of hemiagenesis was established by isotope imaging and surgical exploration for a benign nodule. Seven years later she was seen with a recurrent neck mass, and an isotope scan revealed it to be a cold thyroid nodule. As she was diagnosed to have papillary adenocarcinoma, total thyroid lobectomy was performed and at present she remains disease-free.

Specific immunoglobulin E responses in ZAP-70-deficient patients are mediated by Syk-dependent T-cell receptor signalling.

ZAP-70 deficiency is a rare primary immunodeficiency characterized by the absence of peripheral CD8+ T cells and defects in T-cell receptor (TCR) signalling. T cells in ZAP-70-deficient patients are assumed to have no helper functions for B-cell immunoglobulin synthesis, whereas the patients rarely have antigen-specific antibodies. We experienced a ZAP-70-deficient patient, who had immunoglobulin E (IgE) antibodies specific to food allergens, and we investigated the mechanisms of switching to IgE in the patient. Peripheral blood mononuclear cells from the patient did not proliferate upon stimulation with the antigens but produced distinct levels of interleukin-4 (IL-4). Cell sorting analysis indicated that the cells that produced IL-4 in response to the antigens were enriched in CD4+ T cells. Purified CD4+ T cells from the patient produced IL-4 and expressed CD40L upon stimulation with anti-CD3. Moreover, CD4+ T cells pretreated with anti-CD3 induced mature epsilon transcript on naive B cells. Since the results indicated that there remained sufficient T-cell receptor (TCR)-signalling in the patient's T cells to exert antigen-specific IgE switching on B cells, we next investigated the expression of the ZAP-70-homologous kinase Syk. Syk was present in high levels in patient's CD4+ T cells and was tyrosine-phosphorylated after TCR stimulation. Inhibition of Syk by piceatannol resulted in decreased production of IL-4 and expression of CD40L on patient's CD4+ T cells. Moreover, Syk was expressed on all human T-cell leukaemia virus (HTLV-1)-transformed T-cell lines derived from peripheral blood of the patient, whereas it was low or undetectable in control lines. It was therefore concluded that specific IgE responses in the patient were most likely to be mediated by Syk-dependent TCR-signalling.