Differential effect of the autoimmune Yaa and lpr genes on the acceleration of lupus-like syndrome in MRL/MpJ mice

The Yaa gene (Y chromosome-linked autoimmune acceleration), linked to the BXSB/MpJ Y chromosome, and the autosomal recessive lpr (lymphoproliferation) gene have been shown to accelerate the progression of the lupus-like autoimmune syndrome in the BXSB and MRL strains, respectively. To compare more directly the role of the Yaa and lpr genes in the development of the autoimmune syndrome, the Y chromosome of BXSB mice was transferred to MRL mice by backcross procedures, and the effect of the Yaa gene on the autoantibody formation and the development of lupus-like nephritis in MRL mice was investigated in comparison with those bearing the lpr mutation. The Yaa gene as well as the lpr gene were able to shorten the life span of MRL mice as a result of the accelerated development of lethal lupus-like nephritis. However, the acceleration promoted by the Yaa gene (50% mortality rate: 12 months) was less severe than that induced by the lpr gene (50% mortality rate: 7 months). This may be related to the finding that the lpr gene enhanced the production of a large spectrum of autoantibodies, including anti-DNA, rheumatoid factors and anti-gp70, and of cryoglobulins, whereas only anti-gp70 production among the autoantibodies studies was markedly enhanced by the Yaa gene. The selective autoimmune accelerating effect of the Yaa gene was similarly observed in (NZW X MRL)F1 hybrid mice. Our results suggest that the Yaa gene, unlike the lpr gene, exhibits selective autoimmune accelerating activity, but as a result of increased formation of certain nephritogenic autoantibodies such as anti-gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus-like nephritis in lupus-prone mice.     

M. cervico-humeralis--a case report

An abnormal muscle, so-called M. cervico-humeralis, was found bilaterally in a 50-year-old Japanese male in a dissection practice at Jikei University in 1989. This is the third report of the cervico-humeral muscle in Japan, and the first case which occurred bilaterally. Both muscles were similar in shape, origin, course, and insertion. The flat and triangular-shaped muscle arose by tendinous slips from the transverse processes of the sixth and seventh cervical vertebrae (VC6 and VC7). These two tendons converged to form a single slip which passed through the brachial plexus. This single slip became a muscle running obliquely downward and laterally together with the brachial plexus and subclavian vessels to reach the medial surface of the humerus. The muscle inserted linearly by a thin flattened tendon into the lower end of the lesser tubercle and into the medial lip of the intertubercular sulcus of the humerus. The supplying nerve originated directly from the posterior cord of the brachial plexus in both muscles. The artery to the right cervico-humeral muscle arose from the axillary artery together with a branch to the subscapular muscle.     

Somatic mitochondrial mutation in gastric cancer.

Likely hot spots for mutations are mitochondrial sequences as there is less repair and more damage by carcinogens compared with nuclear sequences. A somatic 50-bp mitochondrial D-loop deletion was detected in four gastric adenocarcinomas. The deletion included the CSB2 region and was flanked by 9-bp direct repeats. The deletion was more frequent in adenocarcinomas arising from the gastroesophageal junction (4/32, 12.5%) compared with more distal tumors (0/45). Topographical analysis revealed the absence of the deletion from normal tissues except in focal portions of smooth muscle in one case. In two cases, apparent mutant homoplasmy was present throughout two tumors, including their metastases. In the two other cases, the mutation was present in only minor focal portions ( < 5%) of their primary tumors. These findings document the presence of somatic mitochondrial alterations in gastric cancer, which may reflect the environmental and genetic influences operative during tumor progression.     

Importance of basophilia in haematopoietic disorders

To the significance of basophilia in haematopoietic disorders, six draw attention to cases have been analyzed. Associated diseases included acute myelogenous leukaemia (AML-M2, M3, M4, and M6), refractory anaemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T). Two AML cases (M2, M6) were preceeded by myelodysplastic syndromes (MDS). All patients showed greater than 3% basophilia in peripheral blood and bone marrow. Basophils were identified successfully by metachromatic staining with toluidine blue in all cases. Three patients (M3, M4, RAEB) presented with lymphadenopathy, suggesting an association with extramedullary involvement. Neutrophil alkaline phosphatase (NAP) activity was significantly reduced in four patients with AML (M2, M3, M4) and RAEB-T. The clinical course was generally unfavourable characterized by short remission duration or disease progression except for the patient with RAEB. Haemorrhage was the main cause of death rather than infection. Cytogenetic analysis revealed unique abnormalities involving chromosomes 3q21, 5q31, and 17q11 where the genes for some haematopoietic growth factors or their receptors are located, in addition to t(6;9) and t(15;17).     

Effects of mutation and growth rates on patterns of microsatellite instability.

The detection of somatic microsatellite (MS) alterations in tumors is often interpreted as a sign of underlying genomic instability. However, it is unclear why the proportions of altered MS loci vary between different mutator phenotype tumors. We present a simple mathematical analysis that can account for some of these differences, recognizing that the mutations accumulated in a tumor reflect both its mutation rate and number of cell divisions. Only a small proportion of mutated MS loci are expected in tumors with normal or low mutation rates. In contrast, tumors with high mutation rates may or may not acquire mutations depending on the numbers of divisions that proceed the onset of the mutator phenotype. The majority of MS loci should accumulate mutations if high mutation rates are acquired early in tumor progression. Somatic MS mutations provide clues to both the mode and tempo of tumori-genesis.     

Beta-catenin mutations are frequent in calcifying odontogenic cysts, but rare in ameloblastomas

We have reported previously that alterations to beta-catenin occur frequently in adamantinomatous craniopharyngioma. Based on its histological resemblance to some odontogenic tumors, we suspected the presence of common genetic alterations among these tumors. To address this issue, 11 cases of calcifying odontogenic cyst (COC) and 20 cases of ameloblastoma were investigated for the presence of beta-catenin mutations and beta-catenin expression. Ten COCs were successfully analyzed by direct sequencing, and nine of them were found to harbor somatic beta-catenin mutations. Immunohistochemically, all of the COCs showed nuclear and cytoplasmic expression of beta-catenin with a heterogeneous pattern. No beta-catenin mutations were found in ameloblastomas, except for one case of the follicular type. All follicular ameloblastomas exhibited moderate nuclear and cytoplasmic accumulation of beta-catenin, in contrast to the predominantly membranous expression seen in the plexiform type. beta-Catenin mutation is considered to be a characteristic genetic feature of COC, and may play a critical role in its histogenesis. Although ameloblastoma closely resembles COC histologically, the two have genetically distinctive features.     

Importance of a biofouling-resistant phospholipid polymer to create a heparinized blood-compatible surface

Heparinization is believed to be one of the methods to suppress thrombus formation on blood-contacting surfaces. However, this study hypothesizes that heparinization alone might not be sufficient to provide a blood-compatible surface; that is, a surface property that resists biofouling is necessary to obtain an effective heparin-modified surface. 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers with 2-aminoethyl methacrylate (AEMA) were synthesized to immobilize heparin through ionic bonding. The primary amino groups of AEMA were considered to be the polymer surface because the zeta-potential of the surface was positive when the mole fraction of the AEMA units was above 0.2. The antithrombogenic character of the polymer surface modified with heparin was evaluated by both Lee-White and microsphere column methods. The coagulation period of human whole blood in the absence of anticoagulant in glass tubing coated with the MPC polymer was longer than that in the original glass tube. Cell adhesion was completely inhibited on the MPC polymer surface after contact with human whole blood without anticoagulant. However, many adherent blood cells were observed on poly(2-ethylhexyl methacrylate-co-AEMA) (no MPC unit) even after heparinization. These results strongly indicate that the MPC polymer is a useful substrate where the heparin works well and that the heparin-immobilized MPC polymer has superior blood compatibility to the simple MPC polymer.     

Structural identification of an epitope of antigenic factor 5 in mannans of Candida albicans NIH B-792 (serotype B) and J-1012 (serotype A) as beta-1,2-linked oligomannosyl residues.

In previous articles, we reported the presence of phosphate-bound beta-1,2-linked oligomannosyl residues in the mannans of strains of Candida albicans serotypes A and B and Candida stellatoidea. To identify the antigenic factor corresponding to this type of oligomannosyl residue, a relationship between chemical structure and antigenic specificity in the mannans of C. albicans NIH B-792 (serotype B, B-strain) and C. albicans J-1012 (serotype A, J-strain) was investigated by using a combination of two-dimensional 1H nuclear magnetic resonance spectroscopy of H-1, H-2, and H-5 regions in the mannans and an enzyme-linked immunosorbent assay that employed concanavalin A-coated microtiter plates. It was shown in the present 1H nuclear magnetic resonance study that an examination of chemical shifts not only in the H-1 region but also in the H-5 region was useful for the quantitative determination of the phosphate-bound beta-1,2-linked oligomannosyl residues. In the enzyme-linked immunosorbent assay using concanavalin A-coated plates, it was revealed that, of factor sera 1, 4, and 5, only factor serum 5 showed a reactivity proportional to the densities of the beta-1,2-linked oligomannosyl residues of the mannan subfractions of different phosphate contents that had been prepared from the bulk B-strain mannan by DEAE-Sephadex chromatography. The above results indicate that the phosphate-bound beta-1,2-linked oligomannosyl residues, Manp beta 1----(2Manp beta 1----)n2Man (n = 0-5), correspond to antigenic factor 5.     

Biological effects of static magnetic fields on the microcirculatory blood flowin vivo: a preliminary report

There have been few studies of the effect of static magnetic fields on microcirculatory haemodynamics in vivo. The rat skinfold transparent chamber technique was used, which provides an excellent means of observing and quantifying direct in vivo microvascular haemodynamic responses to static magnetic fields up to 8 T. An intravital videomicroscope was used to measure the changes in blood flow before and after exposure to a magnetic field for 20 min in a horizontal type superconducting magnet with a bore 100 mm in diameter and 700 mm long. After exposure, microcirculatory blood flow showed an initial increase for about 5 min followed by a gradual decrease and a return to the control value. It is hypothesised that these changes represent rebound hyperaemia following reduced blood flow during exposure.     

Developmental switch from GABA to glycine release in single central synaptic terminals

Early in postnatal development, inhibitory inputs to rat lateral superior olive (LSO) neurons change from releasing predominantly GABA to releasing predominantly glycine into the synapse. Here we show that spontaneous miniature inhibitory postsynaptic currents (mIPSCs) also change from GABAergic to glycinergic over the first two postnatal weeks. Many 'mixed' mIPSCs, resulting from co-release of glycine and GABA from the same vesicles, are seen during this transition. Immunohistochemistry showed that a large number of terminals contained both GABA and glycine at postnatal day 8 (P8). By P14, both the content of GABA in these mixed terminals and the contribution of GABA to the mixed mIPSCs had decreased. The content of glycine in terminals increased over the same period. Our results indicate that switching from GABAergic to glycinergic inputs to the LSO may occur at the level of a single presynaptic terminal. This demonstrates a new form of developmental plasticity at the level of a single central synapse.