B cell development is perturbed in bone marrow from c-fos/v-jun doubly transgenic mice

c-fos and c-jun gene products form a heterodimeric complex (AP-1)that regulates target gene expression by binding to a specificDNA sequence motif. In order to study a role of AP-1 (Fos/Jun)in growth and differentiation of immature B lineage cells, wehave established and mated two independent transgenic mice carryingthe mouse c-fos gene or the viral v-Jun gene fused to the H-2Kpromoter. IL-7 dependent bone marrow cell culture from doublytransgenic (H2-fos/jun) mice demonstrated severe delay of earlyB cell development. Proliferation of pre-B cells in the freshbone marrow from HZ-fos/jun mice to IL-7 stimulation was verylow. These results suggest that the deregulated production ofAP-1 perturbs IL-7 mediated proliferation and differentiationof immature B cells.     

Functional combination of tapering profiles and overlapping arrangements in nonspanning skeletal muscle fibers terminating intrafascicularly

Using digital image analysis and several anatomical methods, morphometric analysis of nonspanning fibers which had tapering profiles at their intrafascicular termination sites and represented overlapping arrangements within the fiber fascicles was performed in the rat rectus abdominis. Special emphasis was focused on dimensional relationships occurring between overlapping portions and tapering segments and sarcomere lengths in non- and overlapping portions. Nonspanning fibers were found to overlap each other for more than 40% of their length. In length, their overlapping portions generally corresponded to their tapering segments, which were also greater than 40% of the fiber length. In addition, despite the presence of overlapping linkages, nonspanning fibers maintained a fairly uniform length irrespective of their overlapping and non-overlapping portions. Overlapping linkages in fibers without tapering profiles have a larger cross-sectional area in the overlapping portion than in the non-overlapping one, resulting in a phenomenon which will cause different sarcomere lengths between the two portions during fiber stretching. The present results suggest that tapering profiles in the overlapping portion ensure uniform sarcomere lengths within nonspanning fibers, thereby providing mechanical stability in each fiber. © 1993 Wiley-Liss, Inc.     

Arpp,a new homolog of carp,is preferentially expressed in type 1 skeletal muscle fibers and is markedly induced by denervation

In this study, we isolated and characterized a murine counterpart of the human Arpp (hArpp) gene. Sequence analysis revealed that the murine Arpp (mArpp) gene is almost identical to the Ankrd2 gene, which has recently been isolated as a mouse gene induced in stretched skeletal muscle. The mArpp gene encodes a protein of 332 amino acids that contains four well-conserved ankyrin-repeat domains in the central portion of the protein. The amino acid sequence of mArpp protein (mArpp) is highly homologous to that of mouse cardiac-restricted ankyrin-repeat protein (Carp), which is proposed to be a putative genetic marker for cardiac hypertrophy. Immunohistochemical analysis revealed that mArpp is preferentially expressed in type 1 skeletal muscle fibers, and that mArpp is localized in both the nucleus and the sarcomeric I-band of muscle fibers, suggesting that Arpp may function as a nuclear and sarcomeric protein. Furthermore, mArpp was also expressed in neurons of the cerebellum and cerebrum, the islets of Langerhans in the pancreas, and the esophageal epithelium, suggesting that mArpp may play a functional physiologic role in brain, pancreas, and esophagus as well as in type 1 muscle fibers. Interestingly, although mArpp was localized in both nucleus and cytoplasm in neurons, its localization was restricted to nucleus in pancreas and esophagus, suggesting that intracellular localization of mArpp is regulated in a tissue-specific manner. Furthermore, we found that mArpp- and Carp-expression in skeletal muscle were markedly up-regulated after denervation. Although the elevated expression level of Carp was kept only for two weeks after denervation, that of Arpp was kept at least for 4 weeks, suggesting that mArpp and Carp may play distinct functional roles in denervated skeletal muscle.     

CORRELATION BETWEEN GLYCOCONJUGATE EXPRESSION AND FUCOSYLTRANSFERASE ACTIVITY IN HUMAN COLORECTAL CARCINOMA

Using the surgically extirpated specimens from 9 patients with colorectal carcinoma, fucosyltransferase activities in the carcinoma tissue and the normal mucosa were measured and were compared with the hlstochemical findings of glycoconjugates which were shown by staining with lectins reacting with blood group antigens and related substances. The fucosyltransferase activities of the carcinoma tissue were well correlated with the overall findings of lectin stainings after neuraminidase treatment. The more intense the carcinoma tissue was stained, the higher the fucosyltransferase activity was shown. However, there were marked differences in the fucosyltransferase activities by the portions measured, depending upon the relative amount of carcinoma tissue and Interstitial tissue; in the invasive portion with less carcinoma tissue, the activity was generally low in comparison with that in the surface area where carcinoma tissue was rather abundant. Thus, the morphological and lectin hlstochemical finding are of paramount importance for the eveluation of glycosyltransferase activity in human colorectal carcinoma.     

p53 and Ki-67 immunoreactivity and nuclear morphometry of 'carcinoma-in-adenoma' and adenoma of the gall-bladder

Twenty lntramucosal tumors of ‘carclnomaln-adenoma’ and 43 ademas (39 pylorlc gland type, 4 Intestinal type) of the gall-bladder were studied to establish more precise histo-logical criteria of carcinoma or adenoma In cases of ‘carcinoma In pyforic gland type adenoma’, to compare carcinoma In adenoma with pure, that Is, without adenomatous components, carcinoma, and to confirm the benign nature of spin-dle cell fd in the adenomas. Ki-67 and p53 immunostaining and nuclear morphomety were used. Eight pure intramucessl cancers were used as controls. The formalin-fixed, paraffln+mbedded sections were stained with p53 and Ki-67 antibodies. Splndle cell foci were observed only In the adenoma area of the pyloric gland type, wlth a frequency of 23% In 39 adenomas, and of 45% in 20 tumors of carclnoma-lrradenoma. Ki-67 staining was negative in 129 of 130 spin-die cell foci examlned, regardless of their size, and positive in only one focus (550 pm in size, Ki-67 Index 0.2%). All of the spindle cell foci were negative for p53 stain. The Ki-67 positive index was 36.6 ± 5.6% In the 8 pure carcinomas, and 12.5 ± 1.9% in the cancer areas of 16 tumors with carcinoma-in-adenoma, while it was 7.9 ± 1.7% in the adenoma areas of 16 tumors with carcinoma-in-adenoma and 4.9 ± 0.5% in the 32 pure pyloric gland adenomas. The p53-protein over-expression was found in seven of eight pure intramucosal cancers, and in one of 16 cancer components of carclnoma-in-adenoma. However, it was not found in any of 16 adenoma components of carcinoma-in-adenoma, and 35 adenomas. Cells of the cancer tissue of carcinoma-In-adenoma showed a significantly larger nuclear area and a larger nuclear minor axis than those of the pyloric gland type adenomas, as well as other architectural and cytologic abnormalities differing from the features of adenomas. These results suggest that clustered spindle cells do not indmte a malignant transformation of adenoma cells and that carcinomas in carcinoma-in-adenoma are dtfferent from pylorlc gland type adenomas In terms of morphology and proliferative activity. Moreover, the results of the present study indicate that carcinomas In carcinoma-ln-adenoma are lower In malignancy than pure carcinomas, and that their genetic abnormaltty may differ from that of pure carcinomas.     

Heterogeneity in intergenic regions of the ribosomal repeat of the pine-blister rustsCronartium flaccidum andPeridermium pini

Mixed aeciospore isolates ofCronartium flaccidum andPeridermium pini were obtained from single-tree infections in Britain, Italy and Greece. The 5.8s ribosomal RNA gene and flanking intergenic transcribed spacer regions ITS 1 and ITS2 were found to be highly similar betweenC. flaccidum andP. pini. Within samples heterogeneity was detected at three nucleotide loci in the ITS1 and at four loci in the ITS2 suggesting that several fungal genotypes may occur at a single infection court. The heterogeneity was confirmed by heteroduplex polymorphism analysis of mixed aeciospore products. RFLP of the ribosomal intergenic spacer region 1 (IGSI) amplified from the same templates indicated limited sequence polymorphism in some copies of this repeated locus. Both the sexual and asexual forms ofC. flaccidum show evidence of sequence polymorphism in two independent, non-coding regions of the ribosomal gene array. Variation appears to be greater in the sexual formC. flaccidum, than in the monoaecious formP. pini.     

Association of genetic variation of the RIL gene,encoding a PDZ-LIM domain protein and localized in 5q31.1, with low bone mineral density in adult Japanese women

Twin and family studies had shown that genetic factors are important determinants of bone mass. Multiple genes might be involved. One candidate gene, the reversion-induced LIM gene (RIL), is a PDZ and LIM-domain-containing protein and has been localized within the cytokine cluster of chromosome 5 (5q31.1). In a genetic study of 370 adult Japanese women, we investigated the correlation between radial bone mineral density (BMD) and a genetic variation (−3333T→C) of the 5'-flanking region of RIL gene. A significant association was identified between the RIL variation −3333T→C and radial BMD (r=0.15, P=0.003). The variation of the RIL locus may be an important determinant of osteoporosis.     

Comparative study of effects of cyclosporins A and G on collagen arthritis in mice

The effects of the immunosuppressive agents cyclosporin G (CsG) and cyclosporin A (CsA) on collagen arthritis were compared in mice. When administered subcutaneously daily on days 0–13 after immunization with type II collagen, CsG and CsA were both capable of suppressing the development of collagen arthritis in mice as well as the immunological response to native type II collagen in a dose-dependent manner. Histopathologically, no marked inflammatory lesions were observed in diarthroidal joints from mice treated with 100 mg/kg per day of CsA or 800 mg/kg per day of CsG. However, an analysis of dose response showed CsG to be 8 times less potent than CsA in inhibiting the development of arthritis.     

Balloon cell nevus of the soft palate: an immunohistochemical and ultrastructural study

An ultrastructural analysis of oral balloon cell nevus of intramucosal type complemented with an immunohistochemical study was performed for the first time. The lesion was composed of large balloon cells with an admixture of small nevus cells and melanophages at the periphery. Balloon cells showed cytoplasmic accumulation of vacuoles of varying sizes and the presence of microgranular and vacuolated melanosomes were found. Residual cytoplasm contained no identifiable organelles. A spectrum of transitional forms between balloon cells and conventional nevus cells with microvacuoles was readily observed. Both cells exhibited intense immunoreactivity to multiple melanocytic markers. Ballooning phenomenon was not evident in melanophages containing a large amount of melanosome complex. It can be inferred, from the present and previous observations, that progressive vacuolization of melanosomes in nevomelanocytes may be responsible for the formation of peculiar ballooning appearance, suggesting an aberrant melanogenesis.     

Changes of cerebral vasoactive intestinal polypeptide-and somatostatin-like immunoreactivity induced by noise and whole-body vibration in the rat

To clarify the role of vasoactive intestinal polypeptide (VIP) and somatostatin, somatropin-release inhibiting factor, (SRIF) neurons in the response to organisms to noise or whole-body vibration stress, VIP and SRIF-like immunoreactivity were determined in various regions of the rat brain following exposure for 90 min to noise (broad band, 102 dB) or whole-body vibration (20 Hz, 4.0 g). Both noise and whole-body vibration significantly increased VIP-like immunoreactivity in the amygdala. A significant reduction of VIP like immunoreactivity in the hippocampus was induced only by whole-body vibration. On the other hand SRIF-like immunoreactivity was decreased significantly in the hypothalamus and increased significantly in the amygdala by noise and whole-body vibration, respectively. The present findings would seem to indicate that the amygdalofugal VIP neural system is involved in regulating hypothalamic and pituitary hormone secretions in non-specific reactions to stress. Responses of hippocampal VIP and the amygdalofugal SRIF to whole-body vibration stress are assumed to be activated as specific reactions to the stress.