Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal.

Recently an essential role of interstitial cells of Cajal (ICC) within myenteric plexus (ICC-MY) was suggested in ascending contraction and descending relaxation in the mouse ileum. The role of ICC in these neural reflexes was examined in the distal colonic segments prepared from the wild type and c-kit mutant, W/W(V) mice, in the present study. Localized distension of the segments from the wild type mice by using a small balloon resulted in ascending contraction and descending relaxation. In the segments from the mutant mice, localized distension also induced these neural reflexes similar to those observed in the wild type mice. Immunohistochemical examination demonstrated that ICC-MY and ICC present in muscle layers (ICC-IM) were severely disrupted in the mutant mouse, but only ICC, present within submucosal plexus (ICC-SMP), remained unchanged. In the small strips with ICC-SMP absent prepared from the mutant mouse, electrical field stimulation induced contraction or relaxation in the absence or presence of atropine, respectively. It was suggested that ICC have no important role in the ascending and descending neural reflexes in the mouse distal colon, this is in direct contrast to the role of ICC-MY in the ileum.     

Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic-denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP–SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA–AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP–AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.     

Localization of mRNA for inflammatory cytokines in radicular cyst tissue by in situ hybridization, and induction of inflammatory cytokines by human gingival fibroblasts in response to radicular cyst contents

The expression of mRNA encoding the inflammatory cytokines interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) have been examined in radicular cysts by in situ hybridization. Furthermore, the biological activity of the contents of radicular cysts (RCC) has been assayed by adding extracts of RCC to cultured human gingival fibroblasts (HGFs) and analyzing the culture medium for the release of inflammatory cytokines. In the epithelial layer, keratinocytes expressed all cytokine mRNAs examined at various levels. Basal layer cells expressed mRNA for each cytokine. In the subepithelial granulation tissue of the cysts, fibroblasts and macrophages expressed mRNA for IL-6, IL-8, IL-1β and TNF-α mRNA at varying levels; especially clear expression of TNF-α and IL-1β mRNA was detected on macrophages. The infiltrating lymphoid cells, largely composed of T cells and plasma cells, expressed these cytokine mRNAs, especially those encoding IL-6 and IL-8, at various levels. In vitro analysis indicated dose-dependent release of both IL-6 and IL-8 by HGFs in response to RCC. After heating to 100°C for 10 min, RCC almost completely failed to stimulate IL-6 release from HGFs. Furthermore, anti-IL-1β antibody (neutralization test) did not prevent the stimulation of IL-6 release by RCC. Significant amounts of IL-6 and IL-8 were detected in RCC in two cases, and a trace amount of IL-1β was detected in one case. This study demonstrated the wide expression of mRNA encoding inflammatory cytokines in radicular cyst tissues, and RCC itself was capable of stimulating 1L-6 and 1L-8 production from HGFs.     

Ubiquitous Presence in Mammalian Cells of Enzymatic Activity Specifically Cleaving 8-Hydroxyguanine-containing DNA

Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh⁸Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh⁸Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh⁸Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh⁸Gua from DNA is widely distributed in mammalian cells.     

Intercostal hemangioma

This paper presents a case of intercostal hemangioma, in which a complete surgical resection was accomplished based upon a tentative diagnosis provided by magnetic resonance imaging (MRI). A 27-year-old man visited our hospital for the evaluation of chest pain and shortness of breath after exertion. Computed tomography showed a soft tissue mass, 5.5×3.5 cm in size, arising from the right lateral 7th intercostal space. Dynamic MRI showed that the mass was enhanced rapidly in the early phase and that this early enhancement was maintained during the delayed phase, which was compatible with a diagnosis of intercostal hemangioma. The patient underwent surgery, and a complete resection of the tumor with the right 7th and 8th ribs and their intercostal muscles was accomplished. Histopathological examination confirmed the diagnosis of intramuscular hemangioma of the large-vessel type. Presently, 6 months after the operation, the patient is doing well, without any evidence of local recurrence.     

Hepatic angiomyolipoma developing during the follow-up of ulcerative colitis: Report of a case and review of the literature

Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5×7.5×7cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma.     

Isolation and radiation hybrid mapping of dinucleotide repeat polymorphism at the human matrix Gla protein (MGP) locus

Matrix Gla protein (MGP) is an 84-residue, vitamin K-dependent protein expressed by chondrocytes and vascular smooth muscle cells, and is a potent regulator of calcium deposition in cartilage and arterial wall. We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human MGP gene. This polymorphism will be useful in genetic studies of arteriosclerosis and osteoporosis. Received: November 5, 1997 / Accepted November 27, 1997     

Cytomegalovirus infection of the central nervous system stem cells from mouse embryo: a model for developmental brain disorders induced by cytomegalovirus

Cytomegalovirus (CMV) is the most frequent infectious cause of developmental disorders of the central nervous system (CNS) in humans. Infection of the CNS stem cells seems to be primarily responsible for the generation of the brain abnormalities. In this study, we evaluated the infectivity of murine CMV (MCMV) in epidermal growth factor (EGF)-responsive CNS stem cells prepared from fetal mouse brains, and studied the effect of infection on growth and differentiation of the stem cells. The CNS stem cells were permissive for MCMV infection, although MCMV replication was slower than in mouse embryonic fibroblasts. MCMV infection inhibited the growth and DNA replication of the stem cells. A clonogenic assay revealed that MCMV infection suppressed generation of colonies from single stem cells. When uninfected stem cells were induced to differentiate, a decrease in expression of the primitive neuroepidermal marker nestin was observed by immunocytochemistry and flow cytometry, whereas expression of neurofilament and glial fibrillary acidic protein (GFAP) were induced. In virus-infected CNS stem cells, nestin expression was retained, whereas the expression of neurofilament was more severely inhibited than that of GFAP in these cells. Two-color flow cytometry showed that differentiated glial precursor cells were preferentially susceptible to MCMV infection. MCMV-infected and uninfected CNS stem cells were transplanted into the neonatal rat brains. The reduced number of infected stem cells were engulfed into the subventricular zone and expressed GFAP, but did not migrate further, in contrast to the uninfected stem cells. These results suggest that suppression of the growth of the CNS stem cells and inhibition of the neuronal differentiation by CMV infection may be primary causes of disorders of brain development in congenital CMV infection.     

Isolation of a polymorphic CA repeat sequence at the human progesterone receptor (PGR) locus

We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the human progesterone receptor (PGR) gene. This polymorphism will be a useful marker in the genetic study of disorders affecting female endocrine systems, such as progesterone resistance and breast, uterine, and ovarian cancers. Received: July 27, 1998 / Accepted: July 29, 1998     

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.