Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.     

Comparison of mesiodistal tooth crown diameters and arch dimensions between modern Mongolians and Japanese

The purposes of this study were to establish normative data for mesiodistal tooth crown diameters and arch dimensions in Mongolian adults and to compare them with those of Japanese adults. The study materials comprised dental casts of 100 modern Mongolian and 100 Japanese subjects (50 males, 50 females for each) with Angle Class I normal occlusion. The mean ages were 20 years 8 months for the Mongolian subjects and 20 years 0 months for the Japanese subjects. On the dental casts, the mesiodistal tooth crown diameters (excluding wisdom teeth) and dental arch dimensions were measured. The following arch dimensions were measured: inter-canine lingual, inter-premolar lingual, inter-molar lingual, inter-molar central, coronal arch length, basal arch length, and basal arch width. In the Mongolian samples, significant sex differences were noted, and most of the items were significantly larger in males than in females. Significant differences between the Mongolian and Japanese samples were mainly noted in the premolar and molar regions, rather than in the anterior region, and were significantly smaller in the Mongolian samples. In the Mongolian samples, the molar section widths and basal arch width and length were significantly larger in males and females compared with the Japanese samples. These results suggest that the tooth crown size and arch dimensions in the Mongolian samples differed from those in the Japanese samples, and that establishment of the clinical norm for Mongolian adults might be helpful in formulating treatment plans for Mongolian patients, given that these parameters are the basic tools for diagnosis.     

Murine colon carcinoma cells engineered to produce human interleukin-2 induce tumor-specific anti-tumor response

Murine colon carcinoma cells (colon 26) transduced by a retrovirus vector with the human interleukin-2 (IL-2) cDNA were studied for their tumorigenicity. Although cell growth in vitro was not affected by integration of the IL-2 gene, s.c. tumors of IL-2-producing colon 26 cells (H2) in syngeneic mice regressed spontaneously after producing small masses. Histological examination of the sites of tumor rejection revealed predominant infiltration of macrophages around the tumor necrotic mass. Subsequent challenge with parent colon 26 cells, but not with Meth A cells (fibrosarcoma of the same genetic background), did not result in tumor formation in mice which had been protected against H2 cells. Inoculation of H2 cells into syngeneic nude mice resulted in tumors with a retarded growth rate. Taken together, T cell-dependent, tumor-specific immunity is obtained by local IL-2 secretion around colon tumors, and this experimental animal model gives us a clue(s) for investigating host anti-tumor responses by cytokine production. © 1996 Wiley-Liss, Inc.     

Spontaneous reconstruction of the canine hypogastric nerve over a long period after removing half of its length

Spontaneous reconstruction of the sympathetic pathway projecting to the seminal tract after serious injury has not been well understood. Multiple cross-innervation mechanisms from the spinal cord via the hypogastric nerve to the seminal tract have been demonstrated currently. This study was undertaken to explore long-term spontaneous reconstruction of the canine hypogastric nerve (HGN), which controls ejaculation, after removing half of its length. Further, the study tried to identify the crossed-pathway(s) reconstructed. Responses of the vas deferens/epididymis and bladder neck to electrical stimulation of the lumbar splanchnic nerve (LSN) or the HGN were examined. In six dogs whose hypogastric nerve was injured bilaterally as described above 4 years before, corresponding to more than 20 years in human, nine (43%) and 13 (57%) of the 21 LSNs stimulated elicited elevation of vasal and bladder neck pressure, respectively. By combining re-transection of a HGN, the following pathways to the vas deferens/epididymis were identified to have been reconstructed: (1) to the ipsilateral was deferens/epididymis without crossing to the other side; (2) to the contralateral vas deferens/epididymis by crossing to the other side at the caudal mesenteric plexus (CMP); (3) to the contralateral vas deferens/epididymis by crossing to the other side from the ipsilateral HGN at the commissural branches between the right and left pelvic plexuses (CBPP); and (4) to the ipsilateral vas deferens/epididymis by crossing twice at the CMP to the other side and at the CBPP again from the contralateral HGN to the ipsilateral side. The similar patterns of reconstruction were also observed in the bladder neck. The above results indicate that the sympathetic pathways via the HGN to the canine seminal tract can be reconstructed spontaneously in a high rate over a long period after serious injuries and that their cross-innervation system can be repaired.     

Galanin-Like Peptide (GALP) Facilitates Thermogenesis via Synthesis of Prostaglandin E2 by Astrocytes in the Periventricular Zone of the Third Ventricle

Administration of galanin-like peptide (GALP) leads to a decrease in both total food intake and body weight 24 h after injection, compared to controls. Moreover, GALP induces an increase in core body temperature. To elucidate the mechanism by which GALP exerts its effect on energy homeostasis, urethane-anesthetized rats were intracerebroventricularly injected with GALP or saline, after which oxygen consumption, heart rate, and body temperature were monitored for 4 h. In some cases, animals were also pretreated with the cyclooxygenase (COX) inhibitor, diclofenac, via intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. c-Fos expression in the brain was also examined after injection of GALP, and the levels of COX and prostaglandin E₂ synthetase (PGES) mRNA in primary cultured astrocytes treated with GALP were analyzed by using qPCR. The i.c.v. injection of GALP caused biphasic thermogenesis, an effect which could be blocked by pretreatment with centrally (i.c.v.), but not peripherally (i.v.) administered diclofenac. c-Fos immunoreactivity was observed in astrocytes in the periventricular zone of the third ventricle. GALP treatment also increased COX-2 and cytosolic PGES, but not COX-1, microsomal PGES-1, or microsomal PGES-2 mRNA levels in cultured astrocytes. We, therefore, suggest that GALP elicits thermogenesis via a prostaglandin E₂-mediated pathway in astrocytes of the central nervous system.     

The DD genotype of angiotensin converting enzyme polymorphism is a risk factor for coronary artery disease and coronary stent restenosis in Japanese patients

Stent implantation has decreased the incidence of restenosis after coronary intervention, but has not eliminated it. The contribution of the angiotensin-converting enzyme (ACE) genotype to the development of coronary artery disease and restenosis after coronary stenting was investigated in 67 Japanese patients in whom 103 lesions in which stents had been successfully implanted were assessed by quantitative coronary angiography, before, immediately after coronary stenting, and during follow-up. The distribution of the patients with the DD, ID, and II genotypes was 13%, 54%, and 33%, respectively. The prevalence of multivessel disease in the DD genotype was significantly higher (DD genotype: 78%; ID genotype: 58%; II genotype: 27%, chi2=8.13, p=0.016) and the late loss in the DD genotype (1.43+/-0.96 mm) was significantly greater (ID genotype: 0.78+/-0.98 mm and II genotype: 0.79+/-0.88 mm, p<0.05 vs DD genotype). However, there was no significant difference in the restenosis rate among the 3 genotypes. The present study in Japanese patients indicates that the DD genotype is associated with more extensive coronary artery disease and progression of the inward remodeling within the stented lesion, which is primarily caused by neointimal hyperplasia.     

The value of combined99mTc-Sn-colloid and99mTc-RBC scintigraphy in the evaluation of a wandering spleen

Wandering spleen is the term commonly applied to splenic hypermobility that results from laxity or maldevelopment of its suspensory ligaments. It comes to medical attention usually as an abdominal mass, or when the spleen undergoes torsion. Diagnosis on clinical grounds alone is rarely made, and ultrasonography, CT and MRI findings have no specific characteristics for this condition.^99mTc-labeled colloid taken up by the spleen may provide a specific diagnosis. We report a case of wandering spleen, in which the preoperative diagnosis was made on the basis of sequential liverspleen scintigraphy with^99mTc-Sn-colloid and blood-pool scintigraphy with^99mTc-RBC. This is a rare case, in which hypermobility was assessed by sequential^99mTc-Sn-colloid scintigraphy, and to our knowledge, is the first case in which^99mTc-RBC scintigraphy provided useful information on splenic blood volume and its location.