Thymectomy modifies androgenizing effects of a testis transplant during critical period for neuroprogramming

Summary Thymectomy simultaneous with transplantation of a syngeneic testis from a littermate to Fischer 344 rats ameliorated the androgenizing effects of the testis transplant on ovarian morphology at 90 days of age.Supported by a Morseman Fellowship, NIH grants HD07097, AM21137 and NSF-RIAS grant SER77-06922.     

Thymectomy modifies androgenizing effects of a testis transplant during critical period for neuroprogramming.

Thymectomy simultaneous with transplantation of a syngeneic testis from a littermate to Fischer 344 rats ameliorated the androgenizing effects of the testis transplant on ovarian morphology at 90 days of age.     

Allotransplantation of rat parathyroid glands: effects of organ culture and transplantation into the adrenal gland.

Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB2) to Fischer rats (AgB1) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.     

Effect of acetylsalicylate on surgical bleeding, postoperative mortality and allograft survival in rats undergoing heart transplantation.

18 rats were treated with L-ASA before heart transplantation and daily thereafter until death or rejection. 22 animals acted as controls. A significantly higher post-operative mortality rate, without any significant modification of the transplant survival time, was found in L-ASA-treated group.     

Changes in gastro-intestinal serotonin content associated with fasting and satiation

Summary Rats fasted for 24 h were fed for 3 h, after whith time food was removed. Food intake decreased serotonin levels in the stomach and duodenum by 30 and 40%, respectively. These changes persisted for about 3 h. Food intake did not change tryptophan content in the stomach, while, in the duodenum, tryptophan level rose by 100% at the end of the feeding period and remained elevated for about 9 h.     

Allotransplantation of rat parathyroid glands: Effects of organ culture and transplantation into the adrenal gland

Summary Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB²) to Fischer rats (AgB¹) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.Acknowledgments. The authors thank Mrs Barbara Lovett for her secretarial assistance.     

HIV/AIDS: modified stem cells in the spotlight

Since HIV/AIDS was first recognized in 1981, an urgent need has existed for the development of novel therapeutic strategies to treat the disease. Due to the current antiretroviral therapy not being curative, human stem cell-based therapeutic intervention has emerged as an approach for its treatment. Genetically modified hematopoietic stem cells (HSCs) possess the potential to self-renew, reconstitute the immune system with HIV-resistant cells, and thus control, or even eliminate, viral replication. However, HSCs may be difficult to isolate in sufficient number from HIV-infected individuals for transplantation and/or re-infusion of autologous HSCs preparations would also include some contaminating HIV-infected cells. Furthermore, since genetic modification of HSCs is not completely efficient, the risk of providing unprotected immune cells to become new targets for HIV to infect could contribute to continued immune system failure. Therefore, induced pluripotent stem cells (iPSCs) should be considered a new potential source of cells to be engineered for HIV resistance and subsequently differentiated into clonal anti-HIV HSCs or hematopoietic progeny for transplant. In this article, we provide an overview of the current possible cellular therapies for treating HIV/AIDS.     

多排螺旋CT扫描对胃癌的诊断价值

目的评价多排螺旋CT扫描对胃癌的诊断价值。方法对62例胃癌病例行气体对比薄层动态增强CT扫描三维重建技术,层厚0．5mm,在此基础上进行CT仿真胃镜和VRT技术,对获取的图像进行分析。全部病例均经手术和病理证实。结果检出痛变位于胃窦部31例（50％）.胃底贲门部10例（16％）,体部9例（15．7％）,弥漫型12例（19．3％）,病变检出率为100％。多薄层动态增强cT扫描三维重建技术表现为局限性胃壁增厚50例,广泛性胃壁增厚12例;其中早期胃癌10例,进展期胃癌52倒;局部和远处淋巴结转移24例;远处转移17例;本组CT定性诊断准确率为96％。结论薄层动态增强CT扫描三维重建技术能清晰显示胃壁及腔内、外病变,并直观反映胃癌大体形态及肿瘤的范围,在胃癌的定位、定性和定量诊断中发挥其独特的优势,是一种最具潜力的检查方法。     

Microsatellite instability in gastric cancer: molecular bases,clinical perspectives,and new treatment approaches

Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.     

Tachykinins in regulation of gastric motility and secretion

The tachykinins constitute a family of neuropeptides with a common C-terminal amino acid sequence. The best known tachykinin is substance P. Tachykinins are found in the nerve plexuses and nerve fibers in the stomach of all species examined. The circular muscle layer is densely innervated, whereas the longitudinal layer and the mucosa are less intensively innervated. Tachykinins are also found in a significant number of afferent neurons with cell bodies in the dorsal root ganglia. Release of tachykinin can be demonstrated in response to both electrical stimulation of the vagus nerves and application of capsaicin. In the stomach all three known tachykinin receptors seem to be present. Although species variations exist, NK-2 receptors are generally present on the musculature, NK-1 receptors on both neurons and muscles, and NK-3 receptors on neurons only. Tachykinins stimulate motility in all parts of the stomach, but tachykinins also appear to inhibit motility in certain situations. Also, motility initiated centrally, mediated through the vagus nerves, is influenced by tachykinins. The precise role of tachykinin in the various motor programs in the stomach is not clear. Gastric acid secretion is influenced by tachykinins in several species. Tachykinins do not seem to act as neurotransmitters directly on parietal cells, but may have a modulatory function. The importance of tachykinins for the regulation of pepsinogen and hormone secretion from the stomach remains unclear. Received 24 August 1999; received after revision 1 December 1999; accepted 3 December 1999     

Nitrate fertilizers as environmental pollutants: Positive correlation between nitrates (NaNO3 and KNO3) used per unit area and stomach cancer mortality rates

Summary Since a significant positive correlation between nitrate fertilizer exposure and stomach cancer mortality has been found, a study of nitrate fertilizer pollution in arable land in terms of amount of nitrates used per unit area (kg/ha) and stomach cancer death rates was carried out. The regression of death rates for stomach cancer, standardized for age, on the nitrates used per unit area, by province (N=25), exhibited a significant association between the 2 variables (p<0.004). When industrialized provinces (N=3) were not considered, a highly significant association was found (F=16.47; d.f.=1,20;p<0.0006). The correlation coefficient was+0.672.     

Epithelial-mesenchymal interaction in differentiation of duodenal epithelium of fetal rats in organ culture

Summary Epithelial-mesenchymal interaction in the differentiation of duodenal epithelium of fetal rats was investigated by recombination experiments in vitro. The proportion of goblet cells in duodenal epithelium was significantly greater on recombination of developing duodenal epithelium with mesenchyme of the glandular stomach than on recombination with that of the duodenum. Mesenchyme of the glandular stomach or forestomach was better than duodenal mesenchyme in supporting morphogenesis of duodenal epithelium. Treatment of tissues with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) did not affect these tissue interactions.This work was supported by grants-in-aid for cancer research from the Ministry of Education, Science and Culture, Japan.Acknowledgment. The authors wish to express their gratitude to Prof. T. Mizuno of the University of Tokyo for valuable suggestions.     

Liminal gastrin does not activate rat stomach histidine decarboxylase

Summary Fasted rats have a low gastric histidine decarboxylase activity. I.v. infusion of heptadecapeptide gastrin for 2 h raised the enzyme activity. Intragastric perfusion with the same dose of gastrin and for the same period of time did not reproduce the effect of circulating gastrin. It is concluded that luminal gastrin, in contrast to circulating gastrin, does not activate rat stomach histidine decarboxylase.This study was supported by the Swedish Medical Research Council (04X-1007, 14X-4144) and by the Albert Påhlsson Foundation.     

Immunoregulatory properties of the cytokine IL-34

Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Until now, studies have demonstrated that this cytokine is released by some tissues that differ to those where CSF-1 is expressed and is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involvement of IL-34 has been shown in areas as diverse as neuronal protection, autoimmune diseases, infection, cancer, and transplantation. Our recent work has demonstrated a new and possible therapeutic role for IL-34 as a Foxp3⁺ Treg-secreted cytokine mediator of transplant tolerance. In this review, we recapitulate most recent findings on IL-34 and its controversial effects on immune responses and address its immunoregulatory properties and the potential of targeting this cytokine in human.     

Effect of splanchnectomy and vagotomy on the pepsinogen response to intragastric acid

Summary Perfusion of the stomach in the anaesthetized rat with saline acidified to pH 2.5 with hydrochloric acid induced a small but significant release of pepsinogen into the perfusate. This stumulus to secretion was unaffected by splanchnectomy but was abolished by vagotomy. It is concluded that to a modest degree acid secretion in the rat may stimulate pepsinogen secretion by a vagal pathway.     

Verlängerte Überlebenszeit von Hauthomotransplantaten bei Mäusen durch ein Methylhydrazinderivat

Summary Extended survival of skin homografts in mice was obtained by treatment with a methylhydrazine derivative (1-methyl-2-p-(isopropylcarbamoyl)-benzylhydrazine hydrochloride), representative of a new class of cytotoxic agents. Administration of 100 mg/kg prior to and continuously after the transplantation led to similar survival times as when 300 mg/kg was given daily only after the transplantation. In mice, the compound seems to be more effective than most of the drugs so far known to suppress transplantation immunity.     

Calcitonin: effect on protein synthesis in different rat tissues

Protein synthesis was inhibited in the pancreas whereas it was enhanced in the kidney and intestine (jejunum-ileum) after a single injection of porcine calcitonin (20 MRC units/kg b.wt). The incorporation of [3H]leucine into total protein in the brain, heart, liver and stomach did not change after the hormone treatment.     

Selective effects of gonadal steroids on the response of peripheral serotonin receptors

The maximal contraction provoked by serotonin (5-HT) in isolated stomach strips of adult rats, a functional index for peripheral 5-HT receptors, was sexually differentiated, androgen-sensitive, and estrogen refractory. This is at variance with the reported sensitivity of central 5-HT receptors to estrogen.     

Different marrow cell number requirements for the haemopoietic colony formation and the curve of the W/Wv anemia.

The lowest cell number in the normal marrow transplant, which allows the cure of W/Wv anemia was found to be between 10(4) and 10(5). This exceeds by several times the lowest cell number necessary for the haemopoietic colony formation. Therefore, either the colony forming cell is not the haemopoietic stem cell but rather its progeny, or this cell requires an aid from some other cells to exert is activity.     

Selective effects of gonadal steroids on the response of peripheral serotonin receptors

Summary The maximal contraction provoked by serotonin (5-HT) in isolated stomach strips of adult rats, a functional index for peripheral 5-HT receptors, was sexually differentiated, androgen-sensitive, and estrogen refractory. This is at variance with the reported sensitivity of central 5-HT receptors to estrogen.