Adolescent anabolic/androgenic steroids: Aggression and anxiety during exposure predict behavioral responding during withdrawal in Syrian hamsters (Mesocricetus auratus)

In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within-subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety-eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time.     

Cytogenetical damage in exfoliated oral mucosa cells in elderly people suffering denture stomatitis

doi:10.1111/j.1741‐2358.2009.00315.x
Cytogenetical damage in exfoliated oral mucosa cells in elderly people suffering denture stomatitis Objectives: The aim of this study was to evaluate comparatively the DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated oral mucosa cells from chronic denture stomatitis patients and healthy controls. Background: Over the course of ageing, individuals may develop many diseases such as denture stomatitis. Material and methods: A total of 23 chronic denture stomatitis patients and 23 controls presenting good oral conditions were included in this study. Individuals had epithelial cells mechanically exfoliated, placed in fixative and placed on clean slides, which were checked for nuclear phenotypes. Results: The results indicated no statistically significant differences (p > 0.05) of micronucleated oral mucosa cells from chronic denture stomatitis patients when compared to healthy controls. Nevertheless, chronic denture stomatitis was able to increase other nuclear alterations closely related to cytotoxicity such as karyorrhexis, pyknosis and karyolysis as depicted by significant differences (p < 0.05) between groups. No interaction was observed between smoking and chronic denture stomatitis. Conclusion: In summary, these data indicated that chronic denture stomatitis was able to induce cytotoxic effects as assessed by a micronucleus test.     

Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities: Applied modifications in the steroidal structure

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.     

Modulation of elevated plus maze behavior after chronic exposure to the anabolic steroid 17alpha-methyltestosterone in adult mice

Exposure to supraphysiological doses of androgens may disrupt affective components of behavior. In this study, behavior of adult C57Bl/6 male mice was studied after exposure to the anabolic androgenic steroid (AAS) 17alpha-methyltestosterone (17alpha-meT; 7.5 mg/kg) via a subcutaneous osmotic pump for 17 days. Controls received vehicle implants (0.9% NaCl + 30% cyclodextrine). On day 15, experimental animals were challenged with an ethanol (EtOH) injection (i.p.; 1 g/kg) while controls received saline injections. Five minutes after the injection, animals were tested in an automated elevated plus maze (EPM) or in automated activity chambers. In addition, injection-free animals were tested for ethanol consumption on day 16 after an overnight water deprivation period. Whereas chronic exposure to 17alpha-meT did not modulate open arm behavior, EtOH-exposed animals made more entries into the open arms than controls (P < 0.05). A significant reduction of risk assessment behaviors (rearing, flat approach behavior, and stretch attended posture) over the EPM was noted for EtOH-exposed animals whereas a reduction in stretch attended postures was observed among 17alpha-meT-exposed animals. Locomotor activity, and light-dark transitions in activity chambers remained unaltered. Exposure to AAS did not modulate EtOH consumption. Our data suggest that exposure to a supraphysiological dose of 17alpha-meT has minimal effects on exploratory-based anxiety.     

Adolescent exposure to anabolic/androgenic steroids and the neurobiology of offensive aggression: A hypothalamic neural model based on findings in pubertal Syrian hamsters

Considerable public attention has been focused on the issue of youth violence, particularly that associated with drug use. It is documented that anabolic steroid use by teenagers is associated with a higher incidence of aggressive behavior and serious violence, yet little is known about how these drugs produce the aggressive phenotype. Here we discuss work from our laboratory on the relationship between the development and activity of select neurotransmitter systems in the anterior hypothalamus and anabolic steroid-induced offensive aggression using pubertal male Syrian hamsters (Mesocricetus auratus) as an adolescent animal model, with the express goal of synthesizing these data into an cogent neural model of the developmental adaptations that may underlie anabolic steroid-induced aggressive behavior. Notably, alterations in each of the neural systems identified as important components of the anabolic steroid-induced aggressive response occurred in a sub-division of the anterior hypothalamic brain region we identified as the hamster equivalent of the latero-anterior hypothalamus, indicating that this sub-region of the hypothalamus is an important site of convergence for anabolic steroid-induced neural adaptations that precipitate offensive aggression. Based on these findings we present in this review a neural model to explain the neurochemical regulation of anabolic steroid-induced offensive aggression showing the hypothetical interaction between the arginine vasopressin, serotonin, dopamine, γ-aminobutyric acid, and glutamate neural systems in the anterior hypothalamic brain region.     

In vivo determination of aluminum,cobalt, chromium,copper, nickel,titanium and vanadium in oral mucosa cells from orthodontic patients with mini-implants by Inductively coupled plasma-mass spectrometry (ICP-MS)

Miniscrews are used as orthodontic anchorage devices in the dentistry clinical practice but the in vivo metallic release from these structures has been not previously investigated. The aim of this study was to determine the content of Al, Co, Cr, Cu, Ni, Ti and V in oral mucosa cells of control subjects, patients under orthodontic treatment and with both, orthodontic treatment and miniscrew, in order to know the contribution of these mini-implants to the total metallic content. ICP-MS measurements revealed the following ascending order: Cr < Ni < Ti < Cu < Al, and Co and V were practically undetected. Significant differences in comparison to the control group were found for Cu in the orthodontic group, and for Ni in both, orthodontic and orthodontic + miniscrew groups. Potential correlations among metallic elements and with some clinical factors were also explored. These findings suggest that miniscrews do not increase significantly the metal release.     

Ozone-mediated cytotoxicity after short-term exposure and its relation to the production of cellular metabolites (NO,H2O2)

Alveolar macrophages secrete numerous mediators, playing an important role in host defence. Among these mediators, nitric oxide (NO) and hydrogen peroxide (H₂O₂) are both involved in bactericidal killing and trigger the release of other cellular metabolites. We have analyzed the effect of an atmosphere polluted with ozone (0.03–0.5 ppm v/v) on the monocytic cell line THP-1, as a model for alveolar macrophages,in vitro. NO and H₂O₂ were chosen to evaluate cell response to ozone. Cell injury was evaluated using lactate dehydrogenase (LDH) liberation into the medium. An exposure to 0.5 ppm ozone proved to be more toxic to the cells, than 0.1 or 0.03 ppm, evidenced by more LDH being liberated and cytotoxicity reaching values up to 64%. For all ozone concentrations, H₂O₂ production reached a peak value after 10–15 min of exposure, after which the concentration of extracellular H₂O₂ production diminished rapidly. The highest NO concentrations were measured with 0.5 ppm ozone, reaching a maximum value of 1460 nmol/L per 5×10⁶ cells, which is 1.55 times higher than for nonexposed cells. Lower concentrations barely induced higher NO concentrations compared to nonexposed cells. The results indicate that ozone effects not only the viability of human monocytes but also the release of antibacterial and defense signaling molecules and suggest that ozone-mediated cytotoxicity may be related to the secretion of NO and H₂O₂. This revised version was published online in July 2006 with corrections to the Cover Date.     

Differential expression of co-signal molecules and migratory properties in four distinct subsets of migratory dendritic cells from the oral mucosa

Variations in co-signal ligand expression and cytokine production greatly influence the antigen-presenting properties of migrating DCs in regional lymph nodes (RLNs). Here we investigated DCs migrating from the oral mucosa using CD326 and CD103 antigens for discriminate CD207⁺ Langerhans cells (LCs) from CD207⁺ submucosal DCs (SMDCs). Similar to DCs migrating from the skin, we identified four distinct oral mucosal DC (OMDC) subsets, CD11c^hiCD207⁻CD103⁻CD326^intCD11b^hi (F1; resident CD11b^hi SMDCs), CD11c^int/loCD207^-CD103^-CD326^loCD11b^int/hi (F2; newly recruited blood-derived SMDCs), CD11c^int/loCD207⁺CD103⁺CD326^int/hiCD11b^lo (CD103⁺ F3; resident CD207⁺ SMDCs), and CD11c^int/loCD207⁺CD103^-CD326^int/hiCD11b^lo (CD103^- F3; resident LCs). F1 DCs migrated rapidly after fluorescein isothiocyanate (FITC) painting and expressed notably high levels of CD86, CD273, and CD274 at an earlier time point. In contrast, CD103⁻ LCs expressing the highest levels of the epithelial cell adhesion molecule CD326 accounted for a minor subset at the earlier time point, but increased slowly with CD103⁺CD207⁺ SMDCs. However, their expression of CD86, CD273, and CD274 was very limited. The delayed migration and limited induction of co-signal ligands suggest that roles of OMLCs are distinct from those of the other three DC subsets. The identification of distinct subsets of OMDCs in RLNs may benefit efforts to determine the functional specialization of each subset in T cell responses against orally administrated antigens.     

MMP-2 and TIMP-2 expression,quantitative analysis and biomechanical changes in scar hypertrophy after autologous free transplantation of rabbit oral mucosa and scrotal skin

This study aimed to investigate the long-term scar hypertrophy in the rabbit transplanted oral mucosa and scrotal skin with changed matrix environment, as well as the scar location expression, quantitative analysis of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) and biomechanical changes in the transplanted tissues. The split-thickness skin grafts were collected from the oral mucosas and scrotal skins of 30 male rabbits, and prepared into reelpipes for autologous transplantation into the rabbit back muscular tissues. Samples were collected to carry out elastic tensile mechanical detection and histological observation. The maximum longitudinal tensile displacement of scrotal skin before 8 weeks of transplantation was greater than that after 8 weeks of transplantation (P < 0.05). The expression intensities of MMP-2 and TIMP-2 in the oral mucosa and in scrotal skin at 2 W time point were higher than those at T_o time point (P < 0.05). The expression quantities of TIMP-2 in oral mucosa and scrotal skin during 8–24 W were higher than those of MMP-2 (P < 0.05). At 8 W time point, the TIMP-2/MMP-2 ratio in scrotal skin was higher than that in oral mucosa (P < 0.05). MMP-2 and TIMP-2 expression in normal oral mucosa and scrotal skin is weak, but their expression is remarkably up-regulated after 2 weeks of transplantation, revealing that scar formation was related to the high expression of MMP-2 and TIMP-2. At the 8th–24th weeks, the AOD values of TIMP-2 in oral mucosa and scrotal skin are apparently higher than those of MMP-2; moreover, the TIMP-2/MMP-2 ratio in scrotal skin at the 8th week was higher than that in oral mucosa, which can well explain the earlier scar formation in scrotal skin than in oral mucosa, and it also suggests that the different expression levels between TIMP-2 and MMP-2 may account for the important cause of scar formation.     

Distribution of aromatase-immunoreactive cells in the forebrain of zebra finches (Taeniopygia guttata): Implications for the neural action of steroids and nuclear definition in the avian hypothalamus

Cells immunoreactive for the enzyme aromatase were localized in the forebrain of male zebra finches with the use of an immunocytochemistry procedure. Two polyclonal antibodies, one directed against human placental aromatase and the other directed against quail recombinant aromatase, revealed a heterogeneous distribution of the enzyme in the telencephalon, diencephalon, and mesencephalon. Staining was enhanced in some birds by the administration of the nonsteroidal aromatase inhibitor, R76713 (racemic Vorozole) prior to the perfusion of the birds as previously described in Japanese quail. Large numbers of cells immunoreactive for aromatase were found in nuclei in the preoptic region and in the tuberal hypothalamus. A nucleus was identified in the preoptic region based on the high density of aromatase immunoreactive cells within its boundaries that appears to be homologous to the preoptic medial nucleus (POM) described previously in Japanese quail. In several birds alternate sections were stained for immunoreactive vasotocin, a marker of the paraventricular nucleus (PVN). This information facilitated the clear separation of the POM in zebra finches from nuclei that are adjacent to the POM in the preoptic area-hypothalamus, such as the PVN and the ventromedial nucleus of the hypothalamus. Positively staining cells were also detected widely throughout the telencephalon. Cells were discerned in the medial parts of the ventral hyperstriatum and neostriatum near the lateral ventricle and in dorsal and medial parts of the hippocampus. They were most abundant in the caudal neostriatum where they clustered in the dorsomedial neostriatum, and as a band of cells coursing along the dorsal edge of the lamina archistriatalis dorsalis. They were also present in high numbers in the ventrolateral aspect of the neostriatum and in the nucleus taeniae. None of the telencephalic vocal control nuclei had appreciable numbers of cells immunoreactive for aromatase within their boundaries, with the possible exception of a group of cells that may correspond to the medial part of the magnocellular nucleus of the neostriatum. The distribution of immunoreactive aromatase cells in the zebra finch brain is in excellent agreement with the distribution of cells expressing the mRNA for aromatase recently described in the finch telencephalon. This widespread telencephalic distribution of cells immunoreactive for aromatase has not been described in non-songbird species such as the Japanese quail, the ring dove, and the domestic fowl. © 1996 John Wiley & Sons, Inc.     

Analysis of apoptosis and DNA damage in bovine cumulus cells after exposure in vitro to different zinc concentrations

The purpose of this study was to investigate the effect of Zn (zinc) concentration on CCs (cumulus cells) during in vitro maturation. For this purpose, DNA integrity of CCs by addition of different Zn concentrations [0 (control); 0.7 μg/ml (Zn1); 1.1 μg/ml (Zn2) and 1.5 μg/ml (Zn3)] to the culture medium was evaluated by comet assay. In addition, early apoptosis was analysed by annexin staining assay. CCs treated with Zn showed a significant decrease in the DNA damage in a dose‐dependent manner. Comet assay analysed for TM (tail moment) was significantly higher in cells cultured without Zn (control, P<0.01) with respect to cells treated with Zn (control: 5.24±16.05; Zn1: 1.13±5.31; Zn2: 0.10±0.36; Zn3: 0.017±0.06). All treatments were statistically different from the control (P=0.014 for Zn1; P<0.01 for Zn2 and Zn3). The frequency of apoptotic cells was higher in the control group (control: 0.142±0.07; Zn1: 0.109±0.0328; Zn2:0.102±0.013; Zn3: 0.0577±0.019). Statistical differences were found between control and Zn1 (P=0.0308), control and Zn2 (P=0.0077), control and Zn3 (P<0.0001), Zn1 and Zn3 (P<0.001) and Zn2 and Zn3 (P=0.0004). No differences were found between Zn1 and Zn2. In conclusion, low Zn concentrations increase DNA damage and apoptosis in CCs cultured in vitro. However, adequate Zn concentrations ‘protect’ the integrity of DNA molecule and diminish the percentage of apoptotic CC.     

Differential distribution of ghrelin-O-acyltransferase (GOAT) immunoreactive cells in the mouse and rat gastric oxyntic mucosa

The enzyme that acylates ghrelin was recently identified in mice as the fourth member of the membrane-bound O-acyltransferases superfamily (MBOAT4) and named ghrelin-O-acyltransferase (GOAT). Only one report showed GOAT mRNA expression in ghrelin-expressing cells of the mouse stomach. We investigated the distribution of GOAT protein in peripheral tissues and co-expression with endocrine markers in the gastric mucosa using a custom-made anti-GOAT antibody. Tissues were collected from male Sprague-Dawley rats and C57BL/6 mice. Western blot revealed two immunoreactive bands in rat and mouse gastric corpus mucosal proteins, a 50 kDa band corresponding to the GOAT protein and a 100 kDa band likely corresponding to a dimer. Western blot also detected GOAT in the plasma and levels were strongly increased after 24-h fasting in mice and slightly in rats. GOAT-immunoreactive cells were located in the gastric corpus mucosa and the anterior pituitary gland, whereas other peripheral tissues of rats and mice examined were negative. In mice, GOAT-immunoreactive cells were mainly distributed throughout the middle portion of the oxyntic glands, whereas in rats they were localized mainly in the lower portion of the glands. Double labeling showed that 95 ± 1% of GOAT-immunoreactive cells in mice co-labeled with ghrelin, whereas in rats only 56 ± 4% of GOAT-positive cells showed co-expression of ghrelin. The remainder of the GOAT-immunopositive cells in rats co-expressed histidine decarboxylase (44 ± 3%). No co-localization was observed with somatostatin in rats or mice. These data suggest species differences between rats and mice in gastric GOAT expression perhaps resulting in a different role of the MBOAT4 enzyme in the rat stomach. Detection of GOAT in the plasma raises the possibility that ghrelin octanoylation may occur in the circulation and the fasting-induced increase in GOAT may contribute to the increase of acylated ghrelin after fasting.     

Responses of lysosomes in the digestive cells of the common mussel,Mytilus edulis,to sex steroids and cortisol

Estradiol-17beta and progesterone at physiological concentrations in vivo induced a reduction in lysosomal stability in the digestive cells of Mytilus edulis. Estradiol-17beta (10(-8) M) also reduced lysosomal stability within 15 min in vitro. Lysosomal stability was determined cytochemically as the labilisation period for latent N-acetyl-beta-hexosaminidase and this was shown to be inversely related to microdensitometric measurements of staining intensity for this enzyme. Estradiol-17beta did not appear to induce complete labilisation or cytochemical activation of lysosomal hexosaminidase and a second, much longer labilisation period could be determined for this hormone. The effects of estradiol-17beta were partially counteracted by cortisol (10(-2) M). There was an increase in PAS staining of secondary lysosomes and an increase in alcian blue staining of residual bodies in digestive cells of animals exposed to estradiol-17beta, while no changes could be observed in basophil cells. The significance of these results is discussed in terms of the physiological role of digestive cells and their possible function as target cells for estradiol-17beta and progesterone.     

Trimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H(2)O(2) from DNA damage

Trimetazidine is a well-established anti-ischemic drug, which has been used for long time in the treatment of pathological conditions related with the generation of reactive oxygen species. However, although extensively studied, its molecular mode of action remains largely unknown. In the present study, the ability of trimetazidine to protect low-density lipoproteins (LDL) from oxidation and cultured cells from H₂O₂-induced DNA damage was investigated. Trimetazidine, tested at concentrations 0.02 to 2.20 mM, was shown to offer significant protection to LDL exposed to three different oxidizing systems, namely copper, Fe/ascorbate, and met-myoglobin/H₂O₂. The oxidizability of LDL was estimated by measuring, (i) the lag period, (ii) the maximal rate of conjugated diene formation, (iii) the total amount of conjugated dienes formed, (iv) the electrophoretic migration of LDL protein in agarose gels (REM), and (v) the inactivation of the enzyme PAF-acetylhydrolase present in LDL. In addition, the presence of trimetazidine decreased considerably the DNA damage in H₂O₂-exposed Jurkat cells in culture. H₂O₂ was continuously generated by the action of glucose oxidase at a rate of 11.8 ± 1.5 μM per min (60 ng enzyme per 100 μl), and DNA damage was assessed by the single cell gel electrophoresis assay (also called comet assay). The protection offered by trimetazidine in this system (about 30% at best) was transient, indicating modification of this agent during its action. These results indicate that trimetazidine can modulate the action of oxidizing agents in different systems. Although its mode of action is not clarified, the possibility that it acts as a lipid barrier permeable transition metal chelator is considered.     

纳米二氧化硅复合寒冷对A549细胞毒性及其炎性因子分泌的影响

目的:本研究旨在探讨纳米二氧化硅(Nano-SiO2)颗粒和寒冷复合对人肺腺癌上皮细胞A549细胞毒性及炎性因子分泌的影响。方法:本研究以A549细胞为实验对象,分别用10,50,100,200μg/ml Nano-SiO2颗粒对A549细胞染毒,以及分别在35℃,33℃,31℃条件下对A549细胞进行低温暴露,培养48 h后,观察细胞形态及测定细胞相对存活率。根据单因素分析结果,选出对A549细胞相对存活率有显著降低作用的Nano-SiO2剂量和温度的基础上,按照2×2析因设计实验,分为4组:①37℃对照组;②Nano-SiO2染毒组;③低温暴露组;④Nano-SiO2和低温复合组,不同条件下暴露48 h后,收集细胞上清液采用比色法检测LDH活性,以及ELISA法测定细胞因子白介素-6(IL-6)和白介素-8(IL-8)的水平,采用q RT-PCR法检测细胞IL-6和IL-8的基因表达水平。结果:100μg/ml Nano-SiO2组和31℃低温组能够显著降低A549细胞活性(P<0.01),在复合条件作用下对A549细胞活性抑制最为显著,且炎性因子IL-6和IL-8及m RN...     

Protective effects of aloe-emodin on scopolamine-induced memory impairment in mice and H2O2-induced cytotoxicity in PC12 cells

Aloe-emodin (AE) is one of the most important active components of Rheum officinale Baill. The present study aimed to investigate that AE could attenuate scopolamine-induced cognitive deficits via inhibiting acetylcholinesterase (AChE) activity and modulating oxidative stress. Kunming (KM) mice were received intraperitoneal injection of scopolamine (2 mg/kg) to induce cognitive impairment. Learning and memory performance were assessed in the Morris water maze (MWM). After behavioral testing, the mice were sacrificed and their hippocampi were removed for biochemical assays (superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), AChE and acetylcholine (ACh)). In vitro, we also performed the AChE activity assay and H₂O₂-induced PC12 cells toxicity assay. After 2 h exposure to 200 μM H₂O₂ in PC12 cells, the cytotoxicity were evaluated by cell viability (MTT), nitric oxide (NO)/lactate dehydrogenase (LDH) release and intracellular reactive oxygen species (ROS) production. Our results confirmed that AE showed significant improvement in cognitive deficit in scopolamine-induced amnesia animal model. Besides, it increased SOD, GPx activities and ACh content, while decreased the level of MDA and AChE activity in AE treated mice. In addition, AE was found to inhibit AChE activity (IC₅₀ = 18.37 μg/ml) in a dose-dependent manner. Furthermore, preincubation of PC12 cells with AE could prevent cytotoxicity induced by H₂O₂ and reduce significantly extracellular release of NO, LDH and intracellular accumulation of ROS. The study indicated that AE could have neuroprotective effects against Alzheimer’s disease (AD) via inhibiting the activity of AChE and modulating oxidative stress.     

The influence of 2-mercaptoethanol (2-ME) treatment of IgG antibody on its ability to induce cytotoxicity in nonsensitized lymphocytes

Administering dextran 2 hr before giving antigen (sheep red blood cells) to X-irradiated mice repopulated with B and T cells caused alterations in antibody synthesis. Besides a slight increase in the number of cells making IgM antibodies, cells producing IgG antibodies were detected at a time when none are usually present in untreated control animals.Repopulating X-irradiated mice with B cells treated with dextran either in vivo or in vitro and immunizing with sheep red blood cells resulted in twice the background number of sheep red blood cell-specific IgM-plaque-forming cells at 4.5 days of immunization as well as a small number of IgG-plaque-forming cells at 8.5 days. At these times, control animals given only B cells and sheep red blood cells possessed a background number of IgM-plaque forming cells and no IgG plaque-forming cells.Incubating B cells with θ-specific antiserum and complement to remove residual T cells prior to transplantation obliterated dextran's stimulus. Dextran's alterations of immunological responses towards unrelated antigens therefore appears to be manifested through T cells. The latter must be in company with B cells at the time of exposure to dextran. Thus, T cells upon contact with dextran apparently release B cell stimulatory factor (s) responsible for increasing the number of IgM-forming cells and for triggering IgG-forming cells.     

The distribution of endocrine cells in the mucosa of the gastrointestinal tract of the house musk shrew,Suncus murinus (Insectivora)

Summary The distribution of endocrine cells in the gastrointestinal tract of the house musk shrew, Suncus murinus (Family Soricidae, Order Insectivora) was studied immunohistochemically. The hormones investigated were gastrin, cholecystokinin (CCK), somatostatin, secretin, glucagon, gastric inhibitory polypeptide (GIP), motilin and neurotensin. In the gastric mucosa, gastrin and somatostatin cells were only found in the pyloric regions, and no other hormonal cell-types were observed. In the intestinal mucosa, the largest number of endocrine cells belonged to the gastrin and glucagon/glicentin cell-types, whereas CCK-33/39 and secretin cells were the least numerous. Numbers of other cell-types were intermediate between these two groups. The gastrin and GIP cells were mostly localized in the proximal portion of the intestine, decreasing in number towards the distal portion. The motilin and CCK-33/39 cells were restricted to the proximal half. The glucagon/glicentin and neurotensin cells were most abundant in the middle portion. The somatostatin and secretin cells, although only present in small numbers, were randomly distributed throughout the intestine. This characteristic distribution of gastrointestinal endocrine cells is discussed in comparison with the distribution patterns of other mammals.Dr. Munemitsu Hoshino, who was Professor of the Department of Pathology and directed this study, passed away on May 23rd 1988