Selective deficiency of IgG and IgA as a first stage defect in B cell differentiation.

A case of selective deficiency of IgG and IgA, in a 13-year old girl, is described. Immunologic investigations, showing an almost complete absence of IgG- and IgA-bearing lymphocytes and significant amounts of IgD and IgM positive cells, suggest the possibility of a block in the shift from IgM to IgG synthesis at the B lymphocyte level.     

A growth-stimulating activity derived from the proximal small intestine is associated with an adaptive response

Luminal nutrition is important for the maintenance of small intestinal structure and function. The equilibrium between crypt cell production and villous cell loss in the mucosal epithelium of the small intestine is altered under certain conditions such as after a small bowel resection. Immediately after resection, there is a marked increase in crypt cell proliferation giving rise to an adaptive hyperplasia in the remnant intestine and for this response luminal nutrition is a critical factor. We have previously demonstrated the presence of a growth-stimulating (GS) activity in a heat-stable acidic extract of the rat proximal intestine 24, 48, and 96 h after resection, which is coincidental with an increase in crypt cell proliferation as measured by thymidine kinase activity. Eight days after resection when the GS activity is no longer detectable, the thymidine kinase activity returns to control values. The molecular weights of the peptides associated with this GS activity are 4500 and 1500, as determined by Sephadex gel filtration. Of note is that the oral intake of food is necessary for the appearance of the GS activity postoperatively. The presence of the GS activity has also been demonstrated upon refeeding after a fast, as well as at weaning in the rat, two physiological situations known to be associated with increased proliferation in the small intestine. This GS activity in the proximal intestine first detected in the resection model may represent a general mechanism by which food controls the cell renewal pattern of the small intestine.     

Apoptosis and regeneration of enterocytes in experimental atrophy of the small intestine mucosa

Apoptosis, one of the types of cell deaths, participates in regulating the size of regenerated tissue. Severe atrophy of small intestine mucosa in mice was caused by the administration of hydroxyurea solution. The degree of atrophy correlated with a lowering mitotic activity and DNA synthesis in the epithelium of crypts. Apoptotic bodies were situated above the basal membrane, in crypt lumen or were phagocytized by adjacent epithelial cells. The development of atrophy, as well as the regeneration of mucosa can be predicted by the relation between mitosis and apoptosis.     

Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression

Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF-beta-producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J chain-containing) Abs to the major allergen Phl p 5 were determined by ELISA before and after a 2-year double-blind trial of grass pollen (Phleum pratense) injection IT. Nasal TGF-beta expression was assessed by in situ hybridization. Sera from five IT patients were fractionated for functional analysis of the effects of IgA and IgG Abs on IL-10 production by blood monocytes and allergen-IgE binding to B cells. Serum Phl p 5-specific IgA2 Abs increased after a 2-year treatment (approximately 8-fold increase, p = 0.002) in contrast to IgA1. Increases in polymeric Abs to Phl p 5 (approximately 2-fold increase, p = 0.02) and in nasal TGF-beta mRNA (p = 0.05) were also observed, and TGF-beta mRNA correlated with serum Phl p 5 IgA2 (r = 0.61, p = 0.009). Post-IT IgA fractions triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding to B cells as observed with IgG fractions. This study shows for the first time that the IgA response to IT is selective for IgA2, correlates with increased local TGF-beta expression, and induces monocyte IL-10 expression, suggesting that IgA Abs could thereby contribute to the tolerance developed in IT-treated allergic patients.     

Ufl1 deficiency causes kidney atrophy associated with disruption of endoplasmic reticulum homeostasis

The UFMylation modification is a novel ubiquitin-like conjugation system, consisting of UBA5(E1), UFC1(E2), UFL1(E3), and the conjugating molecule UFM1. Deficiency in this modification leads to embryonic lethality in mice and diseases in humans. However, the function of UFL1 is poorly characterized. Studies on Ufl1 conditional knockout mice have demonstrated that the deletion of Ufl1 in cardiomyocytes and in intestinal epithelial cells causes heart failure and increases susceptibility to experimentally induced colitis,respectively, suggesting an essential role of UFL1 in the maintenance of the homeostasis in these organs.Yet, its physiological function in other tissues and organs remains completely unknown. In this study, we generate the nephron tubules specific Ufl1 knockout mice and find that the absence of Ufl1 in renal tubular results in kidney atrophy and interstitial fibrosis. In addition, Ufl1 deficiency causes the activation of unfolded protein response and cell apoptosis, which may be responsible for the kidney atrophy and interstitial fibrosis. Collectively, our results have demonstrated the crucial role of UFL1 in regulating kidney function and maintenance of endoplasmic reticulum homeostasis, providing another layer of understanding kidney atrophy.     

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

The small intestine (SI) is the second-greatest source of HDL in mice. However, the selective evaluation of SI-derived HDL (SI-HDL) has been difficult because even the origin of HDL obtained in vivo from the intestinal lymph duct of anesthetized rodents is doubtful. To shed light on this question, we have developed a novel in situ perfusion technique using surgically isolated mouse SI, with which the possible filtration of plasma HDL into the SI lymph duct can be prevented. With the developed method, we studied the characteristics of and mechanism for the production and regulation of SI-HDL. Nascent HDL particles were detected in SI lymph perfusates in WT mice, but not in ABCA1 KO mice. SI-HDL had a high protein content and was smaller than plasma HDL. SI-HDL was rich in TG and apo AIV compared with HDL in liver perfusates. SI-HDL was increased by high-fat diets and reduced in apo E KO mice. In conclusion, with our in situ perfusion model that enables the selective evaluation of SI-HDL, we demonstrated that ABCA1 plays an important role in intestinal HDL production, and SI-HDL is small, dense, rich in apo AIV, and regulated by nutritional and genetic factors.     

Selective decontamination of the intestine and total gnotobiologic isolation in treatment of mice with acute radiation sickness]

Comparative study of ciprofloxacin, pefloxacin and amikacin showed that ciprofloxacin and pefloxacin had a selective action on the intestinal microflora of conventional mice. Amikacin induced inhibition not only of the opportunistic bacteria but also of the representatives of the indigenous microflora. The use of the drugs in combination with total gnotobiological isolation in treatment of experimental radiation sickness provided an increase in survival of the irradiated animals, the more so as ciprofloxacin was used.     

Development of the vertebrate small intestine and mechanisms of cell differentiation

The intestinal epithelium represents an attractive biological model of differentiation from stem cells to highly differentiated epithelial cells, not only during particular developmental events depending upon the vertebrate species considered but also throughout adult life. The ontogenic maturation of the intestinal epithelium arises from both a programmed expression of specific genes and epigenetic influences mainly due to epithelial and mesenchymal interactions and hormonal participation. In the present paper we review the structural and functional changes that occur in the amphibian, avian and mammalian intestine during embryonic and/or post-embryonic development. Furthermore, we review the data concerning the mechanisms which control the cytodifferentiation of the intestinal epithelium.     

Rapid and specific alterations of goblet cell mucin in rat airway and small intestine associated with resistance against Nippostrongylus brasiliensis reinfection

The intestinal parasitic nematode Nippostrongylus brasiliensis is expelled rapidly from the rat in reinfection challenge compared with that of the primary infection owing to the host defense mechanisms raised against the pre-intestinal- and intestinal-stage larvae. We examined the relationship between the mucin alterations in airway and jejunal mucosae and the worm expulsion after third-stage larva reinfection. When rats had been inoculated with fourth-stage larvae and immunized with only the intestinal-stage worms for more than 8 days, the challenge larvae were expelled during the intestinal stage along with a rapid increase of the specific sialomucin in jejunal mucosa, without any effect on the bronchial mucus. When rats had been infected with third-stage larvae and immunized with only the pre-intestinal stage larvae by killing with antihelminthic, the challenge larvae were rejected during the pre-intestinal stage along with marked goblet cell hyperplasia and Muc5AC mucin hyperproduction on the bronchial mucosa, but not as a result of jejunal mucin alteration. Taking these finding together, immunization with pre-intestinal- and intestinal-stage worms independently increases the airway and intestinal goblet cell mucins, respectively, and in both cases, the mucin alterations may contribute to rapid worm expulsion upon reinfection.     

Histochemical changes in the fowl small intestine associated with enhanced absorption after feed restriction

Summary The morphology and histochemical enzyme pattern of the small intestine were investigated in chicks undergoing feed restriction. Corresponding intestinal sites were compared in both restricted birds and in control birds under normal feeding. Intestines from the restricted birds showed some atrophy, the villi being slightly shorter and thinner than normal after eight days restriction, and there was an increase in the activity of alkaline phosphatase, leucine naphthylamidase, acid phosphatase, -glucuronidase, non-specific esterase and succinic dehydrogenase in the absorptive cells.The significance of these findings has been discussed in relation to the enhanced absorptive capacity of the intestine during feed restriction and its similarity to other dietary stress factors that produce enhanced absorption. Possible mechanisms for the production of such mucosal changes have been considered. It was concluded that the enhanced absorption of nutrients in semi-starved animals is correlated with increased mucosal enzyme activities.