Whole-body hyperthermia-induced renal atrophy of mice as evinced by obstruction and degeneration of renal tubules caused by acute ischemia

Effects of microwave-induced whole-body hyperthermia (WBH) on the mouse kidney were examined histologically for acute and late effects up to 150 days after WBH treatment at 43.5 degrees C (rectal temperature) for 20 min or 42 degrees C for 40 min. As a whole the damage could be divided into two types. One was the damage to distorted epithelial cells in the subcapsular region. This lesion was common in most animals, possibly caused by direct hyperthermic effect of microwave. The other was general renal atrophy accompanied with aqueous or protein-rich cysts due to a chain of physiological reactions of the whole body to WBH. The first reaction was characterized by general stasis of the blood stream in all parts of the kidney, which resulted in acute ischemia of some tissues. This was seen immediately by dilatation of the renal and interlobular veins as well as the bundles of capillaries in the medulla region. The subsequent event was rather specific cell necrosis of distal and collecting tubular epithelium as compared to proximal tubules. The cell destruction induced cell proliferation of the proximal tubular epithelia after two days. Later on, in accord with the recovery of the blood circulation, the proliferated cells were carried away into the lumen, these processes then resulting in obstruction of tubules through formation of protein casts in the lumen. The block incidentally led to the destruction of nephrons. The degenerated area sometimes consisted of aqueous or protein-rich cysts of various sizes after 7 to 30 days. Thereafter these cysts degenerated, decreasing in both number and size. Thus irreversible atrophy of the kidney developed after WBH.     

Select types of supporting cell in the inner ear express aquaporin-4 water channel protein

Aquaporins (AQPs) confer a high water permeability on cell membranes and play important parts in secretory and absorptive epithelia in kidney and other organs. Here we investigate whether AQPs are expressed in the sensory epithelia of the inner ear, where a precise volume regulation is crucial. By use of specific antibodies it was found that the inner ear contains AQP1 and 4 while being devoid of detectable levels of AQP2, 3 or 5. Immunofluorescence and postembedding immunogold labelling revealed a strictly non-epithelial distribution of AQP1, confirming previous data. In contrast, AQP4 protein and mRNA (visualized by in situ hybridization) were concentrated in select types of supporting cell, including Hensen's cells and inner sulcus cells. Immunogold particles signalling AQP4 were confined to the basolateral plasma membrane of Hensen's cells and to the basal plasma membrane of Claudius cells and inner sulcus cells. AQP4 was also found in supporting cells of the vestibular end organs, but was absent from transitional epithelial cells and dark cells. Strong labelling for AQP4 and AQP4-mRNA was associated with the central part of the cochlear and vestibular nerves. Hair cells were consistently unlabelled. Our findings indicate that AQP4 may facilitate osmotically driven water fluxes in the sensory epithelia of the inner ear and thus contribute to the volume and ion homeostasis at these sites.     

Successful surgical treatment of secondary kwashiorkor after total gastrectomy: Report of a case

We report herein the case of a 56-year-old woman who developed secondary Kwashiorkor 9 years after undergoing a total gastrectomy for early gastric cancer. Until she began developing the symptoms of Kwashiorkor, including general fatigue, edema of the face and extremities, anemia, alopecia, and weight loss, she had been leading a normal life post-gastrectomy. Her symptoms were alleviated by total parenteral nutrition (TPN) therapy, but reappeared soon after TPN therapy was discontinued. Therefore, she required several subsequent courses of TPN. In an attempt to permanently resolve the ongoing Kwashiorkor symptoms, reconstructive surgery involving transposition of the jejunum from the previous Graham method to the interposition method was performed 10 years after the initial gastrectomy. After the second operation, her malnutrition was completely alleviated, and she has been in good health for the 8 years since. To our knowledge, there has been no other report of the symptoms of secondary Kwashiorkor after total gastrectomy being alleviated by altering the procedure of reconstruction of the intestinal tract. Thus, we recommend surgical treatment to alter the digestive continuity to a more physiological pathway for selected patients with secondary Kwashiorkor syndrome.     

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.     

Effectiveness of the bidirectional Glenn shunt for the univentricular heart

Two cases underwent a modified Fontan operation with simultaneous superior vena cava-right pulmonary artery end-to-side anastomosis, which we called "bidirectional Glenn shunt". This anastomosis seems to be so effective for reduction of right arterial volume loading, and could proved life-saving in the case with the acute obstruction at the site of the right atriopulmonary artery anastomosis immediately after surgery.     

FARP2 triggers signals for Sema3A-mediated axonal repulsion

Sema3A, a prototypical semaphorin, acts as a chemorepellent or a chemoattractant for axons by activating a receptor complex comprising neuropilin-1 as the ligand-binding subunit and plexin-A1 as the signal-transducing subunit. How the signals downstream of plexin-A1 are triggered upon Sema3A stimulation, however, is unknown. Here we show that, in the presence of neuropilin-1, the FERM domain-containing guanine nucleotide exchange factor (GEF) FARP2 associates directly with plexin-A1. Sema3A binding to neuropilin-1 induces the dissociation of FARP2 from plexin-A1, resulting in activation of FARP2's Rac GEF activity, Rnd1 recruitment to plexin-A1, and downregulation of R-Ras. Simultaneously, the FERM domain of FARP2 sequesters phosphatidylinositol phosphate kinase type I isoform PIPKIgamma661 from talin, thereby inhibiting its kinase activity. These activities are required for Sema3A-mediated repulsion of outgrowing axons and suppression of neuronal adhesion. We therefore conclude that FARP2 is a key molecule involved in the response of neuronal growth cones to class-3 semaphorins.     

Human serum albumin incorporating synthetic heme: red blood cell substitute without hypertension by nitric oxide scavenging

The administration of extracellular, hemoglobin-based oxygen carriers often elicits an acute increase in blood pressure by vasoconstriction. This side effect is now recognized to be due to the depletion of nitric oxide (endothelial-derived relaxing factor) by the extravasuated hemoglobins. We have recently found that the administration of a recombinant human serum albumin (rHSA)-based oxygen carrier involving synthetic tetraphenyporphinatoiron(II) derivative (FeP) (rHSA-FeP) does not induce such hypertensive action, because of its low permeability through the vascular endothelium. The heart rate responses after the rHSA-FeP injection were also negligibly small. Visualization of the intestinal microcirculatory changes clearly revealed the widths of the venule and arteriole to be fairly constant. The entirely synthetic rHSA-FeP becomes a promising material as a new type of red blood cell substitute.     

Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1 suppression factor by human CD4+ T cells isolated from HIV-1 immunized hu-PBL SCID mice

We have previously reported that immunization of the severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC) elicits HIV-1-reactive CD4(+) T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5) HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vivo and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4(+) but not CD8(+) T cells. Human CD4(+) T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4(+) T cells. Aliquots of these re-stimulated CD4(+) T cells were then co-cultured with similar APC's that were previously pulsed with 10 microg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-gamma. The data presented herein show that the HIV-1 primed CD4(+) T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4(+) T cells. Simultaneous production of human interferon (IFN)-gamma was observed in some cases. These results indicate that human CD4(+) T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4(+) T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1.     

Traf6 is essential for murine tooth cusp morphogenesis.

Ectodermal appendages such as skin, hair, teeth, and sweat glands are affected in patients with hypohidrotic (anhydrotic) ectodermal dysplasia (HED). It has been established that mutations in the tumor necrosis factor (TNF) superfamily of molecules, i.e., ectodysplasin (EDA), EDA receptor (EDAR), and EDAR-associated death domain (EDARADD; the intracellular adaptor for EDAR), are responsible for several forms of HED in humans and mice. We show here by in situ hybridisation that another TNF family (orphan) receptor, TROY (also known TAJ, TAJ-alpha, TRADE, and TNFRSF19), is strongly coexpressed with Edar in the epithelial enamel knot signalling centres that are believe to regulate cuspal morphogenesis during murine tooth development. Traf6 is known to function as an intracellular adaptor protein for Troy and examination of Traf6 mutant mice revealed abnormalities in molar teeth that are similar but more severe than those produced by mutations in Eda signalling molecules. This finding suggests that, in additional to ectodysplasin, another TNF pathway involving Troy/Traf6 is involved in molar tooth cusp formation and identifies an essential role for a Traf in tooth development. Developmental Dynamics 229:131-135, 2004.