Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family

We report the cloning and expression of the fifth member of the mammalian UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGaNTase) family. Degenerate polymerase chain reaction amplification and hybridization screening of a rat sublingual gland (RSLG) cDNA library were used to identify a novel isoform termed ppGaNTase-T5. Conceptual translation of the cDNA reveals a uniquely long stem region not observed for other members of this enzyme family. Recombinant proteins expressed transiently in COS7 cells displayed transferase activity in vitro. Relative activity and substrate preferences of ppGaNTase-T5 were compared with previously identified isoforms (ppGaNTase-T1, -T3, and -T4); ppGaNTase-T5 and -T4 glycosylated a restricted subset of peptides whereas ppGaNTase-T1 and -T3 glycosylated a broader range of substrates. Northern blot analysis revealed that ppGaNTase-T5 is expressed in a highly tissue-specific manner; abundant expression was seen in the RSLG, with lesser amounts of message in the stomach, small intestine, and colon. Therefore, the pattern of expression of ppGaNTase-T5 is the most restricted of all isoforms examined thus far. The identification of this novel isoform underscores the diversity and complexity of the family of genes controlling O-linked glycosylation.     

DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma

Vaccination with idiotypic protein protects against B-cell lymphoma, mainly through anti-idiotypic antibody. For use in patients, DNA vaccines containing single-chain Fv derived from tumor provide a convenient alternative vaccine delivery system. However, single-chain Fv sequence alone induces low anti-idiotypic response and poor protection against lymphoma. Fusion of the gene encoding fragment C of tetanus toxin to single-chain Fv substantially promotes the anti-idiotypic response and induces strong protection against B-cell lymphoma. The same fusion design also induces protective immunity against a surface Ig-negative myeloma. These findings indicate that fusion to a pathogen sequence allows a tumor antigen to engage diverse immune mechanisms that suppress growth. This fusion design has the added advantage of overcoming potential tolerance to tumor that may exist in patients.     

Quality of life of patients with gastric adenocarcinoma after curative gastrectomy

Quality of life (QOL) was evaluated in 162 patients having radical gastrectomy for cancer. The results showed that more than half of the patients had a good appetite; they consumed a normal diet and a normal volume of food. Approximately 60% of the patients had weight loss of more than 5 kg. Patients who underwent a total gastrectomy had poor tolerance of normal food and frequent eating and body weight loss versus those who had a subtotal gastrectomy. Patients who underwent Billroth II reconstruction after a distal subtotal gastrectomy lost more body weight than those with a Billroth I anastomosis. The extent of lymphadenectomy did not influence the QOL. Patients under 65 years of age had a better QOL. Nearly all patients had normal work and daily living activities. Some patients appeared to lack energy or had a period of anxiety or depression. These data indicate that radical gastrectomy can be performed with an acceptable QOL for a potentially curable gastric carcinoma.     

Vector potential of houseflies (Musca domestica) for Helicobacter pylori

The mode of transmission of Helicobacter pylori is unknown. Since viable bacteria have been shown to be excreted in feces from infected individuals and houseflies habitually develop and feed on excrement, we hypothesized that flies ingest and harbor H. pylori and, in turn, contaminate the human environment. This study examined the possible vector potential of houseflies (Musca domestica) for H. pylori. Caged houseflies were exposed to freshly grown H. pylori on agar plates. After a 6-h feeding period, the plates were removed and were replaced with sterile petri dishes containing a droplet of sterile brucella broth. At regular intervals, small numbers of houseflies were removed for microbiological and histological analysis, and the petri dishes were replaced with fresh sterile plates with fresh drops of brucella broth. The flies' bodies, the flies' dissected alimentary tracts, and excreta on the petri dishes were cultured for H. pylori, whose identity was confirmed by the urease, catalase, and oxidase reactions and Gram staining. In contrast to control flies, viable H. pylori could be isolated from external surfaces for up to 12 h and from gut and excreta for as long as 30 h after the initial feeding period. After 30 h other gram-negative bacteria overgrew the cultures of samples from all locations tested, rendering the selective culture of H. pylori colonies impossible. Histological analysis revealed Helicobacter-like organisms in the gut lumen and attached to intestinal epithelial cells. We conclude that houseflies can harbor viable H. pylori on their bodies and in their intestinal tracts. They are also able to disseminate viable H. pylori in excreta, and they may therefore present a significant reservoir and be a vector in the transmission of H. pylori.     

Gabapentin treatment of mood disorders: a preliminary study

OBJECTIVE: To determine if gabapentin is effective either as adjunctive treatment or as monotherapy for major affective disorders in a naturalistic setting. METHOD: All charts of patients meeting DSM-IV criteria for bipolar disorder or unipolar major depressive disorder treated with gabapentin in a private psychiatric practice were reviewed and clinical response was assessed retrospectively using the Clinical Global Impressions scale for Improvement (CGI-I). RESULTS: Gabapentin was moderately to markedly effective in 30% (15/50) of patients, with statistically nonsignificant differences between patients with bipolar disorder type I, bipolar disorder type II and NOS, and unipolar major depressive disorder. 70% reported side effects, mainly sedation, with 16% of the total sample discontinuing treatment due to adverse events. CONCLUSION: Gabapentin appears to be somewhat effective as add-on treatment in a subgroup of patients with mood disorders in a naturalistic setting. Prospective, controlled studies are required to clarify these pilot data.     

Effect of brain edema on the recurrence pattern of malignant gliomas

PURPOSE: To assess the influence of initial preoperative brain edema in malignant gliomas on regrowth patterns. SUBJECTS AND METHODS: 79 patients with histologically verified supratentorial malignant glioma were prospectively studied by magnetic resonance imaging (MRI) before and every 2-3 months after surgery. The median follow-up time was 11 months. We correlated the configuration of the initial vasogenic edema on T2-weighted images with tumor regrowth patterns on contrast-enhanced T1-weighted images. RESULTS: 35/47 tumor regrowths (75%) imitated the initial edema configuration, while 11/47 occurred within the initial tumor bed; in one case tumor recurrence was multilocal. CONCLUSION: In glioblastoma, tumor regrowth patterns correlate positively with the configuration of the initial vasogenic brain edema. The initial, "presurgical" peritumoral edema should thus be considered when planning further treatment.     

Impaired alloantigen-mediated T cell apoptosis and failure to induce long-term allograft survival in IL-2-deficient mice

We examined whether IL-2 regulates alloimmune responses by studying allograft survival in wild-type (IL-2+/+) and IL-2 gene-knockout (IL-2-/-) mice. The acute rejection of vascularized, cardiac allografts and the generation of allospecific CTLs were not impaired in the absence of IL-2. In contrast, blocking the B7-CD28 T cell costimulation pathway with CTLA4Ig induced long-term allograft survival (> 100 days) in IL-2+/+ recipients but failed to do so in IL-2-/- mice or in wild-type mice that had been treated with IL-2-neutralizing Ab around the time of transplantation. Allografts rejected by IL-2-/- recipients exhibited extensive mononuclear cell infiltrates despite CTLA4Ig administration. In vivo allostimulation in the absence of IL-2 led to exaggerated T lymphocyte proliferation and impaired apoptosis of activated T cells in untreated and CTLA4Ig-treated mice. These findings indicate that endogenous IL-2 is required for the induction of long-term allograft survival, and that IL-2 regulates alloimmune responses by preparing activated T lymphocytes for alloantigen-induced apoptosis.     

Prevalence of herpes simplex virus type 1- and 2- specific antibodies among the acute, recurrent, and provoked types of female genital herpes

Sixty-eight sera from the acute, recurrent, and provoked types of female genital herpes were compared for the seroprevalence of herpes simplex virus (HSV) types 1 and 2 by immunodot assay using HSV glycoprotein G. In the HSV-1-isolated patients, no HSV-2 antibodies were detected, whereas in the HSV-2-isolated patients, HSV-1 seroprevalence was 9% for the acute type, 89% for the provoked type (P < 0.005), and 55% for the recurrent type (P < 0.05). The natural history of female genital herpes and the possible protective role of pre-existing antibodies in preventing the acquisition or clinical manifestation of a subsequent HSV infection are discussed.