Bombesin improves survival from methotrexate-induced enterocolitis.

OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents.     

Differential expression of Neu messenger-RNA and protein in hamster-kidney and estrogen-induced kidney tumors

An inverse relationship between the expression of the neu oncogene and estrogen receptors has been observed in breast cancer patients. In this study, we examined neu expression in the estrogen-induced and -dependent hamster kidney tumors, in kidney and in controls to evaluate the usefulness of this animal model far studying the regulation of genes important in hormonal cancer. The expression of neu mRNA was analyzed by Northern analysis and Neu oncoprotein localization by immunocytochemistry. The Neu oncoprotein was detected in several segments of proximal and distal kidney tubules, the loops of Henle and the parietal epithelial cells of Bowman's capsule but not in the tumor. neu mRNA was expressed in renal tissue after estrogen treatment and in untreated controls, but not in kidney tumors. The absence of Neu oncoprotein and mRNA from those cell types that have previously been shown to overexpress estrogen receptors in response to estrogen, suggests that the estrogen receptor and neu genes are interdependent in this tumor system, which may thus be a useful animal model for studying the regulation of neu by estrogens.     

Water-suppression MRI: role in the evaluation of osseous lesions

The efficacy of chemical shift based water-suppression MRI in the evaluation of bone marrow lesions has not been previously reported. T1-weighted images without and with water suppression were compared in five patients with 16 lesions. There was a significant improvement in the contrast-to-noise ratio (from 4.32 to 5.95, P < 0.01) and contrast ratio (from 1.71 to 5.69, P < 0.004) with water suppression. Water suppression may be useful clinically by increasing the conspicuity of bone marrow lesions.     

Postoperative MRI appearance after transsphenoidal pituitary tumor resection

BACKGROUNDKnowledge of the magnetic resonance imaging (MRI) appearance of the pituitary fossa following transsphenoidal resection of a pituitary adenoma, in the early and late postoperative period, is important for detecting complications and for assessing extent of tumor excision. Few prospective studies have addressed this issue.METHODSFourteen patients with pituitary macroadenomas were prospectively studied with MRI. Maximal tumor resection was accomplished in each patient, and the postoperative histological diagnoses included non-secreting adenoma in 11 patients, prolactinoma in 2 and necrosis in one. Early postoperative scans were obtained within 14 days after surgery, and late studies between 3 and 4 months, in all patients. Four patients also had delayed scans between 8 months and a year. The maximum coronal dimension (MCTD) of the sellar and suprasellar contents was measured on T1-weighted contrast enhanced scans.RESULTSAll patients had normal or improved visual examinations and normal or improved hormonal function postoperatively. The preoperative MCTD ranged from 11 mm to 59 mm in height (mean 30.3 mm). There was little change in MCTD on the early postoperative MRI scans (range 7–49 mm, mean 23.5 mm). However, in all patients the MCTD decreased in height by 4 months (range 2–35 mm, mean 12.7 mm). This change represented a 58% mean reduction in size compared to the preoperative measurements.CONCLUSIONSWe conclude that the appearance of the sellar contents on early postoperative MRI may appear remarkably similar to that seen before surgery, even after technically adequate resection. The postoperative mass may represent a combination of residual tumor, edema, postoperative hemorrhage and hemostatic material. Routine follow-up MRI after transsphenoidal resection of pituitary tumors may be delayed until at least 4 months after surgery in patients who are clinically stable.     

Is the prevalence of HIV-associated nephropathy decreasing?

Initial reports have suggested that approximately 10% of patients with HIV-infection develop HIV-associated nephropathy (HIVAN). It has also been predicted that by the end of the decade, HIVAN is likely to become a third leading cause of end-stage renal disease (ESRD) in African-Americans between the ages of 20-64 years. As the morbidity and mortality from HIV-infection has decreased in the last few years, it is possible that prevalence of HIVAN is also changing. We therefore screened HIV-1-infected patients followed in our hospital for HIVAN. A screening urinalysis was performed in 557 HIV-1-infected adult patients between March and May 1998. Of these, 252 were outpatients and 305 were Texas Department of Criminal Justice inmates (TDCJI). Demographic and laboratory data of these patients was obtained from the HIV patients' database. Fifty percent of the patients were African-American, 36.6% were Caucasian and 12. 7% were Hispanic. The mean age of patients was 37 +/- 8 years. Seventy-nine percent of the patients were males and a history of intravenous drug abuse (IVDA) was present in 28%. Twenty-three percent of the patients were concomitantly infected with hepatitis C virus, 4.1% were positive for hepatitis B surface antigen, and rapid plasma reagin test for syphilis was positive in 9.1%. In 38 patients who had more than 100 mg/dl (2+) proteins on screening urinalysis, total urinary proteins were quantitated by collecting 24 h urine specimens. Fifteen of these patients had urinary proteins more than 1.5 g/day (12 patients >3.5 g/24 h and 3 patients >1.5 g/24 h). A renal biopsy was done in 14 of these patients and clinical diagnosis of HIVAN was made in one patient who refused biopsy. Renal biopsies revealed HIVAN [9], diabetic nephropathy [2], membranoproliferative glomerulonephritis [2], Fibrillary glomerulonephritis [1]. All 10 patients (5 TDCJI and 5 outpatients) with HIVAN were African-American. Two of these 10 patients had a history of IVDA and another two were concomitantly infected with hepatitis C virus. The plasma viral load (Pvl) and total CD4 count was not different in patients with or without HIVAN [(Pvl log 10.05 +/- 1.39 vs. 9.9 +/- 2.18 copies/ml, p = 0.78) (CD4: 187 +/- 192 vs. 288 +/- 249 cells/microl, p = 1.17) mean +/- SD]. We conclude that in our HIV-infected population HIVAN exclusively affected African-Americans and the prevalence in them was 3.5%. Copyright Copyright 1999 S. Karger AG, Basel     

A novel neuronal antigen identified by sera from patients with systemic lupus erythematosus

Using human neuroblastoma cell lines (IMR-6, NMB-7, SK-N-Mc, SK-N-SH) as sources, we characterized surface neuronal antigens as an initial step in determining the pathogenic role and clinical significance of neuronal antibodies in systemic lupus erythematosus (SLE) patients. SLE sera were screened for the presence of surface neuronal antibodies using a mixed hemadsorption assay. Thirty SLE sera were further tested by Western blotting and immunoprecipitation of lysed IMR-6 cells. Western blotting revealed binding to predominantly intracellular antigens, none of which was restricted to neuroblastoma cells. In contrast, immunoprecipitation experiments demonstrated binding to a 97K antigen, which appeared to be of surface origin, by 3 SLE sera. This was not present on non-neuronal cells and was not precipitated by sera from healthy or disease controls. This 97K antigen was also precipitated from the neuroblastoma cell line NMB-7, but was not present on SK-N-Mc or SK-N-SH cells. Precipitation was depleted by preabsorption with viable IMR-6 and NMB-7 cells, but not with non-neuronal cells. Thus, some SLE sera recognize a 97K neuronal antigen on select neuroblastoma cells.     

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on the de novo formation of the [PSI+] prion in yeast and aggregation of Sup35 in vitro

Prions are infectious protein conformations that are generally ordered protein aggregates. In the absence of prions, newly synthesized molecules of these same proteins usually maintain a conventional soluble conformation. However, prions occasionally arise even without a homologous prion template. The conformational switch that results in the de novo appearance of yeast prions with glutamine/aspargine (Q/N)-rich prion domains (e.g., [PSI+]), is promoted by heterologous prions with a similar domain (e.g., [RNQ+], also known as [PIN+]), or by overexpression of proteins with prion-like Q-, N-, or Q/N-rich domains. This finding led to the hypothesis that aggregates of heterologous proteins provide an imperfect template on which the new prion is seeded. Indeed, we show that newly forming Sup35 and preexisting Rnq1 aggregates always colocalize when [PSI+] appearance is facilitated by the [RNQ+] prion, and that Rnq1 fibers enhance the in vitro formation of fibers by the prion domain of Sup35 (NM). The proteins do not however form mixed, interdigitated aggregates. We also demonstrate that aggregating variants of the polyQ-containing domain of huntingtin promote the de novo conversion of Sup35 into [PSI+]; whereas nonaggregating variants of huntingtin and aggregates of non-polyQ amyloidogenic proteins, transthyretin, alpha-synuclein, and synphilin do not. Furthermore, transthyretin and alpha-synuclein amyloids do not facilitate NM aggregation in vitro, even though in [PSI+] cells NM and transthyretin aggregates also occasionally colocalize. Our data, especially the in vitro reproduction of the highly specific heterologous seeding effect, provide strong support for the hypothesis of cross-seeding in the spontaneous initiation of prion states.     

Gastric-type mucinous adenocarcinoma of the uterine cervix with neoadjuvant therapy mimicking clear cell carcinoma

Gastric-type mucinous adenocarcinoma, an uncommon subtype of cervical carcinoma, is characterized by a distinct morphology and immunophenotype. Herein, we report a case of a 71-year-old woman who received neoadjuvant radiotherapy and chemotherapy after cervical biopsy revealed moderately differentiated invasive endocervical adenocarcinoma. Subsequently, the outside patient underwent radical hysterectomy with bilateral salpingo-oophorectomy. The post-neoadjuvant therapy hysterectomy specimen showed tumor cells with clear cytoplasm, hyperchromatic nuclei with irregular contours, which mimicked clear cell carcinoma. However, immunohistochemical staining showed that these tumor cells were positive for carcinoembryonic antigen, cytokeratin 7 (diffuse), and cytokeratin 20 (patchy), After review of the pretreatment cervical biopsy specimen, the tumor was favored to represent a gastric-type mucinous adenocarcinoma of the cervix. Pathologists should be aware of this rare tumor and its post-neoadjuvant therapy morphologic changes, which can make diagnosis more challenging.