Autoantibodies against the serotoninergic 5-HT4 receptor and congenital heart block: a reassessment

The specificity of autoantibodies against the serotoninergic 5-HT4 receptor in congenital heart block has led to conflicting observations. In order to clarify the situation, a collaborative effort was undertaken to discover the reasons for these discrepancies and to reassess the importance of such autoantibodies by making use of the Research Registry for Neonatal Lupus. Sera from 128 patients (101 anti-SSA/Ro52 positive mothers among which 74 have children with congenital heart block (CHB), 9 anti-SSA/Ro52 negative patients of which 1 had a child with heart block and 18 healthy donors) were assessed in a single blind test using an ELISA coated with a 5-HT4 receptor-derived peptide. Discrepancies between previous observations in our two groups could be ascribed to small differences in the set up of the assay. Of the 75 sera from mothers of children with CHB, 12 were reactive with the 5-HT4 peptide. Four sera among which three were from 35 Ro52 negative mothers without affected children as well as 2 in the 18 controls were positive. Interestingly, in 1 mother with an isolated child with CHB but who had no detectable anti-SSA/Ro52 antibodies and 1 mother with a child with a structural heart block and no detectable antibodies to any component of SSA/Ro, reactivity with the 5-HT4 receptor was noted. While 5-HT4 receptor autoantibodies do not have the predictive value of anti-Ro52 autoantibodies, the presence of these antibodies in a minor subset of mothers whose children have CHB suggests an additional risk factor which may contribute to the pathogenesis of disease.     

Essential role for the Legionella pneumophila rep helicase homologue in intracellular infection of mammalian cells

We have previously isolated 32 mutants of Legionella pneumophila that are defective in the infection of mammalian cells but not protozoa. The mutated loci have been designated macrophage-specific infectivity (mil) loci. In this study we characterized the mil mutant GK11. This mutant was incapable of growth within U937 macrophage-like cells and WI-26 alveolar epithelial cells. This defect in intracellular replication correlated with a defect in cytopathogenicity to these cells. Sequence analysis of the GK11 locus revealed it to be highly similar to rep helicase genes of other bacteria. Since helicase mutants of Escherichia coli are hypersensitive to thymine starvation, we examined the sensitivity of GK11 to thymineless death (TLD). In the absence of thymine and thymidine, mutant GK11 did not undergo TLD but was defective for in vitro growth, and the defect was partially restored when these compounds were added to the growth medium. In addition, supplementation with thymidine or thymine partially restored the ability of GK11 to grow within and kill U937 macrophage-like cells. The data suggested that the low levels of thymine or thymidine in the L. pneumophila phagosome contributed to the defect of GK11 within macrophages. Using confocal laser scanning microscopy, we determined the effect of the mutation in the Rep helicase homologue on the intracellular trafficking of GK11 within macrophages. In contrast to the wild-type strain, phagosomes harboring GK11 colocalized with several late endosomal/lysosomal markers, including LAMP-1, LAMP-2, and cathepsin D. In addition, only 50% of the GK11 phagosomes colocalized with the endoplasmic reticulum marker BiP 4 h postinfection. Colocalization of BiP with GK11 phagosomes was absent 6 h postinfection, while 90% of the wild-type phagosomes colocalized with this marker at both time points. We propose that the low level of thymine within the L. pneumophila phagosome in combination with simultaneous exposure to multiple stress stimuli results in deleterious mutations that cannot be repaired in the rep helicase homologue mutant, rendering it defective in intracellular replication.     

Distinguishing characteristics of a new neuroblastoma cell line

The characteristics of a new neuroblastoma cell line (MC-NB-1) established from the bone marrow of a 2-year-old male are described. Morphologically, the cells appear as flattened and epithelial-like or as small and spherical. Electron microscopy demonstrated microtubules and dense core secretory granules. The doubling time was approximately 35 hr. Isoenzyme patterns and catecholamine secretion indicated a human line of neuronal origin. The soft agar tumor colony forming system demonstrated drug resistance in vitro comparable to in vivo nonresponsiveness. The stemline karyotype of MC-NB-1 is 44,Y,del(1) (p22:), -4, -7, +del(7)(q22:), -16, +t(7;16)(16pter leads to 16q24::7q22 leads to 7q32), -17. Additionally, double-minute bodies were observed. However, no evidence of homogeneous staining regions (HSRs) were detected.     

Quality of mobility measures among individuals with acquired brain injury: an umbrella review

Quality of Life Research - While several mobility measures exist, there is large variability across measures in how mobility is conceptualized, the source of information and the measurement...     

The Effect of Neonicotinoids Exposure on Oreochromis niloticus Histopathological Alterations and Genotoxicity

This study aimed to examine the side effects of selected neonicotinoids (Acetamiprid, Aceta, and Imidacloprid, Imid) on Oreochromis niloticus juveniles. The acute toxicity, Probit method, revealed an LC₅₀ of 195.81 and 150.76 ppm for Aceta/96 h and Imid/72 h respectively. The fish were divided into three groups that were exposed, for 21 days (n?=?5/replicate), to 1/10 of the LC₅₀ of either neonicotinoids, however, the third was an unexposed control group. Results of erythrocytic micronucleus (MN), and nuclear abnormalities (NA) showed that Aceta and Imid exposure caused a significant (p?<?0.05) increase in MN by?~?2.2 and?~?10 folds, respectively relative to control. NAs occurred at the order of kidney-shaped?>?budding?>?binucleated in Aceta, however, budding?>?binucleated?>?kidney-shaped was noticed in the Imid group. Histopathological changes in gills, liver, and muscles were observed significantly in both exposed groups with more severity in the Imid group. Collectively, Aceta and Imid have potential genotoxicity and histopathological alterations in O. niloticus.

     

Coloanal anastomosis after resection of low rectal cancer in the elderly

Twenty-two patients had coloanal anastomoses performed after resection of low rectal tumors (16 adenocarcinomas and 6 large degenerated villous adenomas). The patients had an average age of 72 years (range: 62–85). A hand-sewn anastomosis was performed between a J-shaped colonic reservoir and the anal sphincter, except in 3 patients who underwent a straight end-to-end coloanal suture without pouch. A defunctionalized stoma was made in 18 cases. Mortality within 30 days of operation was 9%. Specific complications occurred in 2 patients (9%). Mean follow-up in this series was 20.2±11.7 months (± standard deviation). Fifteen patients were alive and free of disease up to 54 months after surgery. One patient was found to have local recurrence at 19 months. The actuarial 3-year survival rate was 73% in the whole group (operative mortality included). Functional results were good in 16 of 19 patients, with an average 1.8–2.9 stools/24 hours and the continence rate was good. Three patients had complications requiring a permanent colostomy. From these preliminary results, coloanal anastomosis appears to be satisfying in regard to oncologic results and affords good anal function, even in the elderly patient (over 62 years of age).

---

Resumen Veintidos pacientes fueron sometidos a anastomosis después de la resecciôn de tumores rectales bajos (16 adenocarcinomas y 6 grandes adenomas vellosos con degeneración carcinomatosa), con edad promedio de 72 años (rango: 62–85). Se practicó anastomosis manual entre un reservorio colónico construído en forma de J y el esfínter anal, excepto en 3 pacientes sometidos a sutura colo-anal términoterminal sin construcción de bolsa. Se practicó un estoma de funcionante en 18 casos. La mortalidad en los primeros 30 días después de la operación fue 9%. Se presentaron complicaciones específicas en 2 pacientes (9%). El seguimiento promedio en la serie fue de 20.2±11.7 meses (± de). Quince pacientes se encuentran vivos y libres de enfermedad hasta por 54 meses. Un paciente demostró recurrencia local a los 19 meses. La tasa actuarial de sobrevida a 3 anos es de 73% para el grupo total (incluyendo la mortalidad operatoria). Los resultados funcionales fueron buenos en 16 de 19 pacientes, con un promedio de 1.8 a 2.9 deposiciones/24 horas y buena continencia. Tres pacientes presentaron complicaciones que requirieron colostomía permanente. Según estos resultados preliminares, la anastomosis colo-anal aparece como un procedimiento satisfactorio en relación con los resultados oncológicos y provee buena función anal aun en el paciente anciano (mayor de 62 años).

---

Résumé Vingt-deux patients ont eu une anastomose coloanale après résection d'une tumeur rectale basse (16 adénocarcinomes et 6 tumeurs villeuses larges dégénérées). L'âge moyen des patients était de 72 ans (extrêmes 62 et 85 ans). Dix-neuf patients ont eu une anastomose manuelle entre un réservoir colique en J et le canal anal, alors que 3 ont eu une anastomose manuelle termino-terminale coloanale sans réservoir. Une colostomie de décharge a été ajoutée dans 18 cas. La mortalité des 30 premiers jours postopératoires a été de 9%. Deux patients (9%) ont eu des complications spécifiques. La survie moyenne a été de 20.2±11.7 mois (± ET). A 54 mois, 15 patients sont en vie et sans maladie. Une récidive locale a été décelée chez un patient à 19 mois. La survie actuarielle à 3 ans est de 73% pour l'ensemble des patients (mortalité opératoire incluse). Les résultats fonctionnels étaient bons chez 16 des 19 patients. Ces patients avaient en moyenne 1.8 à 2.9 selles par 24 heures et la continence était bonne. Trois patients avaient des complications nécessitant une colostomie permanente. D'après ces premiers résultats, il semble que l'anastomose coloanale donne de bons résultats du point de vue oncologique avec conservation d'une fonction sphinctérienne satisfaisante, même chez le patient âgé (plus de 62 ans).

---

---

Presented at the Société Internationale de Chirurgie in Toronto, Ontario, Canada, September, 1989.     

Synthesis of some heterocycles of potential biological activity

A convenient method for the preparation of imidazobenzimidazole3, imidazoimidazole5, imidazotriazole6 and pyrano [2, 3-c] oxazole7 derivatives is described. This depends on interaction of 2-methyl-4-arylidene-2-oxazolin-5-ones1 with o-diamines, thiosemicarbazide and/or ethylcyanoacetate. The effect of alcoholic potassium cyanide on oxazolinone1 was studied. Antibacterial activity of the obtained products was studied.     

Does JC virus have a role in the etiology and prognosis of Egyptian colorectal carcinoma?

John Cunningham virus (JCV) encodes an oncogenic T‐antigen, which is capable of interacting with key growth regulatory pathways. JCV definite role as causal agent of human cancer, still awaits final confirmation. The present study was conducted to assess the possible role of JCV in Egyptian colorectal carcinoma (CRC) and correlate the expression with the clinicopathological features and survival. JCV in situ hybridization (ISH) signals and large T antigen immunoreactivity were examined in 87 colonic specimens. Positive glandular JCV ISH signals were detected in 20%, 25% and 40% of normal, adenoma and CRC cases respectively. Stromal JCV ISH signals were identified in 26% of CRC cases and 5% of adenoma however, normal mucosa did not show stromal positivity with significant difference (p = 0.03). Glandular JCV expression was significantly associated with high grade (p = 0.03), high mitotic index (p=0.02) and low apoptotic index (p = 0.00). Positive stromal signals were significantly associated with low apoptosis (p = 0.00). No positive nuclear immunostaining of JCV large T antigen was detected in all specimens. JCV stromal expression was the 2nd most powerful indicator of short survival and bad prognosis (p = 0.03) in CRC patients. JCV might play an etiological role in CRC tumorogenesis and short survival in Egyptian CRC patients.