Characterization of intestinal alkaline phosphatase expression and the tumorigenic potential of gamma-irradiated HeLa x fibroblast cell hybrids

Fusion of tumorigenic HeLa cells with human skin fibroblasts results in genetically stable hybrids which are nontumorigenic and no longer express the HeLa tumor-associated antigen, intestinal alkaline phosphatase (IAP). Previous analysis of spontaneous segregants of the nontumorigenic hybrid have implicated the loss of one copy of human fibroblast chromosome 11 with reexpression of IAP and tumorigenicity. This observation suggests that a putative HeLa tumor suppressor gene(s) is located on chromosome 11 and that this gene may be a negative regulator of the IAP gene. We have isolated several gamma-ray-induced mutants (GIMs) of the nontumorigenic HeLa x skin fibroblast hybrid CGL1 that were specifically selected for reexpression of IAP to further investigate the potential linkage between IAP regulation and the putative tumor suppressor locus. The GIMs have a wide range of cell morphology and level of IAP expression (nearly a factor of 40). The tumorigenicity of the GIMs was examined by s.c. injection into nude mice and all were found to be tumorigenic. The tumor volume-doubling time is in the range of 4 to 8 days for all the cell lines; however, the lag time to reach 500 mm3 tumor volume was significantly longer when the GIM IAP activity was low (less than 20% relative activity), suggesting perhaps that there is a threshold level of IAP expression required for tumor formation and selection for high IAP expression in vivo. However, studies with tumor reconstitutes of the GIMs and transfection studies with an IAP complementary DNA expression vector indicate that high IAP expression alone is not sufficient to confer rapid tumor growth. Therefore, while the data lend strong support to the continued tight correlation between IAP reexpression and tumorigenicity and to our proposal that the tumor suppressor may negatively regulate the IAP gene, it suggests that selection for other gene activities may be responsible for aggressive tumor growth in this cell hybrid system.     

Motives and intent: a comparison of views of overdose patients and their key relatives/friends

The purpose of the study was to compare the perceptions of patients with those of key relatives or friends as regards motives for self-poisoning and intent to die, in ninety-eight overdose cases. Patients admitted to the accident and emergency department of a district general hospital in the county of Warwickshire, England, were interviewed following their recovery. Their key relatives/friends were also interviewed concerning their views of the emergency. Analysis of the responses of patients and key persons indicated that there was a significant association between the perceptions of the two classes of subjects as regards selection of escape/relief motives, warning prior to the attempt and intention to die. There was also a significant association between patient and relative perceptions of suicidal intent and relief at being alive. The implication of these findings as regards follow-up therapy is discussed.     

A randomised clinical trial comparing the ‘sniffing’ and neutral position using channelled (KingVision®) and non‐channelled (C‐MAC®) videolaryngoscopes

Head and neck position is one of the factors which can be associated with difficult videolaryngoscopy and tracheal intubation. This prospective randomised clinical trial compared ‘sniffing’ and neutral positions using a channelled (KingVision^®) and a non‐channelled (C‐MAC^® D‐blade) videolaryngoscope in 200 adult patients randomly allocated into four groups (KingVision ‘sniffing’, KingVision neutral, C‐MAC ‘sniffing’ and C‐MAC neutral). The primary outcome was the ease of tracheal intubation using the modified intubation difficulty scale (mIDS) score. Laryngoscopy time, intubation time, laryngoscopic view using the percentage of glottic opening (POGO) score and success rate of tracheal intubation were secondary outcomes. The median (IQR [range]) modified difficulty scale scores for the four groups, respectively, were 0 (0–1 [0–3]), 0 (0–1 [0–4]), 1 (0–1 [0–5]) and 0 (0–1 [0–3]; p = 0.384). There was no significant difference in laryngoscopy time (p = 0.020), intubation time (p = 0.272) and success rate (p = 0.968) between the groups. The percentage of glottic opening score was lower for C‐MAC neutral group as compared with other three groups (p = 0.01). There was no significant difference in the ease of intubation between the ‘sniffing’ and the neutral position when using the KingVision and the C‐MAC videolaryngoscopes. Therefore, either of the two positions could be used with these types of videolaryngoscopes, if deemed advantageous for the patient.     

Association of <Emphasis Type="Italic">IL1B -511C/-31T</Emphasis> haplotype and <Emphasis Type="Italic">Helicobacter pylori vacA</Emphasis> genotypes with gastric ulcer and chronic gastritis

Background  

The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area.     

Screening of autosomal gene deletions in patients with hypogonadotropic hypogonadism using multiplex ligation‐dependent probe amplification: detection of a hemizygosis for the fibroblast growth factor receptor 1

Objective Congenital hypogonadotropic hypogonadism with anosmia (Kallmann syndrome) or with normal sense of smell is a heterogeneous genetic disorder caused by defects in the synthesis, secretion and action of gonadotrophin‐releasing hormone (GnRH). Mutations involving autosomal genes have been identified in approximately 30% of all cases of hypogonadotropic hypogonadism. However, most studies that screened patients with hypogonadotropic hypogonadism for gene mutations did not include gene dosage methodologies. Therefore, it remains to be determined whether patients without detected point mutation carried a heterozygous deletion of one or more exons. Measurements We used the multiplex ligation‐dependent probe amplification (MLPA) assay to evaluate the potential contribution of heterozygous deletions of FGFR1, GnRH1, GnRHR, GPR54 and NELF genes in the aetiology of GnRH deficiency. Patients We studied a mutation‐negative cohort of 135 patients, 80 with Kallmann syndrome and 55 with normosmic hypogonadotropic hypogonadism. Results One large heterozygous deletion involving all FGFR1 exons was identified in a female patient with sporadic normosmic hypogonadotropic hypogonadism and mild dimorphisms as ogival palate and cavus foot. FGFR1 hemizygosity was confirmed by gene dosage with comparative multiplex and real‐time PCRs. Conclusions FGFR1 or other autosomal gene deletion is a possible but very rare event and does not account for a significant number of sporadic or inherited cases of isolated GnRH deficiency.