A novel activation-induced cytidine deaminase gene mutation in a Tunisian family with hyper IgM syndrome

Mutations in activation-induced cytidine deaminase can cause an autosomal recessive form of hyper-IgM syndrome. We have examined a Tunisian family composed of six members: two healthy parents, their two healthy daughters and two affected sons. We found a homozygous transversion G to T in the two sons while heterozygosity for the mutation was found in all other family members. This alteration is localised in intron 2 at the +1 position resulting in defective splicing. Use of various intronic cryptic splice-sites led to expression of various aberrant mRNA species. Conclusion:This is a novel mutation found in the gene encoding for activation-induced cytidine deaminase in a Tunisian family with hyper-IgM type 2 syndrome. This alteration leads to the use of two cryptic splicing sites causing the formation of two different mRNA species.C. Fiorini and S. Jilani contributed equally to this work.     

CDX-2 homeobox gene product expression in neuroendocrine tumors: its role as a marker of intestinal neuroendocrine tumors

CDX-2 is a homeobox gene product essential for intestinal development and differentiation. It can be used as a specific marker of colorectal adenocarcinomas and other tumors with intestinal differentiation, but little is known about its expression in endocrine and neuroendocrine (NE) cells and NE primary and metastatic tumors. Using the Cdx-2-88 monoclonal antibody, we evaluated CDX-2 expression in routine samples of 20 normal endocrine/NE tissues and of 299 samples of well-differentiated NE tumors (WDNET) and high-grade NE carcinomas (NEC) from different sites. For 17 cases, we examined primary and corresponding metastatic lesions. We also examined 8 cytologic samples of liver metastases derived from 4 ileal WDNETs, 1 lung WDNET, and 3 pancreatic endocrine tumors. CDX-2 mRNA expression with RT-PCR technique on frozen material was evaluated in 5 WDNETs. CDX-2 was expressed in normal NE cells of the intestine and gastric fundus. High CDX-2 expression was seen in all ileal and appendiceal WDNET, while low levels were seen in WDNETs from stomach, duodenum, and rectum; no reactivity was seen in other WDNETs. Low levels of CDX-2 expression were seen in one third of nonfunctioning pancreatic WDNET where it was more frequently observed in cases with metastatic disease (P = 0.002). CDX-2 was identified in all cytologic specimens of metastatic ileal WDNETs. CDX-2 mRNA analysis confirmed immunohistochemical results. CDX-2 was expressed at high levels in 81% of intestinal NEC. Unexpectedly, variable levels of expression of CDX-2 were seen also in 39% of NEC of other sites, without any relation with the site of origin. This reactivity frequently overlapped TTF-1 expression, suggesting deregulated expression of homeobox genes in NEC. The restricted pattern of CDX-2 expression may have diagnostic value in the identification of the primary site of a metastatic WDNET. Conversely, a limited diagnostic role is suggested for CDX-2 in NEC because of its frequent expression in nongastrointestinal tumors.     

IL-10 and TNF-alpha polymorphisms in a sample of Sicilian patients affected by tuberculosis: implication for ageing and life span expectancy

Human longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses, in particular cytokine gene polymorphisms. In fact, modification of cytokine network is a constant report in studies on age related modification of immune response. Moreover cytokine polymorphisms studies are indicating their involvement in the reshaping of cytokines network as an integral part of the scenario related to a successful ageing. A particular role might be attributed to the influence of cytokine polymorphisms on the efficiency of immune response against infectious diseases that have been the principal selection in oldest old. Here are reported data on the evaluation of the frequency of the functional polymorphisms at genes coding for TNF-alpha (-308G-->A) and IL-10 (-1082G-->A), analysed by ARMS-PCR, in a group of Sicilian patients affected by chronic lung tuberculosis (TBC) compared to that from a group of healthy individuals living in the same region. Data obtained demonstrated a reduction of -308GG TNF homozygous individuals in TBC affected subject group. In the same group a reduction of IL-10 -1082A/* carriers was found. Our results seem to suggest that multiple genetic traits may affect the capacity to cope with an infectious agents and this might predispose to an overt disease. Moreover these data are in agreement with previous reports suggesting that a balanced interaction among pro- and anti-inflammatory molecules it is a key point for conditioning the life span expectancy.     

New acquisitions in the assessment of breath-by-breath alveolar gas transfer in humans

We summarise recent results obtained in testing some of the algorithms utilised for estimating breath-by-breath (BB) alveolar O₂ transfer (VO_2A) in humans. VO_2A is the difference of the O₂ volume transferred at the mouth minus the alveolar O₂ stores changes. These are given by the alveolar volume change at constant O₂ fraction (F _AiO₂ V _Ai) plus the O₂ alveolar fraction change at constant volume [V _Ai–1(F _Ai–F _Ai–1)O₂], where V _Ai–1 is the alveolar volume at the beginning of the breath i. All these quantities can be measured BB, with the exception of V _Ai–1, which is usually set equal to the subjects functional residual capacity (FRC) (Auchincloss algorithm, AU). Alternatively, the respiratory cycle can be defined as the time elapsing between two equal O₂ fractions in two subsequent breaths (Grønlund algorithm, GR). In this case, F _AiO₂=F _Ai–1O₂ and the term V _Ai–1(F _Ai–F _Ai–1)O₂ disappears. BB alveolar gas transfer was first determined at rest and during exercise at steady-state. AU and GR showed the same accuracy in estimating alveolar gas transfer; however GR turned out to be significantly more precise than AU. Secondly, the effects of using different V _Ai–1 values in estimating the time constant of alveolar O₂ uptake (O_2A) kinetics at the onset of 120 W step exercise were evaluated. O_2A was calculated by using GR and by using (in AU) V _Ai–1 values ranging from 0 to FRC +0.5 l. The time constant of the phase II kinetics (₂) of O_2A increased linearly, with V _Ai–1 ranging from 36.6 s for V _Ai–1=0 to 46.8 s for V _Ai–1=FRC+0.5 l, whereas ₂ amounted to 34.3 s with GR. We concluded that, when using AU in estimating O_2A during step exercise transitions, the ₂ value obtained depends on the assumed value of V _Ai–1.     

Pruritus: a useful sign for predicting the haemodynamic changes that occur following administration of vancomycin

Introduction  

The aim of this study was to investigate the haemodynamic changes that follow the appearance of pruritus during vancomycin administration.     

Polyamine levels and ornithine decarboxylase activity in blood and erythrocytes in human diseases

Serum and erythrocyte levels of the polyamines spermine, spermidine and putrescine, as well as ornithine decarboxylase in erythrocytes, were studied in patients with different neoplasms (breast, lung and colon cancer) and in those with a nonmalignant proliferative disease (familial polyposis). The blood levels of polyamines and the spermine/putrescine ratio were significantly higher in all tumors and in nonmalignant colon polyposis. In erythrocyte ornithine decarboxylase activity, spermine and spermidine levels, as well as spermidine/putrescine and spermine/putrescine ratios showed a significant decrease after surgery and chemotherapy. Our data suggest that high levels of blood polyamines and erythrocyte ornithine decarboxylase activity are related to cell proliferation and cancer treatment, but that levels of polyamines in serum and erythrocytes are still significantly high after cancer treatment and are similar to those in polyposis disease. Polyamines are related to nuclear activity during differentiation; therefore, the altered turnover of polyamines could be a sign of abnormal nuclear function. Since polyamines stimulate protooncogene expression, their high levels could be considered an important cofactor in malignant cell transformation.     

The Fixion expansion nail in the surgical treatment of diaphyseal fractures of the humerus and tibia. Our experience

The authors present their experience in the application of a Fixion expansion intramedullary nail for the treatment of diaphyseal fractures of the humerus and tibia, in a total of 40 surgeries. The features of the nail are: stability and flexibility of the instrumentation, speed of surgery, minimal exposure to radiation. The results obtained up to now are encouraging; there are no significant problems either during or after surgery, and mean consolidation time is 3 months for fractures of the humerus, and 4 months for those of the tibia. The Fixion nail is a versatile type of instrumentation that is easy to use.     

Primary malignant melanoma of the gallbladder in dysplastic naevus syndrome

A case of gallbladder involvement by malignant melanoma in a 57-year-old woman is reported. The gallbladder, resected for cholelithiasis, harboured a pedunculated polypoid dark mass, which histologically revealed sheets and nests of epithelioid cells with hyperchromatic nuclei in the lamina propria and at the junctional level. These cells were pigmented (with positive reaction with Schmorl's stain and bleaching with peroxide) and showed immunohistochemical positivity for S-100, gp 100 antigen (HMB-45 antibody) and vimentin. The patient, affected by dysplastic naevus syndrome, had a melanoma in situ excised from the scalp 8 years earlier. The features of the investigated lesion address towards a diagnosis of primary gallbladder melanoma. Furthermore, this is the first time that the existence of such a controversial entity is sustained by the ultrastructural investigation of melanosomes, demonstrating the presence of two melanocitary populations, a typical one exclusively junctional and an atypical one both at the junctional level and in the lamina propria.