Carbonic anhydrase gene expression in CA II-deficient (Car2−/−) and CA IX-deficient (Car9−/−) mice

Using real-time PCR and immunohistochemistry, we have examined the expression of carbonic anhydrase isozymes (CA) I, II, III, IV, IX, XII, XIII and XIV in the brain, kidney, stomach and colon of the wild-type, CA II-deficient ( Car2^−/− ), and CA IX deficient ( Car9^−/− ) mice. The expression of Car4, Car12, Car13 and Car14 mRNAs did not show any significant deviations between the three groups of mice, whereas both groups of CA deficient mice showed decreased expression levels of Car1 in the colon and Car3 in the kidney. The Car2 mRNA level was greatly reduced but not completely abolished in all four tissues from the Car2^−/− mice in which no CA II protein was expressed. Sequencing the Car2 cDNA isolated from C57BL6 Car2^−/− mice revealed two nucleotide differences from the wild-type C57BL6 mice. One is a silent polymorphism found in Car2 mRNA from wild-type DBA mice, which is the strain that provided the original mutagenized chromosome. The second change is a mutation that causes prematurely terminated translation at codon 155 (Gln155X). Car9 mRNA and CA IX protein expression levels were up-regulated about 2.5- and 3.6-fold, respectively, in the stomach of the Car2^−/− mice. These results suggest that the loss of function of cytosolic CA II in the stomach of Car2^−/− mice leads to up-regulation of an extracellular CA, namely CA IX, which is expressed on the cell surface of the gastric epithelium.     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

The effects in vivo of purified preparations of murine macrophage colony stimulating factor-1, recombinant murine granulocyte-macrophage colony stimulating factor and natural and recombinant murine interleukin 3 without and with pretreatment of mice with purified iron-saturated human lactoferrin

The influence of purified natural colony stimulating factor-1 (CSF-1), purified recombinant granulocyte-macrophage (GM)-CSF, purified recombinant interleukin 3 (IL3) and natural IL3 were assessed in mice that were untreated or pretreated with purified iron-saturated human lactoferrin (LF) in order to first suppress myelopoiesis in the mice. S1/S1d mice responded to recombinant GM-CSF and recombinant IL3 in a manner similar to the response of their +/+ littermates. These 4 factors increased the cycling status of hematopoietic progenitors in vivo. The effects were more noticeable if myelopoiesis was first decreased by LF. The effects do not appear to be due to endotoxin contamination. It cannot be discerned from these studies whether the effects are direct ones on the progenitor cells or indirect ones mediated through growth-factor releasing accessory cells. It is possible that effects can be both direct and indirect.     

The effects of interleukins and other soluble factors on T-lymphocyte colony formation.

When plated in semi-solid media, PHA-stimulated human peripheral blood mononuclear cells (PBMC) form discrete T-cell colonies. By contrast, Sephadex G-10 non-adherent (NA) cells (greater than 96% T lymphocytes) show virtually no clonal growth unless cocultured with soluble factors derived from either normal adherent cells or tumour cell lines. Purified IL-1 was able to initiate colony growth of mitogen-stimulated NA cells; cultures containing 20 U of human IL-1 yielded colony counts that were only slightly less than those with PBMC. In addition, recombinant IL-2, free of measurable IL-1, was able to provide the initiating signal required for clonal expansion. Both recombinant and lymphocyte-derived IL-2 were able to enhance the clonal growth of PBMC. Colony growth could be initiated by supernatants derived from short-term cultures of either monocytic (U937, HL60) or B-cell (Raji, Daudi) tumour cell lines. The abilities of these tumour cell lines to promote clonal responses did not correlate with their contents of either IL-1 or IL-2. By contrast, supernatants derived from either K562 (an erythroleukaemic line) or MOLT 4 (a T-cell lymphoma) cells did not provide the initiating signal.     

IMPORTANCE OF DONOR SELECTION IN RENAL TRANSPLANTATION

Renal transplantation has become a treatment of choice for patients with end stage renal disease. A successful transplant is the result of a combination of several factors acting synergistically, such as the degree of HLA compatibility between donor and the recipient, pretransplant blood transfusions, the recipient''s state of immunoreactivity and sensitization, immunosuppressive therapy given in post operative period etc. Donor selection appears to be the most critical factor for the long term success of the organ graft. In this brief review, some of the important parameters of donor selection in renal transplantation are highlighted.KEY WORDS: Histocompatibility (HLA) matching, Cross match, Sensitization     

Proteus syndrome

Abstract: This female Asian (Malay) baby had clinical features of Proteus syndrome. She had a large right facial lipolymphangioma with hyperpigmentation of the overlying skin. There was a smaller lymphangioma over the left side of her neck with excess nuchal folds, macrodactyly and bilateral talipes equinovarus. Despite the extensive hemifacial swelling, there was no evidence of upper respiratory tract obstruction. Generalized seizures developed on the sixth day of life which were controlled with phenobarbital. The lymphangiomas were excised without recurrence.     

ANTIBIOTIC RESISTANCE PATTERN OF ISOLATES FROM WOUND AND SOFT TISSUE INFECTIONS

Two-hundred and eighty bacterial isolates from wound and soft tissue infections were studied for species identification and antibiotic resistance pattern. Amongst them 122 isolates were from community acquired infection and 158 were from nosocomial infections. The common community acquired pathogens were Staphylococcus aureus (67.8%) and Streptococcus pyogenes (10.7%), whereas Staphylococcus aureus (60.1%) and E. Coli (8.9%) were common in nosocomial infection. Only two anaerobes (Cl perfringens) were isolated. Penicillin resistance was found to be 87% and 92% for Staphylococccus aureus in community acquired and noscomial infections respectively. 85% of Proteus isolates were resistant to ampicillin. There was relatively lower level of resistance by all isolates to cefotaxime. Gentamicin showed higher rate of resistance than netilmicin and amikacin. Resistance of E. coli isolates to fluoroquinolones being 79% for norfloxacin, 81% for ciprofloxacin and 60% for ofloxacin. The study showed a higher resistance of methicillin resistant Staphylococcus aureus (MRSA) to other antibiotics. Amikacin and ofloxacin were the best recommended drugs for empirical therapy for all organisms, the susceptibility rate being 80.7% and 80.4%.KEY WORDS: Antibiotic resistance, Soft tissue infections, Wound infections     

Recycled Untreated Rubber Waste for Controlling the Alkali–Silica Reaction in Concrete

Recycled rubber waste (RW) is produced at an alarming rate due to the deposition of 1.5 billion scrap tires annually around the globe, which causes serious threats to the environment due to its open land filling issues. This study investigates the potential application of RW in concrete structures for mitigating the alkali–silica reaction (ASR). Various proportions of RW (5%, 10%, 15%, 20%, and 25%) partially replaced the used aggregates. RW was procured from a local rubber recycling unit. Cubes, prisms, and mortar bar specimens were prepared using a mixture design recommended by ASTM C1260 and tested for evaluating the compressive and flexural strengths and expansion in an ASR conducive environment for specimens incorporating RW. It was observed that the compressive and flexural strength decreased for specimens incorporating RW compared to that of the control specimens without RW. For example, an 18% and an 8% decrease in compressive and flexural strengths, respectively, were observed for specimens with 5% of RW by aggregates volume at 28 days. Mortar bar specimens without RW showed an expansion of 0.23% and 0.28% at 14 and 28 days, respectively, indicating the potential ASR reactivity in accordance with ASTM C1260. A decrease in expansion was observed for mixtures incorporating RW. Specimens incorporating 20% of RW by aggregate volume showed expansions of 0.17% at 28 days, within the limit specified by ASTM C1260. Moreover, specimens incorporating RW showed a lower reduction in compressive and flexural strengths under an ASR conducive environment compared to that of the control specimen without RW. Micro-structural analysis also showed significant micro-cracking for specimens without RW due to ASR. However, no surface cracks were observed for specimens incorporating RW. It can be argued that the use of RW in the construction industry assists in reducing the landfill depositing issues with the additional benefit of limiting the ASR expansion.     

Prevalence and correlates of COVID-19 vaccine hesitancy among the elderly in Qatar: A cross-sectional study

Older individuals are more vulnerable to severe coronavirus disease 2019 and medical complications. Vaccination stands as an efficient and safe vanguard against infection. However, negative attitudes and perceptions pertaining to available vaccines might hinder community inoculation. The aim of this study was to assess vaccine hesitancy and its psychosocial determinants among the elderly in Qatar.We conducted a cross-sectional study between October 15 and November 15, 2020, using a composite online survey including the Vaccine Attitudes Examination Scale in addition to questions on sociodemographic correlates and the role of healthcare professionals.The vaccine hesitancy rate was 19.5%. The main reasons for willingness to vaccinate included understanding the nature of disease and role of vaccination, in addition to information provided by physicians. Fears mainly centered around vaccine safety. Vaccine hesitators were more likely to be non-Qatari and having received the influenza vaccine at least once. Gender, marital status, socioeconomic status, educational level, and having completed childhood vaccinations were not associated with vaccine hesitancy.Efforts should be directed toward raising awareness of vaccine efficacy and safety profiles. Physicians should additionally be educated about their pivotal role in advocating vaccine acceptance. We recommend reassessing vaccine hesitancy and its associated factors following a year of campaigning and vaccine administration to identify and target vulnerable groups.