Mycobacterium-induced potentiation of type 1 immune responses and protection against malaria are host specific

Malaria and tuberculosis are endemic in many regions of the world, and coinfection with the two pathogens is common. In this study, we examined the effects of long- and short-term infection with Mycobacterium tuberculosis on the course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice, which was especially prominent 5 days after infection with P. yoelii 17XL. Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma interferon (IFN-gamma) and tumor necrosis factor alpha than splenocytes from mice infected with either pathogen alone. Interestingly, mycobacterium-induced protection against lethal P. yoelii is mouse strain specific. BALB/c mice were significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL and were not protected against lethal malaria by coinfection with M. tuberculosis. In addition, M. tuberculosis did not augment IFN-gamma responses in BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that M. tuberculosis-induced potentiation of type 1 immune responses is associated with protection against lethal murine malaria.     

Effects of dexamethasone and transient malnutrition on rabbits infected with aerosolized Mycobacterium tuberculosis CDC1551

Malnutrition is common in the developing world, where tuberculosis is often endemic. Rabbits infected with aerosolized Mycobacterium tuberculosis that subsequently became inadvertently and transiently malnourished had compromised cell-mediated immunity comparable to that of the rabbits immunosuppressed with dexamethasone. They had significant leukopenia and reduced delayed-type hypersensitivity responses. Malnutrition dampened cell-mediated immunity and would interfere with diagnostic tests that rely on intact CD4 T-cell responses.     

Cribriform-morular variant of papillary carcinoma: the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma. A case report with clinical and molecular genetic correlation

The increased incidence of thyroid carcinomas in familial adenomatous polyposis (FAP) patients is well recognised. These thyroid neoplasms display distinctive clinicopathological features and generally show good prognostic outcome. Recently, unusual sporadic tumours that share the morphological features of FAP-associated thyroid carcinomas have also been described. In this report, we document a case of a thyroid tumour in a previously well, 46-year-old female. Histology revealed a circumscribed neoplasm composed of tubular, papillary, cribriform and solid areas. The pseudostratified columnar tumour cells showed occasional nuclear grooves and rare nuclear inclusions. Immunohistochemistry showed positive staining with antibodies to cytokeratin AE1/AE3, oestrogen and progesterone receptor proteins. Focal immunoreactivity was also noted with antibodies to thyroglobulin, epithelial membrane antigen, 34betaE12 and cytokeratin CK7. The absence of polyps on colonoscopy and germline mutation in the adenomatous polyposis coli (APC) gene provides evidence that this tumour represents the sporadic counterpart of FAP-associated thyroid carcinoma. The patient is well with no evidence of disease 7 months following resection of the tumour. The differential diagnoses and molecular genetics of this unusual tumour are discussed.     

The efficacy of montelukast in the treatment of cat allergen-induced asthma in children

BACKGROUND: Montelukast is a leukotriene antagonist approved for the treatment of childhood asthma in children age 2 years and older. There are limited studies on its effects on allergic asthma in children. OBJECTIVE: We sought to evaluate montelukast's effects on upper and lower airway responses to intense cat allergen exposure. METHODS: In a double-blind, placebo-controlled, cross-over trial 18 subjects aged 6 to 14 years with cat-induced asthma were randomly assigned to receive 1 week each of either montelukast or placebo, followed by a 1-hour cat challenge in an environmental exposure unit. Upper and lower respiratory tract symptoms were rated, and spirometry and acoustic rhinometry were performed. Challenges were stopped early if the subject became too uncomfortable or had a greater than 50% decrease in FEV1. RESULTS: Overall changes in FEV1 were significantly different with montelukast treatment and remained significant after adjusting for allergen level (P =.02; adjusted P =.01). Lower respiratory tract symptom scores were significantly reduced with montelukast versus placebo (P =.007) but lost significance after adjusting for allergen level (P =.16). Challenge length was significantly longer with montelukast versus placebo (P <.001) and remained significant after adjusting for allergen level (P =.019). Montelukast did not significantly affect upper respiratory responses, as measured by means of symptom scores (P =.43) and changes in acoustic rhinometry (P =.078). CONCLUSIONS: Montelukast was significantly more effective than placebo in attenuating lower respiratory responses and extending challenge length when cat-sensitive children with mild persistent asthma were exposed to high levels of cat allergen.     

Caffeine protects mice against whole-body lethal dose of gamma-irradiation.

Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of gamma-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the oxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice.     

Cervical cancer screening in Tamilnadu, India: a feasibility study of training the village health nurse

Uterine cervical cancer is the most common malignancy among females in developing countries, including India. The success of cervical cancer screening programs in North America and Western Europe has been the result of centralized cervical-cytology screening. This is not possible in the villages (n=17,000) of Tamilnadu where 58 percent of females in rural areas are illiterate, health infrastructure is mediocre, and cervical cytology is unknow. The present study was undertaken to examine if the village health nurse (VHN) could be trained quickly to identify a cervical abnormality by visual inspection so that we could down stage the cancer to earlier stages, more amenable to treatment. VHNs also would be trained to take an adequate Pap smear. A total of 101 VHNs were trained in batches and returned to their villages. Within two years, 6,459 engible women in the study area were screened. The agreement between the gynecologists and the VHNs in identifying cancer among those with abnormal cervix was 95 percent, and 80 percent of the Pap smears taken by VHNs were adequate by WHO criteria, making the feasibility study highly successful.Authors are with The Cancer Institute (WIA), Adyar, Madras, Tamil Nadu,India. Address correspondence to Dr Gajalakshmi, Epidemiology Division and Cancer Registry, 18, Sardar Patel Road, Cancer Institute (WIA), Madras-600 036, Tamilnadu, India. This project was funded by the Indian Council of Medical Research, Government of India, New Delhi, India.520 Cancer Causes and Control. Vol 7. 1996     

Modification of Radiation-induced Oxic and Anoxic Damage by Caffeine and Potassium Permanganate in Barley Seeds

We show that both the immediate and post-irradiation oxygen effects in barley seeds decrease in magnitude in the presence of potassium permanganate and caffeine. This implies that these two types of oxygen effect have features in common. With the removal of the radiation-induced oxygen-sensitive sites, by anoxic hydration, caffeine potentiates the oxygen-independent component of damage, in seeds irradiated in a dry or pre-soaked state. Potassium permanganate, on the other hand, enhances the anoxic radiation damage only in seeds irradiated in a dry state. The possible mode of action of KMnO₄ and caffeine in barley seeds is discussed.     

Laparoscopic grasper for intramedullary biopsy: a technique to improve tissue sampling

Reaming samples are usually sent for histological testing to establish or confirm the primary source of malignancy while intramedullary nailing is performed for impending or established pathological fracture of the long bones. However, this conventional technique of sampling does not always yield accurate results. Herein, we introduce a technique for intramedullary biopsy using a laparoscopic grasper under image intensifier guidance. This novel technique was applied in three cases, and the tissue samples obtained successfully established or confirmed the primary source of malignancy. In comparison, reaming samples obtained via the conventional method showed negative findings in one case and tumour cells that were of poor sample quality in another case. We opine that this new technique is an effective and reproducible method that could improve tissue sampling and achieve a more reliable histological diagnosis.     

Tyrosine-derived novel antimicrobial hydantoin polymers: synthesis and evaluation of anti-bacterial activities

A new approach for the design and synthesis of cyclic N-halamine polymers having anti-bacterial activity based on a vinyl derivative of tyrosine-derived hydantoin is reported. The synthesis of N-halamine polymers generally involves the chemical modification of 5,5′-disubstituted hydantoin to introduce polymerizable vinyl moieties thereby restricting the halogen capture only on the amide nitrogen. Here we show the possibility of synthesizing vinyl monomers of N-halamine from α-amino acids wherein both the amide and imide nitrogens are available for halogen capture. Thus, a hydantoin monomer was synthesized from L-tyrosine and copolymerized with methyl methacrylate and 2-(hydroxyethyl)methacrylate, to obtain random co-polymers. The monomer and its co-polymers were characterized using NMR, IR, HRMS, GPC, DSC, EDAX and TGA analysis. Films of the co-polymers cast from 10% acetone solutions were exposed to sodium hypochlorite solution to activate the hydantoin moieties. The oxidative chlorine content of the films ranged from 0.6 to 0.9%. The activated films were exposed to both Gram positive (S. aureus) and Gram negative (E. coli) bacteria using standard protocols. Polymers having chlorine content as little as 0.6% exhibited 6 log reduction in the bacterial growth within 30 min of exposure. The method allows the halogenation of both amide and imide nitrogens and could be applied to the preparation of a number of vinyl hydantoins from many amino acids.