Rabson Mendenhall Syndrome caused by a novel missense mutation.

BACKGROUND: Rabson Mendenhall syndrome is a rare endocrine condition characterized by severe insulin resistance and hyperglycemia. It occurs due to mutations in the insulin receptor gene. Few mutations which are associated with Rabson Mendenhall syndrome have been identified and reported in the past. The management of this condition is extremely challenging and will need multi-disciplinary approach. CASE PRESENTATION: An 11 year old boy presented with polyuria and polydipsia. He was noted to have coarse facies, severe acanthosis nigricans, hypertrichosis, retarded growth and developmental delay. Investigations revealed severe hyperglycemia which was poorly responsive to high doses of insulin. A diagnosis of Rabson Mendenhall syndrome was suspected based on his physical characteristics in the presence of insulin resistance. Genetic studies revealed a homozygous missense mutation in the Insulin receptor gene confirming the diagnosis of Rabson Mendenhall syndrome. This is a novel mutation which has not been reported previously. CONCLUSION: Rabson Mendenhall syndrome should be suspected in a patient with characteristic physical features, severe hyperglycemia and insulin resistance. The genetic studies will not only confirm the diagnosis but also will help in counselling. Wider collaboration is needed to identify definitive treatment options for managing this rare condition.

Polymerase chain reaction - restriction fragment length polymorphism analysis for the differentiation of mycobacterial species in bronchial washings.

OBJECTIVES: To identify mycobacterial species in bronchoscopy specimens with a simple assay based on polymerase chain reaction and restriction enzyme digestion. METHODS: Sputum smear negative, bronchoscopy specimens (n=202) were collected from patients attending the Central Chest Clinic and the Teaching Hospital Kandy, Sri Lanka. DNA, extracted from the mycobacterial cultures (n=43) were amplified using known mycobacterial specific Sp1 and Sp2 primers. Resulting products were digested with HaeIII and CfoI restriction enzymes and DNA sequencing was performed for the selected isolates. RESULTS: Among the culture positive patients, PCR was able to distinguish 12 rapid growers (~280-320 bp), 15 slow (~200-220 bp) and 10 patients having both rapid and slow and one having two rapid growing mycobacteria. DNA Sequence analysis revealed the presence of M. intracellulare (n=3), M. phocaicum (n=7), M. tuberculosis complex (n=13), Nocardia (n=2), M. smegmatis (n=1) and Mycobacterium sp (n=12). The identified organisms got digested upon exposure to HaeIII restriction enzyme whereas when exposed to CfoI, only M. phocaicum yielded 80 bp and 230 bp DNA fragments while others remained undigested. Consequently, six patients were confirmed to have M. tuberculosis complex, seven had both M. tuberculosis and non-tuberculosis bacteria (NTM) in their bronchoscopy specimens while 21 had NTM. CONCLUSIONS: Optimised PCR-RFLP assay was able to differentiate M. tuberculosis complex bacteria from nontuberculosis mycobacteria and Nocardia. Molecular analysis confirmed the presence of NTM in bronchoscopy specimens and according to the study a significant proportion of patients (13% to 14%) of the study population were found to have NTM in their bronchial washings.

An unusual case of fatal pulmonary hemorrhage in pregnancy.

Rickettsial diseases are common in Srilanka. The spotted fever group of rickettsiae presents in many ways, including very severe disease causing significant morbidity and mortality. A regional variation of the Rickettsia conorii subspecies and differences in clinical presentations are reported. This case describes disseminated Rickettsia conorii infection in a pregnant woman presenting with endocarditis.

Organic Material Soil Amendment Effects on Root Rot and Sugarcane Growth and Characterization of the Materials.

Soil amendment with different organic materials was evaluated in greenhouse experiments for effects on root rot and growth of sugarcane. Materials included composts prepared from cotton gin trash, cottonwood bark, mixed hardwood bark, municipal solid waste, and municipal yard waste; municipal biosolids; and a sugar mill by-product, filterpress cake. Field soil, steam-treated field soil, and steam-treated soil infested with Pythium arrhenomanes were amended with nonsterile or steam-treated organic materials. A metalaxyl fungicide treatment was included for comparison. When added in nonsterile form, cotton gin trash compost, filterpress cake, and biosolids suppressed disease and increased plant growth in field soil and soil infested with P. arrhenomanes, but this ability was reduced after steam treatment. Bark composts were capable of suppressing root rot and increasing plant growth in field soil and Pythium-infested soil when added in either nonsterile or steam-treated forms. Plant growth in steam-treated soil was not promoted by nonsterile or steam-treated materials. Disease suppression provided by organic materials resulted in plant growth increases generally lower than those resulting from metalaxyl treatment in steam-treated soil infested with P. arrhenomanes, but some amendments resulted in growth increases comparable to those obtained with the metalaxyl treatment in field soil. Municipal waste composts had no effect or were detrimental to sugarcane growth. Differences in microbial community composition and chemical properties, including N content, C:N ratio, and other mineral nutrient levels, distinguished organic materials that may suppress disease and promote plant growth by different mechanisms. Microbial activity level of a material was an indicator of potential for disease suppression. The study results suggest that the severity of root rot in sugarcane may be reduced by amending soil with some organic materials.

Modulation of skin cell functions by transforming growth factor-beta1 and ACTH after ultraviolet irradiation.

The adaptive responses in skin to ultraviolet (UV) radiation include increased cornification of keratinocytes and increased synthesis and distribution of melanin by melanocytes. The possible involvement of paracrine factors in the generation of these responses was studied in a novel two-stage culture model. Human melanocytes or keratinocytes were first irradiated or sham-irradiated and then the conditioned media collected from these cells after 24 h were used to treat unirradiated skin cells. Immunofluorescent staining for transforming growth factor (TGF)-beta1 was increased in UV-irradiated keratinocytes compared with sham-irradiated cells. Increased TGF-beta1 was also detected in the culture media of irradiated keratinocytes. Treatment of unirradiated keratinocytes with conditioned media collected from UV-irradiated keratinocytes resulted in increased absolute numbers and percentages of cornified envelopes per well compared with treatment with conditioned media from sham-irradiated keratinocytes. The magnitude of this effect increased with increased dose of initial irradiation. The effects of conditioned media from UVR-treated cells were mimicked by authentic TGF-beta1. Treatment of conditioned media from irradiated cells with an antibody shown to neutralise the effects of TGF-beta1 but not with a non-immune antibody of similar isotype, abolished this bioactivity of the conditioned media from UV-irradiated cells. Immunofluorescent staining for ACTH was also increased in UV-irradiated keratinocytes. Conditioned media from UV-irradiated keratinocytes increased tyrosinase activity of unirradiated melanocytes, an effect which was mimicked by authentic ACTH. This bioactivity of conditioned media from irradiated keratinocytes was abolished in the presence of an antibody which neutralised the activity of ACTH but not MSH. These results provide evidence to support the involvement of TGF-beta1 and ACTH in the cornification and pigmentary responses respectively of skin cells after UV exposure.

Herbicide Effects on Sugarcane Growth, Pythium Root Rot, and Pythium arrhenomanes.

ABSTRACT Six herbicides were evaluated for their effects on Pythium root rot and growth of sugarcane in greenhouse experiments and on in vitro mycelial growth rate of Pythium arrhenomanes. Pendimethalin and atrazine were most inhibitory to mycelial growth, but neither reduced root rot severity. Asulam, atrazine, and metribuzin were not phytotoxic to sugarcane and did not affect root rot symptom severity in clay loam or silt loam field soils. Atrazine and metribuzin increased shoot number, and atrazine increased total shoot weight for treated plants in silt loam soil. Glyphosate, pendimethalin, and terbacil were phytotoxic to sugarcane. These herbicides increased root rot severity, but the extent to which growth reductions resulted from increased disease severity or from direct herbicide injury was not clear. Adverse effects on plant growth and root rot severity were greater in clay loam than in silt loam soil. The results suggest that sugarcane injury from some herbicides is compounded by increased severity of root rot.

Weed Hosts of the Sugarcane Root Rot Pathogen, Pythium arrhenomanes.

Weeds in the Poaceae and Cyperaceae families prevalent in sugarcane fields were evaluated as potential hosts for the root rot pathogen, Pythium arrhenomanes. In greenhouse studies, bermudagrass, broadleaf signalgrass, browntop panicum, barnyardgrass, large crabgrass, goosegrass, itchgrass, johnsongrass, Italian ryegrass, and purple nutsedge became infected when grown in steam-treated soil infested with P. arrhenomanes. However, the extent of root colonization, symptom severity, and growth reductions varied among species. Symptom severity and root colonization by P. arrhenomanes were less when weeds were grown in sugarcane field soil in the greenhouse than when weeds were grown in Pythium-infested, steam-treated field soil. Levels of root colonization by P. arrhenomanes in both experiments were greatest for johnsongrass and itchgrass and lowest for browntop panicum, goosegrass, and Italian ryegrass. For weeds collected from sugarcane fields, frequencies for colonized plants were moderate to high, but the extent of root colonization by P. arrhenomanes was low for all except johnsongrass. The results indicate that weeds can serve as hosts for P. arrhenomanes and may play roles in the epidemiology of Pythium root rot on sugarcane.

Effects of ultraviolet irradiation on human skin-derived epidermal cells in vitro.

The effects of UVA, mixed UVA + B, and solar-simulated irradiation were examined in human keratinocytes and melanocytes cultured in vitro. Irradiation with UVA, UVA + B, or the solar simulator caused a dose-dependent decrease in keratinocyte cell numbers and thymidine incorporation at 24 hours, with recovery after 48 and 72 hours. Divided dose regimens reduced the inhibitory effect of ultraviolet (UV) irradiation on cell numbers measured 24 hours after the last irradiation. Exposure to both UVA and UVA + B increased formation of cornified envelopes. Similar irradiance doses of UVA 80 minutes (1.12 J/cm2) and UVA + B 40 minutes (1.04 J/cm2) caused 2.4- and 3.3-fold increases in cornified envelope formation, respectively. With solar-simulated irradiation, the cornified envelope formation was increased by 3.5-fold after exposure of 8 minutes (2.6 J/cm2). Irradiation of melanocytes with UVA, UVA + B, or solar-simulated irradiation resulted in a dose-dependent decrease in melanocyte numbers after 24 hours compared with sham-irradiated controls. As a result of UV irradiation, tyrosinase activity of melanocytes measured at 24 hours was stimulated. UVA + B irradiation (1.04 J/cm2) increased tyrosinase activity approximately twofold, while UVA alone (1.1 J/cm2) increased tyrosinase four to sixfold and solar-simulated irradiation (1.3 J/cm2) increased tyrosinase approximately twofold compared to the control cells. Melanin content increased in cells after both UVA and mixed UVA + B irradiation. These results indicate that both UVA and mixed UVA + B irradiation had qualitatively similar effects on the proliferative and functional activity of skin-derived cells but that the type of irradiation and the dosage regimen affect the dose-response relationship.