Hypersensitivity to airborne spitting cobra snake venom.

BACKGROUND: Although the cytolytic, neurotoxic, and hemolytic actions of snake venoms are well known, the ability of airborne inhaled snake venom of the spitting cobra to induce asthma in snake handlers has not been reported. OBJECTIVE: To report the allergenicity of inhaled snake venom in a snake handler who developed increasing hypersensitivity to airborne venom, produced by spitting cobras during public demonstrations. METHODS: Serum samples were obtained from 2 handlers (our study patient and another snake handler who reported developing wheezing when handling spitting cobras), and desiccated venom was obtained from 9 species to which the handlers were exposed. Serum from an asymptomatic and nonatopic snake handler exposed to the same snake species was used as a control. Phosphate-buffered saline extracts were prepared from the desiccated venom, proteins in the venom extracts were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting was performed. Inhibition enzyme-linked immunosorbent assays (ELISAs) were performed to demonstrate cross-reactivity. RESULTS: The study patient had never been previously bitten by a cobra. Wheezing occurred rapidly on inhalational exposure and was reversed by inhalation of salbutamol. The patient had developed IgE antibodies to 9 different snake venoms on Western immunoblots, with major IgE binding proteins of 59 to 63 kDa and 8 to 15 kDa. The cross-reactive nature of the IgE epitopes in the venoms in the different species was also confirmed by 50% inhibition of IgE binding in an ELISA by preincubation with unrelated species. Life-threatening sensitivity of the patient was sustained after a long period of avoidance. CONCLUSIONS: We propose that aerosolized snake venom be considered a new potential source of allergens that may result in anaphylaxis on subsequent exposure. Further studies of the development of specific IgE sensitization following snakebites and the risks of such sensitization should be conducted on snake handlers, particularly those who demonstrate the spitting species.     

The effect of caffeine ingestion on physical performance after prolonged exercise

Summary The purpose of this study was to determine the effect of caffeine ingestion on physical performance after prolonged endurance exercise. Twenty three trained male volunteers participated in a 40-km march and were divided into two groups, matched for caffeine clearance rate and aerobic capacity. The experimental group ingested, prior to the march, a caffeinated drink at a dose of 5 mg·kg⁻¹ body mass and at the 3rd and 5th h of marching an additional drink at a dose of 2.5 mg·kg⁻¹ body mass. The control group ingested a drink of equal volume at the same times. Upon termination of the march each subject performed a cycle ergometer test at an intensity of 90% maximal oxygen consumption. Time to exhaustion and rate of perceived exertion (RPE) were recorded. Blood samples were drawn predrink, at the 3rd and 5th h of marching and immediately after the cycle ergometer test, and were analysed for caffeine, free fatty acids (FFA), lactate and glucose levels. Plasma FFA levels increased during the march (p<0.05), with no significant difference between groups. Lactate levels increased in the experimental group (p<0.05), with no significant change in the control group. Glucose levels did not change significantly in either group. After the cycle ergometer test, lactate levels were significantly higher in the experimental, as compared to the control group (3.77±0.33 vs 2.52±0.35 mmol·l⁻¹, respectively). There was no significant difference between treatments in the time to exhaustion on the cycle ergometer, but RPE was different (p<0.05). Under the conditions of this study, the results do not indicate caffeine ingestion as an ergogenic aid which will postpone exhaustion following prolonged endurance exercise. This work was presented, in part, at the Canadian Association of Sports Sciences Annual Meeting, October 1987, Lake Louise, Alberta, Canada     

Growth, morbidity, and mortality in a cohort of institutionalized HIV-1-infected African children

OBJECTIVE: As a result of the HIV epidemic in Africa, much debate exists on whether institutionalized compared with community-based care provides optimum management of infected children. Previous reports calculated 89% mortality by age 3 years among outpatients in Malawi. No similar data are available for infected children in institutionalized care. We characterized patterns of morbidity and mortality among HIV-1-infected children residing at an orphanage in Nairobi. METHODS: Medical records for 174 children followed over 5 years were reviewed. Mortality was analyzed by Kaplan-Meier methods with adjustment to account for survival in the community before admission. Anthropometric indices were calculated to include mean z scores for weight for length and length for age. Low indices reflected wasting and stunting. Opportunistic infections were documented. RESULTS: Of 174 children, 64 had died. Survival was 70% at age 3 years. Morbidity included recurrent respiratory tract infections, gastroenteritis, parotitis, and lymphoid interstitial pneumonitis. No new cases of tuberculosis disease were noted after admission. Mean z scores for length for age suggested overall stunting (z = -1.65). Wasting was not observed (z = -0.39). CONCLUSION: The optimal form of care for HIV-infected children in resource-poor settings may be the development of similar homes. Absence of tuberculosis disease in long-standing residents may have contributed to improved survival. Stunting in the absence of wasting implied that growth was compromised by opportunistic infections and other cofactors.     

The pelvic epithelium of the rat kidney: A scanning and transmission electron microscopic study

The renal pelvis of the rat is characterized by extensions called specialized fornices that penetrate into the outer zone of the outer medulla (a type II as classified by Pfeiffer, 1968, 1970). The renal pelvic epithelium, therefore, covers areas of the kidney from the inner medulla, the inner and outer stripe of the outer medulla, and the cortex. The renal pelves of seven rats were studied by transmission and scanning electron microscopy. The transitional epithelium on the nonparenchymal surface of the pelvis was three to four cell layers thick (zone 0–1). This epithelium became thinner where it covered the renal cortex (zone 1–2) or the outer medulla. Although the apical cells of the epithelium retained the asymmetric luminal unit-membrane plaques, the number of cytoplasmic fusiform vesicles decreased as one studied the epithelium progressing over the zones from cortex toward papilla. Scanning electron microscopy demonstrated a small number of surface cells of a different morphology that were characterized by apical microvilli. The number of these microvillous lining cells increased as the epithelium covering the outer (zone 2–3) and inner (zone 3–4) stripe regions of the outer medulla was viewed, until the inner medulla was entirely covered by this cell type. In a reciprocal manner, the cells with the asymmetric apical plaques decreased in numbers and in their morphologic specialization in each successive region. The epithelium surrounding the inner medulla (zone 6–7) was completely devoid of this transitional cell type. Judging from the morphologic characteristics of the epithelia, one could surmise that little exchange of urea, water, and salts would occur with the extrarenal connective tissue or the cortical parenchyma. Recycling of urea might become more important physiologically with the outer stripe parenchyma, and even more so with the increased surfaces of the inner stripe parenchyma that lined the secondary pyramid, as well as with the epithelium lining the inner medulla.     

Mechanical properties of dilated human ascending aorta

Dilation of the ascending aorta, associated with Marfan Syndrome, bicuspid aortic valve, or advanced age, may lead to aortic dissection and rupture. Mathematical models can be used to assess the relative importance of increased wall stresses and decreased strength in these mechanical failures. To obtain needed inputs for such models, mechanical properties of dilated human ascending aorta were measured in vitro. Specimens for opening angle, biaxial elastic, and uniaxial circumferential strength tests were cut from excised tissue obtained from 54 patients (age 18–81 years) undergoing elective aortic graft replacement surgery. Opening angle was significantly greater in patients older than 50 years (262°±76°, n=21) compared to younger patients (202°±70°, n=13 All biaxial elastic specimens n=40 exhibited nonlinear stress-strain behavior. Rapid increases in circumferential and axial stresses occurred at lower strains in the older patient group than in the younger. Mean strength was significantly lower in older patients (1.35±0.37 MPa, n=14) than younger (2.04 ± 0.46 MPa, n=11, age <50 years). These changes in mechanical properties suggest that age may influence the risk of aortic dissection or rupture of dilated ascending aorta. © 2002 Biomedical Engineering Society. PAC2002: 8719Rr, 8719Hh     

Neutrophils Injure Bronchial Epithelium after Ozone Exposure

Neutrophil (PMN) influx is an early, prominent finding in the airways of humans after experimental inhalation of ozone (O3), however the potential for PMN to contribute to epithelial injury in this setting is unknown. Bronchial epithelial cells of the human BEAS 2B R1.4 cell line or primary human bronchial epithelial cells underwent DNA labeling by incubation with BrdU. Monolayers were exposed to O3 (0.05 to 1 ppm) or filtered air for 60 min., and subsequently incubated with PMN for 2 h. Epithelial cell cytolysis was significant only in BEAS exposed to O3 and co-cultured with PMN. Apoptosis was maximal in BEAS exposed to O3 + PMN. Primary bronchial epithelial cells were resistant to injury; no cytolysis was detected, and apoptosis was detected only after treatment with 10 mM H₂O₂. Neutrophils may increase damage to the respiratory epithelium after O3 exposure, but primary bronchial epithelial cells are resistant to PMN and ozone induced injury.     

From segment to somite: segmentation to epithelialization analyzed within quantitative frameworks.

One of the most visually striking patterns in the early developing embryo is somite segmentation. Somites form as repeated, periodic structures in pairs along nearly the entire caudal vertebrate axis. The morphological process involves short- and long-range signals that drive cell rearrangements and cell shaping to create discrete, epithelialized segments. Key to developing novel strategies to prevent somite birth defects that involve axial bone and skeletal muscle development is understanding how the molecular choreography is coordinated across multiple spatial scales and in a repeating temporal manner. Mathematical models have emerged as useful tools to integrate spatiotemporal data and simulate model mechanisms to provide unique insights into somite pattern formation. In this short review, we present two quantitative frameworks that address the morphogenesis from segment to somite and discuss recent data of segmentation and epithelialization.     

Summary of complementation groups of UV-sensitive CHO cell mutants isolated by large-scale screening

A summary is given for the lineage and complementation groupassignments of 153 UV-sensitive mutants of the CHO AA8 cellline. The distribution of mutants among six complementationgroups was highly non-random, with the great majority of theisolates belonging to groups 1 and 2. This asymmetry is consistentwith the known hemizygosity of these two linked loci in CHOcells. The relative numbers of mutants induced in group 2 wasfound to depend greatly on the type of mutagen used. Mutagenesiswith UV radiation, ethyl methanesulfonate (EMS), N-methyl-N'-nitro-N-nitroso-guanidine and 7-bromomethylbenz[a]anthraceneproduced high frequencies of group 2 mutants. In contrast, ICR170and ICR191, which are thought to produce mostly frameshift mutations,yielded very few mutants in group 2. These results are of particularimportance in light of the recent finding that the human ERCC2gene, which corrects group 2 mutants, has very strong homologywith the yeast gene RAD3. RAD3 is an essential gene for viabilityin yeast, and the low recovery of group 2 mutants using theframeshift agents strongly suggests that frameshift mutationstend to be lethal in the hamster ERCC2 locus. Several mutagen-sensitivedouble mutants were isolated in two-step selections from EMS-,mitomycin C- or UV-sensitive parental cells, including the lineUVU1, the first mammalian line with two mutations that affectUV sensitivity. The first mutation inactivated excision repair,and the second mutation appears to have affected some otherrecovery process. UVU1 should be useful for studying recoveryprocesses that are separate from nucleotide excision repair. ¹To whom correspondence should be addressed