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Analysis of T-cell reactive regions and HLA-DR4 binding motifs on the latex allergen Hev b 1 (rubber elongation factor).

BACKGROUND: The rubber elongation factor in Hevea rubber (Hev b 1) is one of the important latex-allergenic proteins inducing the production of specific IgE antibodies in latex-exposed subjects. In addition, Hev b 1 induces lymphocyte proliferation responses. A study about detailed T-cell epitope analysis of major latex allergens has not been published yet. OBJECTIVE: The aim of this study was to define the T-cell reactive regions on the latex allergen Hev b 1. METHODS: Nine overlapping peptides with 19 or 17 amino acid lengths representing the complete sequence of Hev b 1 were used for T-cell epitope mapping. Peripheral blood mononuclear cells (PBMCs) of latex-sensitized patients and healthy subjects were isolated and stimulated with the synthetic peptides to determine the specific proliferation response. The examined patients were sensitized to latex by occupational exposure (n=14) and suffered from rhinitis, conjunctivitis, contact urticaria and/or asthma. Two control groups of non-sensitized subjects were studied, one occupationally exposed to latex (n=4), the other one not exposed to latex (n=4). RESULTS: Positive proliferation response induced by one or more peptides was detected in 10 of the latex-sensitized patients and in two of the latex-exposed non-sensitized subjects. Each patient exhibited an individual epitope reactivity pattern. The whole protein was found to be immunogenic, but the intensity of lymphocyte responses induced by the peptides was different. The majority of the patients' PBMCs (more than 66%) responded to the peptides 31-49 and 91-109. Using the peptide selection of Stille's algorithms, three epitopes were predicted covering region 38-74 and two others covering region 82-104; the two peptides 31-49 and 91-109 are part of these regions. A strong HLA-DR4Dw4 (DRB1*0401)-binding motif according to published DR4w4 binding motifs was predicted in the region of 102-110 including peptide 91-109 to which the majority of tested HLA-DR4-positive patients responded. CONCLUSIONS: Our data indicate that the whole 14 kDa protein Hev b 1 is immunogenic having regions that demonstrate individual and varying PBMC stimulation. Experimental data of T-cell reactive regions based on PBMC-stimulation complement the information on T-cell epitope prediction. In addition, the Hev b 1 molecule contains a HLA-DR4Dw4 (DRB1*0401)-binding motif.

Adult↗

Applications of microscopy to the deformation and fracture of rubber-toughened polymers.

The principal mechanisms of inelastic deformation in rubber-toughened plastics, and in other similar multiphase polymers, are shear yielding and multiple crazing in the rigid matrix phase, and cavitation in the soft disperse phase. Microscopy has played a very important part in the identification and study of these mechanisms. However, no one technique has been predominant. Polarized-light microscopy is useful for observing crazing, and has proved to be the most effective method for studying shear yielding, whereas transmission electron microscopy has provided valuable insights into the cavitation behaviour of complex rubber particles. Scanning electron microscopy has made significant contributions in the study of all three micromechanisms. In some microscopy investigations, thin sections have been strained in situ on the microscope stage. In others, specimens have been deformed in the bulk state before being polished and etched, or stained and microtomed, or coated with a thin layer of metal, in preparation for examination in the microscope. The importance of combining microscopy with other, complementary methods for studying deformation micromechanics is emphasized, and two novel methods for detecting cavitation in multiphase polymers are discussed briefly.

Journal Article↗

Development of silicone rubber hollow fiber membrane oxygenator for ECMO.

Silicone rubber hollow fiber membrane produces an ideal gas exchange for long-term ECMO due to nonporous characteristics. The extracapillary type silicone rubber ECMO oxygenator having an ultrathin hollow fiber membrane was developed for pediatric application. The test modules were compared to conventional silicone coil-type ECMO modules. In vitro experiments demonstrated a higher O2 and CO2 transfer rate, lower blood flow resistance, and less hemolysis than the conventional silicone coil-type modules. This oxygenator was combined with the Gyro C1E3 centrifugal pump, and three ex vivo experiments were conducted to simulate pediatric V-A ECMO condition. Four day and 6 day experiments were conducted in cases 1 and 2, respectively. Case 3 was a long-term experiment up to 2 weeks. No plasma leakage and stable gas performances were achieved. The plasma free hemoglobin was maintained within a normal range. This compact pump-oxygenator system in conjunction with the Gyro C1E3 centrifugal pump has potential for a hybrid total ECMO system.

Animals↗

[Rubber band ligation--an alternative treatment for haemorrhoids (author's transl)].

Rubber band ligation, first described by Blaisdell, is an effective way of treating internal haemorrhoids. Treatment is ambulatory, thus saving time and costs. Experiences with 72 patients show this method to be superior to injection therapy and haemorrhoidectomy because of the simplicity of technique, the short period of treatment and the minimal discomfort for the patients. In our opinion rubber band ligation is the treatment of choice in managing internal haemorrhoids.

Adult↗

Blue rubber bleb nevus syndrome and gastrointestinal haemorrhage: which treatment?

PURPOSE: To describe a paediatric case of "Blue Rubber Bleb Nevus Syndrome" (BRBNS) or Bean's syndrome, a rare systemic disorder characterised by cutaneous and gastrointestinal vascular malformations that often lead to overt life-threatening gastrointestinal bleeding or occult blood loss with severe anaemia and iron deficiency. CASE REPORT: A 6-year-old girl with multiple characteristic cutaneous vascular lesions was admitted for a massive rectal bleeding. A few months previously she was endoscopically treated for gastric angiomas which developed into melaena. Preoperative investigations revealed the recurrence of gastric lesions. At laparotomy, more than 25 angiomas of the GI tract were found. Multiple intestinal resections were carried out. RESULTS: No intraoperative or postoperative problems occurred and the girl is completely healthy without further bleeding after a follow-up period of three years. CONCLUSIONS: BRBNS belongs to the group of vascular venous malformations. Most of the time it occurs sporadically, but it can be inherited as an autosomal dominant trait. Recent analysis identified a locus on chromosome 9 responsible for venous malformations. BRBNS patients present typical skin lesions, with some lesions having a rubber-like nipple appearance; the number of skin and GI lesions and the severity of anaemia are correlated. Treatment is dependent on the extent of gut involvement and the severity of the clinical picture. In the absence of massive bleeding, a conservative treatment will be sufficient; otherwise resections are mandatory, but additional lesions may subsequently develop. Management with electrocautery or laser photocoagulation are usually not effective even if some reports recommend them. Pharmacological treatment is useless. Prognosis of BRBNS is unknown.

Child↗

A 19-year-old female with blue rubber bleb nevus syndrome. Endoscopic laser photocoagulation and surgical resection of gastrointestinal angiomata.

A case of a blue rubber bleb nevus syndrome in a 19-year-old female patient with multiple cutaneous and gastrointestinal hemangiomata is described. Recurrent GI bleeding resulted in severe chronic anemia, which was successfully treated by endoscopic laser photocoagulation and surgical resection. Both forms of therapy had to be repeated 4 years later, the patient having been well in the meantime. This combined endoscopic and surgical approach might also improve the survival of patients with severe GI hemorrhage due to blue rubber bleb nevus syndrome.

Adult↗

Constrained Rouse model of rubber viscoelasticity.

In this work we use a new approach to investigate the equilibrium and linear dynamic-mechanical response of a polymer network. The classical Rouse model is extended to incorporate quenched constraints on its end-boundary conditions; a microscopic stress tensor for the network system is then derived in the affine deformation limit. To test the model we calculate the macroscopic stress in equilibrium, corresponding to the long-time limit of relaxation. Particular attention is paid to the treatment of compressibility and hydrostatic pressure in a sample with open boundaries. Although quite different in general, for small strains the model compares well with the classic equilibrium rubber-elasticity models. The dynamic shear modulus is obtained for a network relaxing after an instantaneous step strain by keeping track of relaxation of consecutive Rouse modes of constrained network strands. The results naturally cover the whole time range--from the dynamic glassy state down to the equilibrium incompressible rubber plateau.

Journal Article↗

Digestibility of allergens extracted from natural rubber latex and vegetable foods.

BACKGROUND: Several cross-reactive allergens are now known to be involved in the defense responses of higher plants. Such proteins are drawing the attention of plant breeders because of their antimicrobial or stress-alleviating activities. Plants genetically modified to express defense-related proteins are being developed. The current concern is focused on the allergenicity of these intentionally expressed proteins. OBJECTIVE: It is believed that food allergens are proteins resistant to digestion. Digestibility tests have been accepted as an appropriate method for evaluating the allergenicity of newly introduced proteins. In this study we investigated the usefulness of this method for detecting allergens from natural rubber latex and vegetable foods. METHODS: Proteins were extracted from rubber latex, potato, and 5 kinds of fruits. Simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were used for the digestibility test. An aliquot of each digest was periodically withdrawn and analyzed. Allergens were detected with pooled sera from individuals with latex allergy or patients given a diagnosis of oral allergy syndrome. RESULTS: Most latex and vegetable food proteins were digested by the SGF within 4 minutes. Numerous allergens were also decomposed by the SGF within 8 minutes. Although vegetable food allergens were relatively stable in the SIF, kiwi allergens were substantially degraded by the SIF within 16 hours. CONCLUSION: The pronounced lability of the plant-derived allergens was thought to reflect the discrete sensitization and elicitation processes of patients with latex-fruit syndrome or oral allergy syndrome. These results indicate that the allergenicity of a newly expressed protein should be carefully evaluated according to not only its digestibility but also other important properties.

Allergens↗

In vivo sensitization to purified Hevea brasiliensis proteins in health care workers sensitized to natural rubber latex.

BACKGROUND: Thirteen proteins of natural rubber latex (Hevea brasiliensis) known to bind human IgE have been isolated and characterized as Hev b allergens. However, the in vivo importance of native Hev b allergens has not been defined in health care workers (HCWs) with natural rubber latex (NRL) allergy. OBJECTIVES: The principal aim of this study was to identify the major in vivo Hev b allergens in HCWs with NRL allergy confirmed by percutaneous sensitivity to nonammoniated latex (NAL). METHODS: Skin prick testing was performed with 7 (native) proteins purified from NAL (Hev b 1, 2, 3, 4, 6.01, 7.01, and a newly described Hev b 13) and recombinant Hev b 5 in 62 HCWs with histories of NRL allergy (group 1) confirmed by percutaneous reactivity to NAL and in 49 atopic HCWs without NRL allergy (group 2). Serial 10-fold concentrations of Hev b proteins (5 x 10(-5) microg/mL to 50 microg/mL) were tested; serum samples of subjects were assayed for serum specific IgE by immunoassays. RESULTS: Hev b 2, Hev b 5, Hev b 6.01, and Hev b 13 produced skin reactions in more than 60% of group 1 subjects, with Hev b 1, 3, 4, and 7.01 eliciting reactions in less than 50%. Only 1 of 49 group 2 workers reacted to a single Hev b antigen (Hev b 13). Specificity of 7 Hev b allergens was 100% and 98% for Hev b 13 in identifying workers with confirmed NRL allergy. Specific IgE by AlaSTAT and CAP immunoassays was elevated in 40 of 60 (67%) and 33 of 62 (53%) of NAL-reactive workers and produced false-positive test results in 4 of 49 (8%) and 3 of 48 (6%) group 2 subjects, respectively. CONCLUSION: Hev b 2, 5, and 6.01 are major in vivo allergens and Hev b 13 is a new major in vivo allergen among HCWs with allergy to NRL.

Adult↗

Studies of respiratory morbidity in rubber workers. Part IV. Respiratory morbidity in talc workers.

Pulmonary function tests, chest x-rays, and respiratory questionnaires were administered to eighty talc workers and 189 non-exposed rubber workers from three rubber tire manufacturing plants. The talc workers, who were exposed to talc at levels below the current threshold limit value (TLV) of 20 mppcf for nonfibrous talc, had a statistically significantly greater prevalence of productive cough and of positive criteria for chronic obstructive lung disease (COLD) than did the control workers. The talc workers with more than 10 years of exposure had significantly decreased residual FEV 1.0. Multiple regression analysis of FEV 1.0 in the talc workers estimated that each year of exposure to talc dust reduced the FEV 1.0 by 26 ml. Talc workers had a clear increase in respiratory morbidity, despite the absence of chest roentgenographic changes. Based on this study, a safe exposure level for talc appears to be 25 mg/m3 as a time-weighted average.

Bronchitis↗

Blood pressure, heart rate, hormonal and other acute responses to rubber-ring castration and tail docking of lambs.

AIM: To examine cardiovascular, hormonal and other physiological responses of 2-month-old lambs to rubber-ring castration and tail docking. METHODS: Twenty-two male lambs, well accustomed to handling and prepared with femoral artery and jugular vein cannulae, were studied during a 5 h control period and, at least 2 days later, for 1 h before and 4 h after castration and tail docking using rubber rings. Pressure recordings were made via femoral cannulae and blood samples for analysis of plasma constituents were taken from jugular cannulae. RESULTS: Mean systolic, diastolic and mean arterial blood pressure, heart rate and the plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol all increased markedly during the first 1 h after ring castration and tail docking. Although plasma ACTH and cortisol concentrations had returned to control levels by 2.5-3 h, blood pressures and heart rate were still elevated 4 h after ring application. In contrast, there were no significant changes in mean plasma concentrations of renin, electrolytes, minerals, glucose, lactate, urea, creatinine, total carbon dioxide and total proteins, plasma osmolality or the haematocrit after ring application. There were no significant changes in the mean values for any parameter during the 5 h control period or the 1 h period before ring application. CONCLUSION: Systolic, diastolic and mean arterial blood pressure and heart rate may be more sensitive than plasma ACTH or cortisol concentrations as indices of low-grade pain induced by ring castration and tail docking. Alternatively, it is possible that by 4 h after ring placement a small shift in sympathetic tone still persists in the absence of low-grade pain.

Journal Article↗

The thermal biology of digestion in rubber boas (Charina bottae): physiology, behavior, and environmental constraints.

Coadaptation predicts a match between the thermal physiology and thermoregulatory behavior of reptiles. We tested this prediction by studying the digestive biology of rubber boas (Charina bottae). We measured the thermal dependence of gastric digestive rate and passage rate in rubber boas from 10 degrees C to 35 degrees C. We examined the effect of digestion on their thermal preference by measuring the temperatures of C. bottae in a thermal gradient before and after feeding. While the passage rates calculated from the body temperatures of digesting snakes were higher than the passage rates calculated from the body temperatures of nondigesting snakes, there was no difference in calculated digestive rates. These results indicate that the thermoregulatory behavior of C. bottae may be more tightly correlated with factors affecting passage rate than with digestive rate alone. Results of simulating the constraints of the thermal environment on the digestive biology of C. bottae showed that digestion would take more than twice as long in the spring as in the summer. In addition, during the summer, snakes thermoregulating as digesting snakes would pass food 12% faster than those thermoregulating as nondigesting snakes. These results demonstrate how interpretation of laboratory studies can be improved when combined with measurements of appropriate environmental conditions.

Animals↗

Fabrication of implantable microelectrode arrays by laser cutting of silicone rubber and platinum foil.

A new method for fabrication of microelectrode arrays comprised of traditional implant materials is presented. The main construction principle is the use of spun-on medical grade silicone rubber as insulating substrate material and platinum foil as conductor (tracks, pads and electrodes). The silicone rubber and the platinum foil are patterned by laser cutting using an Nd:YAG laser and a microcontroller-driven, stepper-motor operated x-y table. The method does not require expensive clean room facilities and offers an extremely short design-to-prototype time of below 1 day. First prototypes demonstrate a minimal achievable feature size of about 30 microm.

Biocompatible Materials↗

Lack of latex allergen contamination of solutions withdrawn from vials with natural rubber stoppers.

The effect on latex allergen contamination and microbial growth of a latex-allergy precaution technique for preparing injectable products was studied. The study consisted of three parts: (1) preparation of 20 samples from vials with latex-containing stoppers in accordance with conventional guidelines, (2) preparation of 20 samples in accordance with latex-allergy precaution guidelines, and (3) preparation of 5 latex-free samples and 1 latex-contaminated sample as negative and positive controls, respectively. The conventional method involved swabbing a vial top with an alcohol prep pad, puncturing the dry natural rubber stopper with an 18-gauge needle attached to a latex-free syringe, and withdrawing the contents of the vial into the syringe. The latex-allergy precaution preparation technique was similar, except that the stopper was removed before the vial contents were withdrawn. There was essentially no difference in latex allergen concentrations between the two drug preparation methods. None of the samples prepared with the standard method supported any microbial growth. One sample prepared with the latex-allergy precaution method grew bacteria. Removal of the dry rubber stopper from vials did not yield solutions with less latex allergen than solutions prepared according to conventional guidelines.

Allergens↗

Dental surgeons with natural rubber latex allergy: a report of 20 cases.

Latex allergy is becoming a major occupational health issue and dental surgeons are at risk from becoming sensitized to natural rubber latex. A study was conducted to investigate risk factors and glove-related symptoms reported by dentists with natural rubber latex allergy. Twenty dentists, who had undergone serological or dermatological testing for a Type I allergy to latex, were identified from a questionnaire survey. Risk factors investigated were: gender, years in clinical practice, exposure to latex gloves, atopic history and food allergy. The majority of dentists (75%) gave an atopic history. Glove-related adverse reactions ranged from cutaneous to systemic manifestations. All twenty dentists reported itching of the hands in response to latex gloves. One respondent was unable to continue in dental practice because of her glove-related allergies; nineteen dentists were able to continue by using synthetic, non-latex gloves.

Dentists↗

Ranking of allergenic potency of rubber chemicals in a modified local lymph node assay.

A modified local lymph node assay (LLNA) with ex vivo tritium thymidine (3H-TdR) labeling of the proliferating lymph node cells was used for determination of the allergenic potency of chemicals used in the production of rubber for latex medical gloves. Fifteen chemicals known to induce contact hypersensitivity reactions in man, including various thiuram, carbamate, and benzothiazole compounds, and one amine were tested. The EC3 (effective concentration inducing a 3-fold increase in proliferation of lymph node cells [Stimulation Index, SI = 3]) was calculated with nonlinear regression analysis, including a bootstrap method for determination of the 5-95% confidence interval of the EC3 value. This procedure identified 14 out of the 15 chemicals tested as sensitizers, while for one chemical, ZDBC, no EC3 could be calculated due to low responses and a lack of a dose-response relationship in the data obtained. The ranking order of the chemicals with increasing EC3 values (and thus decreasing allergenic potency) was found to be in the following order: ZDEC < TMTD < TETD < ZPC < ZDMC < MBTS < PTD < TMTM < MBT < MBI < PTT < ZMBT < TBTD < DEA < ZDBC. Our results indicate that the chemicals of choice for use in the production of natural rubber latex products would be for the thiuram compounds, TBTD; for the carbamates, ZDBC; and for the benzothiazoles, ZMBT. However, one has to be aware that besides potency, the total amount of residual chemical present in the final product is also important for allergy induction.

Administration, Cutaneous↗

Growth, photosynthetic performance and shade adaptation of rubber (Hevea brasiliensis) grown in natural shade.

We compared growth, photosynthetic performance and shade adaptation of rubber (Hevea brasiliensis Muell. Arg.) plants growing in natural shade (33, 55 and 77% reduction in incoming radiation) to control plants growing in full sunlight. Stem diameter and plant height, measured over a 15-month period, were greatest in plants grown in full sunlight, and both parameters decreased with increasing shade. At 7 and 14 months after planting (MAP), total plant dry mass was highest in control plants and lowest in plants in 77% shade. Expansion of the fourth leaf whorl, monitored at 5-6 MAP, was slowest in plants in 77% shade and fastest in unshaded plants, which had more leaves and higher leaf areas and inter-whorl shoot lengths. In response to increasing shade, specific leaf area increased, whereas leaf weight ratio and relative growth rate decreased. Chlorophyll a/b ratio decreased with increasing shade, indicating shade-induced partitioning of chlorophyll into light-harvesting complexes. Compared to the response in unshaded plants, CO2 assimilation saturated at lower photosynthetic photon flux densities in plants in 77% shade, with a lower upper-asymptote to the light response curve. Chlorophyll fluorescence revealed no evidence of sustained photoinhibitory damage in unshaded plants. Dynamic photoinhibition decreased with increasing shade, with the greatest depression in the ratio of variable to maximal fluorescence around midday. We conclude that shade adaptation and shade-induced reductions in dynamic photoinhibition account for the enhanced early growth of rubber in light shade.

Adaptation, Physiological↗

Corneal edema after overnight lid closure of rabbits wearing silicone rubber contact lenses.

Elastofilcon A silcone rubber contact lenses induce less corneal swelling than no lens wear during sleep, and increasing the central thickness and volume of the lens does not influence its overnight performance. We sought to elucidate whether a silicone rubber lens can promote the distribution of atmospheric O2 on the cornea through a small interpalpebral opening under closed-eye conditions. Three groups of rabbit eyes comprised 12 eyes wearing Silflex (Dk 79.8 barrer) lenses, 12 with elastofilcon A (Dk 340 barrer) lenses, and 12 without lenses. All eyes were surgically closed overnight; six eyes in each group had a complete lid closure and six eyes had a partial tarsorrhaphy that left a small, central gap approximately 3 mm in length. When the lids were opened the next morning, the partially closed elastofilcon A eyes showed less corneal swelling (6.2 +/- 1.4%) than the partially closed no-lens eyes did (9.6 +/- 1.3%) (p less than 0.01), whereas the partially closed Silflex eyes were significantly more swollen (12.8 +/- 2.1%) (p = 0.01) than the other two partially closed groups were. The completely closed eyes showed no significant difference in corneal swelling among the groups. These results indicate that small lid gaps during sleep may lead to less corneal swelling when elastofilcon A lenses are used than with no lenses.

Animals↗