Genetic map construction and QTL mapping of resistance to blackleg (Leptosphaeria maculans) disease in Australian canola (Brassica napus L.) cultivars.

Genetic map construction and identification of quantitative trait loci (QTLs) for blackleg resistance were performed for four mapping populations derived from five different canola source cultivars. Three of the populations were generated from crosses between single genotypes from the blackleg-resistant cultivars Caiman, Camberra and (AV)Sapphire and the blackleg-susceptible cultivar Westar(10). The fourth population was derived from a cross between genotypes from two blackleg resistant varieties (Rainbow and (AV)Sapphire). Different types of DNA-based markers were designed and characterised from a collection of 20,000 EST sequences generated from multiple Brassica species, including a new set of 445 EST-SSR markers of high value to the international community. Multiple molecular genetic marker systems were used to construct linkage maps with locus numbers varying between 219 and 468, and coverage ranging from 1173 to 1800 cM. The proportion of polymorphic markers assigned to map locations varied from 70 to 89% across the four populations. Publicly available simple sequence repeat markers were used to assign linkage groups to reference nomenclature, and a sub-set of mapped markers were also screened on the Tapidor x Ningyou (T x N) reference population to assist this process. QTL analysis was performed based on percentage survival at low and high disease pressure sites. Multiple QTLs were identified across the four mapping populations, accounting for 13-33% of phenotypic variance (V (p)). QTL-linked marker data are suitable for implementation in breeding for disease resistance in Australian canola cultivars. However, the likelihood of shifts in pathogen race structure across different geographical locations may have implications for the long-term durability of such associations.

Cellular immune responses against proinsulin: no evidence for enhanced reactivity in individuals with IDDM.

Investigations of humans and nonobese diabetic mice suggest that proinsulin and/or a fragment of the region spanning C-peptide and the B-chain of insulin (i.e., proinsulin peptide) may serve as key autoantigens in IDDM. Therefore, we analyzed cellular immune reactivities against these molecules in people with or at varying risks for the disease to clarify their role in the pathogenesis of IDDM. In vitro peripheral blood mononuclear cell (PBMC) responses against these antigens, a control antigen (tetanus toxoid), and phytohemaglutinin were determined in 60 individuals with newly diagnosed IDDM (< or = 1 day from diagnosis) in 34 islet cell cytoplasmic autoantibody- and/or insulin autoantibody-negative first-degree relatives of the IDDM subjects, and in 28 autoantibody-negative control subjects. Unlike previous reports suggesting diabetes-associated elevations in cellular immunity to other beta-cell antigens (e.g., GAD, IA-2, etc.), we observed equivalent levels of phytohemaglutinin stimulation and cellular proliferation in all groups against these antigens (all P values were not significant). The mean stimulation index +/- SD and frequency of reactivity to proinsulin for healthy control subjects and IDDM patients, respectively, were as follows: 1 microg/ml (1.5 +/- 1.0, 1 out of 17 [6%]; 1.9 +/- 1.4, 4 out of 33 [12%]); 10 microg/ml (1.7 +/- 1.3, 1 out of 17 [6%]; 1.2 +/- 0.6, 0 out of 28 [0%]); and 50 microg/ml (1.2 +/- 0.6, 1 out of 16 [6%]; 1.1 +/- 0.6, 1 out of 27 [4%]). The response in healthy control subjects, autoantibody-negative relatives, and IDDM patients, respectively, against the proinsulin peptide fragment were as follows: 1 microg/ml (0.9 +/- 0.4, 1 out of 12 [8%]; 1.3 +/- 1.1, 4 out of 34 [11%]; 1.1 +/- 0.3, 2 out of 28 [7%]); 10 microg/ml (0.9 +/- 0.6, 1 out of 12 [8%]; 1.2 +/- 0.6, 3 out of 34 [9%] 1.4 +/- 1.7, 2 out of 28 [7%]); and 50 microg/ml (1.0 +/- 0.7, 1 out of 12 [8%]; 1.2 +/- 0.5, 2 out of 34 [6%]; 1.3 +/- 0.5, 2 out of 28 [7%]). Taken together with previous studies reporting relatively infrequent occurrences of autoantibodies to proinsulin, the role of immunity to this molecule in the pathogenesis of IDDM in humans remains unclear.

Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group.

BACKGROUND: Patients with Sjögren syndrome (SS) experience slowly progressive infiltration of lacrimal and salivary glands by mononuclear cells. This leads to diminished secretions, with resultant symptoms of xerostomia and xerophthalmia. Although pilocarpine hydrochloride tablets are currently indicated for the treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes in patients with SS are unclear. OBJECTIVE: To assess the safety and efficacy of pilocarpine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes caused by SS in a multicenter, doubleblind, placebo-controlled trial. METHODS: After providing written informed consent, 373 patients with primary or secondary SS and clinically significant dry mouth and dry eyes were randomized to receive 2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12 weeks. Symptoms were assessed by questionnaires with visual analog scales or categorical checkboxes. Whole-mouth salivary flow rates were measured. RESULTS: A significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement compared with the placebo group (P< or =.01) in global assessments of dry mouth, dry eyes, and other symptoms of dryness (P< or =.05). Salivary flow was significantly increased 2- to 3-fold (P<.001) after administration of the first dose and was maintained throughout the 12-week study. The most common adverse effect was sweating, and no serious drug-related adverse experiences were reported. CONCLUSION: Administration of 5-mg pilocarpine tablets 4 times daily (20 mg/d) was well tolerated and produced significant improvement in symptoms of dry mouth and dry eyes and other xeroses in patients with SS.

Cellular immune responses to beta casein: elevated in but not specific for individuals with Type I diabetes mellitus.

Elevated cellular immune responses against the cows' milk protein beta casein have been reported in individuals with Type I diabetes mellitus, a finding supportive of the concept that cows' milk consumption may be causative for the disease. We analysed cellular immune reactivities against beta casein in newly-diagnosed Type I diabetic patients, their immediate autoantibody negative relatives, and unrelated healthy individuals in order to further elucidate the role of anti-beta casein immunity in the pathogenesis of Type I diabetes mellitus. Peripheral blood mononuclear cells were stimulated in vitro with various concentrations of three different beta casein preparations, control antigens (tetanus toxoid, mumps extract) and a mitogen (phytohemagglutinin). The frequency and/or mean simulation index of cellular proliferation against two of the beta casein preparations at high antigen concentrations (i.e. 10 or 50 microg/ml) were significantly higher in newly-diagnosed Type I diabetic subjects compared with autoantibody negative healthy control subjects. However, reactivities against beta casein in the Type I diabetic probands and their autoantibody negative relatives, individuals with a very low-rate of disease development, were almost identical. Cellular immune reactivities to other antigens were similar between the subject groups. In addition to indicating the need for appropriately matched subject populations (e.g. human leukocyte antigen (HLA) matched relatives) when analysing cellular immune responses, these findings support our previous contention that individuals genetically prone to autoimmunity may be deficient in forming tolerance to dietary antigens. However, the significance of anti-beta casein immunity as a specific causative factor in the pathogenesis of Type I diabetes mellitus remains unclear.

The relationship between humoral and cellular immunity to IA-2 in IDDM.

Autoantibodies to the neuroendocrine protein insulinoma-associated protein 2 (IA-2), a member of the tyrosine phosphatase family, have been observed in individuals with or at increased risk for IDDM. Because this disease is thought to result from a T-cell-mediated autoimmune destruction of the insulin-producing pancreatic beta-cells, we analyzed humoral and cellular immune reactivity to this autoantigen to further define its role in the pathogenesis of IDDM. Peripheral blood mononuclear cells (PBMC) from individuals with newly diagnosed IDDM or at varying levels of risk for the disease were stimulated in vitro with the entire 42-kDa internal domain of IA-2 (amino acids 603-979), a series of control antigens (glutathionine-S-transferase, tetanus toxoid, Candida albicans, mumps, bovine serum albumin), and a mitogen (phytohemagglutinin). The frequency and mean stimulation index of PBMC proliferation against IA-2 was significantly higher in newly diagnosed IDDM subjects (14 of 33 [42%]; 3.8+/-4.5 at 10 microg/ml) and autoantibody-positive relatives at increased risk for IDDM (6 of 9 [66%]; 3.9+/-3.2) compared with autoantibody-negative relatives (1 of 15 [7%]; 1.8+/-1.0) or healthy control subjects (1 of 12 [8%]; 1.5+/-1.0). The frequencies of cellular immune reactivities to all other antigens were remarkably similar between each subject group. Sera from 58% of the newly diagnosed IDDM patients tested were IA-2 autoantibody positive. Despite investigations suggesting an inverse association between humoral and cellular immune reactivities against islet-cell-associated autoantigens, no such relationship was observed (rs=0.18, P=0.39) with respect to IA-2. These studies support the autoantigenic nature of IA-2 in IDDM and suggest the inclusion of cellular immune responses as an adjunct marker for the disease.

Diagnosis and patient management of oral cancer.

With an average age of 60 at diagnosis, oral cancer is largely a disease of older adults. This article reviews the incidence, risk factors, early detection and diagnosis of oral cancer, as well as the principles of multidisciplinary management. Considerations for dental treatment planning prior to radiation therapy and surgery for oral cancer are included.

Mucormycosis of the mandible after dental extractions in a patient with acute myelogenous leukemia.

Mucormycosis is a fulminant fungal infection that occurs most often in diabetic and immunocompromised patients including those with hematologic malignancies. In this case, a patient with acute myelogenous leukemia developed mucormycosis in a recent mandibular extraction site. The successful management of this patient demonstrated that early diagnosis, aggressive surgical and medical treatment and resolution of the underlying disease could improve the prognosis for survival. A case is made for the role of smoking as an initiator of mucormycosis, and treatment considerations for controlling periodontal and pulpal disease before chemotherapy are discussed.

Smokeless tobacco: epidemiology, health effects and cessation strategies.

Smokeless tobacco is an extremely addictive substance with a high rate of use in certain demographic groups, such as adolescents and Native Americans. In the past 20 years, the use of smokeless tobacco has almost tripled. Health risks include leukoplakia (a premalignant oral lesion), oral cancer and systemic nicotine effects such as elevated blood pressure and serum cholesterol levels. To avoid or control these effects, family physicians should identify patients who use smokeless tobacco and encourage and support cessation efforts. Patients who are unsure about quitting need the risks of their habit personalized, and those who are actively trying to stop using smokeless tobacco need emotional and, in some cases, therapeutic support (e.g., nicotine replacement therapy). The family physician should encourage patients who appear motivated to stop using smokeless tobacco to set a quit date in the very near future. However, all smokeless tobacco users--regardless of their motivation to quit--need to be followed to ensure compliance with cessation advice or to detect medical complications from use of this form of tobacco.

Oral lesions in systemic lupus erythematosus. Do ulcerative lesions represent a necrotizing vasculitis?

BACKGROUND: It has been suggested that oral lesions in patients with systemic lupus erythematosus (SLE) may be grouped clinically as erythema, discoid lesions, or oral ulcerations. Oral ulcerations have been said to foretell a severe systemic disease flare and the proposal that oral ulcers represent a mucosal vasculitis has been suggested to explain this hypothesis. OBJECTIVE: Our objective was to test the hypothesis that oral ulcers in patients with SLE result from vasculitis. METHODS: We studied 10 patients with American College of Rheumatology (ACR) criteria for a diagnosis of SLE who had oral lesions of lupus (six prospectively and four retrospectively) clinically and by routine and immunofluorescence microscopy. Biopsy specimens were reviewed in a single-blinded fashion. RESULTS: In our patients, no oral lesion, regardless of morphology, demonstrated vasculitis histologically. All lesions demonstrated an interface mucositis. CONCLUSION: Our data strongly contradict the hypothesis that leukocytoclastic vasculitis explains a possible unproven correlation between oral ulceration and disease flares in patients with SLE.

Issues in the care of infants and toddlers with insulin-dependent diabetes mellitus.

Infants and children in the preschool age group who have insulin-dependent diabetes mellitus present a unique set of problems to the health care provider and to their families. These management issues include difficulty in achieving maximal metabolic control; the limited ability of the child to communicate feelings and needs; a significant financial burden to many young families; and the increased family stress and altered psychodynamics seen in families with very young children with chronic illnesses. The lability of diet, exercise, emotions, and overall life-style seen in this age group exacerbates each of these problems markedly. This paper addresses the challenges that these children present; discusses the issues and controversies; and describes how the Diabetes Clinic at Michigan State University uses a combination of methodologies and disciplines to deal with these problem areas.

Interstitial radioactive implants for oral and oropharyngeal cancer: dentistry's role.

Five patients with oral or oropharyngeal cancer were treated with external beam radiation therapy and interstitial radioactive implants as part of their tumor management. The radiation oncologists used various radioisotopes and techniques for placement. Local anesthesia, and in most cases conscious sedation, were used instead of general anesthesia to insert the implants. The dental team, working in conjunction with the radiation oncologists, was able to provide this service which resulted in safe, cost-effective care for the patients.

The safety of dental extractions in patients with hematologic malignancies.

Dental disorders have been recognized as major sources of infection in patients with hematologic malignancies (HM). Management of severe dental infections usually includes dental extractions (DE), but the safety of extractions in patients with HM who are at risk for bleeding, sepsis, and poor wound healing has not been well established. In conjunction with an aggressive program of dental care, 142 DE were performed in 26 patients with acute leukemia, myelodysplastic syndromes, and myeloproliferative disorders. Granulocytopenia (less than 1,000 granulocytes/microL) was present during or within ten days following surgery in 14 patients. In these 14 patients (101 DE), the mean granulocyte count was less than 450/microL, with a median duration of granulocytopenia following surgery of 32 days (range, four to 169 days). Thrombocytopenia (less than 100,000 platelets/microL) occurred during or within two days following surgery in 13 patients (80 DE), with a mean platelet count of 63,500/microL. Transfusions were given for platelet counts less than 50,000/microL. All DE were performed without significant complications. Bleeding was minor to moderate and easily controlled with local measures; no patient required transfusion due to hemorrhage. Average maximum temperature 24 hours after DE was 37.7 degrees C. No episodes of bacteremia were documented within ten days of DE. Minor delay in wound healing was observed in two patients. We conclude that DE can be safely performed in patients with HM in combination with aggressive supportive care.

Afterloaded radiation carrier for carcinoma of the palate. A clinical report.

Although every brachytherapy procedure is individualized, similar factors must be considered for each patient. Dental prostheses with modification may be useful in brachytherapy for managing selected patients with malignancies of the oral cavity. The prosthesis described in this article allowed an irregular surface to be treated with a relatively uniform radiation dose, while minimizing radiation exposure to uninvolved tissues and medical personnel. Whereas uniformity of dose is usually desirable in brachytherapy, it assumed even greater importance for this patient because of previous RT.

Mandibular fractures. Their effect on growth and dentition.

Findings in 28 subjects having had childhood mandible fractures with long-term follow-up document asymmetric facial growth and dental abnormality in a high proportion. Facial growth abnormalities, five of which were moderate to severe, were detected by trained medical-dental examiners in 13 of the subjects (47%). Cephalometric abnormalities were detected in 18 (67%) of the 27 subjects so analyzed, with five (18%) meeting multiple roentgenographic criteria for abnormality. Frontal and lateral cephalometric abnormalities were found in nearly equal percentages among condylar-only, condylar-body, and noncondylar fracture groups, but abnormalities were most severe in association with the condylar injuries. The single best screening tool for facial abnormality was clinical examination. Frontal cephalometric roentgenograms correlated with clinical findings better than lateral cephalometric roentgenograms. However, roentgenograms alone had a 35% false-positive incidence of abnormality when correlated with the clinical-dental examination. Abnormalities of occlusion and dentition were seen in ten (36%) of the 28 subjects. Pterygoid muscle exercises following prolonged intermittent, nocturnal, intermaxillary fixation are discussed as a possible means to reduce the incidence of these abnormalities as the child matures.

Work satisfaction and career aspirations of internists working in teaching hospital group practices.

This paper presents data on the characteristics, work activities, job-related stress, work satisfaction, and career aspirations of 150 faculty and 595 housestaff physicians who regularly provide continuous primary care in 15 teaching hospital-based group practices. The faculty were young, board-certified generalists; they had been recruited from local training programs and spent the majority of their time seeing patients and supervising housestaff. Job satisfaction among faculty and housestaff was generally high. Dissatisfaction occurred most often with aspects of work over which physicians had little control. Although work-related stress was common, it was not related to job satisfaction. Compared with housestaff in traditional residency programs, housestaff enrolled in special Primary Care Training Programs reported significantly greater job satisfaction. For all housestaff, satisfaction with work in the group practice was consistently associated with decreased interest in subspecialty training.