Differential immunogenicity of HLA mismatches: HLA-A2 versus HLA-A28

The immunogenicity of human leukocyte antigen (HLA)-A2 versus HLA-A28 was analyzed by antibody production, cytotoxic T-lymphocyte (CTL) induction, and graft survival. We observed that an HLA-A2 mismatched child in HLA-A28 women leads to HLA-A2 specific antibodies in 32% of the women (n=31), whereas in the case of an HLA-A28 child and HLA-A2 women (n=30), no HLA-A28 specific antibodies were found ( P<0.002). Also, the CTL precursor frequencies were significantly lower against HLA-A28 compared with CTLp frequencies against HLA-A2 ( P=0.012). Finally, the kidney graft survival was slightly better in HLA-A2 positive recipients transplanted with HLA-A28 mismatches. We can conclude that single HLA-A28 mismatches are less immunogenic in HLA-A2 individuals compared with single HLA-A2 mismatches in HLA-A28 individuals, which is probably because the mismatched epitopes on the HLA-A2 molecule are unique epitopes, whereas the mismatched epitopes on HLA-A28 are shared by other HLA-A and HLA-B molecules.     

Merkel cell carcinoma: report of seven cases

Merkel cell carcinoma (MCC) is an infrequent, highly malignant, primary skin tumor derived from neuroendocrine cells. Most MCCs occur in elderly individuals, on sun-exposed areas of the body, with the head and neck being the most common sites. We present 7 patients (2 male and 5 female, age 45-80 years) suffering from MCC and treated between 1993 and 2000. All tumors were located on the head and neck and varied from 0.9 to 2.3 cm in size. Five of the patients had stage II disease, 1 patient had stage Ia disease and 1 patient had stage III disease. Six of the patients had positive regional lymph nodes. All patients had local excision of the tumor. Six of them also had lymph node dissection and in 5 of them a superficial parotidectomy was performed. Five patients received adjuvant radiotherapy and 3 of them also received chemotherapy. Local and cervical lymph node recurrence was observed in only 1 patient. Metastases occurred in 5 patients. One patient died within 10 days for other reasons. The patient with the stage III tumor had a survival of 7 months. The other 5 patients had survivals varying from 15 to 54 months. MCC is a skin tumor with very poor prognosis and high recurrence and metastatic rates. Its treatment is still under discussion. Radical excision of the tumor is the main method of treatment. Selective lymph node dissection is suggested. Superficial parotidectomy seems necessary, especially if the tumor is on the auricle. Adjuvant radio- and chemotherapy may extend survival in case of small-size tumors.     

The problem of predicting food intake during the period of adaptation to a new food: a model

A model is described which aims to predict intake immediately following a change from one food to another that is higher in bulk content; it deals with the transition from one 'equilibrium' intake to another. The system considered is an immature pig fed ad libitum on a single homogeneous food, which is balanced for nutrients and contains no toxins so that the first limiting resource is always energy. It is assumed that an animal has a desired rate of food intake (DFI) which is that needed to meet the energy requirements for protein and lipid deposition and for maintenance. DFI may not be achieved if a bulk constraint to intake exists. Where a bulk constraint operates intake is calculated as constrained food intake (CFI) where (where WHC is the water-holding capacity of the food (kg water/kg dry food) and Cwhc is the animal's capacity for WHC (units/kg live weight per d)). Where intake is not constrained it is assumed that genetic potential will be achieved. Potential growth rate is described by the Gompertz growth function. Where intake is constrained, growth will be less than the potential. Constrained growth rate is predicted as where W is pig weight (kg), EI is energy intake (MJ/d), Em is the energy required for maintenance (MJ/d) and eg is the energy required for unit gain (MJ/kg). The value of eg depends on weight and the fattening characteristics of the pig. Actual growth is predicted to be the lesser of potential and constrained growth. To deal with adaptation it is assumed that the time taken to reach equilibrium depends on the difference in WHC values between the previous and current food and that the capacity to consume food bulk is related to the WHC of the current food. It is proposed that the capacity for WHC on the first day on a new food will be equal to the current capacity for WHC on the last day of the previous food. Thus where FI is food intake (kg/d). Thereafter Cwhc will gradually increase over time to a maximum of 0.27 g/kg. The rate of change in Cwhc is made to be the same for all pigs and all foods. The increase in capacity over time is assumed to be linear at the rate of 0.01 units/d. The model was tested using published data. Qualitatively the predictions of the model were in close agreement with the relevant observed data in at least some cases. It is concluded that the underlying theoretical assumptions of the model are reasonable. However, the model fails to predict initial intake when changed to foods high in wheat-bran content and fails to predict the intake of a non-limiting food where compensatory increases in intake and gain occur. The model could be adapted to overcome the first failure by taking into account the time course of digestive efficiency following a change in food. To deal with the second would require a sufficient understanding of the time course of compensatory growth.     

Nutrient partitioning between reproductive and immune functions in animals

The physiological processes that underlie the reproductive cycle impose considerable metabolisable protein (MP) demands on a female, especially during the periparturient period. When MP supply falls short of MP demand (i.e. MP becomes scarce), certain, if not all, bodily functions are expected to be penalised. It has been proposed that partitioning of scarce MP is prioritised to reproductive rather than to immune functions. In other words, at times of MP scarcity, the penalty on expression of immunity would be expected to be greater than that on reproduction. This hypothesis forms a nutritional basis for the occurrence of periparturient breakdown of immunity to parasites (BIP), which can be observed in many host-parasite systems. In the present review we explore this nutritional basis, using periparturient sheep infected with the abomasal nematode Teladorsagia circumcincta as an example, and attempt to quantify its occurrence. Evidence supporting the nutritional basis of periparturient BIP is reviewed, covering experiments in which nutrient supply (from both exogenous and endogenous sources) and/or nutrient demand were manipulated. Quantitatively, MP requirements for expression of immunity to T. circumcincta were estimated to be about 1 g/kg metabolic body weight (body weight 0.75) per d, approximately 5% of the maximum MP requirements of periparturient sheep. The major component of this requirement was assumed to be for replenishing irreversible plasma protein losses into the gastrointestinal tract. Although confirmation of this estimate is required, such estimates may be used to improve the known MP requirements of periparturient animals, enabling the extent and the consequences of periparturient BIP to be minimised.     

Hypercalcaemia in Greek patients with tuberculosis before the initiation of anti-tuberculosis treatment

Hypercalcaemia has been known to occur in association with granulomatous diseases. The aim of this study was to ascertain the incidence of hypercalcaemia and determine the prevalence of symptoms associated with it in Greek patients with newly-diagnosed tuberculosis (TB), before the initiation of anti-tuberculosis treatment. We prospectively evaluated all patients with newly-diagnosed TB presenting, either as inpatients or as outpatients, to our hospital, during a 3-year period. We evaluated 88 patients with TB (50 males and 38 females), aged between 23 and 89 years (mean age+/-SD: 46.4+/-19 years), and 65 age- and sex-matched controls with chronic obstructive pulmonary disease (36 males and 29 females), aged between 28 and 88 years (mean age+/-SD: 47.2+/-18 years). Among TB patients, 56 had pulmonary TB, 20 had pleural TB without evidence of pulmonary parenchyma involvement, eight had pulmonary and pleural TB, and four had disseminated disease. The mean (+/-SD) albumin-adjusted serum calcium concentration and the mean ionized calcium concentration were significantly higher in the TB group (2.49+/-0.21 mmol l(-1) and 1.27+/-0.02 mmol l(-1) respectively) than in the control group (2.36+/-0.11 mmol l(-1) and 1.19+/-0.02 mmol l(-1), P<0.05). In the TB group no correlation between type of disease and albumin-adjusted or ionized calcium concentration was seen. Hypercalcaemia was detected in 22 patients with TB (25%) but only three showed symptoms associated with it. We conclude that, although hypercalcaemia is a common laboratory finding among Greek patients with TB before anti-TB chemotherapy, it is usually asymtomatic.     

A cohort study on Helicobacter pylori serology before and after induction in the Hellenic Navy

BACKGROUND AND AIMS: To determine whether military personnel are at increased risk of Helicobacter pylori (HP) infection in proportion to their occupation during their national service in the armed forces. MATERIALS AND METHODS: Serum samples were obtained from 142 young male Hellenic Navy recruits (mean age, 23.6 years; range, 20-30 years). The first specimen was obtained during their induction into the Hellenic Navy, and the second was obtained after having served for 8 months in different services within Greece. An enzyme-linked immunosorbent assay was used to detect HP-specific immunoglobulin G antibodies. Statistical analysis was performed using the sign test, logistic regression, and the chi 2 test. RESULTS: The crude seropositivity rate increased from 19.01% to 28.16% (p = 0.007). Of the 115 initially seronegative subjects, 17 (14.8%) seroconverted. The most important predictive variable for seroconversion was deployment in a crowded commission (> 20 subjects) combined with the absence of air conditioning in personnel sleeping quarters (p = 0.03, odds ratio = 3.14). CONCLUSION: Our data suggest that the risk of HP infection increases among 20- to 30-year-old individuals during their national service. Degrading environmental conditions may play a major role in HP transmission between young adults who serve in the armed forces.     

Typing for HLA Class I Gene Products Using Plasma as Source

Soluble HLA class I proteins have been found in serum or plasma of healthy and diseased individuals. Here we present evidence that these molecules can be readily used for determination of the HLA type by biochemical methods. Immunoprecipitation of the soluble class I gene products using monomorphic monoclonal antibodies coated to immunobeads and one-dimensional isoelectric focusing followed by immunoblotting represents a feasible and reproducible technique for typing. Analysis of these gene products in families (n = 12, with a total of 62 individuals) as well as in the population (n = 82) showed that all serologically defined antigens tested to date were present in plasma. A reference chart established primarily for the membrane-bound antigens could also be used for the soluble ones.