Anti-melanoma cytotoxic T lymphocytes (CTL) recognize numerous antigenic peptides having 'self' sequences: autoimmune nature of the anti-melanoma CTL response

A line of tumor-infiltrating lymphocytes (660TIL) specifically lysed the autologous HLA-A2+ melanoma (660MEL) and also most A2+ melanoma cell lines. We immunoprecipitated A2 from a large number (>10(12)) of 660MEL cells, extracted naturally processed peptides, fractionated them by HPLC, screened the fractions for recognition by 660TIL, and found a single predominant and a minor peak of activity. Although too little was recovered of the major 660MEL peptide to establish its sequence, HPLC fingerprinting showed that it did not correspond to any of the known A2-associated melanoma peptides recognized by T cells, including peptides from tyrosinase, MART-1/Melan-A, gp100 and MAGE-3. The major 660MEL antigenic peptide appears to be derived from MART-1/Melan-A but is neither AAGIGILTV nor ILTVILGVL nor any other MART-1/Melan-A peptide containing the A2 consensus motif. The multiplicity of melanoma peptides recognized by CD8+ T cells, most of which are non-mutated (including most likely the present 660MEL peptide), suggests the existence of unknown mechanisms, perhaps similar to those operating in autoimmune disorders, whereby T cells that recognize normal 'self' sequences become activated.      

Zimbabwean adolescents' condom use: what makes a difference? Implications for intervention.

PURPOSE: To examine risk and resilience factors at multiple ecological levels related to Zimbabwean adolescents' practice of protected or unprotected sex. METHODS: Data were collected from adolescents in eight secondary schools in Zimbabwe. A 140-item instrument designed by the authors assessed adolescent perceptions, behaviors, and attitudes. Youth who had engaged in sexual intercourse (n = 730) were included in analyses. Risk and resilience factors related to self, peer, family, and community domains were examined. Data were analyzed separately by gender using discriminant analysis to identify factors that predict whether youth engage in safe or unsafe sex. RESULTS: Boys who engaged in safe sex were older, more likely to report their parents were there when needed, spent more time in extracurricular activities, and reported a lower drop out likelihood. Girls who engaged in safe sex worried about HIV/AIDS more than those who engaged in unsafe sex. CONCLUSIONS: Although both boys and girls need medically correct sexuality education, including education on HIV/AIDS and sexually transmitted diseases (STDs), the findings suggest that such education is not enough. Program planners must consider the influences of multiple ecological levels. Gender differences raise several issues for intervention.     

A survey of red cell use in 45 hospitals in central Ontario, Canada

BACKGROUND: The purpose of this survey was to establish baseline information on blood component use in relation to patient diagnoses, procedures, and demographics and to identify patterns of blood use that may be used for blood program planning and transfusion audits. STUDY DESIGN AND METHODS: A cross-sectional survey of the transfusion of blood components in teaching and nonteaching hospitals in central Ontario between September 1991 and August 1992 was carried out. Coders of hospital medical records routinely record demographics, procedures, diagnoses, and other relevant information. A protocol was created by which medical records coders could add the components transfused to the discharge abstract for this study. Red cell use is reported here. RESULTS: Of the 61 hospitals invited to participate, from which 547,279 patients were discharged during the 12-month period of the study, 45 (74%) agreed to participate. Information was collected on 439,373 discharged patients. Of these, 26,611 (6.1%) received at least 1 unit of red cells. Of a total of 101,116 red cell units transfused, more than 74 percent were used in patients discharged with neoplasms, gastrointestinal diseases, circulatory system diseases, and trauma. High-transfusion-use procedures included operations and procedures on the digestive and cardiovascular systems, diagnostic and therapeutic procedures, musculoskeletal system, and hemic or lymphatic system procedures. CONCLUSION: This survey provides baseline blood transfusion information for a specific period that can help determine the need for hospital audits and maximum surgical blood-order schedule guideline reviews. This information is relevant to current recommendations to reduce patient's exposure to blood components. These transfusion data will assist in blood program planning based on known disease trends, demographics, and population changes.     

Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination

Non-disjoined chromosomes 15 from 115 cases of uniparental disomy (ascertained through Prader-Willi syndrome) and 13 cases of trisomy of maternal origin were densely typed for microsatellite loci spanning chromosome 15q. Of these 128 cases a total of 97 meiosis I (MI) errors, 19 meiosis II (MII) errors and 12 mitotic errors were identified. The genetic length of a map created from the MI errors was 101 cM, as compared with a maternal length of 137 cM based on CEPH controls. No significant differences were detected in the distribution of recombination events along the chromosome arm and a reduction was seen for most of the chromosome 15 intervals examined. It was estimated that 21% of tetrads leading to MI non-disjunction were achiasmate, which may account for most or all of the reduction in recombination noted. The mean age of mothers of cases involving MI errors which showed no transitions from heterodisomy to isodisomy was significantly lower (32.7) than cases showing one or more observable transitions (36.3) (P < 0.003, t -test). However, even among chiasmate pairs the highest mean maternal age was seen for multiple exchange tetrads. Chromosome- specific differences in maternal age effects may be related to the normal distribution of exchanges (and their individual susceptibilities) for each chromosome. However, they may also reflect the presence of multiple factors which act to ensure normal segregation, each affected by maternal age in a different way and varying in importance for each chromosome.      

CHOLINERGIC CRISIS FOLLOWING TREATMENT OF POSTOPERATIVE URINARY RETENTION WITH DISTIGMINE BROMIDE

SUMMARY Distigmine bromide is a long-acting anticholinesterase, available for the treatment of postoperative urinary retention. Its effectiveness is unproven and administration may be hazardous. We describe a case in which oral distigmine bromide was used for postoperative retention, resulting in a potentially life-threatening ‘cholinergic crisis‘. We review the literature and conclude that the use of oral distigmine bromide in postoperative urinary retention is not justified.     

Effects of Treatments by Calcium and Sex Hormones on Vertebral Fracturing in Osteoporosis

Lateral radiographs of the thoracic and lumbar spine were takenperiodically in 49 patients with osteoporosis. Thirty patientswere postmenopausal, and 19 nonmenopausal with osteoporosisdue to steroids, male hypogonadism, alcoholism, thyrotoxicosisor unknown cause. Patients were studied before, during and aftertreatment with high calcium alone, or with combined calciumand sex steroids. Calcium was given as effervescent calciumlactate gluconate, and sex hormones as oestradiol valerate,testosterone oenanthate, or methenolone oenanthate. A totalof 964 films covering 409 patient-years were available for measurement.On each vertebra, deformity due to loss of anterior height wasmeasured and assigned to one of four grades. For the time intervalbetween each consecutive pair of films, a patient's vertebralfracture rate score was calculated and expressed per thousandpatient-years. In comparison with the corresponding pretreatment fracture ratescore, both the postmenopausal and the nonmenopausal groupswho had not received sex hormones previously, failed to showsignificant changes (p=0.144; p=0.017) on high calcium aloneduring mean periods of 4.3 and 2.8 years respectively. If thefirst 2 years on high calcium were excluded for the postmenopausalgroup, they still failed to show a reduction in fracture ratescore (observed for a mean period of 5.0 years; p=0.04). When treated with combined calcium and sex hormones, both postmenopausaland nonmenopausal groups showed a lower fracture rate scoreof 20 and 207 respectively when compared with the pretreatmentlevels of 1500 and 1697 (in mean treatment periods of 3.2 and4.4 years; p<0.001 in each case). When given high-dose calciumalone, but after treatment with sex hormones as well, the postmenopausalgroup showed no change in fracture rate score from pretreatment(in a mean of 3.1 years; p=0.069); however the nonmenopausalgroup still showed a significant reduction in fracture ratescore from 1697 to 42 over a mean period of 2.3 years (p=0.001).The postmenopausal group, after stopping all treatment, showeda higher fracture rate score of 1286 (in a mean of 2.6 years)than did those on combined calcium and sex hormones, in whomthe fracture rate score was 20 (in a mean of 3.2 years; p=0.008).A subgroup of 11 patients with osteoporosis of both the menopausaland nonmenopausal types, had data both before (in a mean of5.5 years) and during (for a mean of 2.5 years) treatment withcalcium alone; the fracture rate scores were 1473 and 918 (p=0.247).Data were available for nine patients both before (for meanof 5.5 years) and during (for a mean of 5.5 years) treatmentwith calcium and sex hormones; the fracture rate score fellfrom 1397 to 100 (p=0.001). It is concluded that in groups with both menopausal and nonmenopausalosteoporosis, vertebral fracturing was reduced by treatmentwith combined calcium and sex hormones, but no significant effectfrom calcium alone was shown. In both groups, cessation of therapywas associated with a return to near the pretreatment fracturerate score, strongly suggesting the need for lifelong treatment.