Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Facilitation of penicillin haptenation to serum proteins.

Traditionally, penicillin binding to serum proteins was believed to be a passive chemical process; however, it appears to be facilitated by serum factors. The objectives of this in vitro investigation were to examine facilitated penicillin haptenation, to study the kinetics of haptenation, and to determine the nature of haptenation-facilitating factors. The model involved addition of [3H]benzylpenicillin to serum or albumin solutions (at pH 7.3 to 7.4) and incubation at 37 degrees C for up to 72 h. The extent of penicillin binding to proteins in serum was found to be four- to fivefold higher than with solutions having comparable concentrations of purified albumin, total protein, or total immunoglobulin. Ultrafiltration of serum reduced penicillin binding to serum proteins substantially. An ultrafiltrable haptenation-facilitating factor(s) was found to be less than 0.5 kDa but was not calcium or magnesium. Finally, the extent of penicillin binding was related to albumin purity, as binding substantially increased with albumin purity. These findings suggest that there is a factor(s) in serum that facilitates covalent binding of penicillin to serum proteins. The factor(s) can be removed and then restored to increase penicillin binding to albumin. It appears that at least one component of the facilitation factor is less than 0.5 kDa, which suggests that it is not a peptide and that it is some simple serum component other than calcium or magnesium.     

Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair

The association between MSHR coding region variation and hair colour in humans has been examined by genotyping 25 red haired and 62 non-red Caucasians, all of whom were 12 years of age and members of a twin pair study. Twelve amino acid substitutions were seen at 11 different sites, nine of these being newly described MSHR variants. The previously reported Val92Met allele shows no association with hair colour, but the three alleles Arg151Cys, Arg160Trp and Asp294His were associated with red hair and one Val60Leu variant was most frequent in fair/blonde and light brown hair colours. Variant MSHR genotypes are associated with lighter skin types and red hair (P < 0.001). However, comparison of the MSHR genotypes in dizygotic twin pairs discordant for red hair colour indicates that the MSHR gene cannot be solely responsible for the red hair phenotype, since five of 13 pairs tested had both haplotypes identical by state (with three of the five having both identical by descent). Rather, it is likely that additional modifier genes exist, making variance in the MSHR gene necessary but not always sufficient, for red hair production.      

Inflammatory mediators in late antigen-induced rhinitis

To investigate the mechanisms responsible for the late-phase response in patients with allergies, we measured four biochemical mediators (histamine, tosyl-L-arginine methyl ester [TAME]-esterase, kinin, and prostaglandin D2) in nasal secretions after nasal challenge with pollen antigen in 12 patients with allergy. Nine patients had an immediate response and a recurrence of symptoms 3 to 11 hours after challenge. The clinical symptoms during recurrence were accompanied by a second increase in levels of histamine, TAME--esterase, and kinin over base-line values, although kinin levels were lower than during the immediate response. In contrast, although the levels of prostaglandin D2 were significantly increased during the immediate response, they did not increase above base line during the late response. Rechallenge with allergen 11 hours after the initial provocation, however, was associated with reappearance of all four biochemical mediators, including prostaglandin D2. We conclude that the late response to nasal challenge with allergen is accompanied by a second increase in the concentrations of histamine and TAME--esterase but differs from the immediate response in the lack of prostaglandin D2 production and in the amount of kinin generated. Since histamine is released only by mast cells and basophils and prostaglandin D2 is not produced by basophils, we suggest that these cells are partly responsible for the late-phase response.     

Basophil histamine release remains unaffected by clinical desensitization to penicillin

A penicillin-allergic patient who required therapy with beta-lactam antibiotics was desensitized with increasing parenteral doses of benzylpenicillin. After desensitization, the patient tolerated, without signs of allergic reaction, intravenous piperacillin. Immunologic studies were undertaken to investigate humoral and cellular changes accompanying desensitization. Serum penicilloyl IgG and IgE antibodies did not change significantly during induction of clinical tolerance to the drug. The patient's previously positive immediate skin reaction to penicilloyl polylysine (PPL) converted to negative. Nonspecific releasability of skin mast cells as tested with polymyxin B skin test was unchanged. In contrast, in vitro blood basophil activation, both by specific antigen (penicilloyl-human albumin) and a nonspecific IgE-dependent stimulus (anti-IgE) remained strong after the desensitization procedure and during weeks of high-dose piperacillin therapy. A monovalent penicilloyl hapten inhibited penicilloyl-albumin-induced basophil histamine release, whereas the patient's own serum taken while the patient was receiving treatment did not. Moreover, the patient's treatment serum, while the patient was receiving piperacillin, was able to trigger histamine release from passively sensitized basophils of a donor not allergic to penicillin, suggesting the presence of a sufficient amount of complete multivalent antigen to initiate release and/or desensitization. The presence of high concentrations of penicilloated serum proteins in the patient's treatment serum was confirmed by immunoassay. Basophil histamine release could, nevertheless, be elicited from the patient's whole blood sample taken while the patient was receiving piperacillin treatment by adding penicilloyl-human albumin in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of IgG-blocking antibodies by ELISA using monoclonal antibody and fluorogenic substrate

An enzyme-linked immunosorbent assay (ELISA) using mouse monoclonal antihuman gamma-chain antibody and a fluorogenic substrate has been developed for quantitation of IgG-blocking antibodies in human serum. Generation of fluorescent product was linear with time to 60 min. Using optimal conditions the ELISA was sensitive to less than 1 ng/ml of specific IgG to short ragweed pollen. The assay demonstrated consistently parallel dilution curves with 51 sera (mean interdilutional coefficient of variation = 8.8%). Reproducibility was determined by constructing precision profiles for intra and interassay variation for the entire working range of the assay. Intraassay CVs ranged from a mean of 13% at threshold to less than 5% at higher antibody concentration. Interassay reproducibility similarly ranged from 18 to 10%. In this assay the effect of serum dilution on nonspecific binding was minimal and specific binding of 4-10 ng IgG antibody to the antigen-adsorbed wells was largely complete (75.8 +/- 4.8%) and highly specific (greater than 98%). This application of ELISA for ragweed IgG antibody measurement has performance specifications equal or superior to previously developed radioimmunoassay and ELISA systems.     

Prostaglandin D2 and histamine during the immediate and the late-phase components of allergic cutaneous responses

With a skin blister technique in which the mediators generated by the trauma of forming the blister are allowed to subside, we have collected human interstitial skin fluid during the course of allergic reactions to ragweed, and measured levels of histamine and prostaglandin D2 (PGD2). Of 18 ragweed-allergic individuals tested, 11 developed both an immediate and a late-phase reaction (LPR) with fivefold-elevated levels of histamine (40 ng/ml) at 30 minutes and a peak level of PGD2 (6.5 ng/ml) later at 2 1/2 hours after ragweed challenge. The other seven allergic individuals had immediate reactions without an LPR lesion and demonstrated somewhat smaller elevations of histamine (25 ng/ml) but much lower levels of PGD2 (1.6 ng/ml; p less than 0.05). The time course of appearance of these mediators was identical in both groups of patients. The fluids from unchallenged blisters of allergic and nonallergic patients and the fluids of nonallergic patients challenged with ragweed had similar levels of histamine, at the lower limit of detection, and undetectable PGD2 levels. The peak levels of PGD2 in allergic individuals correlated with the size of the LPR lesion (p less than 0.05). These data suggest that the LPR involves the secondary elaboration of mediators different from mediators responsible for the immediate manifestations of the allergic skin reaction.     

Assessment of venom-specific IgG antibody in patients treated for hymenoptera allergy

The IgG antibody (Ab) response achieved with specific venom immunotherapy was explored in 32 patients with Hymenoptera hypersensitivity. Venom-specific IgG Ab was quantitated before and after 1 year of immunotherapy using two solid phase radioimmunoassay (SPRIA) methods. An agarose-based test using 125I-Staphylococcus aureus Protein A (SPRIA) was used to determine specific IgG for five Hymenoptera species: yellow jacket (YJ), honeybee (HB), yellow-faced hornet (YH), white-faced hornet (WFH), and Polistes (POL). A cellulose disk test using 125I-anti-IgG (IgG RAST) was available only for YJ and HB venoms. Acceptable agreement (90% concordance) was observed with IgG anti-HB levels measured in the two assays. For the YJ-IgG, however, 17/69 (25%) of sera positive in the SPRIA were negative in the IgG RAST, whereas the converse was not observed. This result suggests that the IgG RAST is insufficiently sensitive to detect YJ-IgG responses in all patients on maintenance level immunotherapy. Using the Protein A SPRIA, there was excellent agreement between the venom used for immunotherapy and the specificity of the IgG Ab response. In 31 patients treated with a total of 90 venom species, 90/90 venom IgG levels were increased or maintained at high pretreatment levels in response to immunotherapy. In the same patients venom IgG levels obtained for venom species not included in therapy were undetectable or declined in 55/60 cases; in 4 cases treatment with YJ venom stimulated a WFH and/or YH IgG response, the remaining case, YJ venom stimulated a small rise in POL IgG. These apparent discrepancies can be explained by variable cross-reactivity among vespid and POL venoms. Among 32 patients with a combined total of 87 positive venom skin tests, 1 year of specific immunotherapy resulted in greater than 5 micrograms/ml of venom-specific IgG in 61 instances. In 25 instances, the level of venom IgG was detectable but less than 5 micrograms/ml, and in 1 case venom IgG could not be detected. Based on recent analyses by Golden et al., some or all of these latter 26 cases may represent suboptimal therapy despite a standard immunotherapy regimen. We conclude that venom IgG measurements can provide a specific and quantitative assessment of the immunologic response to venom therapy, and that such assessment may be clinically useful in detecting instances of suboptimal immunotherapy.