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Background: High-energy pulsed or computer-scanned continuous-wave carbon dioxide (CO2) laser resurfacing has gained popularity as a wrinkle treatment because of its minimal thermal injury and precise control of tissue vaporization depth. Manual tumescent dermabrasion has also been effective for treating facial wrinkles. This is, to our knowledge, the first study comparing the use of CO2 laser to manual tumescent dermabrasion for the treatment of wrinkles on the upper lip., Objective: To compare prospectively the clinical efficacy of the 950 microsec dwell time CO2 laser to that of manual tumescent dermabrasion in the treatment of upper lip wrinkles., Methods: Twenty female subjects with moderate to severe upper lip wrinkles were randomly treated with the 950 microsec dwell time CO2 laser on one side of the upper lip and manual tumescent dermabrasion on the other., Results: The average upper lip laser-treated wrinkle score (0 = none to 5 = severe) decreased from 4.3 +/- 0.2 before treatment to 1.8 +/- 0.3 at 6 months after treatment. The average upper lip dermabrasion-treated wrinkle score decreased from 4.4 +/- 0.2 to 1.5 +/- 0.3. The degree to which the wrinkle score improved after laser treatment compared with that after dermabrasion was not statistically significant (P =.216)., Conclusion: Manual tumescent dermabrasion and 950 microsec dwell time CO2 laser resurfacing are equally effective for the treatment of upper lip wrinkles.

Background: The high energy, pulsed, or computer-scanned continuous wave carbon dioxide laser (CO2 laser) has gained popularity as a wrinkle treatment because of its minimal thermal injury and precise control of tissue vaporization depth. Chemical peels such as phenol have also been effective in treating facial wrinkles. This is, to our knowledge, the first study comparing the use of CO2 laser to phenol for treatment of wrinkles on the upper lip., Objective: To compare the effectiveness and side effect profile of the 950 microsec dwell time CO2 laser to that of unoccluded Baker's phenol chemical peel in the treatment of upper lip wrinkles., Methods: Twenty female subjects with moderate to severe upper lip wrinkles were randomly treated with Baker's phenol on one side of the upper lip and the 950 microsec dwell time CO2 laser on the other side., Results: The average upper lip laser-treated wrinkle score (0 = none to 5 = severe) decreased from 4.30+/-0.20 before treatment to 1.11+/-0.28 at 6 months after treatment. The average upper lip phenol-treated wrinkle score decreased from 4.20+/-0.20 to 0.47+/-0.12. The degree in which the wrinkle score improved after phenol treatment compared with that after laser treatment was statistically significant (p<0.03)., Conclusion: Treatment of upper lip wrinkles with Baker's phenol resulted in greater improvement than treatment with the 950 microsec dwell time CO2 laser.

A simple, sensitive ELISA that is performed in 96-well microtiter plates and that requires less than 90 minutes to complete was developed for HLA-DRB oligotyping. The second exon of HLA-DRB1 was amplified using an unlabeled forward primer and a biotinylated reverse primer and the PCR product was immobilized in avidin-coated wells. Subsequent treatment included exposure to 0.4 N NaOH to remove the nonbiotinylated sense strand, addition of a fluorescein-labeled oligonucleotide probe, one or more 5-minute stringency washes, addition of an alkaline-phosphatase-labeled anti-FL FAB, and then alkaline-phosphatase substrate and amplifier. An intense red-violet color developed within 15 minutes in positive wells and could be quantitated by OD readings at 490-495 nm. To control for stringency and to establish threshold OD values for positive reactions, biotin-labeled antisense oligos that were complementary to the probe or that differed by one or more bases were immobilized in wells in place of PCR products. The assay was sensitive to < 0.05 pmol (approximately 4 ng)/well and required only standard incubators and waterbaths and an optional microplate reader. All reagents were commercially available. The method should facilitate oligotyping of both class I and class II alleles and is adaptable for analysis of other polymorphic gene products.

Several South, Central and North American Indian populations have been characterized over the past 9 years. A summary is given here. Very few major antigens have been found, namely A2, A9, A28 and Aw31 and B5, B15, Bw16, Bw35 and B40. However, several known splits of these antigens have been identified, and new variants are also likely. Immunogenetic analyses of the Amerindians should be able to provide clues both to the origins of the Amerindian cultures and migrations of early man, and also provide new insights into the antigens and the loci of the MHC.

We compared H-2D products of B10.D2 and the mutant B10.D2-H-2dml spleen cells using two monoclonal antibodies designated D3.179 and S11.7. D3.179 reacts with public specificities and appears to define more than one product as shown by cytotoxicity and binding studies. Strong reactivity was obtained in both binding and cytotoxicity to B10.D2 and marginal cytotoxicity and low binding were observed with B10.D2-H-2dml cells. The second monoclonal antibody S11.7, in contrast, reacts only with H-2Dd bearing strains and gave strong binding to B10.D2-H-2dml and weaker binding to B10.D2. Taken together, the observations indicate that the mutant not only expresses H-2D encoded antigens but bears quantitatively greater amounts of some specificities than the parent. A product of approximately 46,000 daltons was immunoprecipitated from B10.D2 cells by D3.179. Very small amounts of this product were seen in B10.D2-H-2dml immunoprecipitates.

Tissue culture medium supplemented with bovine serum albumin (BSA), rather than human serum, was found capable of supporting the proliferative response of cryopreserved human lymphocytes to allogeneic cells in a one-way mixed lymphocyte culture. Although total tritiated thymidine uptake was lower in BSA supplemented cultures than in serum supplemented cultures, stimulation indices were equivalent. Using 0.5% (w/v) BSA, peak tritiated thymidine uptake was observed on day 5 using 2 X 10(5) responders and 4X 10(5) stimulators per microtitre well. Calf skin gelatin was also found capable of substituting for serum, but gave lower levels of proliferation. Use of BSA offers distinct advantages for investigating the proliferative responses of human lymphocytes in serum-free media.

A computer program initially written by the Milwaukee Blood Bank has been modified to use a new algorithm for the assignment of HLA specificities to antisera. The assignment is based on the reactions of cells with known specificities. Specificities which are present only on cells which do not react are first ruled out. This step is followed by one or more steps in which the 'least reactive' specificities are ruled out. The rationale for the algorithm is discussed and an example is presented.

Effect of "anti-NK" sera on NK and ADCC activities was examined to study further the relationship between the effector cells for NK and ADCC in specific pathogen-free miniature swine. An appropriate dilution of "anti-NK" sera that had no effect on ADCC activity not only inhibited NK activity but also eliminated NK cells in the presence of C which supports the presence of NK cells distinct from K cells for ADCC.

We identified 35 homozygotes for hemochromatosis through pedigree studies. Thirteen were asymptomatic. Arthropathy was present in 20, hepatomegaly in 19, transaminasemia in 16, skin pigmentation in 15, splenomegaly in 14, cirrhosis in 14, hypogonadism in six, and diabetes in two. No homozygote was in congestive failure. Only one had the triad of hepatomegaly, hyperpigmentation, and diabetes. Serum iron was increased in 30 of 35, transferrin saturation was increased in all 35, serum ferritin in 23 of 32, urinary iron excretion after deferoxamine in 28 of 33, hepatic parenchymal cell stainable iron in 32 of 33, and hepatic iron in 27 of 27. Iron loading was 2.7 times greater in men than in women. No female had hepatic cirrhosis. Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy. Clinical diagnosis of early hemochromatosis is difficult. Persons with unexplained elevation of transferrin saturation should be studied for hemochromatosis.

Two hybrid clones from a fusion of C57BL/6 anti-DBA/2 spleen cells and the myeloma line Sp2/0 secrete antibodies reactive with a product of the murine major histocompatibility complex (MHC). The two antibodies are provisionally designated S13.11 and S13.29. Both react in rabbit-complement-mediated cytotoxicity with spleen cells of H-2d, H-2f, H-2r, and H-2p strains. In addition, both antibodies hemagglutinate red blood cells from these strains. S13.11 is also cytotoxic for H-2a, H-2k, H-2u, and H-2v spleen cells but does not hemagglutinate red blood cells from mice bearing these haplotypes. With the exception of H-2v, this strain pattern mimics the public specificity H-28. Quantitative absorption of S13.11 shows that H-2d cells are twice as efficient as H-2k cells in their ability to remove the S13.11 antibody. S13.29 reacts weakly in cytotoxicity with H-2k spleen cells and does not react with cells from H-2u or H-2v. Blocking studies indicate that S13.11 and S13.29 react with the same or a closely related molecule on the cell surface.

A cytotoxic monoclonal antibody, SFR8-B6, produced by immunizing KGH rats with partially purified glycoprotein from JY, a human B lymphoblastoid cell line, detects HLA-Bw6, a unique public antigen on the HLA-B molecule. By cytotoxicity, SFR8-B6 has complete concordance with the presence of Bw6 as defined by alloantisera, and its reactivity segregates with HLA in families. Because sera detecting Bw4 and Bw6 are rare, this monoclonal antibody has value as a perpetual standard. In addition, SFR8-B6 offers potential as a probe for investigating the molecular relationships of HLA antigens.

Polynesians living on the island of Mauke in the Cook Island group were typed for HLA-A and -B locus antigens. The Mauke population has restricted HLA polymorphism, with five A-locus antigens and four B-locus antigens accounting for a majority of the HLA phenotypes. Although some differences in antigen frequency were found when Mauke Islanders were compared with Polynesians from Easter Island and Samoa, the Mauke Islanders were closer in their HLA antigenic profile to polynesians than to Melanesians.

Varying the sensitization time of the complement-dependent antibody mediated cytotoxicity test, while carefully controlling other test conditions, has enabled us to characterize the subtle reactivities of several broadly reactive sera. In particular, we can discriminate between classes of cells, e.g., HLA-B7 from B27; subclasses cells, e.g., Bw51 from Bw52; and cells carrying new antigens, e.g., Ao79. This manipulation of the cytotoxicity test is discussed in view of its usefulness in separating primary from cross-reactive specificities and in detecting new specificities.

Fourty-four unrelated North American Blacks and one Black family were tested for B-cell specific antigens with 7th International Workshop antisera. DR specificities were clearly defined in this group, but were generally less frequent than reported for Black Americans in the 7th Workshop report and were most similar in frequency to those reported for African Blacks. Five new B-cell specificities (DuB40-43, 45) were identified. In contradistinction to Caucasians, Black Americans type for HLA-D with homozygous typing cells failed to exhibit strong linkage disequilibrium between D and DR types.

We have developed a monoclonal antibody with HLA-DR5 serologic specificity. The antibody, SFR3-DR5, binds specifically to DR5-positive lymphoblastoid cell lines, and immunoprecipitates alpha- and beta-chains characteristic of DR antigens from them. Cytotoxic activity of the antibody segregates with the DR5-bearing haplotype in a family. The antibody reacted with the cells of 16 of 17 DR5 individuals and was negative on all DR5-negative cells tested. SFR3-DR5 reacted weakly with PWM-activated cells of the single DR5 individual whose B lymphocytes were unreactive with the monoclonal antibody by cytotoxicity. Possible interpretations of these results are discussed.

The effects on some host defenses of murine cytomegalovirus (MCMV) and(or) EL(4), a mouse ascites homograft, were studied in mice. Assays of cellular and humoral immunity in response to either or both of these perturbations were carried out by quantitation of various immune activities.Limited studies demonstrated no effect of EL(4) inoculation on the host response to MCMV by organ viral titer, duration of viral persistence, or anti MCMV complement-fixing antibody titer. Prior infection with MCMV, however, resulted in greatly reduced numbers of splenocytes, the source in this study of immune effector cells. Residual splenocytes demonstrated less response to both phyto-hemagglutinin and lipopolysaccharide, particularly in the 2-3-wk interval after infection. Similarly, responder cells in mixed lymphocyte cultures were less reactive when derived from infected animals. Lymphocyte-mediated cytolysis of EL(4) was significantly less in mice infected on the day of and 7, 14, and 21 days before the tumor homograft with a return to control levels by 28 days. 90% of the cell-mediated cytolysis could be eliminated by treatment with anti-theta serum. Serum-mediated cytolysis of EL(4) was also reduced in infected animals. No suppressor cells or serum inhibitory factors could be identified in infected animals. Although alternative explanations exist, this study suggests that in infected animals there is a significant reduction in both the number and function of bone marrow-derived and thymus-derived cells directed against the alloantigens in EL(4).

Asymmetry in the relationship between the H-2K mutant strain C57Bl/6.CH-2ba (H-2ba) and the wild-type congenic C57Bl/6 has been demonstrated both in MLR and serologically by haemagglutination. MLR between these strains, when B6 was the responder, was as strong as that toward allogeneic stimulator cells: H-2ba was regularly less responsive toward B6. Responses in both directions were increased, in terms of augmented proliferative responses, by prior immunization. In this context the MLR resembles that towards minor H-locus antigens rather than those controlled by the H-2 locus. Immunization of (H-2ba X BALB/c)F1 hybridgs with B6 lymphoid cells induced the production of a haemagglutinating antibody not directed toward any known H-2 specificity. The B6 haemagglutinogen, termed He, was present on B6 lymphoid as well as red blood cells. Segregation studies of F2 and back-cross progeny of (H-2ba X BALB/c)F1 hybrids suggest that the response to He is controlled by two Ir genes, one of which is linked to H-2.

Peripheral blood lymphocytes from Minnesota miniature pigs were tested for natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) in a 2- to 4-hr 51Cr release assay against human myeloid and lymphoid tumor target cells. Adult specific pathogen-free and germfree animals exhibited normal levels of activity in both assays. In addition, the NK and ADCC activities of peripheral blood lymphocytes from colostrum-deprived newborn piglets were examined. These animals were obtained by hysterectomy and previously shown to be immunologically "virgin." We found that these newborn piglets exhibited normal ADCC but lacked NK activity. The differences in the ontogeny of the two activities suggest that they are distinct. Preliminary effector cell characterization studies suggest that: (i) NK and ADCC in the pig are physically not separable; (ii) the majority of the cytotoxic activity on a cell-per-cell basis is mediated by the non-T lymphocyte fraction; and (iii) the rosetted T cells, which account for about 60% of the total pig peripheral blood lymphocytes, have low but demonstrable cytotoxic activity as well.

A positive association of Ra3 skin test responses with HLA-A2 has previously been reported to be evident in individuals with low IgE levels and to a greater extent in these individuals than those with high IgE levels. We give evidence based on an analysis of data from 133 individuals that Ra3 response is positively correlated with HLA-A2 among individuals with low Antigen E response and negatively associated with HLA-A2 among individuals with high Antigen E response. Furthermore, we have evidence that any observed interaction between Ra3, IgE, and HLA-A2 can be explained by the correlation between IgE and Antigen E response, and that it is Antigen E response which interacts in the relationship between HLA-A2 and Ra3 skin test response.

We summarize current understanding of the genetics of human diseases and of the major histocompatibility complex related factors regulating immune responsiveness. Special factors are involved in atopic diseases as a result of the intersection between the immune system, the targets in the tracheobronchial tree and the endocrine, neurologic and genetic mechanisms affecting both the effectors and the targets. The evidence from investigations of human subjects and their families and from laboratory animals for the underlying genetic and immunologic mechanisms of asthma are reviewed. The genetic control of asthma is complex. The evidence suggests a gene or genes associated with and linked to HLA. The disease phenotype may also be regulated by genetically determined levels of IgE and the outcome of the balance between immune response and immunosuppression.

Data illustrating the inheritance of a Gm1,2,17,5,13,14 haplotype in a Caucasian family are presented. The mother and two children are heterozygous for this unusual haplotype. The possible origin of the haplotype is discussed.

Sera, previously found to react specifically with B lymphoid cultured cells, were tested on isolated T and B peripheral blood lymphocytes in a microcytotoxicity assay. Studies were performed on lymphocytes obtained from several large Amish families. The sera used in these studies were cytotoxic to peripheral blood, B lymphocytes, but not cytotoxic to T lymphocytes. The antigens detected followed the inheritance pattern of HL-A haplotypes. The strong linkage disequilibrium with HL-A antigens suggests that genes controlling the expression of B lymphocyte antigens are linked to genes controlling HL-A alloantigens.

The cytotoxicity activity of an anti-HL-A2 antiserum cross-reactive with W28 appeared in three distinct peaks after the serum was subjected to isoelectric focusing. The pH at which the peaks formed was reproducible using pH 5-8 or pH 3.5-10 gradients. Anti-HL-A2 activity occurred in each peak, but the cross-reactive anti-W28 cytotoxicity appeared to be largely confined to the second and third peaks. The first peak was exclusively IgG, the second contained IgG and IgM, and the third contained IgG, IgA, and IgM.

The HLA-B5,B35 cross-reacting group is a large and serologically complex antigen family which includes the World Health Organization-recognized specificities HLA-B5,B51,Bw52,B35,Bw53,B18,Bw70,Bw71, and Bw72. In addition, several variants of antigens in this cross-reacting group have been described in the past but have not yet gained official recognition. A genetic basis for the complexity and the protein and molecular bases of this highly cross-reactive and polymorphic cross-reacting group have yet to be established. The potential contributions of shared amino acid sequences, the occurrence of multiple epitopes on a single HLA-B molecule, and the presence of new HLA-C antigens have been difficult to resolve. To address this issue, we have carefully examined the serologic reactions of more than 900 allo- and monoclonal antibodies (Tenth International Workshop, Third Asia-Oceanic Workshop, and local reagents) versus lymphocytes from 92 individuals of diverse ethnic origin (North American Caucasians, North American blacks, Amerindians, Middle Eastern Caucasians), 84 of whom were informative for the HLA-B5,B35 cross-reacting group and related antigens. Our results demonstrate that the HLA-B5,B35 gene products share different combinations of distinct epitopes. We have constructed a model for the evolution of this cross-reacting group by assigning polarity to distinct diversification steps utilizing principles of maximum parsimony.