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HLA typing was performed on 384 individuals of an isolated population of 1,500 people with a.familial aggregate of lymphoma and immunodeficiency cases. Eighty-five % of the total population were descendants of the founding couple. First cousin marriages were common. There was a three-fold or higher increase of the following haplotypes as compared to the frequencies in Sheffield: HLA-A28, Bw35, HLA-A28, B18, HLA-A10, B18, HLA-A2, B18, HLA-A11, Bw40 and HLA-A11, B7. The frequency of HLA-A1, B8 was low (5.4%). The most common genotype was HLA-A2, B12/A2, B12 followed by HLA-A2, B12/A28, Bw35. We found 30 HLA homozygous individuals, of these 15 were HLA-A2, B12/A2, B12. There were two possible HLA cross-overs which may be confirmed and three postulated cross-overs which can never be confirmed as one or both parents of the individuals in question are deceased. Some of the haplotypes could be traced back to the first, second and third generations, i.e. to the first half of the nineteenth century. No single haplotype or antigen was shared by the patients.

A mouse monoclonal antibody is described which reacts with HLA-DR4 positive cells. Gel analysis of the immunoprecipitated antigen is consistent with it being a DR molecule.

Frequencies of persons having particular HLA-A, -B, and -C antigens were compared for 113 urolithiasis clinic patients, a subset of 24 patients who had hypercalcuria , and 225 controls. The frequency of HLA- A30 was significantly elevated among the patients. A suggestion (S afwenberg et al. 1978) that HLA-B27 frequency is elevated among hypercalcuric patients with recurrent kidney stones was not confirmed.

Five hundred and fourteen individuals from an isolated NewFoundland population have been typed and haplotyped for HLA and Factor B (Bf locus). The Bf gene frequencies were: S0.704, F0.226, F1 0.052 and S1 0.018. Tracing the haplotypes backwards on the various pedigrees it was shown that 202 HLA/Bf haplotypes had been introduced into the study population. Some HLA alleles always appeared in association with particular Bf alleles and vice versa. Bf S1 had entered the population four times, always with HLA--A9, B12. Bf F1 had entered three times, always with HLA--B18. There were 17 entries of HLA--Al, B8 that had given rise to the 78 such haplotypes that were now present in the population; all were Bf S. There were 68 family units informative for Bf. They accounted for 240 children and 304 informative meioses. There were three recombinants in the HLA region but none could be shown to have occurred between the HLA-B and Bf loci.

We have made a panel of murine anti-DP monoclonal antibodies for serological typing of HLA-DP polymorphisms; they can be used in microcytotoxicity (for 7 epitopes) and binding assays (for 8 epitopes). The antibodies detect polymorphic differences in both alpha and beta chains. As immunogens we sometimes used B-lymphoblastoid lines or purified DP molecules but mostly used mouse fibroblast transfectants expressing DP molecules. The DP beta genes were made from a cloned DPB1*0201 gene by replacing its major area of polymorphism with matching stretches of DNA amplified from other alleles; cloned DPA1*01 and DPA1*02 genes were used for transfection along with the beta chain genes. The monoclonal antibodies showed reaction patterns that correlated with the presence of particular amino-acid sequence motifs; thus none of the antibodies is allele-specific. They bind instead to epitopes which are found on a number of different HLA-DP types. We have constructed frequency tables so that the epitope (motif) data can be interpreted as the most likely genotype in each case. The basic assumption to justify this work is that HLA-DP matching or mismatching will likely influence transplant outcome, particularly in bone marrow transplantation. The present challenge is to define permissive and nonpermissive combinations of HLA-DP; it may be that matching for epitopes, rather than for full alleles, will help to resolve this issue.

A shared amino-acid sequence on the alpha helix of certain DR beta 1 chains is predicted to generate a 'shared epitope' that is implicated in susceptibility to the development of rheumatoid arthritis (RA). Different relative risks (RR) for disease susceptibility and severity conferred by these DR beta 1 chains suggest that their 'shared epitopes' are not equivalent. A set of monoclonal antibodies (MoAb) that map to the critical region, and for which optimal binding depends on DR context and cell lineage, was used to test this idea. Mapping experiments using mutated DR beta 1* molecules showed that the antibody-binding epitopes are overlapping; residue 70Q is pivotal for each, but neighbouring residues on the alpha helix and on the floor of the groove are also involved. Importantly, these epitopes are profoundly modified by peptide loading of DR beta 1*0401 molecules. These data suggest that 'shared epitopes' on DR molecules that are associated with RA are influenced by their context; such structural modifications may be the basis for the varying susceptibilities conferred by these DR molecules for the development of RA.

The human immunodeficiency, type II bare lymphocyte syndrome (BLS), has been attributed to a defect in the transcription of class II histocompatibility genes. Immunocompetence, as assessed by functional exogenous antigen presentation, was not restored in immortalized B cells, derived from a BLS patient, after transfection with HLA-DR class II structural genes. Incubation of protein antigens, as well as infectious virus, with DR-transfected BLS cells failed to induce activation of antigen-specific helper T lymphocytes. Peptide antigens were presented by class II molecules displayed on BLS cells, although the conformation of these class II proteins was altered as indicated by epitope mapping. This defect in antigen presentation was independent of the specific class II DR allele transfected into BLS cells. Genetic complementation analysis has been used with BLS cells to demonstrate that the defect in class II gene transcription is linked to the absence of a trans-acting factor. Similarly, functional class II dimers were restored after in vitro fusion of cells derived from two distinct BLS complementation groups, implying that specific transcriptional control elements are shared by a gene critical for antigen presentation and genes encoding HLA class II antigens. Thus, two important functionally linked pathways of class II molecules, structural gene expression and antigen presentation, share a common regulatory pathway defective in BLS.

Primary pediatric liver tumors are a unique group of neoplasms. The age at presentation, clinical sigma symptoms, and imaging characteristics provide helpful clues in making a prospective diagnosis and in tailoring a differential diagnosis. The role of imaging is fourfold: characterization, localization, determination of resectability, and follow-up use. MR is usually complementary to ultrasound and CT.

The HLA-DR4 association with rheumatoid arthritis (RA) was revealed in several pioneering observations by Stastny and others between 1974 and 1980 [1]. It is interesting that even in those early days there was an awareness that DR4 was not just associated with RA but was associated with severity of RA, as will be discussed later. As knowledge of the HLA system advanced and as further studies of RA were undertaken it became evident that the HLA association was by no means straightforward. For example, when it was found that DR4 was supertypic to a series of alleles - the subtypes of DR4 - it was noted that only a few of them were associated with RA; indeed one (DwlO or DRB1*0402) actually appeared to be protective. Later DR1 and DR14 were associated in some studies and DR10 was prominent in others. This confusing situation was considerably clarified when Gregersen et al. in 1987 [2] put forward the “shared epitope hypothesis”. These authors realised, from examination of the amino-acid sequence data that the alleles which were associated with RA all had a similar sequence in the beta chain, QKRAA or QRRAA at positions 70-74. This unifying hypothesis showed that the closest association between HLA and RA is with the shared sequence which lies on the edge of the MHC groove midway along one of its alpha helices. This is referred to as the “shared epitope”. The epitope concept leads into the purpose of this report which is to describe a series of monoclonal antibodies to DR4 and some of its subtypes as well as to the shared epitope. As will be discussed later, these antibodies may be useful in determining prognosis in early cases of RA.

The purpose of this study was to identify polymorphic residues of DQ2 beta chains which are involved in the epitopes recognized by DQ2-reactive mAbs. Binding studies were performed on a panel of DQ2 mutant cells made by transfection of a DQ (alpha 1*0501, beta 1*0301)-positive B-LCL with DQB1 genes encoding either wild-type or mutated DQ beta 1 *0202. Several aa substitutions were found to influence the binding of DQ2 mAbs. All but one of the mAbs were clearly sensitive to the introduced aa substitutions, but individual mAbs were differentially influenced, suggesting that they recognized different epitopes on the DQ2 molecule. Substitutions in positions 30 and 37 of the peptide-binding cleft were also found to influence the binding of some mAbs. Second, two mAbs, NFLD.M71 and NFLD.M102, which bound to DQ(alpha 1*0501, beta 1*0202) expressed in human cells and were sensitive to the introduction of aa substitutions in the cleft, bound weakly to the DQ(alpha 1*0501, beta 1*0202) heterodimer when expressed in a transfected murine NIH 3T3 cell line. Together this indicates that some DQ2-reactive mAbs may recognize peptide-dependent epitopes.

Many residues involved in polymorphic antibody-binding epitopes on class II molecules are located on the alpha-helix of DR beta chains. Although they have received less attention, residues in the peptide-binding groove and second domain of the DR beta chain may also be critical for polymorphic anti-DR antibody epitopes. In this study, we used transfectants expressing site-directed mutations at positions in the HLA-DR beta 1 and beta 2 domains and flow cytometry to define the epitopes of several polymorphic anti-DR antibodies. Both DR(beta 1*0403) residues 14 and 25 were shown to be involved in the epitopes of mAbs DA6. 164, HU-20, Q5/6, and 50D6, and DR(beta 1*0701) residue 14 was shown to be critical for the epitopes of two DR7-specific mAbs, SFR 16-DR7M and TAL13.1. Unlike most other residues shown to be important in antibody-binding epitopes, residue 14 is located in the floor of the peptide-binding groove and residue 25 is in an outer loop, each with their side chains pointing down, such that antibodies may directly contact these residues from below the binding groove. Two residues in the beta 2 domain, beta 180 and beta 181, were also shown to be involved in the epitopes of three polymorphic anti-DR mAbs, NFLD.D1, NFLD.M1, and LY9. Although these two residues are close to the transmembrane domain in the linear sequence, their solvent accessibility in the DR1 structures is quite impressive. Our data provide new evidence that residues accessible under the peptide-binding groove contribute to polymorphic antibody-binding epitopes.

Two class I major histocompatibility complex (MHC) proteins with molecular masses of 43- and 39-kDa were identified in the cell surface membranes of normal woodchucks using a newly developed anti-woodchuck class I monoclonal antibody (mAb) B1b.B9 and immuno-blotting. B1b.B9 was generated by immunizing mice with viable wood-chuck peripheral blood mononuclear cells and was selected for anti-class I MHC reactivity using a cellular enzyme–linked immunoassay, indirect immunofluorescence on tissue sections and flow cytofluorimetry. The distribution pattern of class I MHC antigen on woodchuck lymphoid cells was found to be similar to that reported in other species. Also, the antigen expression on normal woodchuck hepatocytes was comparable to that observed on normal human liver parenchymal cells; thus, the antigen was not detected on hepatocytes by staining of liver tissue sections, but was found by indirect immunofluorescence staining of isolated liver cells. Western blot analysis of the plasma membranes from normal woodchuck hepatocytes revealed the presence of a single species of class I MHC heavy chain protein with a molecular mass of 43-kDa, whereas splenocyte plasma membranes showed intense expression of a 43-kDa species, as well as the presence of a 39-kDa protein. The 39- and 43-kDa proteins were extracted with Triton X-114 to the hydrophobic protein phase, suggesting that they both contain a hydrophobic transmembrane domain. The data obtained indicate that the B1b.B9 identifies a nonpolymorphic epitope of woodchuck class I MHC heavy chains, providing an important reagent for the study of the pathogenesis of hepatitis B virus infection in a woodchuck model.

The specificities for seven mAbs to HLA-DR4 were determined initially using homozygous BCLs and L-cell transfectants expressing wild-type DR molecules. Three antibodies (NFLD.D1, NFLD.M1, and NFLD.D7) bound all DR4 molecules, but only one was specific for DR4. Four antibodies (NFLD.D2, NFLD.D3, NFLD.D8, and NFLD.D10) reacted with some but not all DR4 subtypes and had extra reactions, particularly with DR gene products associated with susceptibility to RA. To localize the antibody-binding epitopes on DR4 molecules, the antibodies were then analyzed on transfectants expressing hybrid genes, which were generated by exon shuffling of DRB1 ∗ 0403 and DRB1 ∗ 0701. Two of the pan-DR4 antibodies bound epitopes that require the β 2 domain while the third mapped primarily to the HVR-I region. One antibody NFLD.D10 to subtypes of DR4 mapped to residues 40–97 on DRβ1 ∗ 0403 chains. Comparison of reaction patterns with amino acid sequences suggest that the antibodies against subtypes of DR4 are specific primarily for a region containing sequences postulated to determine susceptibility to RA.

Three hundred twenty-four carotid endarterectomies (CEAs) were performed on 303 patients over 5 years. Sixty per cent of the patients were symptomatic with completed stroke (36.4%), amaurosis fugax (35.4%) or transient ischemic attack (TIA) (50.5%). Some patients had multiple symptoms. Perioperative stroke occurred in four patients (1.2%) and 30-day mortality in five (1.5%). The combined stroke-mortality rate was 2.8 per cent. Other postoperative complications included TIA (1.9%), cranial nerve injury (3.1%), wound hematoma (6.5%), and hypertensive reperfusion syndrome (9.6%). Ten early reoperations were performed for wound hematoma (7) or technical problems (3). Follow-up of 284 CEAs (88%) at a means of 31 months revealed 33 late deaths, with two due to stroke. Late strokes occurred in 11 patients (3.9%). Five late strokes were ipsilateral (1.8%) and six were contralateral (2.1%) to the operated carotid artery. Ninety-seven carotid arteries were evaluated by duplex ultrasound scanning at a mean postoperative interval of 27.2 months. Ninety-two per cent had 0-30 per cent restenosis, 5 per cent had 40 per cent to 60 per cent restenosis and 3 per cent had 70 per cent or greater restenosis. The authors conclude that CEA can be performed with acceptable morbidity and mortality rates and that it is a durable operation that reduces the risk of late stroke.

Mouse L cells expressing HLA genes are potentially useful for producing and analyzing monoclonal antibodies (mAb) to HLA molecules. This paper describes the preparation of transfectants using uncloned human DNA and three methods to isolate the HLA-expressing transfectants. Transfectant libraries were made by contransfecting mouse thymidine kinase (tk)-deficient L cells with a calcium phosphate precipitate containing genomic DNA and tk plasmid DNA. Transfectants expressing HLA genes were isolated using these methods: immunomagnetism, replicate-plating combined with cellular enzyme-linked immunoassay, and sorting using a fluorescence-activated cell sorter. Two HLA-A2 transfectants were isolated using immunomagnetism, two HLA-A24 transfectants by replicate plating, and one HLA-Bw60 transfectant by FACS. However, no transfectants were isolated that stably expressed class II genes. The class I transfectants have been useful in characterizing several locally prepared mAbs which bind to monomorphic determinants on class I HLA molecules. Two of the transfectant lines, one expressing HLA-A2 (8001) and the other HLA-A24 (8008), have been included in the collection of lines distributed for use in the Eleventh International Histocompatibility Workshop.

The historical development of genetic isolation has been evaluated for three outport Newfoundland study areas. An attempt was made to ascertain all livebirths in each study area, and determine the parentage of each. Data from records of baptism and marriage were used for this, supplemented with other historical and ethnographic information. Parent-offspring migration was used as a measure of genetic exchange between subpopulations within study areas, and gene flow into the study areas. Currently, 1-8% of parents originate outside the study areas; these rates are low compared to earlier periods, and compared to present-day rates for European isolate populations. Average kinship was estimated, to measure genetic relatedness within and between subpopulations of each area and the potential for random inbreeding; these values, which are minimum estimates, are now at historically high levels. Increased migration into the study areas, which would decrease average kinship, is not likely. Thus, any regionally or locally elevated frequencies of deleterious alleles will persist, and must be taken into account in providing genetic counseling and evaluating the utility of local screening programs.

To investigate the locations of antibody binding epitopes on HLA class II molecules, four DR4/7 beta 1 hybrid cDNA were constructed by exchanging the DNA encoding the NH2-terminal portions (amino acids 1 to 40) or the COOH-terminal portions (amino acids 41 to 94) of the first domains of DR4 beta 1- and DR7 beta 1-chains, in association with DNA encoding either the DR4 beta 1 or DR7 beta 1 second domains. Transfectants expressing a DR alpha cDNA and a wild-type DR4 beta 1 or DR7 beta 1 cDNA or one of four hybrid DR4/7 beta 1 cDNA were produced, and the binding to the transfectants of anticlass II mAb, which detect polymorphic epitopes on either DR4 or DR7 molecules, was analyzed. Four different patterns of mAb binding to the transfectants were observed, indicating that multiple regions of DR beta 1-chains play the predominant roles in the contributions of these chains to polymorphic epitopes recognized by mAb on intact molecules. The relevant regions of these chains and the number of mAb that recognize the associated polymorphic epitopes are: 1) the COOH-terminal portion of the first domain of DR4 beta 1; a DR4-specific mAb, 2) the NH2-terminal portion of the first domain of DR7 beta 1; two mAb, including a DR7-specific mAb, 3) the NH2-terminal portion of the first domain of DR4 beta 1; seven mAb, and 4) the second domain of DR4 beta 1; one mAb.

Three experiments were conducted in which ground beef patties were prepared to contain 20 or 30% fat and O-50% of rehydrated textured soy protein (TSP). Among patties with 20% fat, those with 20, 25 or 30% of a reference soy protein (TSP I) were desirable in appearance on the first day of retail display; among patties with 30% fat only those with 20% soy protein (TSP I) were desirable in appearance on day-l of retail display. Comparison of 7 brands of textured soy protein (TSP Ill through TSP IX) revealed differences among blended beef patties in cooking loss, appearance and palatability traits. Not all soy products that were available for these tests were of equal efficacy for use in blended ground beef patties. Selection of an appropriate soy protein can overcome deficiencies in appearance, can materially reduce cooking shrinkage and can be used without significantly detracting from the palatability of cooked beef patties. The choice of a specific soy protein for use in blended-beef patties should be predicated upon organoleptic evaluation of the products under consideration and knowledge of intended form of sale (cooked vs raw). If the product is to be sold in cooked form, the fat percentage should exceed 20% to optimize flavor desirability and overall palatability. If the product is to be sold at retail in the raw form, the combined proportion of fat plus textured soy protein should not exceed 50% of the final batch composition.

A familial aggregate of seven cases of Hodgkin's disease (HD) has been investigated by HLA typing. Over 600 people in the immediate population (i.e. about half) have been HLA typed and haplotypes have been obtained for 95% of them. It was expected that the cases would share a particular HLA haplotype or at least that they would have one or two HLA antigens of the same series in common. However, this was not the case so no simple idea of association of HLA with HD cases was upheld. When antigen frequencies were examined in the whole population, it was found that HLA B18 increased progressively in incidence from 0.08 to 0.4 in successive groups of individuals each one more closely related to the HD cases. Similarly the community with the highest incidence of HD also had the highest incidence of B18. Thus B18, which in the world figures carries the highest relative risk, emerged as important in this study. Of four proposed interpretations of the data, we are most interested in the idea that the important HLA association is at a population level rather than at the level of the individual patient. A hypothesis, based on the concept of a "healthy carrier" for the HD agent, explains how such an association might operate. It is possible that B18-linked complement deficiency could be the basis for such a carrier state.

Phantoms designed to simulate cysts or avascular masses and other material encountered in computed tomographic (CT) body and head scanning were used to evaluate the effect of beam hardening in a GE CT/T 8800 scanner. The phantoms were scanned before and after the addition of iodinated contrast material to various compartments within the phantoms. The results indicate that in general the addition of contrast material in the CT body phantom resulted in a decrease in the CT numbers recorded from the cyst phantoms. Conversely, the addition of contrast material in a concentric peripheral cylinder (simulating the addition or presence of the calvarium in CT head scanning) resulted in a generalized inhomogeneous increase in CT numbers of specimen materials contained in that ring.

A familial aggregate of 7 cases of Hodgkin’s disease, 3 of common variable immunodeficiency, 8 of other lymphoreticular malignancies, and 4 of embryonic tumours is being studied in a multidiscipline fashion to search for clues to aetiology. Part of the investigation was to examine immunoglobulin concentrations in the whole population, both in family members and in other members of the same communities. Analysis of the data on some 1,200 people revealed the expected changes with age in IgG, IgA and IgM. A striking age-related pattern for IgD with a peak in puberty and young adulthood was noted. The expected sex differences were also seen which were marked for IgM and mild for IgG. The immunoglobulin concentrations in families in which there had been a case of malignancy or immunodeficiency showed two deviations from values derived from controls: (i) relatives of the common variable immunodeficiency patients showed an elevated mean IgM, and (ii) relatives of the Hodgkin’s disease patients and of the lymphosarcoma patients showed mean IgD concentrations that were 20 times as high as that of controls from outside the study population and were the highest of all the groups within it. However, when compared with the controls from elsewhere in the province, the mean IgD values in all subgroups of the study population were significantly elevated including in a genetically separate group not descended from an important founding couple. It is concluded that factors causing elevated IgD in this high lymphoma incidence population are likely to be predominantly determined by environment rather than by genetic factors. We postulate that the increase may be partly due to the low socio-economic status of the population, but the reason why the highest values are found in the lymphoma families is not immediately clear.

We studied the diallelic system HLA--Bw4/w6 in patients with Graves' disease and control subjects. Twenty-one out of the 22 patients with Graves' disease were found to be HLA--Bw6 positive and 16 of these were homozygous, contrasted with 28 and 9 out of 34 controls, respectively. HLA--Bw6 positivity results in a relative risk for Graves' disease of 3.27; homozygosity for that allele further increases the risk to 7.4. It is possible that the increased risk attached to HLA--Bw6 is secondary to the increase in HLA--B8 previously described in Graves' disease.

SummaryFibrinolytic activity and factor VIII concentration were studied in 30 patients with moderate to minimal hypothyroidism and in 7 patients with hyperthyroidism. In the hypothyroid group, the results were related to serum thyroxine levels, HL-A phenotypes and thyroid autoantibody titres. As serum thyroxine decreased so did factor VIII concentration, however, euglobulin lysis time was correspondingly prolonged. Factor VIII appears to be the most sensitive among coagulation factors to the deterioration of thyroid function tests. There was a significant correlation between the reciprocal of thyroid antibody titres and fibrinolysis; however, there was no relationship between factor VIII concentration or fibrinolysis and a specific HL-A phenotype although the incidence of HL-A8 was increased in the group as a whole.Euglobulin lysis time was prolonged in 6 out of 7 patients with Graves’ hyperthyroidism. Factor VIII was elevated in only 3 of these patients.

Ninety-eight members of a large Newfoundland family, seven of whose members over three generations suffered from Graves' disease, were studied with respect to the mode of transmission of the disease and its association with HLA. Compared to Newfoundland communities of similar size and geographical location, very little consanguinity was documented in this family. The susceptibility to Graves' disease appeared to be inherited as a dominant with a variable degree of expressivity; the degree of expressivity being determined by the female sex. In part of the pedigree, the susceptibility to Graves' disease entered the family with a wife. Three of her offspring who subsequently developed Graves' disease shared with her the haplotype A9, Bw16. Of the three remaining affected family members, two shared the haplotype A1, B8, whereas the third carried the haplotypes Aw32,b8; a9,bw16. Graves' disease could be associated with either of these two haplotypes in the last individual. This study shows that the susceptibility to Graves' disease is inherited associated with HLA and that whereas the disease susceptibility gene for Graves' disease is in linkage disequilibrium with HLA-B8 in Caucasians, it can be randomly associated with other HLA-B antigens.

Twelve batches of frankfurters were prepared to contain 10, 25 or 40% mechanically deboned (MDB) meat from each of four sources (young goat, old goat, mutton and pork) and compared to a control frankfurter batch comprised of manually deboned beef and pork. MDB pork (derived from neckbones, vertebrae and ribs which had been previously debohed manually) contained less (P < 0.05) moisture and protein as well as more (P < 0.05) fat, ash and calcium than old goat, young goat and mutton (all of which were obtained by mechanically deboning whole carcasses). There were no major differences in moisture, fat or protein among the 13 batches of frankfurters. Processing characteristics (extent of fatting-out, ease of peelability, external surface color) differed very little when frankfurters containing MDB goat or MDB mutton were compared with control frankfurters. Frankfurters containing 10% MDB pork were acceptable in processing traits, but those containing 25% or 40% of MDB pork were very susceptible to mechanical deformation. Consumer panelists (n = 95) generally preferred or did not dislike the flavor, juiciness and texture of frankfurters containing 10, 25 or 40% MDB goat (young or old); 10, 25 or 40% MDB mutton; or 10% MDB pork when compared to control frankfurters. Frankfurters containing 25% or 40% MDB pork were assigned lower (P < 0.05) palatability ratings than were control frankfurters. Data suggest than desirability of MDB meat for use in processed meats may depend more on the proportion of bone in the meat that is mechanically deboned than upon differences in species.

Cooking and chemical properties were investigated on beef patties formulated from UDSA Choice or Cutter-Canner cow beef; processed by either grinding, flaking, or flaking, then grinding; and subjected to final broiling from the precooked or raw state. Quality grade of lean exerted minimal influence on the cooking and chemical properties. Precooked patties had more total cooking losses than nonprecooked patties. For precooked patties made from flaked beef, most of the losses in weight; and configuration occurred during precooking rather than final broiling. The opposite was true for precooked patties made from gro and beef. Thus, in order to maximize yield and minimize configurational changes the method of patty processing should be considered in deciding whether to precook patties prior to freezing.

Ground beef with added beef plasma protein concentrate was evaluated mechanically and organoleptically to measure the effect on the binding forces in the cooked meat. The meat patties were cooked, cooled and tested in a constant loading rate, pneumatically operated testing machine with output fed into an X-Y plotter. From the force-deformation curves, the following values were determined: (1) force, stress and deformation at the bioyield point; (2) area under the curve to represent work performed; (3) initial tangent modulus; (4) tangent modulus; and (5) secant modulus. A special holding device was developed to permit tension loading of the patties at a rate of 5 cm/min until rupture of the meat occurred. Treatments consisted of: (1) all meat (control); (2) addition of 1% plasma protein; (3) 2% plasma protein added; (4) addition of 1% plasma protein rehydrated to equivalent moisture content of control; and (5). addition of 2% plasma protein rehydrated to equivalent moisture content of control. Treatments 2, 3, 4 and 5 were significantly higher (P < 0.01) than the control group for force and stress at bioyield and area under the curve. Significant differences (P < 0.05) among treatments were obtained for deformation at bioyield and tangent modulus. Companion samples from the above treatments were evaluated for elasticity and toughness by a taste panel. The sensory panel ratings for toughness were significantly and positively correlated (P < 0.01) with values obtained in the mechanical tests for force at bioyield point, tangent modulus and area under the curve. Sensory evaluations for the elasticity property of the patties were not significantly influenced by the formulation treatments nor was elasticity (sensory panel rating) sigkcantly associated with the mechanical properties considered in the current study.

An association between Graves' disease and the human leukocyte antigen (HLA) system has previously been reported. The disease was more strongly associated with the HLA D locus antigen Dw3 than with HLA B8. Products of the HLA D locus are determined by the interaction of test cells with standard typing lymphocytes, a technically difficult procedure. Recently, it has been possible to type serologically for D locus related (DRw) specificities on peripheral bone marrow-derived (B) lymphocytes. Blood B lymphocytes from 50 unrelated controls and 41 patients with Graves' disease were typed for seven HLA DRw specificities. 28 patients with Graves' disease (68%) were positive for DRw3, in contrast to 14 controls (28%); whereas only 21 patients (50%) were HLA B8 positive, compared with 13 (26%) controls. Thus, positivity for DRw3 afforded a relative risk for Graves' disease of 5.5, whereas that for HLA B8 amounted to 3.0. Additionally, a family with multiple cases of Graves' disease in which the disease was previously shown to be inherited with the haplotype, was linked to DRw2, which suggests that the susceptibility to the disease was inherited in association with that antigen. Two HLA B/glyoxalase recombination events were observed in this family; in both instances HLA DRw followed HLA B. This study thus demonstrates that the disease susceptibility gene for Graves' disease is in strong linkage disequilibrium with DRw3; however, it may be associated with other DRw specificities and inherited within family units in association with them.

In view of the reported variation in the association between HLA antigens and Juvenile Diabetes Mellitus (J.D.M.) among different Caucasian populations, we have undertaken a study of these antigens among 44 Caucasian Newfoundlanders and 135 matched controls. We have also studied the allotypic markers for Immunoglobulin G (Gm) and variants of C3 among 36 of these patients. We found that both HLA--B8 and B15 were increased among the patient group, resulting in a relative risk of 3.9 and 4.4 respectively. While these values are the highest to be described for J.D.M. among Caucasians, and fell outside the 95% confidence intervals for the combined relative risk calculated from published series, it is still possible that they can be accounted for by sampling. The combination of the two antigens increased the relative risk for J.D.M. in an additive fashion. Additionally, we also found that the combination of HLA B8 and B18, but not B15 and B18, also appear to act in an additive manner. The incidence of Gm allotypes and variants of C3 were not different in the J.D.M. group from those observed among controls.

Suspensions of human peripheral blood lymphocytes have been obtained by centrifuging blood in which the red cells were agglutinated with a phytohaemagglutinin (PHA). After 2 and 3 days culture, these suspensions frequently contained numerous large dividing cells. It is thought that it is the small lymphocyte which grows during the period of culture into a cell capable of dividing since on occasion greater than 98 per cent of the cells in the original suspension were small lymphocytes. The changed lymphocytes are pyroninophilic. Electron micrographs of these cells show no extensive endoplasmic reticulum.

Continuous time-lapse cinematography of human small lymphocytes, in tissue culture with phytohaemagglutinin, has been carried out by confining the cells in microchambers. It has been shown that small lymphocytes can enlarge and divide after incubation in such cultures. The large cells so formed, and the daughter cells produced by their division, move in a characteristically lymphocytic fashion. The daughter cells have been shown to double their size and then themselves divide. Evidence is presented which suggests that a line of large proliferating cells with lymphocytic motility is formed and that these continue for some days to reproduce their own kind rather than differentiate into any other cell type. The time taken for cell division is about 30 min. Interphase has been measured on two occasions giving times of 23 and 38½ hr. respectively.

We report an example of four generation familial retinoblastoma in which there are three distinct categories of RB gene expression: frank retinoblastoma, unilateral or bilateral; retinoma; and no visible evidence of retinal pathology other than normal degeneration with age. Two large sibships derived from matings informative for RB and EsD provide strong confirmatory evidence for tight linkage between these loci (P = 0.0002), and thus assignment of RB to chromosome 13q14. There is a striking difference (P less than 2%) in RB penetrance between the two principal generations, which suggests that an additional epistatic, host-resistance gene may also be segregating within the family.

The following observations, some confirmatory, based on experiments on 8 cats and 2 monkeys, were made during an exploration of the cerebral cortex and underlying structures for spontaneous and evoked activity. Anatomical relations given are only approximate; the work is being continued with the aid of a Horsley-Clark stereotaxic instrument. Action potentials picked up by an Adrian-Bronk electrode, amplified, and fed into a loud speaker and high-voltage cathode ray oscillograph, were the index of activity. Numerous controls have convinced us that extraneous pick-up did not confuse true action potentials in the phenomena described. For example, during penetrating movement of the needle of less than 1 mm. there appeared successively: nothing, strong auditory responses, nothing, strong optic responses, nothing. Clearly, responses may be highly localized, and a non-specific spread is excluded.Auditory responses were obtained from the temporal cortical surface, projection tracts, auditory thalamus, and lower s...

Previous reports of increased numbers of rhesus-negative individuals in series of Hodgkin's disease (HD) patients have received a unique type of confirmation. In an extended family of over 1,200 people in which an aggregate of 7 cases of HD has occurred, there were twice the usual number of rhesus-negative individuals. Thus, these HD patients also arose in a population containing an excess of rhesus negatives. Detailed analysis of rhesus antigens and haplotypes with the aid of five antisera and blood samples from 1,133 community members revealed that the patients and their families carried R1 and r but that there was exclusion from those groups of Ro and ra. Ra may have been excluded from the patients but was found in members of their immediate families. No other haplotypes were identified. The differences between HD families and members of the remainder of the extended family are statistically significant (p < 0.0005). The data are consistent with two interpretations which are not mutually exclusive. First, certain rhesus complexes, notably r, may confer susceptibility to the development of HD, probably by virtue of a closely linked gene, conversely other complexes such as Ro may confer resistance. The second interpretation is that the postulated HD agent may flourish better in populations of certain rhesus make-up than it does in others. Individuals of a particular rhesus genotype may be ‘carriers’ or ‘spreaders’. Further investigations are suggested which should contribute to the solution of this epidemiological puzzle.

Fibrinolytic activity and factor VIII concentration were studied in 30 patients with moderate to minimal hypothyroidism and in 7 patients with hyperthyroidism. In the hypothyroid group, the results were related to serum thyroxine levels, HL-A phenotypes and thyroid autoantibody titres. As serum thyroxine decreased so did factor VIII concentration, however, euglobulin lysis time was correspondingly prolonged. Factor VIII appears to be the most sensitive among coagulation factors to the deterioration of thyroid function tests. There was a significant correlation between the reciprocal of thyroid antibody titres and fibrinolysis; however, there was no relationship between factor VIII concentration or fibrinolysis and a specific HL-A phenotype although the incidence of HL-A8 was increased in the group as a whole. Euglobulin lysis time was prolonged in 6 out of 7 patients with Graves' hyperthyroidism. Factor VIII was elevated in only 3 of these patients.