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Biomedical subjects

L M Jerry

Publications and source records attributed to L M Jerry.

At least 37 records · Page 2Linked to original sources
PubMed1986

Circulating immune complexes in malignant melanoma: serial studies in 130 patients.

We evaluated the ability of repeated measurements of circulating immune complexes (CIC) to predict for tumor recurrence in 130 patients with malignant melanoma. Twenty-two patients had level 2, 45 had level 3, and 51 had level 4/5, stage I disease in remission at the start of monitoring, while 12 had stage II disease. The polyethylene glycol precipitation assay was used for serial studies, based on an initial comparative evaluation with the Clq-binding and Raji assays. The study averaged 22 +/- 11 months (6-43 months) and an average of 22 +/- 5.3 assays were performed per patient (range 3-36), with a follow-up of 4 years. CIC were present in sera in recurrent, irregular 'bursts' of activity. Serial measurements doubled the incidence of CIC compared to single determinations. Only 23% of these bursts of activity were clearly related temporarily to documented recurrences, while 34% occurred with treatment events such as surgery or immunotherapy, and 42% occurred without correlation to either recurrence or treatment. CIC activity was greater and more closely related to recurrence in high-risk stage I (level 4,5) and stage II patients. Whether analyzed as positive sera or as bursts of elevated CIC activity, CIC assays predicted for recurrence at the 5% significance level. The assay was highly sensitive (97%), but with poor specificity (21%) with many false positives (79%). The assay was helpful at ruling out recurrences (95%), but poor at ruling them in (29%). The advantage was seen only in high-risk stage I and II patients, and there was no advantage to serial assays over random single determinations. Although generally, CIC in the sera of melanoma patients were found to predict for recurrence, the use of serial CIC measures monitoring of individual patients cannot be recommended.

Antigen-Antibody Complex↗
PubMed1986

Mythylation of human HLA-D/DR genes: derangement in chronic lymphocytic leukemia.

HLA-DR antigens are expressed as differentiation markers in certain human leukemias. To investigate whether DNA methylation plays a role in expression of DR genes in leukemia, we analyzed methylation patterns of the DR-alpha and D/DR-beta genes in the DR antigen-positive and -negative B-cell lines, in normal adults and in chronic lymphocytic leukemia (CLL) patients using Southern blot hybridization of DNA digested with Msp I and Hpa II. The DR-alpha and D/DR-beta genes of a DR antigen positive B-cell line, T5-1, were heavily methylated, while those of DR antigen-negative variant, 6.1.6, were hypomethylated. Blood cells collected from four normal adults contained different levels of DR-alpha and D/DR-beta mRNAs, but their relative amounts were about the same among the individuals. By contrast, the relative amounts of these mRNAs in CLL cells varied widely, indicating aberrant expression of one or both of these genes in CLL. The DR-alpha gene in four normal adults and six CLL patients produced only a 3 kb hybridizable band after Msp I digestion. Normal adult DR-alpha genes were resistant to Hpa II digestion, suggesting that all Hpa II sites are methylated. In contrast, digestion of CLL DNA with Hpa II yielded various bands of larger sizes which differed among the CLL patients, suggesting that Hpa II sites are differentially methylated in the CLL DNA. In the case of D/DR-beta genes, normal adult DNA gave Msp I bands which were slightly polymorphic among four individuals tested. In contrast, CLL DNA showed a high degree of restriction fragment length polymorphism (RFLP) on Msp I digestion. We speculate that the high RFLPs in the CLL DNA may result from differential methylation in CpG clusters in the D/DR-beta genes, and that this characteristic may be of use for diagnosis of CLL.

Adult↗
PubMed1985

Circulating lymphocytes bearing DR antigens in human melanoma.

B cell DR antigens were studied with lymphocyte markers in the peripheral blood of 62 staged melanoma patients and 37 normal individuals matched for age and sex. 47 patients had early disease (31 in stage I; 16 in stage II) and 15 had advanced disease (stage III). Phagocytic cells were removed prior to testing. Specific rabbit antisera and monoclonal antibodies to purified human B cell DR and Fc molecules were used for detection of membrane immunofluorescence. Mild declines of total lymphocytes and of E-rosetting T cells were observed in comparing early to late disease. The drop of Ig(+) B cells was more striking. DR(+) cells, however, showed no change in percentage and a lesser drop in absolute numbers, suggesting an increase with advancing disease of DR(+), Ig(-) null cells, which may represent immature B cell precursors. Fc(+) cells increased markedly in 14 patients who received levamisole, with little effect on the markers. Elevations of OKT4/OKT8 ratios were seen with a relative reduction in OKT8 cells, especially in late disease. These changes in lymphocyte subpopulations may reflect imbalance between the B and T arms from deranged immune regulation caused by chronic antigenic stimulation from progressively growing tumor. In addition to T cell suppression there is B cell hyperactivity with appearance of immature forms peripherally (shift to left).

Antibodies, Monoclonal↗
PubMed1984

Adjuvant BCG immunotherapy for malignant melanoma.

A total of 199 patients with stage I malignant melanoma at Clark's level 3 to 5 of invasion were entered into a prospectively controlled randomized clinical trial that attempted to assess the value of local and systemic immunotherapy with BCG (bacille Calmette-Guérin) after surgery. The patients were randomly assigned, with stratification by Clark's level, to receive either routine follow-up or immunotherapy with BCG, administered intradermally with a Heaf gun around the site of wide excision and then given orally for 2 years. Intradermal administration of BCG was repeated after 1 year's oral therapy with BCG. Of the 99 patients in the treatment group 66 had Clark's level 3, 28 had level 4, and 5 had level 5 invasion. Of the 100 patients in the control group, 61 had level 3, 36 had level 4, and 3 had level 5 invasion. Other prognostic factors, such as sex, depth of invasion, histologic features, site of disease and type of surgery, were evenly distributed. There were 57 recurrences of the melanoma, 24 in the treatment group and 33 in the control group. However, this trend was not statistically significant (p = 0.194). The suggestion that BCG may reduce the likelihood of local/regional recurrence has not been confirmed with longer follow-up. There were 13 such recurrences in the BCG group, compared with 21 in the control group; the proportions of patients in each group who had such a recurrence were not significantly different. Of the 199 patients 41 died, 24 in the control group and 17 in the treatment group; again, this difference was not significant. While there may be minor activity in selected patients, there appeared to be no benefit from this form of adjuvant BCG therapy in patients with malignant melanoma.

Administration, Oral↗
PubMed1984

Phenol-soluble nonhistone chromatin proteins in chronic lymphocytic leukemia.

The altered gene expression seen in cancer could relate to differences in nonhistone chromatin proteins between normal and malignant tumor cells. Phenol-soluble nonhistone chromatin proteins were isolated from human normal and leukemic (chronic lymphocytic leukemia) B-cells, as well as long-term cultured human B-lymphocyte cell lines. High-resolution two-dimensional electrophoretic maps identified a group of three nuclear proteins with a molecular weight of 45,000 to 50,000 and an isoelectric range of 4.5 to 4.7, which were associated only with the human leukemic B-cells. Leukemic B-cells and cultured B-cell lines also expressed a variant form of nuclear actin and tubulin.

B-Lymphocytes↗
PubMed1983

Cutaneous malignant melanoma in Alberta: 1967-1976.

The records of 519 patients with cutaneous malignant melanoma (CMM) were analyzed for the period 1967 to 1976 from the population-based cancer registry of the Province of Alberta in Canada. During this period, the incidence of CMM rose more rapidly in men (especially those older than age 50 years) than in women. Five-year survival rates were 59% and 74% for men and women, respectively. Women survived longer mainly because of a longer disease-free interval. Once the disease recurred, however, the mean time to death was similar for both men and women. Primary lesions were most frequent on the trunk, and head and neck in men, and on the lower limbs in women. The proportion of trunk lesions is increasing in both sexes, especially in persons younger than age 50 years. The lack of a consistent upward trend for lesions on the lower limbs in women was unexpected. The data predict a growing contribution of trunk lesions is young men to the increasing incidence and mortality of CMM in Alberta.

Adult↗
PubMed1982

Control of HLA-DR antigen gene expression at the pretranslational level: comparison of an HLA-DR-positive B lymphoblastoid cell line and its HLA-DR-negative variant.

An HLA-DR-positive human B lymphoblastoid cell line, T5-1, and its HLA-DR negative variant, 6.1.6, were studied to elucidate mechanisms resulting in the nonexpression of HLA-DR genes in 6.1.6. The cell lines were labeled with 35S-methionine in vivo, their proteins immunoprecipitated with a monoclonal HLA-DR-specific antibody, and their two-dimensional gel electrophoresis patterns compared. The T5-1 map showed DR-antigen heavy and light chains, while the 6.1.6 map showed neither chain. When the cells were labeled in the presence of tunicamycin, the two-dimensional map of T5-1 showed nonglycosylated heavy and light chains of DR antigen while that of 6.1.6 did not. RNA was extracted from T5-1 and 6.1.6 cells and translated in rabbit reticulocyte lysates. Two-dimensional gel analysis of the immunoprecipitated proteins from T5-1 revealed spots which were identified as HLA-DR light chain and I invariant on the basis of their precipitation by monoclonal and specific allo- and heteroantibodies, and their molecular weight and pI values. These spots were absent in the 6.1.6 maps, indicating that 6.1.6 has no detectable translatable messenger RNA for HLA-DR light chains. The addition of dog pancreas microsomes to the T5-1 cell-free translation mixture resulted in an increase in the molecular weight of the precursor HLA-DR proteins consistent with glycosylation. Together with earlier cell fusion studies showing that DR structural genes were intact in 6.1.6, these data suggested that the lesion in 6.1.6 is an alteration in a regulatory element required for transcription of DR genes or mRNA processing.

B-Lymphocytes↗
PubMed1982

Adaptation of human long-term B lymphoblastoid cell lines to chemically defined, serum-free media.

Attempts were made to adapt human long-term B lymphoblastoid cell lines to prolonged growth in serum-free, chemically defined media. A newly described medium, which is an enriched modification of Dulbecco's modified Eagle's medium containing additional amino acids and vitamins, was used. The serum is totally replaced by albumin, transferrin, and soybean lipid. The cell lines were all adaptable from RPMI 1640 over a period of time during which the 10% fetal bovine serum (FBS) concentration was reduced and then eliminated in successive steps. After 3 to 6 wk minor alterations in cell shape and adhesion were noted without significant histological changes. Growth characteristics were comparable in the new medium provided a double initial inoculum was used. A panel of cell surface markers, including surface immunoglobulins, Ia antigens, Fc and complement receptors, and T and B erythrocyte rosettes, all showed no altered expression. Molecular genotyping of Ia antigens was carried out by 3-D gel electrophoresis. The antigens showed their full polymorphism without change and were shed into the new culture medium without alteration. Chromosome analysis was performed on Q-banded karyotypes from one of the lines and showed no alteration resulting from the change to serum-free conditions. Thus long-term B lymphoblastoid cell lines can be adapted to prolonged growth in serum-free medium. This will facilitate the assay and isolation of cell products regulating lymphocyte function and the identification and characterization of cell surface molecules free of interference from undefined serum components.

Adaptation, Physiological↗
PubMed1982

Changes in HLA-DR antigen expression on cultured human melanoma cells during theophylline treatment.

Two human malignant melanoma cell lines, differing in their patterns of HLA-DR antigen expression, were examined for changes in antigen expression following theophylline treatment. In one line, the basal HLA-DR antigen content of which remained constant during culture, theophylline decreased HLA-DR expression, accompanied by morphological changes indicating increased differentiation. In the second line, the surface HLA-DR antigen expression decreased with time during culture and showed no decrease in antigen expression or morphological changes when cultured in the presence of theophylline.

Animals↗
PubMed1982

Defective expression of DR antigens in chronic lymphocytic leukemia.

HLA-DR (or Ia-like) antigens which were detergent-solubilized from plasma membranes of leukemic cells of patients with chronic lymphocytic leukemia of the B cell variety were purified by gel filtration, followed by affinity chromatography on Con A-Sepharose. After radioiodination, the DR antigens were immunoprecipitated with specific antisera and analyzed by two-dimensional gel electrophoresis. Repeated mapping revealed several different patterns of DR antigen expression. Most patients (18 out of 42) gave map patterns resembling those obtained from normal peripheral blood B cells. Such maps revealed light (27 kDa) and heavy (33 kDa) DR chains as well as a non-dissociated 60 kDa DR complex. All components, and especially DR light chains, were polymorphic and could be resolved further into several characteristic isoelectric variants. Maps from eleven patients showed decreased levels of 33 and 60 kDa antigen components, while eleven further patients expressed only DR light chains. Two patients lacked detectable DR antigens. Sequential mapping of individual patients indicated that expression of 33 and 60 kDa DR components fluctuates over months. This temporal fluctuation was independent of other B cell markers, including a newly defined group of surface membrane proteins of 28 000 daltons. The patterns are reminiscent of the biochemical dedifferentiation characteristic of immunoglobulin biosynthesis seen in the plasma cell dyscrasias.

Epitopes↗
PubMed1980

Ocular melanoma: a population-based study.

During the 10-year period ending December 1976 ocular malignant melanoma developed in 99 patients in Alberta. To investigate the natural history of this disease we reviewed certain clinical and epidemiologic features of these cases. Of all the melanomas during that time 16% occurred in the eye, and of all the ocular malignant diseases 70% were malignant melanomas. The more malignant mixed cell tumours were much more frequent in the women than in the men, while the converse was true of the less malignant spindle cell melanomas. Within each cell type the women survived longer than the men. The actuarial 5-year survival rate of the entire group was 62%. Metastases occurred in 29 of the 99 patients; the liver was the only or initial site in 22 (76%). Our study shows that there has been no improvement in the survival rate of patients with ocular melanoma over the past 10 years. Our therapeutic methods must be improved.

Adult↗
PubMed1979

Isolation of a human B lymphocyte membrane protein with Ia-like properties.

A rapid method for isolation of a major surface membrane glycoprotein from whole, unfractionated cultured human B lymphoblasts is described. After detergent solubilization the method uses gel filtration followed by affinity chromatography on Sepharose Con A and then alkaline acrylamide gel electrophoresis. Specific high-titre, rabbit antisera to the isolated protein reacted with cultured and normal peripheral blood B lymphocytes, as well as peritoneal macrophages from a renal dialysis patient. The antisera selectively inhibited the mixed lymphocyte reaction at high dilution. The protein reacted with a heterologous antiserum to HL-B antigens and contained subunits of MW 33 000 and 27 000. Resolution of the subunits, however, required a discontinuous SDS gel system. These properties indicate its similarity to murine Ia antigens. The protein was not associated with beta 2 microglobulin and showed no structural or antigenic similarity to the major erythocyte glycoprotein, glycophorin. Antisera to the protein failed to precipitate surface-radiodinated components from similarily treated extracts of cultured human T lymphoblasts. This method now makes available a reference membrane glycoprotein from a differentiated, nucleated human cell in sufficient purity and quantity for kinetic and biosynthetic studies.

Antigens, Surface↗
PubMed1978

Small lymphocyte T-cell leukemia in the adult.

A 49-year-old man is described with morphologic T cell chronic lymphocytic leukemia, whose clinical course, however, progressively deteriorated with central nervous system involvement, resistance to treatment and death within eight months. In addition to widespread organ invasion by leukemic cells there was depression of cellular immunity. The leukemic lymphocytes showed an aberrant response to mitogens, and despite undetectable Ia-like surface antigens were able to stimulate allogeneic cells in the mixed leucocyte reaction. From this and similar cases reviewed herein, it appears that the syndrome of small T-lymphocyte leukemia of the adult is a rapidly aggressive and resistant disease with characteristic clinical and laboratory findings.

Humans↗
PubMed1978

Malignant melanoma (stage 1): a clinical trial of adjuvant BCG immunotherapy.

A prospectively controlled randomized clinical trial of adjuvant BCG immunotherapy in patients with stage 1B malignant melanoma (Clark's level 3--5) is described. The combination of intradermal and oral BCG allows approximation of the bacilli to any microscopic foci of residual disease. The trial was activated in May 1975 and to date 107 patients have been admitted to the trial, 49 patients being randomil entered patients, there have been five relapses of 49 patients in the treatment group and ten relapses of 58 patients in the control group. This encouraging trend is not yet statsitically significant at the 5% level (P = 0.17). If evaluable patients with Clark's level 3 and 4 lesions are assessed separately, there is a significant trend in favour of the immunotherapy group (P less than 0.05) with three relapses in the treatment group and ten relapses in the control group.

BCG Vaccine↗
PubMed1977

Complications of cancer immunotherapy with levamisole.

In a group of 69 patients receiving levamisole the drug had to be discontinued in 15 (21-7%) because of intolerable but reversible side-effects including gastrointestinal upset, "flu-like" syndrome, central nervous system disturbances, and skin rash. Reversible agranulocytosis with life-threatening sepsis occurred in a patient receiving levamisole immunotherapy for colonic carcinoma. Neutrophils and platelets were both severely affected. Levamisole-dependent leucoagglutinins appeared with circulating immune complexes during the acute phase of the illness, suggesting an immune drug reaction.

Adult↗