RESUMO
BACKGROUND: Alpha-1-antitrypsin (A1AT) deficiency disease results from mutations in the A1AT gene. Controversy exists in regards to treatment of heterozygous carriers of the S and Z deficiency alleles. Quantitation of allelic expression has not been possible with standard laboratory methods. Here we show that the recently described method for liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of A1AT tryptic peptides can differentiate between mutated (S and Z) and wild-type (non-S and non-Z) proteins allowing for quantitation of circulating allelic expression in heterozygous patients. METHODS: Serum (244 M/M, 61 M/Z, and 63 M/S) was combined with isotopically labeled peptide standards, digested with trypsin, and quantitated by LC-MS/MS. Total and allele-specific A1AT quantitation was performed by comparison of peptide peak height ratios to a standard curve for each peptide. Linear regression was used to compare results and central 95(th) percentile intervals were calculated using parametric analysis. RESULTS: Quantitation of circulating wild-type A1AT based on the proteotypic and allelic (non-S and non-Z) peptides was validated in M/M patients. Proteotypic peptide concentrations correlated linearly with quantitation by non-Z and non-S peptides [slopes (Spearman correlation coefficient) of 1.09 (0.89) and 0.98 (0.80), respectively]. Allele-specific quantitation showed significant differences in wild-type protein expression in M/Z and M/S patients. Although average total A1AT concentration was lower for M/Z patients, the percentage of wild-type protein in M/Z patients was significantly higher at 82 % (55- > 95 %) compared to 63 % (43-83 %) for M/S heterozygotes. In a cohort of M/Z patients with sufficient total A1AT (≥80 mg/dL), half had insufficient wild-type protein that could have clinical implications for pulmonary dysfunction. CONCLUSIONS: For the first time, a method to quantitate A1AT allele protein expression is described. Given the wide range of circulating wild-type protein observed in heterozygous patients, this method has the potential to reveal correlations between allele concentration and development and/or severity of clinical symptoms.
Assuntos
Alelos , Heterozigoto , Deficiência de alfa 1-Antitripsina/sangue , alfa 1-Antitripsina/sangue , Biomarcadores/sangue , Cromatografia Líquida/métodos , Feminino , Humanos , Masculino , Espectrometria de Massas em Tandem/métodos , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/genéticaRESUMO
We studied the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in younger individuals, age 10-49 years, using samples from the National Health and Nutritional Examination Survey (NHANES) III. NHANES prevalence rates were standardized to the 2000 US total population. Among 12 372 individuals (4073 blacks, 4146 Mexican-Americans, 3595 whites, and 558 others), MGUS was identified in 63 persons (0.34%, 95% CI 0.23-0.50). The prevalence of MGUS was significantly higher in blacks (0.88%, 95% CI 0.62-1.26) compared with whites (0.22%, 95% CI 0.11-0.45), P=0.001. The prevalence of MGUS in Mexican-Americans was at an intermediate level (0.41%, 95% CI 0.23-0.73). The disparity in prevalence of MGUS between blacks and whites was most striking in the 40-49 age-group; 3.26% (95% CI 2.04-5.18) versus 0.53% (95% CI 0.20-1.37), P=0.0013. There was a trend to earlier age of onset of MGUS in blacks compared with whites. MGUS was seen in only two persons in the 10-19 age-group (both Mexican-American), and in three persons in the 20-29-year age-group (all of whom were black). In persons less than 50 years of age, MGUS is significantly more prevalent, with up to 10 years earlier age of onset, in blacks compared with whites.
Assuntos
Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Mieloma Múltiplo/diagnóstico , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/patologia , Mieloma Múltiplo/patologia , Inquéritos Nutricionais , Prevalência , Fatores de Risco , Adulto JovemRESUMO
A new human myeloma cell line, ANBL-6, was established and characterized at the genotypic and phenotypic levels. The cells exhibit a clonally rearranged immunoglobulin gene locus and resemble plasma cells morphologically. The ANBL-6 cells also exhibited an absolute dependence on exogenous interleukin 6 for growth. Of interest, DNA ploidy analysis suggested the existence of a near-diploid as well as a near-tetraploid population in this cell line. Cytogenetic studies confirmed the existence of two aneuploid karyotypes and further revealed a clonal relationship between the two karyotypes, as evidenced by numerous shared structural abnormalities. To determine whether the near-diploid cells functioned as stem cells for the near-tetraploid population, the near-diploid population was separated via flow cytometry and recultured prior to ploidy analysis. This population was observed to remain predominantly near-diploid over time, suggesting that these cells did not function as stem cells for the near-tetraploid population. However, the near-tetraploid cells did exhibit a growth advantage in vitro. Moreover, sequential ploidy analysis performed retrospectively on fresh bone marrow cells from the patient also suggested that there was an expansion of the near-tetraploid population during clinical relapse. These results suggest that both populations are self-regenerating and reflect the consequences of clonal evolution in the myeloma tumor. The coexistence of clonally related subclones with shared chromosomal abnormalities, however, suggests that the near-tetraploid subclone was derived from the near-diploid subclone at an unknown time during tumorigenesis.
Assuntos
Aneuploidia , Citocinas/farmacologia , Rearranjo Gênico , Genes de Imunoglobulinas , Mieloma Múltiplo/genética , Mieloma Múltiplo/imunologia , Antígenos CD/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Southern Blotting , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Células Clonais , Técnicas de Cultura/métodos , DNA de Neoplasias/análise , Feminino , Genótipo , Humanos , Imunofenotipagem , Interleucina-6/farmacologia , Cariotipagem , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Fenótipo , Proteínas Recombinantes/farmacologia , Mapeamento por RestriçãoRESUMO
Labeling indices (LI) provide a rapid measure of the bone marrow (BM) plasma cell proliferation rate and are useful in the diagnosis and prognosis of monoclonal gammopathies. Because circulating B cells may be a part of the neoplastic clone, we examined peripheral blood B cells that were producing the same cytoplasmic light chain isotype as the patient's monoclonal; protein (M-protein) and determined the peripheral blood LI (PBLI) by a two-color immunofluorescence bromodeoxyuridine method. The 105 patients studied were divided into three disease activity groups by standard clinical criteria. Median PBLI was 0.2% for the 29 patients with inactive monoclonal gammopathies (monoclonal gammopathy of undetermined significance [MGUS] and smoldering multiple myeloma [SMM]), 0.8% for the 35 patients with new, untreated multiple myeloma (MM), and 1.7% for the 41 patients with relapsed MM. These differences between groups were statistically significant (P less than .001, Wilcoxon). Four patients had high PBLI but clinically inactive gammopathy at the time of study, and all developed active MM within 6 months that required treatment. In 92 patients a BMLI was performed simultaneously with the PBLI (rank correlation coefficient, 0.69). In patients with new, untreated MM, use of both tests identified 72% of patients (23 of 32) with high LI, rather than 56% (18 of 32) by BMLI alone or 63% (20 of 32) by PBLI alone. These results suggest that PB B cells bearing the same cytoplasmic light chain isotype as the monoclonal protein are part of the malignant clone and can be kinetically active. The LI of these cells can provide a measure of disease activity and may help to differentiate active from inactive disease.
Assuntos
Linfócitos B/patologia , Paraproteinemias/diagnóstico , Divisão Celular , Diagnóstico Diferencial , Imunofluorescência , Humanos , Imunoglobulinas/análise , Mieloma Múltiplo/sangue , Paraproteinemias/sangueRESUMO
PURPOSE: To evaluate the prognostic significance of p53 expression in epithelial ovarian cancer, including a subset of stage I patients, and to look for correlations between p53 expression and other disease parameters, including stage, grade, age, histologic subtype, second-look results, ploidy, and percent S phase. PATIENTS AND METHODS: We analyzed p53 expression in 284 patients with epithelial ovarian cancer using immunohistochemical techniques in paraffin-embedded specimens. There were 36 patients with stage I disease, 20 with stage II disease, 186 with stage III disease, and 42 with stage IV disease. RESULTS: p53 immunoreactivity was present in 177 cases (62%). p53 expression was associated with grade 3 to 4 disease (P = .003). The following factors were associated with a decrease in overall survival in a univarate analysis: stage III or IV disease (P = .0001), grade 3 or 4 disease (P = .0001), age above the median (P = .0002), and p53 reactivity (P = .04). In a multivariate analysis, stage, grade, and age retained independent prognostic significance. In the subset of 36 stage I patients, p53 positively approached statistical significance (P = .10) as a negative prognostic factor in a univariate analysis. CONCLUSION: Abnormalities of p53 expression occur commonly in epithelial ovarian cancer. Although associated with decreased survival in a univariate analysis, this biologic marker did not retain independent prognostic significance in a multivariate analysis. p53 expression should be studied in a larger cohort of early-stage patients, where accurate prognostic information is needed to direct therapy.
Assuntos
Carcinoma/química , Neoplasias Ovarianas/química , Proteína Supressora de Tumor p53/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Estatística como Assunto , Análise de SobrevidaRESUMO
PURPOSE AND METHODS: To help clarify the clinical utility of flow-cytometric parameters, we performed flow cytometry on archival paraffin-embedded primary breast cancers from 502 patients treated on two adjuvant chemotherapy protocols performed by the North Central Cancer Treatment Group (NCCTG) and Mayo Clinic. DNA ploidy and percent S-phase (%S) were examined in univariate and Cox model multivariate analyses along with tumor size, menopausal and estrogen receptor status, Quetelet's index (QI), number of positive nodes and nodes examined, and Fisher and nuclear grades. RESULTS: Ploidy analysis showed that 40% of tumors were DNA diploid and 60% were DNA nondiploid (12% tetraploid and 48% aneuploid). There was no difference in relapse-free survival (RFS) (P = .82) or overall survival (OS) (P = .78) between the ploidy groups. Tetraploid patients had the longest RFS and OS of any group, but this did not achieve statistical significance. The %S was computed in 98% of cases and the medians were 9.0% for all patients, 6.4% for diploid patients, and 11.7% for nondiploid patients (P < .0001). By use of a %S greater than 12.3 as a prognostic variable in a univariate analysis, there was a significant difference in the RFS (P = .02) and OS (P = .007) of patients with low- versus high-proliferative tumors. However, when the %S was adjusted for clinical characteristics in the multivariate analysis, it was not a significant factor for RFS (P = .23) or OS (P = .36). CONCLUSION: These results indicate that DNA content and %S measurements by flow cytometry are not clinically useful independent prognostic factors in women with resected node-positive breast cancer administered adjuvant chemotherapy.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ploidias , Fase S , Adulto , Idoso , Neoplasias da Mama/mortalidade , DNA de Neoplasias/análise , Feminino , Citometria de Fluxo , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Recidiva , Análise de Regressão , Análise de SobrevidaRESUMO
We measured the serum concentrations of 2 biochemical markers of bone formation, bone Gla-protein (BGP) and bone alkaline phosphatase (BAP), in 164 normal subjects and 164 patients with metabolic bone disorders. The data were reported as Z scores (deviation in SDs from the sex-specific age regression in normal subjects). Both serum BGP and BAP distinguished abnormalities well (mean Z scores for BGP and BAP, respectively) and gave concordant results in patients with hypoparathyroidism (-1.7, -1.4), hyperthyroidism (+1.1, +1.8), primary hyperparathyroidism (+3.6, +2.5), acromegaly (+1.2, +2.8), and postmenopausal osteoporosis (+0.4, +1.9). The 2 markers gave discordant results, however, in patients with glucocorticoid excess (-2.4, +0.9), Paget's disease (+1.8, +41.8), chronic renal failure (+16.3, +0.4), and osteolytic metastases (-1.4, +5.9). These discrepancies may have occurred because serum BGP and BAP concentrations reflect different aspects of osteoblast function or because there are differences in their clearance from the circulation. Consequently, more information is derived about the level of bone formation across the wide range of metabolic bone disorders when both biochemical markers are assayed.
Assuntos
Fosfatase Alcalina/sangue , Doenças Ósseas Metabólicas/sangue , Proteínas de Ligação ao Cálcio/sangue , Adulto , Fatores Etários , Doenças Ósseas Metabólicas/enzimologia , Osso e Ossos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina , Fatores SexuaisRESUMO
Lung cancer (LC) and chronic obstructive pulmonary lung diseases (COPDs; including emphysema and chronic bronchitis) share a common etiology. Despite the known associations of alpha1-antitrypsin deficiency (alpha1AD) with COPD and COPD with LC, few studies examined the association of alpha1AD alleles and LC. We hypothesize that heterozygous individuals who carry a deficient allele of the alpha1AD gene Pi (protease inhibitor locus) are at an increased risk of developing LC. The Pi locus is highly polymorphic with >70 variants reported. There are at least 10 alleles associated with deficiency in alpha1-antitrypsin. Using an exact binomial test, we compared the alpha1AD carrier rate in 260 newly diagnosed Mayo Clinic LC patients to the reported carrier rate in Caucasians in the United States (7%). alpha1AD carrier status, determined by isoelectric focusing assay, was examined with respect to the history of cigarette smoking, COPD, and histological types. Thirty-two of the 260 patients (12.3%; 95% confidence interval, 8.6-16.9%) carried an alpha1AD allele, which was significantly higher than expected (P = 0.002). Twenty-four of the 32 carriers had allele S, 6 had allele Z, and 2 had allele I. Patients who never smoked cigarettes were three times more likely to carry a deficient allele (20.6%; P = 0.008), although smokers had a higher carrier rate (11.1%; P = 0.025) when compared with the 7% rate. Patients with squamous cell or bronchoalveolar carcinoma had a significantly higher carrier rate than expected (15.9% and 23.8%, P < or = 0.01, respectively). Our preliminary findings suggest that individuals who carry an alpha1AD allele may have an increased risk for developing LC, specifically squamous cell or bronchoalveolar carcinoma.
Assuntos
Adenocarcinoma Bronquioloalveolar/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Heterozigoto , Neoplasias Pulmonares/epidemiologia , Deficiência de alfa 1-Antitripsina/genética , Adenocarcinoma Bronquioloalveolar/genética , Alelos , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologiaRESUMO
We measured the concentration of C9 in the CSF and plasma of 93 consecutive patients referred for CSF examination in an outpatient multispecialty clinic. We noted no differences in CSF C9 or C9 index between patients with multiple sclerosis and neurologic controls.
Assuntos
Complemento C9/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Adulto , Fatores Etários , Idoso , Complemento C9/análise , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Valores de ReferênciaRESUMO
A double staining technique for the simultaneous determination by flow cytofluorometry of cell surface phenotype and cell cycle phase is described. Peripheral blood mononuclear cells were stained with fluorescein-conjugated monoclonal antibodies for cell surface phenotype, fixed serially with 2% paraformaldehyde and 71.25% ethanol, and stained with propidium iodide to label cellular DNA. The cells were then analyzed by flow cytofluorometry for both green and red fluorescence. A variety of cells, including T cells and their subsets, B cells, NK cells and monocyte/macrophages, can be identified by this technique with simultaneous determination of cell cycle phase.
Assuntos
Anticorpos Monoclonais , Separação Celular/métodos , Citometria de Fluxo/métodos , Fluoresceínas , Monócitos/citologia , Antígenos de Superfície/análise , Ciclo Celular , DNA/análise , Fluoresceína , Humanos , Leucócitos/classificação , Monócitos/imunologia , FenótipoRESUMO
The detection of peripheral blood plasma cells is clinically important, but difficult to perform by use of routine smears. To simplify the detection process, the peripheral blood T cells from ten patients with known active multiple myeloma were depleted using anti-CD2 coated magnetic beads. In all cases, there was enrichment of the immunoglobulin (Ig) positive cells after T cell depletion (mean enrichment factor, 3.4; median, 3.2; range, 1.2-5.1) with a mean pre-bead %Ig+ cells of 7.3 compared to 20.4 for the post-bead sample (p = 0.005). The monoclonal plasma cells were similarly enriched and more easily enumerated on the microscope slides prepared from the T cell depleted sample.
Assuntos
Antígenos de Diferenciação de Linfócitos T/imunologia , Depleção Linfocítica/métodos , Plasmócitos , Receptores Imunológicos/imunologia , Antígenos CD2 , Contagem de Células , Humanos , MagnetismoRESUMO
We have developed techniques for the production of monoclonal antibodies using Coomassie blue-stained protein spots cut from high resolution 2-dimensional polyacrylamide gels. The gel spots were homogenized with Freund's adjuvant and injected sub-cutaneously into a mouse, at several places along the flank. After boosting twice the spleen cells were hybridized by standard methods. Hybrids, clones and ascitic fluids were also screened with antigen prepared from 2-dimensional gel spots. The spots were cut from gels, homogenized in the presence of guanidinium chloride, and extracted by shaking overnight. The acrylamide was removed, the sample dialyzed to remove denaturant and the protein labeled with 125I. An alternative method for the production of screening antigen using column chromatography is described. These techniques allow the production of monoclonal antibodies to specific protein components of complex mixtures, even in the presence of other immunodominant proteins.
Assuntos
Anticorpos Monoclonais/biossíntese , Antígenos/urina , Eletroforese em Gel de Poliacrilamida/métodos , Proteinúria/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Antígenos/imunologia , Antígenos/isolamento & purificação , Líquido Ascítico/imunologia , Humanos , Hibridomas/imunologia , Camundongos , Peso MolecularRESUMO
We have previously described a monoclonal antibody (BU-1) to 5-bromo-2-deoxyuridine (BrdUrd) that is useful for measurement of cell cycle S-phase. BU-1 hybridoma supernatant reacted with incorporated BrdUrd after the cells had been ethanol fixed; without a requirement for acid or base denaturation. We have found that this reactivity is lost if purified antibody is used, if the culture supernatants are heated, or if a mycoplasma-free hybridoma line is isolated. The supernatant contained endogenous DNase activity that was a result of mycoplasma infection of the cell line. This DNase activity was required for staining the cells with BU-1 in the absence of other denaturation steps. The endogenous DNase could be substituted for by the addition of bovine pancreatic DNase I. The disruption of the double stranded DNA structure with an enzyme rather than with harsh chemical or heat treatments does not affect protein structure or cellular morphology and allows the detection of incorporated BrdUrd of morphologic or antigenic cell subsets. DNase pre-treatment may also be useful for detection of other 'hidden' DNA antigens.
Assuntos
Anticorpos Monoclonais/imunologia , Bromodesoxiuridina/imunologia , Desoxirribonucleases/farmacologia , Interfase , Linhagem Celular , Desoxirribonucleases/análise , Mycoplasma/enzimologia , Desnaturação de Ácido NucleicoRESUMO
Between 1966 and 1979, biclonal gammopathy was recognized in 57 patients. Clinical and laboratory features differentiated three groups: biclonal gammopathy of undetermined significance, 37 cases (65 percent); multiple myeloma, nine cases (16 percent); and lymphoproliferative disease--including lymphoma, macroglobulinemia, chronic lymphocytic leukemia and unclassified lymphoproliferative disorders--11 cases (19 percent). With biclonal gammopathy of undetermined significance, symptomatic multiple myeloma developed after two years in one patient; the others remained stable. One patient with multiple myeloma had osteosclerotic myeloma and a severe sensorimotor peripheral neuropathy, and another presented with plasma cell leukemia. In the remainder response to therapy and survival were much the same as in patients with multiple myeloma with a monoclonal protein. Patients with lymphoproliferative disease responded to chemotherapy like that for monoclonal gammopathy. Of the 57 patients, 30 (53 percent) had IgG and IgA components, 15 (26 percent) had IgG and IgM, six had two IgG components, three had IgA and IgM, one had IgA proteins, one had IgA and IgE and 1 had triclonal gammopathy. Of the 115 light chains, 70 percent were kappa; the chains were both kappa and lambda in 63 percent of biclonal pairs. In many cases, serum electrophoresis produced only a single band on the acetate strip, and the biclonal gammopathy was not recognized until immunoelectrophoresis was done. Although the clinical features of biclonal gammopathy and its response to therapy are similar to those of monoclonal gammopathy, this subject is of importance because of the lack of clinical data in the literature.
Assuntos
Hipergamaglobulinemia/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Mieloma Múltiplo/diagnóstico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Cadeias Pesadas de Imunoglobulinas/análise , Cadeias Leves de Imunoglobulina/análise , Imunoglobulina M/análise , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
PURPOSE: The study assessed whether beta 2-microglobulin levels predict survival or response in patients with primary systemic amyloidosis without associated multiple myeloma. PATIENTS AND METHODS: The study group consisted of 131 untreated patients with biopsy-proven primary systemic amyloidosis diagnosed and evaluated at the Mayo Clinic. No patient had multiple myeloma. The minimum follow-up of surviving patients is 8 years. No patient was lost to follow-up. RESULTS: The median survival of patients with an increased beta 2-microglobulin level was 10.8 months, compared with patients with a normal beta 2-microglobulin level (less than or equal to 2.7 micrograms/mL, 0.23 mumol/L) of 32.9 months (p less than 0.001). In a multivariate proportional-hazards model, the best model included congestive heart failure (p less than 0.0001) and increased beta 2-microglobulin levels (p less than 0.05). After adjustment for the presence of congestive heart failure, beta 2-microglobulin level remained significant. When the analysis was restricted to those patients with normal renal function, the median survival of those with an elevated beta 2-microglobulin level was 9.1 months versus 39.4 months for those with a normal level (p less than 0.001). The serum level of beta 2-microglobulin was increased in patients with nephrotic-range proteinuria with or without renal insufficiency (p = 0.05). CONCLUSION: The serum beta 2-microglobulin level should be measured routinely in all patients with primary systemic amyloidosis because it provides a useful objective factor to identify subsets of patients with this disease who have unfavorable outcomes.
Assuntos
Amiloidose/mortalidade , Microglobulina beta-2/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/sangue , Amiloidose/tratamento farmacológico , Estudos de Coortes , Creatinina/sangue , Creatinina/urina , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Probabilidade , Modelos de Riscos Proporcionais , Proteinúria/sangue , Análise de SobrevidaRESUMO
PURPOSE: Evaluate the discriminatory value of plasma interleukin-6 or C-reactive protein levels in clonal thrombocytosis compared with those in reactive thrombocytosis. PATIENTS AND METHODS: A comparative analysis of quantitatively measured laboratory values in a prospectively studied group of consecutive patients. The setting was a tertiary referral center consisting of two hospitals and an outpatient clinic. Plasma interleukin-6 and C-reactive protein levels were measured in 91 consecutive patients with thrombocytosis (platelet count > or = 600 x 10(9)/L). The cause of thrombocytosis was determined by reviewing the medical histories and follow-up data without knowledge of the corresponding laboratory values. Sixty-four patients had reactive thrombocytosis, 20 had clonal thrombocytosis, and 7 had clonal thrombocytosis plus reactive thrombocytosis. Plasma interleukin-6 was measured by an enzyme-linked immunosorbent assay, and C-reactive protein was measured with rate immunonephelometry. RESULTS: Interleukin-6 levels were undetectable in all the patients with clonal thrombocytosis, whereas they were increased in 60% of the patients with reactive thrombocytosis or clonal thrombocytosis plus reactive thrombocytosis. There was a correlation between interleukin-6 and C-reactive protein levels (r = .6), and the median and range values of both levels differed significantly between the clonal thrombocytosis group and the other two groups (P < 0.0001). In 81% of the patients with reactive thrombocytosis, levels of either interleukin-6 or C-reactive protein were elevated. There was no correlation between interleukin-6 and C-reactive protein levels and the platelet count. CONCLUSIONS: An elevated interleukin-6 level is rare in uncomplicated clonal thrombocytosis and suggests reactive thrombocytosis. However, an isolated normal value has little discriminatory value. Measurement of C-reactive protein level may be used as a less expensive surrogate for measurement of interleukin-6. Repeatedly low levels of both interleukin-6 and C-reactive protein are most consistent with clonal thrombocytosis.
Assuntos
Proteína C-Reativa/metabolismo , Interleucina-6/sangue , Trombocitose/sangue , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Nefelometria e Turbidimetria , Contagem de Plaquetas , Estudos Prospectivos , Trombocitose/etiologia , Trombocitose/imunologiaRESUMO
An elderly woman is described with infectious mononucleosis in whom cervical node biopsy was interpreted as showing immunoblastic lymphoma. Concomitant reactive lymphocytosis, Epstein-Barr virus serologic results consistent with an acute infection, and demonstration of polyclonal B cell infiltration of other tissues argued against intervention. Defective in vitro T cell responses were demonstrated during the acute phase of Epstein-Barr virus infection. Infectious mononucleosis has rarely been reported as mimicking a non-Hodgkin's lymphoma. At 18 months, our patient's course has been typical for infectious mononucleosis with no evidence of disseminated malignancy.
Assuntos
Mononucleose Infecciosa/diagnóstico , Linfoma não Hodgkin/diagnóstico , Linfócitos T , Idoso , Linfócitos B/patologia , Medula Óssea/patologia , Diagnóstico Diferencial , Feminino , Humanos , Mononucleose Infecciosa/patologia , Contagem de Leucócitos , Fígado/patologia , Linfonodos/patologia , Linfoma não Hodgkin/patologia , Linfócitos T/patologiaRESUMO
Before presenting to the Mayo Clinic, a 24-year-old white woman had received 35 transfusions of blood products over a 72-hour period in February 1981. Two and one half years later, the diagnosis of polymicrobial cholangitis (Cryptosporidium, Candida albicans, and Klebsiella pneumoniae) was established. Further evaluation demonstrated profound helper T lymphocyte suppression, disseminated Mycobacterium avium-intracellular infection with mycobacteremia, and Kaposi's sarcoma of lymphoid tissue, confirming a diagnosis of acquired immune deficiency syndrome (AIDS). This case represents an unusual infectious complication of AIDS. Additionally, this is believed to be the first report of Kaposi's sarcoma occurring in a patient with AIDS associated with blood product transfusion.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Colangite/complicações , Síndrome da Imunodeficiência Adquirida/etiologia , Adolescente , Candida albicans , Colangite/microbiologia , Cryptosporidium , Feminino , Humanos , Klebsiella pneumoniae , Sarcoma de Kaposi/complicações , Reação TransfusionalRESUMO
Lyme disease is a multisystem disorder caused by a tick-transmitted spirochete, Borrelia burgdorferi. The diagnosis is based on clinical findings in most patients, particularly those with erythema migrans or exposure to geographic locations endemic for the disease. Detection of a specific antibody to B. burgdorferi is a useful confirmatory test in many patients. In atypical cases, however, a positive test result can be pivotal for determining the diagnosis and can lead to institution of definitive treatment. Serologic testing should not be used indiscriminately to diagnose Lyme disease or as the sole basis for administration of antibiotic therapy.
Assuntos
Doença de Lyme/imunologia , Idoso , Anticorpos Antibacterianos/análise , Sedimentação Sanguínea , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Doença de Lyme/sangue , Doença de Lyme/tratamento farmacológico , Doença de Lyme/patologia , MasculinoRESUMO
Total lymphoid irradiation (TLI) is a novel type of adjuvant immunosuppression for patients who undergo cardiac transplantation and have refractory allograft rejection during standard immunosuppressive therapy. TLI consists of 6 to 10 fractions of 80 cGy (1 cGy = 1 rad) of irradiation to lymphatic tissues with use of the standard mantle and inverted Y fields. We have used TLI in six patients with biopsy-proven rejection that was refractory to standard treatments, including cyclosporine, azathioprine, antilymphocyte antibodies, and corticosteroids. In five patients, recalcitrant rejection was resolved after completion of TLI, and resolution persisted during long-term follow-up (17 to 30 months; mean, 22.2 months). In each patient, a substantial increase in the CD8 (suppressor T-lymphocyte) subset and elimination of B lymphocytes were demonstrated, findings that also persisted. Side effects were mild and primarily limited to transient leukopenia. In four patients, a readily treated cytomegalovirus reactivation was noted during TLI; thus, a causal relationship was suggested. In recipients of cardiac allografts who have refractory rejection, TLI provides long-lasting amelioration of the rejection profile. This result may be attributable to a relative enhancement of the suppressor T-cell subset and elimination of the B-lymphocyte line. Side effects are minimal, but monitoring for cytomegalovirus activation or reactivation is recommended.