Diffuse mesenteric amyloidosis.
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Biomedical subjects
Publications and source records attributed to M Rabin.
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OBJECTIVE: As aerobic exercise capacity, as defined by VO2max, is associated with patient functioning and possibly prognosis in cystic fibrosis (CF), correlations between VO2max phenotype and genotype may be of value. DESIGN: Retrospective clinical series. SETTING: Cystic fibrosis referral clinic. PATIENTS: Convenience sample of 35 patients with CF consecutively referred for exercise testing. MAIN OUTCOME MEASURES: Blood samples were examined for mutations of cystic fibrosis transmembrane regulator (CFTR), Height, wight, pulmonary function, resting-energy expenditure, VO2max, and other exercise variables were assessed in each referred patient. RESULTS: Statistical comparison of 10 patients who were homozygous for the dF508 mutation of CFTR with 20 patients heterozygous for dF508 revealed no significant differences for height, weight, pulmonary function, resting-energy expenditure, VO2max, or any other exercise variables. CONCLUSIONS: These results imply a limited effect of the mutation status on overall patient functioning and prognosis. Future identification of more rare CFTR mutations and other genes and subsequent classification of patients in a manner reflective of the cellular physiology may lead to different results.
A total of 113 patients with infection due to human T-cell leukemia virus type 1 (HTLV-I) were evaluated at the University of Miami from January 1988 to March 1993. Forty patients were identified with adult T-cell leukemia/lymphoma (ATLL) and 63 with HTLV-I-associated myelopathy (HAM). Three had concomitant ATLL and HAM. Two HAM patients co-infected with human immunodeficiency virus type 1 (HIV-I) developed clonal lymphoproliferative disease during the study period. Patients with ATLL have a poor prognosis; multiple chemotherapy regimens including high-dose cytotoxic agents have been utilized with a small impact on survival. Most of our patients are currently treated with experimental regimens. Rheumatologic or autoimmune illnesses were identified, mostly in HAM patients, and a small number developed immunodeficiencies in the absence of other definable etiologic factors. Most of the patients were immigrants from areas of endemicity in the Caribbean basin, although many Americans were also recognized. HTLV-I/II infection was diagnosed serologically and typed as HTLV-I by polymerase chain reaction (PCR) or a modified Western blot when a DNA sample was not available. In 24 of 40 patients with ATLL, Southern blot hybridization performed on DNA extracted from peripheral blood lymphocytes or tumor tissue demonstrated clonal HTLV-I integration. In South Florida, ATLL and HAM are now seen frequently. Since HTLV-I infection is associated with a 4% lifetime risk of developing ATLL and an additional 0.25% lifetime risk for developing HAM, a large pool of asymptomatically infected individuals must exist here.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: To determine the type of cardiac disease causing left bundle branch block (LBBB) in Porto Alegre, Brazil, and to assess the role of associated left axis deviation (-30 degrees or more in the frontal plane) in order to identify a specific etiology of LBBB. METHODS: Through reports from the assistant physicians or through examination of the patients, the underlying heart disease in 264 cases of LBBB was assessed. The chi-square test was used to determine a possible association between left anterior hemiblock LBBB and one or more specific type of underlying heart disease. RESULTS: Systemic arterial hypertension (30.7%), ischemic heart disease (30.3%), valvar heart disease (8.7%), cardiomyopathies (7.5%), idiopathic degenerative disease of the conduction system (1.6%) and miscellaneous heart diseases (1.2%) were the underlying heart diseases. The presence of LBBB did not indicate any specific type of cardiac disease. CONCLUSION: The causes of LBBB in Porto Alegre are the same as reported in the international medical literature. Upward and leftward deviation (> or = -30 degrees) of QRS axis in the frontal plane did not show statistical significant association with any type of underlying cardiac disease.
Analysis of major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL) capable of killing human immunodeficiency virus type 1 (HIV-1)-infected targets is essential for elucidating the basis for HIV-1 disease progression and the potential efficacy of candidate vaccines. The use of primary CD4+ T cells with variable infectivity as targets for such studies has significant limitations, and immortal autologous cells with high levels of CD4 expression that can be consistently infected with HIV-1 would be of much greater utility. Therefore, we transduced Epstein-Barr-virus-transformed B-lymphoblastoid cell lines (LCL) with a retroviral vector, LT4SN, containing the human CD4 gene. Stable LCL in which more than 95% of cells expressed membrane CD4 were obtained. Aliquots were infected with HIV-1, and, after 4 to 7 days, nearly all of the cells contained cytoplasmic gag and produced high levels of p24 antigen. The ability of major histocompatibility complex-restricted CD8+ CTL to lyse such HIV-1-infected CD4-transduced LCL (LCL-CD4HIV-1) was evaluated. These autologous targets were lysed by CTL generated from an HIV-1-uninfected vaccinee over a broad range of effector-to-target ratios. Similarly, the LCL-CD4HIV-1 were efficiently lysed by fresh circulating CTL from HIV-1-infected individuals, as well as by CTL activated by in vitro stimulation. Both HIV-1 env- and gag-specific CTL effectors lysed LCL-CD4HIV-1, consistent with the cellular expression of both HIV-1 genes. The LCL-CD4HIV also functioned as stimulator cells, and thus are capable of amplifying CTL against multiple HIV-1 gene products in HIV-1-infected individuals. The ability to produce HIV-1-susceptible autologous immortalized cell lines that can be employed as target cells should enable a more detailed evaluation of vaccine-induced CTL against both homologous and disparate HIV-1 strains. Furthermore, the use of LCL-CD4HIV-1 should facilitate the analysis of the range of HIV-1 gene products recognized by CTL in seropositive persons.
PURPOSE: To search for the existence and degree of correlation between total 12 lead ECG amplitude and the sum of RaVL + SV3 > 28 mm (for men) or > 20mm (for women) and left ventricular hypertrophy (LV mass calculated by echocardiography > 215g for both sexes). METHODS: ECG and echocardiograms of 227 consecutive patients were examined and submitted to statistical analysis searching for correlation between total 12 lead ECG amplitude and Cornell criteria and LV mass (ASE formula modified by Devereux). RESULTS: Patients had ischemic heart disease, hypertension, valvular disease, cardiomyopathy or other less common heart diseases, or had no cardiac illness at all. There was statistically significant association of total 12 lead amplitude > 120mm and Cornell criteria with LV mass > 215g (p = 0.02 and p = 0.01 respectively). Total ECG amplitude showed 74.3% sensitivity, 42.6% specificity, and 52.4% accuracy. Cornell criteria showed values of 37.8%, 82.7% and 68.7% respectively. CONCLUSION: Total 12-lead amplitude presented limited diagnostic performance for detecting LV hypertrophy, as well as did ECG Cornell criteria, although the latter was more specific and more accurate.
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In a neuroanatomical study of dyslexia, measurements were made of the superior surface of the temporal lobe (SSTL) on MRI scans in a sample of 17 dyslexics and 21 non-dyslexic subjects. Both anterior and posterior halves of the SSTL area showed significant leftward asymmetry in non-dyslexics, but showed symmetry in dyslexics. The total SSTL area showed greater leftward asymmetry in non-dyslexics than in dyslexics. The dyslexics also revealed a significant correlation (r = 0.69, P = 0.005) between Woodcock-Johnson Passage Comprehension scores and posterior SSTL asymmetry, such that those with higher scores had more leftward asymmetry. This suggests that among dyslexics the direction of SSTL asymmetry may serve as a risk factor and/or a marker for the severity of reading comprehension problems.
This study investigated the developmental, demographic, educational, and psychosocial outcome of 36 adults with third-generation familial dyslexia. Control subjects were 44 unaffected age-matched family members. Compared with control subjects, those with familial dyslexia 1) had similar incidences of perinatal complications, left-handedness, and right-left confusion but reported more early speech/language problems; 2) performed worse in reading and spelling but had similar educational achievement; 3) were more likely to report depression/anxiety symptoms and to have attention-deficit disorder with hyperactivity; and 4) were similar in medical history, marital stability, and mean income. Data suggest that, despite continued isolated reading deficits, carefully selected subjects with adult familial dyslexia do not show the previously described downward course of the learning-disabled population.
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The human pathogen CMV, is a major cause of morbidity and mortality in immunocompromised hosts. The CD8+ class I-restricted CTL response to CMV assists in preventing progression of CMV infection to life-threatening disease; however, the viral Ag recognized by CD8+ CTL are not well characterized. In general, virus-specific CTL recognize endogenously synthesized viral proteins processed and presented associated with class I MHC molecules. Although proteins or inactivated virions have been experimentally delivered to the cytoplasm to result in class I MHC presentation, this mode of Ag delivery to the class I processing pathway after natural viral entry has not been documented in humans. Our data demonstrate that the CMV-specific class I-restricted CTL response in individuals latently infected with CMV is predominantly specific for selected structural virion proteins introduced into the cell after viral penetration and efficient recognition occurs in the absence of de novo viral gene expression. This CTL response may provide a biological advantage for limiting the spread of infection after CMV reactivation because infected cells are lysed before viral assembly.
The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region.
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We report here 10 cases of adult T-cell leukemia/lymphoma (ATL) seen in South Florida between February 1988 and July 1989. All were seropositive for human T-lymphotropic virus type I (HTLV-I) and seronegative for human immunodeficiency virus type 1 (HIV-1). DNA extracted from tumor biopsies/peripheral blood lymphocytes of nine patients was shown by the polymerase chain reaction (PCR) to contain HTLV-I proviral DNA. Blot hybridization of DNA extracted from seven patients with an HTLV-I cDNA probe revealed a monoclonal pattern of proviral integration consistent with a diagnosis of ATL. Eight of the 10 patients were women. Six patients were from Haiti, three from Jamaica, and one from the Bahamas. All patients had very aggressive non-Hodgkin's lymphoma. Two patients presented with sinus and retro-orbital involvement; another had gastric lymphoma that perforated. Nine patients developed hypercalcemia. Eight patients died within 1 year of diagnosis. Two were lost to follow-up. During the course of this study, 66 new cases of non-Hodgkin's lymphoma were diagnosed at this hospital. Ten of these cases were ATL. The prevalence of HTLV-I-related lymphoma in this sample was 15%. Since tissue from all patients was not available for HTLV-I screening, however, it is possible that other cases of ATL went undetected. We conclude from this initial survey that a retroviral etiology should be considered in patients from populations known to be at risk for HTLV-I infection who present with non-Hodgkin's lymphoma.
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Between 1972 and 1982 Seattle experienced a diphtheria outbreak involving 1,100 cases, primarily adults with cutaneous lesions. Biotyping revealed three consecutive overlapping outbreaks including 433 toxinogenic intermedius cases. Isolates from each quarter year were examined for DNA restriction fragment patterns and hybridization patterns with three DNA probes. All intermedius outbreak isolates appeared identical in all analyses and most stock cultures had the outbreak DNA fragment pattern, but DNA probes detected six patterns within 11 intermedius stock cultures. The mitis outbreak was heterogeneous, involving at least five restriction fragment patterns. In contrast, DNA restriction fragment analyses indicated that 22 of 25 gravis outbreak isolates belonged to a single strain, whereas there were seven strains within eight gravis stock cultures. DNA probe analyses of gravis outbreak isolates detected seven different patterns, five involving copy numbers of the toxB fragment and attB sites that presumably reflected lysogenic events that occurred during the outbreak.
Considerable information has accumulated on mouse homeo box gene organization and expression. Homeo box genes are expressed in a wide variety of tissues, developmental stages, and cell lines. How can this be interpreted in view of the relationship of these genes to Drosophila morphogenetic loci? One view is that homeo box genes control determinative decisions by modulating transcription of as yet unidentified target genes. Proponents of this view are faced with two tasks: to identify developmental processes that are controlled by homeo box genes, and to identify the target genes that mediate this control. Such target genes might be identified on the basis of in vitro homeo domain-DNA interactions. Candidate morphogenetic processes might be identified on the basis of the observed patterns of homeo box gene expression. It must be stressed that finding expression in a given tissue in no way demonstrates that the expression is necessary for the determination of that tissue. The role of Drosophila homeo box genes in determinative decisions is based upon analysis of mutants to demonstrate that the pattern of homeo box gene expression determines the morphogenetic outcome. To test whether the expression of a mouse homeo box gene is involved in a determinative decision, one must disrupt the normal pattern of expression of that gene and observe the resulting morphogenetic effect. In mouse this can be approached by looking for allelism with known morphogenetic loci, by isolating mutants in homeo box genes through large-scale mutagenesis screens, or by introducing altered homeo box genes into transgenic mice. One of the most intriguing possibilities is that homeo box genes are involved in regional specification along the anteroposterior axis. In situ hybridization and Northern blot analysis have demonstrated that at least four different homeo box genes display distinct regional patterns of expression along the anteroposterior axis of the developing CNS. The expression of each of these genes has a unique anterior boundary from which expression extends posteriorly within the CNS. Hox 1.5 expression has an anterior boundary within the hindbrain just posterior to the pontine flexure. The anterior boundary of Hox 2.1 expression lies more posteriorly within the medulla of the hindbrain. Weak expression of Hox 2.5 is detected in the spinal cord just posterior to the first cervical vertebra, and maximal expression is found posterior to the second cervical vertebra.(ABSTRACT TRUNCATED AT 400 WORDS)