Precursor B-lymphoblastic transformation of grade I follicle center lymphoma

Part of the natural history of follicle center lymphoma (FCL) is transformation to a more aggressive neoplasm, almost always a diffuse large B-cell lymphoma. We describe a rare example of a precursor B-lymphoblastic transformation of grade I FCL occurring in a 45-year-old woman 12 years after initial presentation and 3 years after successful treatment for a diffuse large cell transformation. The lymphoblastic lymphoma shared the same immunoglobulin heavy chain gene rearrangement as the FCL as assessed by polymerase chain reaction amplification and direct sequencing, as well as identical kappa light chain gene rearrangements by Southern blot analysis. The immunoglobulin heavy chain variable gene sequences of both tumors showed numerous identical base substitutions compared with germline sequences and 3 additional mutations in the lymphoblastic lymphoma not present in the low-grade FCL. These results indicate origin of the lymphoblastic process from the mature follicle center B-cell clone, rather than divergent origin of the 2 tumors from a common immature B-cell precursor.     

Autonomic Correlates of Depression and Clinical Improvement Following Electroconvulsive Shock Therapy

Electrodermal responses (EDRs) and heart rate (HR) were recorded during a variety of tasks from 20 hospitalized depressed patients before and after a series of electroconvulsive shock treatments (ECTs). The depressed patients, compared to nondepressed controls during the pre-ECT test, exhibited lower skin conductance levels, smaller phasic skin conductance responses with longer latencies, higher tonic HR, and smaller HR changes to stimuli. This response pattern suggests a complex state of “environmental rejection” coupled with “low arousal” in the depressed patients. Certain EDR measures were related to the severity of depressive symptomatology while tonic HR was related to the agitation/retardation symptoms. Patients who subsequently responded well following ECT were more like the controls on certain pre-treatment measures than those who failed to respond favorably. There were little EDR or HR changes following ECT and what changes did occur were unrelated to differences in clinical improvement. It was suggested that, despite temporary clinical improvement following ECT, depressed patients have a chronic affective disorder which is reflected in the EDR and HR measures.     

Cardiac drift during prolonged exercise with echocardiographic evidence of reduced diastolic function of the heart

This study examined whether, in 16 male subjects, a continuous increase in heart rate (HR) during 4 h of ergometry cycling relates to cardiac fatigue or cardiomyocyte damage. Serum cardiac troponin T (cTnT) was determined and echocardiographic assessment was carried out prior to and after 2 h of exercise, within 15 min of completing exercise and after 24 h. Left ventricular contractile function (end-systolic blood pressure–volume relationship [SBP/ESV]) and diastolic filling (ratio of early to late peak left ventricular filling velocities [E:A]) were calculated. During exercise HR was 132±5 beats min^–1 after 2 h and increased to 141±5 beats min^–1 (mean ± SD; P<0.05), but there was no evidence of altered LV contractile function (SBP/ESV 39.0±5.1 mmHg cm^–1 to 36.5±5.2 mmHg cm^–1 and SBP/ESV was not correlated to maximal oxygen uptake (r²=0.363). In contrast, E:A decreased (1.82±0.32 to 1.48±0.30; P<0.05) and returned towards baseline after 24 h (1.78±0.28), and individual changes were correlated to maximal oxygen uptake (r²=0.61; P<0.05). Low levels of cTnT were detected in two subjects after 4 h of exercise that had normalised by 24 h of recovery. During prolonged exercise cardiovascular drift occurred with echocardiographic signs of a reduced diastolic function of the heart, especially in those subjects with a high maximal oxygen uptake.     

Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis

Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic neural cell death occurs remains unknown. Proteins encoded by two other genes in which mutations cause familial PD, parkin and UCH-L1, are involved in regulation of the ubiquitin-proteasome pathway, suggesting that dysregulation of the ubiquitin-proteasome pathway is involved in the mechanism by which these mutations cause PD. We established inducible PC12 cell lines in which wild-type or mutant alpha-synuclein can be de-repressed by removing doxycycline. Differentiated PC12 cell lines expressing mutant alpha-synuclein showed decreased activity of proteasomes without direct toxicity. Cells expressing mutant alpha-synuclein showed increased sensitivity to apoptotic cell death when treated with sub-toxic concentrations of an exogenous proteasome inhibitor. Apoptosis was accompanied by mitochondrial depolarization and elevation of caspase-3 and -9, and was blocked by cyclosporin A. These data suggest that expression of mutant alpha-synuclein results in sensitivity to impairment of proteasome activity, leading to mitochondrial abnormalities and neuronal cell death.     

Evidence that [3H]forskolin binding in the substantia nigra is intrinsic to a striatal-nigral projection: an autoradiographic study of rat brain

The neuronal localization of binding sites for the diterpene activator of adenylate cyclase, forskolin, has been determined. Kainic or ibotenic acid lesions were administered into the caudate-putamen or substantia nigra of Sprague-Dawley rats. The binding of 20 nM [3H]forskolin was examined autoradiographically and quantitated using computerized densitometry with tritium standards. Neurochemical lesions placed in the caudate-putamen markedly reduced [3H]forskolin binding in this structure and distal to the site of injection in the substantia nigra. Ibotenic acid lesions placed in the substantia nigra did not appreciably alter binding in the substantia nigra, caudate-putamen, nucleus accumbens or olfactory tubercle. These results indicate that 'forskolin-identified' adenylate cyclase in the substantia nigra is located in nerve terminals from the caudate-putamen. In addition, these sites are presumably located on cell bodies or interneurons in the caudate-putamen.     

Quantitation of 8 human herpesviruses in peripheral blood of human immunodeficiency virus-infected patients and healthy blood donors by polymerase chain reaction

Human herpesviruses are associated with morbidity and mortality in persons with compromised immune systems, including patients infected with human immunodeficiency virus (HIV). To investigate the basis for this association, the levels of all 8 human herpesviruses (herpes simplex virus, types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6, human herpesvirus 7, and human herpesvirus 8) were measured with the quantitative polymerase chain reaction (PCR). Viral DNA was measured in the whole blood of 20 HIV-infected patients and compared with levels in 20 healthy blood donors. There was no significant difference in the frequency of virus detection of the 8 human herpesviruses between HIV-infected patients and healthy adults. These results indicate that HIV infection is not associated with a general increase in the circulating levels of human herpesviruses, and suggest that quantitative PCR analysis is superior to qualitative PCR analysis for detection of clinically relevant disease in HIV-infected patients.     

Characterization of RNA-dependent RNA polymerases in uninfected and cowpea chlorotic mottle virus-infected cowpea leaves: selective removal of host RNA polymerase from membranes containing CCMV RNA replicase.

Extracts from Cowpea chlorotic mottle virus (CCMV)-infected Cowpea leaves contained membrane-bound (31,000 g pellet) and soluble (31,000 g supernatant) RNA-dependent RNA polymerase activities. The membrane-bound RNA-dependent RNA polymerase (CCMV RNA replicase) increased 12-fold 4 days after inoculation. The viral RNA synthesis in vitro proceeded linearly for 20 min and required the four nucleoside triphosphates and Mg²⁺ ions for activity. Manganese ion was a poor substitute for Mg²⁺. Optimal enzymatic activity in vitro was unaffected by exogenous RNA or KCI. The CCMV RNA replicase product was predominantly heterodisperse single-stranded RNAs, some of which comigrated with CCMV virion RNA. Small amounts of large double-stranded RNAs were also products of the replicase reaction. The soluble RNA-dependent RNA polymerase from CCMV-infected or healthy Cowpea leaves required the four nucleoside triphosphates and Mg²⁺ ions for activity. Its activity in the in vitro assay was stimulated by adding exogenous RNAs but was inhibited by KCI. The product of the soluble RNA-dependent RNA polymerase was predominantly double-stranded RNA of approximately 4 to 6 S. RNA-dependent RNA polymerase activity, similar to that detected in the soluble fraction, was detected in the membrane pellet. This activity, which complicates the analysis of viral replicase assay, was removed without affecting CCMV RNA replicase activity by washing the 31,000 g pellets with buffer containing 0.5 M KCI. The KCI treatment aids in preparation of membrane-bound fractions devoid of host RNA-dependent RNA polymerase activity and high in viral replicase activity.     

Human genome,race and medicine

In closing, with the new revelations of the Human Genome Project, notions on whether land-based race identity or ethnicity with genetic markers has been proven valid, with few exceptions. This has caused me to revisit the attempted effort to discard concepts on race, especially in medicine. Obviously there are outliers to this new work. But contrary to popular belief, and to some, the unthinkable, there may be, in fact, a biologic basis for our human distinctions. And I for one do not feel shame or seem perplexed by it. Moreover, it appears that Dr. Welsing in her earlier work was onto something, and was indeed ahead of her time. The problem African Americans, and other persons of color face, to some extent, has to do with the social political context of racism, and the biologic impact it has and is often expressed in the form of stress and injuries, simply put. Therefore, and more importantly, eliminating the nomenclature of how we classify ourselves in our intellectual interchange in science and other areas, will not correct our problems, but may in fact, if abandon, spell our doom. Because what we are murderously burdened by has to do with racism and its effects. Which are in effect, based on physical features, not mere classification. Further, the current thought on racism and why it is practiced by some is that racism serves an evolutionary drive to survive by humans, by forming alliances in among similar groups of people. Therefore, if that is the case, we had better be ready for the long haul in this battle as our history and ongoing struggles tell us. Besides, if not for racism, "we would not have had all of these problems over all these years." The National Medical Association and its publishing instruments must remain vigilant and stay focused.     

Electrodermal Lability: Individual Differences Affecting Perceptual Speed and Vigilance Performance in 9 to 16 Year-Old Children

Studies on adults have suggested that a deterioration in performance (within session vigilance decrement) on a continuous performance task may be related to individual differences in baseline levels of electrodermal activity (electrodermal lability). This study investigated this relationship in 153 children, aged 9–16 years. A significant vigilance decrement was observed, as indicated by average decreases in perceptual sensitivity (d') over an 11.5-min time period. Although electrodermal labiles were overall more perceptually sensitive than electrodermal stabiles, results did not support the premise that the performance of stabiles decreases over time more than that of labiles. Performance on other cognitive tasks, involving tests of perceptual speed ability, did not appear to be highly related to vigilance performance. However labiles were not only better able to sustain their attention, but also performed better and faster on these cognitive tasks.     

Female phenotype and multiple abnormalities in sibs with a Y chromosome and partial X chromosome duplication: H--Y antigen and Xg blood group findings.

A mentally retarded female child with multiple congenital abnormalities had an abnormal X chromosome and a Y chromosome; the karyotype was interpreted as 46,dup(X)(p21 leads to pter)Y. Prenatal chromosome studies in a later pregnancy indicated the same chromosomal abnormality in the fetus. The fetus and proband had normal female genitalia and ovarian tissue. H--Y antigen was virtually absent in both sibs, a finding consistent with the view that testis-determining genes of the Y chromosome may be suppressed by regulatory elements of the X. The abnormal X chromosome was present in the mother, the maternal grandmother, and a female sib: all were phenotypically normal and showed the karyotype 46,Xdup(X)(p21 leads to pter) with non-random inactivation of the abnormal X. Anomalous segregation of the Xga allele suggests that the Xg locus was involved in the inactivation process or that crossing-over at meiosis occurred.