CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia

Background  

Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition in vivo via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP.     

Immune response of New Zealand mice to trinitrophenylated syngeneic mouse red cells.

NZB and NZB/W mice have reduced anti-sheep red cell (SRC) and 2,4,6-trinitrophenyl-plaque-froming cell (TNP-PFC) responses with age after injection of either the thymus-dependent antigen TNP-SRC or the thymus-independent antigen TNP-mouse red cells (MRC). However, the thymus-dependent response diminished much faster than the thymus-independent response. As a consequence, young New Zealand mice have a higher anti-TNP response after injection of TNP-SRC than after injection of TNP-MRC, while old New Zealand mice have a higher anti-TNP response after injection of TNP-MRC than after injection of TNP-SRC. The PFC avidity of NZB/W mice injected with TNP-SRC diminished with age, while the PFC avidity of mice injected with TNP-MRC did not change with agrc or TNP-SRC. Old NZB/W mice had few spontaneous anti-MRC-PFC. The number of anti-MRC PFC in old mice was increased 4 to 10 times after injection with either TNP-SRC or TNP-MRC. It is suggested that surveillance mechanisms are responsible for suppressing the autoimmune response to modified self-antigens. The unregulated immune system of NZB and NZB/W mice appears to be an expression of impairment of such a hypothetical surveillance mechanism.     

Cumulative subject index volumes 36–37

Suckling Wistar rats of different ages were inoculated intracerebrally with the neuradapted HNT strain of measles virus. In animals that survived for 10 or more days postinoculation (pi), there was frequently a chronic granulomatous encephalitis and cerebral atrophy was sometimes observed. Retinal lesions were a striking feature, and varied from discrete perivascular cuffing to gliosis, atrophy, and retinal dysplasia. Infectious virus was not isolated from the central nervous system (CNS) in conventional tissue culture, and ultrastructural examination of materials from the CNS and retina failed to demonstrate viral nucleocapsid material, findings similar to those seen in weanling mice inoculated with this virus. Viral antigen was readily demonstrated in the CNS and retina of measles-inoculated rats by immunofluorescent microscopy. Infectious virus was demonstrated in inoculated rats up to 30 days pi of HNT by the intracerebral inoculation of CNS tissue into suckling hamsters. Changes seen in the CNS and retina of HNT-inoculated rats have certain similarities to those seen in measles-induced encephalitis and retinopathy in man.     

A de novo X;3 translocation in Rett syndrome

Rett syndrome is a neurodegenerative disorder that occurs exclusively in females. The syndrome is sporadic in most cases with the exception of a few familial cases with an inheritance pattern through maternal lines. These observations raised the possibility that Rett syndrome may be due to an X-linked dominant mutation which is lethal in the male. To evaluate this hypothesis, we have systematically performed high-resolution chromosome analysis on 28 patients with Rett syndrome searching for deletions and/or translocations. In one patient, a de novo balanced translocation was observed with the chromosome constitution of 46,X,t(X;3) (p22.11;q13.31). This finding supports the hypothesis of an X-linked dominant mutation and suggests that the Rett gene might map to distal Xp21 or proximal Xp22.     

Risk factors for diabetic retinopathy: a population-based study in Rochester, Minnesota

Retinopathy is an important sequela of diabetes mellitus, but clinical risk factors for this condition have rarely been assessed in a geographically defined population. In this population-based study, the 1135 Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort) were followed through their complete medical records in the community to January 1, 1982. Because most of the cases of diabetic retinopathy in Rochester residents developed in patients with non-insulin-dependent diabetes mellitus (NIDDM), risk factors for diabetic retinopathy were examined in this group (N = 1031). A proportional hazards model identified the following risk factors for diabetic retinopathy in NIDDM: elevated initial fasting blood glucose level, marked obesity, and earlier age at onset of diabetes. Stratified analyses indicated that duration of diabetes was also significantly associated with an increased risk of retinopathy. Two secular trends, increasing detection of "mild" NIDDM and decreasing risk of diabetic retinopathy, had a major effect on retinopathy risk assessment. These data also suggest that insulin therapy is not an independent risk factor for diabetic retinopathy.     

The role of the principal clinical coordinator in the Health Care Financing Administration's Health Care Quality Improvement Initiative

The Health Care Quality Improvement Initiative (HCQII) is the Health Care Financing Administration's latest approach to quality management by peer review organizations (PROs) of the health care delivered to Medicare beneficiaries. The principal clinical coordinator (PCC) of each PRO, a physician with both clinical and methodological expertise, has the overall responsibility for all HCQII-related activities. The PCC works with a clinical coordinating team to analyze patterns of care and provide feedback about these patterns to the medical community for the purpose of improving the quality of care. Each PRO provides its PCC with the necessary infrastructure and expertise to conduct pattern analyses and implement the dissemination process. However, the effectiveness of the HCQII will depend largely on the PCC's ability to maintain the full support and cooperation of the local medical community. The success of the PCC role under the HCQII may enable it to serve as a useful model of physician leadership in the quality oversight organizations that will accompany national health care reform.     

Predictive coding in the visual cortex: a functional interpretation of some extra-classical receptive-field effects

We describe a model of visual processing in which feedback connections from a higher- to a lower-order visual cortical area carry predictions of lower-level neural activities, whereas the feedforward connections carry the residual errors between the predictions and the actual lower-level activities. When exposed to natural images, a hierarchical network of model neurons implementing such a model developed simple-cell-like receptive fields. A subset of neurons responsible for carrying the residual errors showed endstopping and other extra-classical receptive-field effects. These results suggest that rather than being exclusively feedforward phenomena, nonclassical surround effects in the visual cortex may also result from cortico-cortical feedback as a consequence of the visual system using an efficient hierarchical strategy for encoding natural images.     

Medial temporal lobe atrophy on MRI in dementia with Lewy bodies

OBJECTIVE: To investigate whether medial temporal lobe atrophy (MTA) on MRI is less frequent in dementia with Lewy bodies (DLB) compared with AD and vascular dementia (VaD), and to determine the diagnostic utility of MTA in the differential diagnosis of dementia. METHOD: Coronal T1-weighted 1.0-T MR images were acquired in patients with DLB (consensus criteria; n = 26; mean age, 75.9 years), AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association; n = 28; mean age, 77.4 years), VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences; n = 24; mean age, 76.9 years), and normal control subjects (n = 26; mean age, 76.2 years). Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized scale. RESULTS: MTA was more frequent and severe in all dementia groups compared with control subjects (AD, 100%; VaD, 88%; DLB, 62%; control subjects, 4%; p < 0.001). Comparing dementia groups, MTA scores were significantly lower in DLB than AD (p = 0.002), with a trend toward less atrophy in DLB compared with VaD (p = 0.07). The absence of MTA had a specificity of 100% and 88% for separating DLB from AD and VaD respectively, and a sensitivity of 38%. In patients with DLB, MTA increased with age (r = 0.58, p = 0.002), and in all dementia patients MTA correlated with memory impairment (combined memory score, r = -0.34, p = 0.003) but not total CAMCOG score or other subscales. CONCLUSION: Patients with DLB have significantly greater MTA than control subjects but significantly less than those with AD. The authors confirmed that the presence of MTA is useful in detecting AD but less useful in differentiating between dementias. However, in the differentiation of DLB from AD and VaD, the absence of MTA is highly suggestive of a diagnosis of DLB.     

Psychotic symptoms, aggression and restlessness in dementia

The current article reviews the literature pertaining to psychosis, aggression and restlessness in dementia sufferers examining frequency, course and associations as well as treatment considerations. All of these problems are highly prevalent, with a high impact upon dementia sufferers and their carers. Although there has been an expansion in this literature over the last few years there are still very few studies describing the natural course of behavioural and psychological symptoms in dementia (BPSD) and a paucity of data relating to non-Alzheimer dementias. Several large treatment studies have recently been completed, but there are still very few double blind controlled trials focusing upon BPSD in particular respect to non-pharmacological interventions.