C2H2-171 : A novel human cDNA representing a developmentally regulated poz domain/zinc finger protein preferentially expressed in brain

We describe a novel human zinc finger cNDA, C2H2-171. This cDNA represents an mRNA which encodes a protein of 484 amino acids and a calculated molecular weight of 54 kD. Four zinc finger-like domains are found in the C-terminal end of the protein. At the N-terminus, C2H2-171 contains a POZ/tramtrack-like domain similar to that found in the tumor associated zinc finger proteins LAZ-3/BCL-6 and PLZ-F, as well as in non-zinc finger proteins. C2H2-171 RNA is preferentially expressed in the brain, and increases during the course of murine development, with maximal expression in the adult. C2H2-171 RNA is differentially expressed in brain regions, with the highest level of expression in the cerebellum. C2H2-171 RNA was expressed at high levels in primary cerebellar granule cell neurons compared to astrocytes. The gene encoding C2H2-171 is highly conserved in vertebrates, and maps to the terminus of human chromosome 1 (1q44-ter). This chromosomal location is associated with a number of cytogenetic aberrations including those involving brain developmental anomalies and tumorigenesis. These data suggest that C2H2-171 may play an important role in vertebrate brain development and function.     

Assessment of aldehyde dehydrogenase in viable cells

Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations.     

Synergistic effect of aqueous extract of Telfaria occidentalis on the biological activities of artesunate in Plasmodium berghei infected mice

Background

Resistance to most antimalarial drugs has encouraged the use of herbal preparations along with prescribed orthodox drugs.

Objective

To investigate effect of co-administration of aqueous extract of T. occidentalis leaves; commonly used as antimalarial and haematinic agent in Nigeria and artesunate using P. berghei animal model.

Methods

In vivo curative antiplasmodial effect of T. occidentalis (200mg/kg) alone and combination with artesunate (2mg/kg) were evaluated using albino mice infected with 10⁶ parasitized erythrocytes of P. berghei intraperitoneally. The haematological parameters: haemoglobin level, red blood cells and white blood cells and packed cell volume were monitored using standard methods.

Results

Aqueous extract of T. occidentalis, artesunate and the combination gave 72.17±4.07%, 70.43± 4.27% and 85.43±3.65% reduction in parasitaemia after 48hours respectively. A significant enhancement of the PCV was obtained with the coadministration of artesunate and aqueous extract (p< 0.01). Similar trends were also observed with heamatological parameters at 72hours of administration.

Conclusion

This study revealed a synergistic effect of the co-administration on parasite clearance rate of P. berghei infection in mice, with a significant enhancement of haematological parameters within 48 hours of administration. This indicates a rapid rate of recovery from plasmodial infections with the co-administration.     

Clinical Outcome of Acute Upper Gastrointestinal Hemorrhage among Patients Admitted to a Government Hospital in Egypt

Background/Aim:

Acute upper gastrointestinal hemorrhage (AUGIH) is a life-threatening emergency that results in high morbidity and mortality. The mortality rate varies between 4% and 14%. The aim of the study was to determine the clinical outcome of AUGIH among patients admitted to a government hospital in Egypt.

Patients and Methods:

This was a cross-sectional hospital-based study performed in 1000 patients presenting with AUGIH over a 7-year period between January 2004 and January 2011.

Results:

One thousand patients were analyzed. Fifty-four percent were male. Mean age was 52 ± 17 years. Eighty-eight percent were emergency admissions and 12% were inpatients at the time of bleeding. At presentation 68% had major comorbidity and 50% had liver disease. Seven hundred and twenty-four patients (72%) underwent endoscopy. Bleeding varices accounted for 31% of AUGIH and peptic ulcer 28%. Two hundred and thirty-two patients had endoscopically diagnosed bleeding varices or peptic ulcer with a visible vessel or active bleeding. These received endoscopic therapy. Initial hemostasis was achieved in 207 (89%). Thirteen patients (6%) had therapy at a subsequent endoscopy for further bleeding. Surgery was performed on 9 patients (0.9%) with AUGIH. Complications were reported in 70 patients (7%) mainly liver failure (4%). Six hundred and eighty-four patients (68%) were discharged improved, 162 (16%) left hospital without a diagnosis and 4 (0.4%) were referred to another facility. The overall mortality was 15%. Mortality was 24% in patients ≥60 years, 37% among inpatients, and 21% in those who had a major comorbidity. Mortality was 22% in patients who had liver disease and 9% in variceal bleeding.

Conclusion:

The most common cause of AUGIH was variceal in origin. Endoscopic therapy was successful in most cases. Mortality after AUGIH was particularly high among elderly patients, inpatients, and patients who had a major comorbidity, liver disease, and variceal bleeding.     

Changes in hippocampal volume and shape across time distinguish dementia of the Alzheimer type from healthy aging

Rates of hippocampal volume loss have been shown to distinguish subjects with dementia of the Alzheimer type (DAT) from nondemented controls. In this study, we obtained magnetic resonance scans in 18 subjects with very mild DAT (CDR 0.5) and 26 age-matched nondemented controls (CDR 0) 2 years apart. Large-deformation high-dimensional brain mapping was used to quantify and compare changes in hippocampal shape as well as volume in the two groups of subjects. Hippocampal volume loss over time was significantly greater in the CDR 0.5 subjects (left = 8.3%, right = 10.2%) than in the CDR 0 subjects (left = 4.0%, right = 5.5%) (ANOVA, F = 7.81, P = 0.0078). We used singular-value decomposition and logistic regression models to quantify hippocampal shape change across time within individuals, and this shape change in the CDR 0.5 and CDR 0 subjects was found to be significantly different (Wilks's lambda, P = 0.014). Further, at baseline, CDR 0.5 subjects, in comparison to CDR 0 subjects, showed inward deformation over 38% of the hippocampal surface; after 2 years this difference grew to 47%. Also, within the CDR 0 subjects, shape change between baseline and follow-up was largely confined to the head of the hippocampus and subiculum, while in the CDR 0.5 subjects, shape change involved the lateral body of the hippocampus as well as the head region and subiculum. These results suggest that different patterns of hippocampal shape change in time as well as different rates of hippocampal volume loss distinguish very mild DAT from healthy aging.     

High-dimensional mapping of the hippocampus in depression

OBJECTIVE: Abnormalities of the hippocampus may play a role in the pathophysiology of depression, but efforts to identify a structural abnormality in this brain structure among depressed patients have produced mixed results. Previous research may have been limited by exclusive reliance on measures of hippocampal volume. High-dimensional brain mapping is a new analytic method that quantitatively characterizes the shape as well as volume of a brain structure. In this study, high-dimensional brain mapping was used to evaluate hippocampal shape and volume in patients with major depressive disorder and healthy comparison subjects. METHOD: By using magnetic resonance imaging, brain scans were obtained from 27 patients with major depressive disorder and 42 healthy comparison subjects. High-dimensional brain mapping generated a series of 10 variables (components) that represented hippocampal shape, and hippocampal volumes were also computed. Analysis of variance techniques were used to compare depressed patients and comparison subjects on hippocampal shape and volume. RESULTS: While the depressed patients and comparison subjects did not differ in hippocampal volume, there were highly significant group differences in hippocampal shape. The two groups did not overlap on a discriminant function computed from a model comprising the 10 components. The pattern of hippocampal surface deformation in the depressed patients suggested specific involvement of the subiculum. CONCLUSIONS: Patients with major depression may have structural abnormalities of the hippocampus that can be detected by analysis of hippocampal shape but not volume. A specific defect in the subiculum could have widespread effects throughout neurocircuits that appear to be abnormal in depression.     

Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Dementia of the Alzheimer type

OBJECTIVE: To determine the feasibility of using high-dimensional brain mapping (HDBM) to assess the structure of the hippocampus in older human subjects, and to compare measurements of hippocampal volume and shape in subjects with early dementia of the Alzheimer type (DAT) and in healthy elderly and younger control subjects. BACKGROUND: HDBM represents the typical structures of the brain via the construction of templates and addresses their variability by probabilistic transformations applied to the templates. Local application of the transformations throughout the brain (i.e., high dimensionality) makes HDBM especially valuable for defining subtle deformities in brain structures such as the hippocampus. METHODS: MR scans were obtained in 18 subjects with very mild DAT, 18 healthy elderly subjects, and 15 healthy younger subjects. HDBM was used to obtain estimates of left and right hippocampal volume and eigenvectors that represented the principal dimensions of hippocampal shape differences among the subject groups. RESULTS: Hippocampal volume loss and shape deformities observed in subjects with DAT distinguished them from both elderly and younger control subjects. The pattern of hippocampal deformities in subjects with DAT was largely symmetric and suggested damage to the CA1 hippocampal subfield. Hippocampal shape changes were also observed in healthy elderly subjects, which distinguished them from healthy younger subjects. These shape changes occurred in a pattern distinct from the pattern seen in DAT and were not associated with substantial volume loss. CONCLUSIONS: Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.     

The peripheral zone of increase density in cranial computed tomography.

The band of increased attenuation seen on in vivo CCT images of adults, frequently designated as the cerebral cortex, has been proved clinically and experimentally to be an artifact in the reconstructed image. Recognition of this artifact may be of help in identifying intracranial lesions, such as shallow subdural hematomas. Attenuation values of isolated cortex and white matter were also studied and do not account for the band of high attenuation.     

Computerized tomography in the diagnostic evaluation of multiple sclerosis.

Sixty-six patients with a tentative or certain diagnosis of multiple sclerosis (MS) were examined with cranial computerized tomography (CT). Abnormalities found in 19 (29%) included discrete areas of decreased white matter density, enlarged ventricles, cortical atrophy, and focal areas of contrast enhancement. The presence of white matter lucencies and ventricular dilatation correlated with an increased incidence of diffuse hyperreflexia and mental impairment. Since half the patients with contrast-enhancing lesions were clinically stable, their lesions may represent acute asymptomatic plaques. Abnormalities on CT scan were observed more often in older patients whose disease had lasted longer and was clinically more definite. Since findings were sparse in early, less definite disease, the use of CT as a purely diagnostic tool is limited.