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Biomedical subjects

K Rao

Publications and source records attributed to K Rao.

At least 127 records · Page 7Linked to original sources

Hemin, chelatable iron, and the regulation of transferrin receptor biosynthesis.

We have examined the mechanism by which hemin regulates the expression of the human transferrin receptor. Previous work led to the suggestion that the regulatory signal is provided by heme (Ward J. H., Jordan, I., Kushner, J. P., and Kaplan, J. (1984) J. Biol. Chem. 259, 13235-13240). We demonstrated that hemin regulates the expression of the receptor via alterations in the rate of receptor biosynthesis. However, this effect can be completely abolished by addition of desferrioxamine, an intracellular iron chelator. Competition curves demonstrate that desferrioxamine and hemin affect the same intracellular iron pool. Since the chelator cannot remove iron from heme, we propose that hemin acts simply by delivering iron to a chelatable iron pool and that levels of chelatable iron provide the regulatory signal for expression of the transferrin receptor gene.

Cell Line↗

A two-year longitudinal study of poststroke mood disorders. In-hospital prognostic factors associated with six-month outcome.

In a prospective study of mood disorders in stroke patients, variables obtained during the acute hospitalization were examined for their relationship to outcome at either 3- or 6-month follow-up. Distance of the lesion on computerized axial tomography scan from the frontal pole in patients with left anterior infarcts was significantly associated with severity of depression at 3 and 6 months poststroke. In addition, intellectual and functional physical impairment in-hospital were significantly correlated with severity of depression and social functioning scores at 3 and 6 months poststroke. Thus, patients who develop depression during the first 6 months poststroke may be responding to the severity of their impairment whereas the patients who develop depressions during the acute poststroke period may have a neuroanatomical and neurophysiological basis for their depression. Although other explanations might be proposed, the dynamic nature of the relationship between depression and associated variables during the first 6 months poststroke indicates that etiology of poststroke depression may be different depending upon the time of onset of the depression after brain injury.

Acute Disease↗

Mood disorders in left-handed stroke patients.

Thirty left-handed patients hospitalized for stroke were examined for mood disorders. Patients with left hemisphere lesions and nondominant hand impairments had significantly higher depression scores and more depressive diagnoses than patients with right hemisphere lesions and dominant hand impairments. Major depression was strongly associated with left anterior brain injury, and depression severity was significantly correlated with proximity of the lesion on CAT scan to the left frontal pole. These findings are almost identical to previously reported results from right-handed patients and suggest that cerebral lateralization of poststroke mood disorders may be independent of cerebral motor dominance and language dominance.

Aphasia↗

The dexamethasone suppression test and mood following stroke.

Dexamethasone suppression tests (DSTs) were given to 65 acute and chronic stroke patients. For patients who had had a stroke less than 1 year earlier, nonsuppression on the DST was significantly associated with the presence of poststroke depression. The authors, who used the DSM-III symptom criteria for major depression, found that DST sensitivity was 67% but specificity was only 70%. False positive tests in the stroke patients seemed related to large lesion volume. The DST, although of limited clinical utility in this population because of false positive tests, may help define more homogeneous subtypes of poststroke depression for research.

Aged↗

Biosynthetic regulation of the human transferrin receptor by desferrioxamine in K562 cells.

Treatment of K562 cells with the iron chelator desferrioxamine results in the gradual increase in total cell receptors for transferrin. Receptor number rises 2.5-4.5-fold over 24 h and remains at the elevated level if the chelator is continuously present. Preincubation of the chelator with ferric chloride abolishes the effect. The drug has no effect on the 7-h half-life of the receptor. The increased number of receptors can be accounted for by a specific increase in the rate of receptor biosynthesis which reaches 3-4 times that seen in untreated cells by 6 h after the addition of the chelator. Isolation of mRNA from treated cells reveals that, after 8 h in the presence of desferrioxamine, there is a 3-fold increase in the specific translation of transferrin receptor over untreated cells. Total protein synthesis is not changed under these conditions.

Animals↗

Nortriptyline treatment of post-stroke depression: a double-blind study.

The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients. Half of the patients had major depression. There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients. Depression was measured by the Hamilton depression scale, Zung depression scale, present state examination, and an overall depression scale. Successfully treated patients had serum nortriptyline levels in the therapeutic range. Post-stroke depressions are common, severe, and longstanding, and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients.

Brain↗

Failure to release iron from transferrin in a Chinese hamster ovary cell mutant pleiotropically defective in endocytosis.

A Chinese hamster ovary cell mutant defective in the receptor-mediated endocytosis of several unrelated ligands (Robbins, A. R., S. S. Peng, and J. L. Marshall, 1983, J. Cell Biol., 96:1064-1071) failed to accumulate iron provided in the form of diferric transferrin. Analysis of the steps of the transferrin cycle indicated that binding and internalization of transferrin proceeded normally in mutant cells. However, the mutant appeared unable to dissociate iron from transferrin, as evidenced by release of diferric transferrin from the mutant versus apotransferrin from the parent. Uptake of ferric ions from the growth medium was enhanced in the mutant.

Animals↗

Mood disorders in stroke patients. Importance of location of lesion.

In a selected group of right-handed patients with single stroke lesions of either the right (n = 14) or left (n = 22) hemisphere and no predisposing factors for psychiatric disorder, we found that the severity of depression was significantly increased in patients with left anterior lesions as opposed to any other lesion location. In addition, the severity of depression correlated significantly with proximity of the lesion on CT scan to the frontal pole in the left anterior group. The right hemisphere lesion group showed the reverse trend: patients with right posterior lesions were more depressed than patients with right anterior lesions, who were unduly cheerful and apathetic. These findings suggest that intrahemispheric lesion location is in some way related to mood disorder in stroke patients and that there is a graded effect of lesion location on severity of mood change. The neuroanatomy of the biogenic amine-containing pathways in the cerebral cortex might explain this graded effect and provide a neurochemical basis for the mood change.

Aphasia↗

Separation of Fe+3 from transferrin in endocytosis. Role of the acidic endosome.

NH4Cl and monensin, two agents which neutralize intracellular acidic compartments, block the segregation of iron from transferrin after endocytosis, while neither of these reagents affects internalization of diferric transferrin into the cell. In conclusion the molecular separation of iron from transferrin inside the cell requires a non-lysosomal acidic compartment.

Ammonium Chloride↗

Mood change following bilateral hemisphere brain injury.

Fifteen patients with bilateral hemisphere brain injury secondary to thromboembolic stroke or trauma were evaluated for depression, cognitive impairment, and functional physical impairment. Analysis of CT scans and standardized mood scales revealed that patients with left anterior brain injury were significantly more depressed than patients without such injury. Depression severity was directly and significantly correlated with left lesion proximity to the frontal pole. Left lesion age, lesion temporal sequence, right lesion location, cognitive impairment, and functional physical impairment did not significantly correlate with depression. Depressive symptomatology previously shown to be associated with single left frontal lobe lesions appeared to dominate post-brain injury psychopathology regardless of location or temporal sequence of other brain lesions.

Activities of Daily Living↗

Central retinal vein obstruction associated with mitral valve prolapse.

Fifteen patients under age 50 years with central retinal vein obstruction (CRVO) and no obvious predisposing ocular or systemic condition underwent a comprehensive medical investigation, including platelet function studies and, in 11 cases, echocardiography. Only 1 patient was found to have a systemic disease (hyperlipoproteinemia), but 11 patients (73%) were found to have abnormalities of platelet function, usually platelet coagulant hyperactivity. Of the 11 patients who underwent echocardiography, 7 (64%) were found to have mitral valve prolapse, a condition predisposing to vascular occlusion, and 4 (60%) of the 7 had abnormalities of platelet function. These findings suggest that mitral valve prolapse contributes to platelet hyperactivity and, ultimately, CRVO.

Adult↗