Biomedical subjects
Publications and source records attributed to N Haque.
In this study the effect of various disintegrates on the disintegration time of laboratory prepared Acetaminophen tablets at different hardness has been determined. The disintegration time was found to be directly related with the hardness of the tablets for all formulations studied except in tablets containing veegum.
Diseases resulting from defects in a single gene may be more amenable to treatment by conventional gene therapy strategies than idiopathic or polygenic disorders. We have attempted to reduce the expression in vivo of the Huntington's disease gene protein, Huntingtin, using an 18-mer fluorescein-labeled phosphorothiorated antisense oligodeoxynucleotide (ODN) targeted against the start site of the first exon of the IT15 gene. Animals were given repeated intrastriatal infusions (5 microliters of a 100 nmol/microliter solution daily over 4 days) of the antisense ODN. The treatments ended on Day 5 and the tissue was processed for immunohistochemical and Western blot analysis. The fluorescein-labeled ODN appeared to penetrate several cells and did not cause any obvious toxicity to the neurons. The average reduction in levels of Huntingtin (16.9 +/- 7.2%) did not differ significantly between striatal tissue of antisense ODN-treated animals compared to those treated with a sense ODN or vehicle. Improved methods for molecular modifications of the IT15 gene may be needed for therapeutic initiatives.
Eucaryotic expression vectors bearing a 1.4 kb cDNA encoding the 4 repeat isoform of human tau, tau441, in either the sense or anti-sense orientation with respect to a cytomegalovirus (CMV) promoter were constructed. The resulting constructs were used to transiently express tau in Chinese Hamster Ovary cells and to generate non-neuronal stable cell lines. Immunocytochemical studies of these cells show that tau is expressed in the sense but not the anti-sense or vector containing lines. Some of the cells expressing tau showed fine elongated processes which were stained by tau antibodies. The general tau immunostaining pattern appeared diffuse and punctuate. The expressed tau was seen both unbound and bound to microtubules. In some cells labeling with antibodies that specifically recognize hyperphosphorylation of tau was observed. The size of this population increased with increasing numbers of cell passages. However, no increase in steady-state tubulin level was observed following tau441 expression. These studies show that tau can accumulate in the cells without a concomitant increase in tubulin.
Tau protein from Alzheimer disease (AD) brain is phosphorylated at eleven Ser/Thr-Pro and nine Ser/Thr-X sites. The former sites are phosphorylated by proline-dependent protein kinases (PDPKs), the latter by non-PDPKs. The identities of both the PDPKs and non-PDPKs involved in AD tau hyperphosphorylation are still to be established. In this study we have analyzed the interactions between a PDPK (GSK-3) and several non-PDPKs (A-kinase, C-kinase, CK-1, CaM kinase II) in the phosphorylation of one isoform (tau 39) of human tau. We found that the rate of phosphorylation of tau 39 by GSK-3 was increased several-fold if tau were first prephosphorylated by the non-PDPKs. Further, several Alzheimer-like epitopes in tau can be induced only slowly after phosphorylation of tau by GSK-3 alone. After a prephosphorylation of tau by the non-PDPKs, however, the rate of induction of these epitopes by GSK-3 is increased several-fold. These results suggest that one role of non-PDPK-catalyzed phosphorylation is the modulation of PDPK-catalyzed phosphorylation of tau in AD brain.
Spaceflight causes considerable atrophy in hindlimb muscles of the rat. The purpose of this study was to investigate the effect of a 14-day spaceflight (COSMOS 2044) on selected morphological and metabolic properties of single muscle fibers in a nonhuman primate, Macaca mulatta. Biopsies were taken from the soleus (Sol), medial gastrocnemius (MG), and tibialis anterior (TA) muscles of two rhesus monkeys 107 days before flight and 24 h after return from flight. Muscle biopsies were taken from two independent sites in each muscle by use of a small (3-mm OD) Bergstrom biopsy needle. The biopsies weighed 8-14 mg and contained 100-200 fibers, of which an average of 40 fibers were acceptable for metabolic and size analyses. The 14-day spaceflight had little effect on fiber size in the Sol and MG muscles, whereas there appeared to be a slight decrease in size in the TA. In each of the flight animals, the mean fiber size in the postflight biopsies increased relative to preflight values. An increase in fiber size over the same period of time was also observed in four control monkeys that were the same age and approximately the same weight as the flight monkeys. The relative increase in size was related to the body weight of the monkey at the time of the pre- and postflight biopsies. The mean fiber succinate dehydrogenase activity appeared to decrease in the MG, whereas there was no apparent effect of spaceflight on the Sol and TA muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
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In experiments involving primates, e.g. before and after spaceflight, needle biopsies were thought to be a logical and feasible means of obtaining metabolic and morphological information from skeletal muscles. However, the feasibility of obtaining consistent, repeatable biopsies from individual muscles had to be demonstrated prior to the acceptance of this procedure. To study this approach, the architectural properties and the fiber type distributions at three levels and two regions along the proximo-distal axis of the soleus, medial gastrocnemius and tibialis anterior of adult rhesus monkeys were determined. In each muscle, biopsies were taken from specific regions where the fiber type distribution was determined. Within each region of each muscle, the fiber type populations were similar at the three levels studied. The percentage of fast or oxidative fibers in the biopsies and in the regions of the same muscle were highly correlated, i.e. r = 0.98 for both comparisons. In addition, based on normalized values (z scores), 25/26 and 22/26 biopsies were within the 95% confidence interval, i.e. the biopsies were a representative sample of the mean fiber type population of that region of the muscle. In all muscles, the mean fiber lengths were no more than one third the length of the muscle. Together, these data indicate the feasibility of obtaining independent, repeated biopsies having similar fiber types from each of the muscles studied.
Malathion, known as a low toxic pesticide, is frequently used in the third world. Neurotoxic manifestations of malathion were evaluated on various lipids and lipid peroxidation in different brain areas following intraperitoneal injections (150 mg/kg body weight for 7 consecutive days) to albino rats. Clinical investigations show that malathion produced hypomotor activity and hyperthermia. Lipid components were differently affected by this pesticide, where total lipids and phospholipids were diminished in the spinal cord and brain stem, respectively. Increased contents of cholesterol were found in the cerebellum and spinal cord. Also, total lipids were increased in the cerebellum. The cholesterol/phospholipids ratio was increased in the cerebellum, brain stem and spinal cord. Rate of lipid peroxidation was found to be increased in all parts of the brain following malathion intoxication.
Hypercalcemia was found in a patient with an endobronchial granular cell tumor. To the best of our knowledge, the association of hypercalcemia and granular cell tumor has not been previously reported in the literature. Resection of the tumor resulted in the return of the serum calcium levels to normal. Investigation of the metabolic status of the patient suggested that the tumor was not producing parathormone.
Vaccination of 21,007 children between the ages of three months and five years was completed with five different lots of the meningococcal group A capsular polysaccharide vaccine. A correlation was found between the frequency and severity of adverse reactions and the endotoxin content of the vaccine lots. All vaccine lots elicited a serum antibody response. The endotoxin content of the vaccines did not correlate with the serum antibody response.
Adverse reactions occurring when 1.5 million children and young adults were vaccinated with different lots of group A meningococcal and one lot of Haemophilus influenzae type b capsular polysaccharide vaccines were analyzed on the basis of records kept by local health personnel and 19,000 special questionnaires. The incidence of anaphylactic reactions was 0.8 per 100,000 injections. A pyrogen-like reaction--high fever appearing soon after injection and disappearing within six hours--was seen in 1.8% of children 3 months to 5 years old who received the meningococcal vaccine in the first vaccination project. This reaction was most common in children below three years. Its frequency varied with different vaccine lots and was found to be correlated with the endotoxin content of the vaccines estimated by either the limulus assay or by pyrogen test in rabbits. On the basis of these results we propose that capsular polysaccharide vaccines should pass the pyrogen test with a dose of one mug polysaccharide per kg of rabbit weight. With such vaccines, the incidence of high fever was reduced to 0.5% in children of the same age group.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.