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Biomedical subjects

N Akhtar

Publications and source records attributed to N Akhtar.

At least 55 records · Page 3Linked to original sources

Conformational change of human lens insoluble alpha-crystallin.

Human lens alpha-crystallin becomes progressively insoluble with age and is the major crystallin component in the water-insoluble (WI) fraction. The mechanism that causes the originally water-soluble (WS) alpha-crystallin to become insoluble is unknown. A conformational change by chemical modification may be the cause, but the nature of insolubility renders it impossible to study protein conformation in the WI fraction by most spectroscopic measurements. In the present study, alpha-crystallin in the WI fraction was extracted by urea and reconstituted to a folded protein by dialysis. The refolded urea-soluble (US) alpha-crystallin was compared with WS alpha-crystallin. The US alpha-crystallin has a greater amount of polymeric species, but fewer degraded subunits than the WS alpha-crystallin as shown by SDS-PAGE and Western blot. Circular dichroism (CD) measurements indicate that they have the same secondary structure but a different tertiary structure, possibly a partial unfolding in the US alpha-crystallin. This is supported by fluorescence measurements: Trp residues are more exposed and protein has a more-hydrophobic surface in the US than in the WS alpha-crystallin. Blue fluorescence further indicates that the US alpha-crystallin has a greater amount of pigment than the WS alpha-crystallin. Together, these results indicate that the US alpha-crystallin is a chemically and conformationally modified protein.

Aged↗

Osmoregulation and protein expression in a pbs2delta mutant of Saccharomyces cerevisiae during adaptation to hypersaline stress.

We deleted the PBS2 gene encoding the MAP kinase activator of the osmosignaling HOG pathway in Saccharomyces cerevisiae and examined the effects on the kinetics of the osmoregulatory glycerol response and protein induction during adaptation to 0.7 M NaCl. Changes in protein expression as analyzed by two-dimensional polyacrylamide gel electrophoresis (2D PAGE) demonstrated that for the 29 proteins showing a 6-fold induction in wild-type cells during adaptation to NaCl stress, all displayed a decreased and delayed response in pbs2delta cells. Of the seven proteins that were identified, two were previously not known to be under HOG pathway control: Ald6p, an isoform of aldehyde dehydrogenase and Dak1p, a putative dihydroxyacetone kinase. The presence of a remaining significant induction in pbs2delta cells for about half of the examined proteins indicates existence of alternative osmosignaling pathway(s). Northern analysis of the salt induced transcription of GPD1 and GPP2, encoding the cytosolic glycerol-3-phosphate dehydrogenase and glycerol-3-phosphatase involved in the osmostress induced glycerol production, demonstrated an about 20-fold PBS2-dependent transient activation, in agreement with the previously reported transient nature of the signal transduced by the HOG pathway.

Adaptation, Physiological↗

Differential productivity in young children's use of nouns and verbs.

A fundamental question of child language acquisition is children's productivity with newly learned forms. The current study addressed this question experimentally with children just beginning to combine words. Ten children between 1;6 and 1;11 were taught four new words, two nouns and two verbs, over multiple sessions. All four words were modelled in minimal syntactic contexts. The experimenter gave children multiple opportunities to produce the words and made attempts to elicit morphological endings (plural for nouns, past tense for verbs). Overall, children combined the novel nouns productively with already known words much more often than they did the novel verbs-by many orders of magnitude. Several children also pluralized a newly learned noun, whereas none of them formed a past tense with a newly learned verb. A follow-up study using a slightly different methodology confirmed the finding of limited syntactic productivity with verbs. Hypotheses accounting for this asymmetry in the early use of nouns and verbs are discussed.

Child Language↗

Young children's productivity with word order and verb morphology.

Four studies examined English-speaking children's productivity with word order and verb morphology. Two- and 3-year-olds were taught novel transitive verbs with experimentally controlled argument structures. The younger children neither used nor comprehended word order with these verbs; older children comprehended and used word order correctly to mark agents and patients of the novel verbs. Children as young as 2 years 1 month added -ing but not -ed to verb stems; older children were productive with both inflections. These studies demonstrate that the present progressive inflection is used productively before the regular past tense marker and suggest that productivity with word order may be independent of developments in verb morphology. The findings are discussed in terms of M. Tomasello's (1992a) Verb Island hypothesis and M. Rispoli's (1991) notion of the mosaic acquisition of grammatical relations.

Child, Preschool↗

Intracranial meningiomas: factors that influence the development of cerebral edema after stereotactic radiosurgery and radiation therapy.

PURPOSE: To evaluate causative factors of cerebral edema after stereotactic radiosurgery or stereotactic radiation therapy in intracranial meningiomas. MATERIALS AND METHODS: Of 43 adult patients with intracranial meningiomas, three received 13.5-18-Gy single-fraction stereotactic radiosurgery; one received 19.8 Gy in three fractions, one received 42 Gy in six fractions, and 31 received 32-36 Gy in six to eight fractions of stereotactic radiation therapy; and seven received 45-54-Gy external-beam radiation with 20-28 Gy in five to seven fractions as concomitant stereotactic boosts. Brain edema was estimated by calculating the edema index. RESULTS: After irradiation, all 11 patients with parasagittal and four patients with nonparasagittal tumors developed worsening cerebral edema that necessitated the administration of steroids (P < .001). The statistically significant factors for the development of edema were parasagittal location, presence of pretreatment edema, sagittal sinus occlusion, and the use of more than 6 Gy per fraction. Five patients with parasagittal tumors developed life-threatening panhemispheric edema, which was fatal in one. The causative factors of panhemispheric edema were a large tumor, single-fraction stereotactic radiosurgery, or use of more than 6 Gy per fraction. CONCLUSION: A smaller dose per fraction and aggressive use of steroids may help prevent life-threatening complications due to worsening edema.

Brain Edema↗

Comparative bioavailability of sulfamethoxazole in three formulations of cotrimoxazole suspensions.

The pharmacokinetic parameters and relative bioavailability of sulfamethoxazole were estimated using three commercially available cotrimoxazole suspensions on six human volunteers. Maximum concentration in plasma was shown by product 1, i.e., 89.69+/-0.84 and were lower in products 2 and 3, i.e., 38.33+/-0.58 and 16.50+/-0.89, respectively. The time for maximum concentration was 4 hours in products 1 and 3 while it was 3.50 in product 2. There was prolonged elimination half-life of formulation 2 (7.50+/-0.94) than formulation 3 (7.43+/-0.54) while product 1 (4.54+/-0.15) showed lowest half-life. The values of absorption half-lives for formulations 1, 2 and 3 were 1.92+/-0.05. 1.80+/-0.41 and 2.78+/-0.25, respectively. The volume of distribution was highest in formulation 1 (0.9+/-0.00) lower in formulation 3 (0.40+/-0.03) and was lowest in formulation 2 (0.21+/-0.03). The values for total body clearance was lowest i.e., 0.24+/-0.00 in formulation 1, higher in formulation 2 i.e., 0.35+/-0.05 and still higher in formulation 3, i.e., 0.62+/-0.02. By taking the formulation 1, as standard (100%), the relative bioavailabilities of formulation 2 and 3 were 79.05 and 38.53%, respectively.

Journal Article↗

Purification and characterization of two isoenzymes of DL-glycerol-3-phosphatase from Saccharomyces cerevisiae. Identification of the corresponding GPP1 and GPP2 genes and evidence for osmotic regulation of Gpp2p expression by the osmosensing mitogen-activated protein kinase signal transduction pathway.

The existence of specific dl-glycerol-3-phosphatase (EC 3.1.3.21) activity in extracts of Saccharomyces cerevisiae was confirmed by examining strains lacking nonspecific acid and alkaline phosphatase activities. During purification of the glycerol-3-phosphatase, two isozymes having very similar molecular weights were isolated by gel filtration and anion exchange chromatography. By microsequencing of trypsin-generated peptides the corresponding genes were identified as previously sequenced open reading frames of unknown function. The two genes, GPP1 (YIL053W) and GPP2 (YER062C) encode proteins that show 95% amino acid identity and have molecular masses of 30.4 and 27.8 kDa, respectively. The intracellular concentration of Gpp2p increases in cells subjected to osmotic stress, while the production of Gpp1p is unaffected by changes of external osmolarity. Both isoforms have a high specificity for dl-glycerol-3-phosphate, pH optima at 6.5, and KmG3P in the range of 3-4 mM. The osmotic induction of Gpp2p is blocked in cells that are defective in the HOG-mitogen-activated protein kinase pathway, indicating that GPP2 is a target gene for this osmosensing signal transduction pathway. Together with DOG1 and DOG2, encoding two highly homologous enzymes that dephosphorylate 2-deoxyglucose-6-phosphate, GPP1 and GPP2 constitute a new family of genes for low molecular weight phosphatases.

Amino Acid Sequence↗

PCR diagnosis of viral pneumonitis from fixed-lung tissue in children.

Viral infection in children commonly causes acute lung disease leading to respiratory decompensation requiring intensive supportive therapy. Definitive diagnosis of the causative virus may be difficult, relying on serologic data since viral cultures are frequently negative; lung biopsy may be necessary to increase the diagnostic yield. The objective of this study was to develop a rapid and sensitive diagnostic method using the polymerase chain reaction (PCR). Analyzing Formalin-fixed lung tissue from autopsies of 32 patients with pneumonitis in whom cultures, serology, and histopathology results were blinded to the investigators, and 10 negative control samples, PCR was performed for cytomegalovirus, adenovirus, enteroviruses, herpes simplex virus, and Epstein-Barr virus. Among the 32 affected specimens, 7 were culture-positive for a specific virus in the lung; 6/7 of these were PCR-positive for the identical virus. In the culture-positive specimen not PCR amplified, influenza B was the cultured agent, but this virus was not evaluated by PCR. In the remaining 25 samples which were culture-negative, 11 were PCR-positive. All 10 negative controls were negative by PCR. Three specimens with CMV inclusions but culture-negative were also negative by PCR. We conclude that PCR is sensitive and accurate in the evaluation of lung tissue for viral pneumonitis.

Adolescent↗

Eighteen-month-old children learn words in non-ostensive contexts.

Previous studies have demonstrated that children aged 2;0 can learn new words in a variety of non-ostensive contexts. The current two studies were aimed at seeing if this was also true of children just beginning to learn words at 1;6. In the first study an adult interacted with 48 children. She used a nonce word to announce her intention to find an object ('Let's find the gazzer'), picked up and rejected an object with obvious disappointment, and then gleefully found the target object (using no language). Children learned the new word as well in this condition as in a condition in which the adult found the object immediately. In the second study the adult first played several rounds of a finding game with each of 60 children, in which it was first established that one of several novel objects was always in a very distinctive hiding place (a toy barn). The adult then used a nonce word to announce her intention to find an object ('Let's find the toma') and then proceeded to the barn. In the key condition the barn was mysteriously 'locked'; the child thus never saw the target object after the nonce word was introduced. Children learned the new word as well in this condition as in a condition in which the adult found the object immediately. The results of these two studies suggest that from very early in language acquisition children learn words not through passive, associative processes, but rather through active attempts to understand adult behaviour in a variety of action and discourse contexts.

Adult↗

Down's syndrome screening using free beta hCG: instability can significantly increase the Down's risk estimate.

The stability of free beta hCG (human chorionic gonadotrophin) was assessed using a dual alpha-fetoprotein and free beta hCG assay. A significant increase in free beta hCG concentration was observed in heparinized samples left unseparated for 24 h or more, the mean increase in 21 samples being 10.2% after 24 h (P = < 0.001), increasing to 45.7% after 96 h. Similar results were also obtained in clotted samples. The effect of the increase in free beta hCG on the Down's risk estimate was calculated to assess the impact of delayed sample transport and separation. The Down's risk increased in all samples with increasing separation time, but this was most significant in two samples where, using a cut off of one in 250, the risk classification changed from low risk to high risk. These results suggest that delayed sample separation can have a significant effect on screening programmes using free beta hCG, particularly with respect to those patients whose risk classification is changed.

Blood Specimen Collection↗

CT and MR evaluation of a wooden foreign body in an in vitro model of the orbit.

We made an in vitro model of a wooden foreign body using both fresh and dry pine wood in both fat and soft-tissue background mediums. Air/wood/background medium interfaces were studied with MR and CT to determine which method provided the best image contrast for detecting a wooden foreign body. CT was demonstrated to be superior to MR in the evaluation of the orbit in the in vitro model.

Animals↗

Nutritional evaluation of desi and kabuli chickpeas and their products commonly consumed in Pakistan.

Physicochemical and nutritional quality of five improved cultivars of desi and kabuli chickpeas and their products were studied. The kabuli chickpea had larger seed (26 g/100 seeds) than desi type (21 g/100 seeds). The hydration capacity per seed of desi (0.16 g) was lower than kabuli type (0.26 g). A positive correlation (r = 0.87) between seed weight and hydration capacity was observed. The mean cooking time of dry desi vs kabuli seed (124.5 vs 113.8 min) was reduced to 37.5 vs 32.8 min and to 28.8 vs 22.5 min when soaked overnight in water and in 0.5% solution of sodium bicarbonate respectively. The mean value of protein (25.4 vs 24.4%), fat (3.7 vs 5.1%), carbohydrate (47.4 vs 55%), crude fibre (11.2 vs 3.9%), ash (3.2 vs 2.8%) and caloric value (327 vs 365 kcal/100 g) were for desi vs kabuli chickpeas respectively. There was no difference in the essential amino acid contents and in chemical scores of desi (65) and kabuli (67) chickpeas. The order of limiting amino acid was methionine+cystine, threonine and valine in both types. The chickpeas products contained 8.9-21.1% protein (N x 6.25), 3.1-21.8% fat, 53.4-75.9% carbohydrate, 1.6-11.1% crude fibre, 1.2-5.9% ash, 226-360mg Ca, 126-315 mg P, 3.8-8.2 mg Fe, 1.8-5.4 mg Zn, 1.5-5.4 mg Mn, 0.6-1.1 mg Cu and 370-490 kcal per 100 g. All chickpea products provided 7-23%, 7-40% and 52-78% of the total calories from protein, fat and carbohydrates respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Extradural causes of myelopathy.

Myelopathy, the rapid or insidious onset of motor and sensory abnormalities referable to the spinal cord, occurs as a result of a variety of causes that may be classified on the basis of their location of origin (intramedullary, intradural-extramedullary, and extradural). The first goal of imaging is to appropriately assign the observed abnormality to its location of origin and, therefore, into the correct diagnostic list. This article focuses on the plain film, computed tomography, and magnetic resonance demonstration of extradural causes of myelopathy.

Bacterial Infections↗

Interaction of 1,9-dimethylmethylene blue with glycosaminoglycans.

The specific binding of 1,9-dimethylmethylene blue (DMB) with glycosaminoglycans (GAGs) was studied including molecular analysis of the GAG species using mass spectrometry. The dye solution was unstable under any storage conditions. Inorganic analysis showed that the purity of the dye was variable from different sources. False negative results could be obtained when using impure dye. Binding of the dye with GAG resulted in the formation of a complex with an absorption maximum at 525 nm. The absorbance of the complex was linearly correlated with GAG concentration up to 150 mg/L. The specific molar extinction coefficients of individual GAG molecules were calculated in relation to the molar absorbance of the GAG-dye complex and the carbon and nitrogen contents of the GAGs. The results indicated that binding of dye occurred at both the ionized sulphate and carboxyl groups on the GAG molecules. Improvements of the DMB-binding method for the measurement of GAGs are suggested.

Drug Storage↗