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Biomedical subjects

A Khan

Publications and source records attributed to A Khan.

At least 217 records · Page 12Linked to original sources
PubMed2000

The role of cell cycle regulatory protein, cyclin D1, in the progression of thyroid cancer.

Cell cycle progression is facilitated by cyclin-dependent kinases that are activated by cyclins including cyclin D1 and inactivated by cyclin-dependent kinase inhibitors (CDKIs) such as p27. Our previous studies have demonstrated decreased p27 expression in both papillary and more aggressive carcinomas of the thyroid compared to thyroid adenoma and almost similar level of cyclin D1 expression between thyroid adenoma and papillary carcinoma. These results indicate that CDKIs may have an important role in the carcinogenesis of the thyroid and that they probably have a limited role in malignant progression of the thyroid cancer. The role of cyclin D1 in malignant progression of thyroid carcinoma has yet to be established. We studied the expression of cyclin D1 by immunohistochemistry in 34 cases of conventional papillary carcinoma (CPC), 10 cases of minimally invasive follicular carcinoma (MIFC), and 32 cases of more aggressive thyroid carcinoma (ATC), which included 11 tall cell variants, one columnar cell variant of papillary carcinoma, seven insular carcinomas, and 13 anaplastic carcinomas. Cyclin D1 staining was classified by staining score as 0, negative; 1+, less than 25%; 2+, 25 to 50%; and 3+, more than 50% tumor cells staining positive. Kruskal-Wallis one-way ANOVA and Wilcoxon Rank Sum/Mann-Whitney U Test was used to assess the difference in the expression of cyclin D1 between the study groups. Twenty-eight out of the 34 CPCs were cyclin D1 positive, 24 (70%) were 1+, 3 (9%) were 2+, and one (3%) were 3+ positive. Seven of 10 MIFCs were cyclin D1 positive, five (71%) were 1+, and the remaining two (29%) were 2+ positive. On the other hand, 28 of 32 ATCs showed cyclin D1 immunostaining. Of these, three (9%) were 1+, five (13%) were 2+, and 20 (63%) were 3+ positive. This study demonstrates a significant overexpression of cyclin D1 in ATC compared CPC (P < .001) and MIFC (P < .005), suggesting that the cyclin D1 expression may play a role in tumor progression and may have prognostic significance in thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed2000

The C5a receptor is expressed by human renal proximal tubular epithelial cells.

The C5a receptor is expressed by a variety of cell types. These studies demonstrate by immunohistochemistry that the receptor is present on the surface of proximal and distal tubular epithelial cells from normal kidney. In addition, the receptor was detected on transitional epithelial cells of the ureter and bladder. Primary proximal tubular cultures and a proximal tubular cell line both also expressed the C5a receptor, as demonstrated by immunofluorescence and by FACS analysis. The presence of mRNA encoding the receptor was confirmed by reverse transcriptase-polymerase chain reaction analysis. As opposed to its effect on glomerular mesangial cells, the receptor did not mediate a proliferative response by the proximal tubular cells. C5a also did not enhance the synthesis/secretion of transforming growth factor-beta 1, monocyte chemoattractant protein-1, platelet-derived growth factor-AB or tumour necrosis factor-alpha by cultured proximal tubular cells. Therefore, although the C5a receptor clearly is expressed by proximal tubular cells, clarification of its functional relevance on this cell type awaits further studies.

Antigens, CD↗
PubMed2000

The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing.

Research studies clearly indicate that age-related changes in cellular and tissue function are linked to decreases in the anabolic hormones, growth hormone and insulin-like growth factor (IGF)-1. Although there has been extensive research on the effects of these hormones on bone and muscle mass, their effect on cerebrovascular and brain ageing has received little attention. We have also observed that in response to moderate calorie restriction (a treatment that increases mean and maximal lifespan by 30-40%), age-related decreases in growth hormone secretion are ameliorated (despite a decline in plasma levels of IGF-1) suggesting that some of the effects of calorie restriction are mediated by modifying the regulation of the growth hormone/IGF-1 axis. Recently, we have observed that microvascular density on the surface of the brain decreases with age and that these vascular changes are ameliorated by moderate calorie restriction. Analysis of cerebral blood flow paralleled the changes in vasculature in both groups. Administration of growth hormone for 28 d was also found to increase microvascular density in aged animals and further analysis indicated that the cerebral vasculature is an important paracrine source of IGF-1 for the brain. In subsequent studies, administration of GHRH (to increase endogenous release of growth hormone) or direct administration of IGF-I was shown to reverse the age-related decline in spatial working and reference memory. Similarly, antagonism of IGF-1 action in the brains of young animals impaired both learning and reference memory. Investigation of the mechanisms of action of IGF-1 suggested that this hormone regulates age-related alterations in NMDA receptor subtypes (e.g. NMDAR2A and R2B). The beneficial role of growth hormone and IGF-1 in ameliorating vascular and brain ageing are counterbalanced by their well-recognised roles in age-related pathogenesis. Although research in this area is still evolving, our results suggest that decreases in growth hormone and IGF-1 with age have both beneficial and deleterious effects. Furthermore, part of the actions of moderate calorie restriction on tissue function and lifespan may be mediated through alterations in the growth hormone/IGF-1 axis.

Aging↗
PubMed2000

Functional magnetic resonance imaging (fMRI) clinical studies in ALS--paradigms, problems and promises.

Functional magnetic resonance imaging (fMRI) provides high-resolution, non-invasive estimates of neural activity detected by a blood oxygen level dependent signal by assessing the increase in blood flow to the local vasculature that accompanies neural activity in the brain. fMRI studies with standard hand motor test (index-thumb opposition, ITO, or pinch) in ALS patients show good test-retest reliability and similar amplitude of signals in ALS patients compared with control subjects. Isometric force can be performed with careful control for the force exerted, recruitment of other muscles and motion artefact. The volume (number of voxels above threshold) of sensorimotor and cerebellar cortex activated by ITO is reproducibly larger in ALS patients compared with control subjects. Imagined movements in ALS have been studied, as in amputees, and larger volumes are activated in ALS patients with imagined movements as well, compared with control subjects. fMRI studies in ALS patients evaluating cortical activation during pure somatosensory stimulation cutaneous stimulation of the hand to elicit the palmomental response and cutaneous stimulation of the sole to elicit the plantar response - indicate that ALS patients activate a significantly smaller volume of the contralateral sensorimotor cortex compared to control subjects. No statistically significant difference was seen in other areas, including the ipsilateral cerebellum and the contralateral thalamus. An anterior shift in the volume of cortex activated by these paradigms occurs in ALS patients, with a volume of activation, anteriorly, not activated in control subjects. fMRI studies will complement other clinical neurophysiological and neuroimaging techniques in our future attempts to solve the riddle of ALS and other motor neuron diseases.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Site-specific administration of antisense oligonucleotides using biodegradable polymer microspheres provides sustained delivery and improved subcellular biodistribution in the neostriatum of the rat brain.

Antisense oligonucleotides (ODNs) are being increasingly used in the central nervous system as biological tools, as drug-target validation agents and as potential therapeutic agents. Although the local delivery of naked ODNs to the brain can result in the desired biological effects, the duration of efficacy is relatively short lived due to the combined effects of rapid ODN degradation and elimination half-lives in vivo. In this study, we have examined the use of biodegradable polymer microspheres as a site-specific delivery system for targeting ODNs to the neostriatum of the rat brain. Model phosphorothioate backbone-modified ODNs were entrapped within poly(D,L-lactide-co-glycolide) (PLAGA) microspheres using a double emulsion-deposition method and the formulations characterised in terms of particle size, surface morphology, percent encapsulation efficiency, ODN loading and in vitro release profiles. For in vivo evaluation, PLAGA microspheres containing fluorescently-labelled ODNs were stereo-taxically administered to the neostriatum of the rat brain and biodistribution of ODNs monitored after 48 h. Administration of free fluorescently-labelled ODNs to the neostriatum resulted in a punctate cellular distribution of ODNs after 24 h with little or no ODN remaining in the neostriatum after 48 h. In comparison, fluorescently-labelled ODNs delivered using polymer microspheres were intensely visible in cells after 48 h post-administration and the fluorescence appeared to be diffuse covering both cytosolic and nuclear regions. Dual-label immunohistochemical analyses suggested that ODNs were mainly distributed to neuronal cells. These data indicate that site-specific administration of ODNs using biodegradable polymer microspheres will not only provide sustained delivery of nucleic acids but can also improve the cellular distribution of ODNs to brain cells. Sustained or controlled-release biodegradable polymer formulations, therefore, represent an attractive strategy for improved local delivery of ODNs to the CNS.

Animals↗
PubMed2000

Factors influencing function of temporary dialysis catheters.

AIM: To determine risk factors for failure of temporary dialysis catheters, we prospectively studied the outcome of 178 non-tunneled dual lumen catheters placed in 126 consecutive patients requiring treatment of acute renal failure (ARF) or end-stage renal disease (ESRD). METHODS: Internal jugular (IJ) or subclavian (SC) catheters were used in 122 instances and femoral catheters were employed in 56. RESULTS: IJ or SC catheters with tips in the right atrium or superior vena cava (n = 112) failed (defined as a blood flow < 250 ml/min) 17% of the time, compared with a 40% failure rate for catheters with more peripherally located tips (n = 10), p < 0.05, chi2 testing. In a multivariate analysis, use in ESRD and location peripheral to the SVC were risk factors for catheter failure. Use of one of three catheter brands was associated with a lower failure rate. Although mean venous pressures at 200 ml/min blood flow were higher in IJ or SC catheters that failed, the presence of a high venous pressure, number of catheter uses, IJ vs. SC placement, inpatient vs. outpatient status, and fresh venipuncture vs. placement over a guidewire passed through a previous catheter did not predict catheter malfunction. With femoral catheters, the only risk factor for failure was use in ESRD. CONCLUSION: Of the factors that can be influenced by placement technique, catheter tip location is most important. Whether one catheter brand is superior awaits further confirmation.

Catheterization↗
PubMed2000

Mouse mammary tumor virus-like ENV gene sequences in human breast tumors and in a lymphoma of a breast cancer patient.

DNA sequences with very high similarity (95-98%) to the mouse mammary tumor virus (MMTV) ENV gene have been amplified by PCR in 38.5% of human breast tumors and in <2% of normal breast tissue (Wang et al., Cancer Res., 55: 5173-5179, 1995). Intrigued by these findings, which suggested an exogenous viral etiology for a certain percentage of human breast tumors, we have screened a panel of human breast tumors and normal breast tissue for the presence of MMTV-like DNA sequences. Using similar PCR procedures and stringent hybridization techniques, we have detected the presence of MMTV-like ENV gene sequences in 37% of the human breast tumors that we have analyzed. DNA sequencing has shown these sequences to be 99% homologous to the BR6 strain of MMTV and 100% homologous to the GR and C3H strains of MMTV. We have not detected these MMTV-like sequences in normal breast tissue. However, we have detected these sequences by PCR and stringent hybridization in a T-cell lymphoma of a breast cancer patient who was simultaneously diagnosed with both diseases. Our results support the possibility of an exogenous retroviral etiology for a certain percentage of human breast tumors. Our results also suggest that a similar exogenous retroviral etiology may exist for certain human T-cell lymphomas. In many inbred strains of mice, both breast cancer and T-cell lymphoma are caused by MMTV, hence, in a certain percentage of humans, one or both of these diseases may be caused by an MMTV-like retroviral entity.

Adult↗
PubMed2000

Out-of-pocket expenses borne by the users of obstetric services at government hospitals in Karachi, Pakistan.

OBJECTIVE: Financing health services is a challenge for health policy makers world over, especially in developing countries. Alternate mechanisms such as user fees are being proposed. However, there is a feeling that in developing countries, users of government hospitals spend appreciable personal income to obtain "free services" at these facilities. METHODS: This study aimed to measure the extent and the factors associated with of out-of-pocket expenses borne by the users of obstetric care at government hospitals. It also aimed to determine willingness of consumers to bear out of pocket expenses. It was conducted in three government hospitals in Karachi. RESULTS: Seven hundred cases were registered in the study. Sixty-five percent of them had a monthly household income of less than Rupees (Rs.) 3000. Overall, users spent mean of Rs. 590 as out-of-pocket expenses for obstetric services. Of this Rs. 330 was spent on drugs and Rs. 24 on user fees. Thirty-nine percent of the patients were willing to spend out of pocket for services provided at government hospital and 39% declined to do so. Of the patients indicating willingness to spend, 98% agreed to do so for drugs. CONCLUSION: The results suggest that considerable expenses are borne out of pocket by the users of government hospitals for supposedly "free services". If user fees are to be increased the government needs to provide services for which the people will pay, such as drugs, otherwise increase in this fees will simply add to financial burden on the users.

Adult↗
PubMed1999

Phase Behavior and Phase Structure of Protein-Surfactant-Water Systems.

Phase behavior of oppositely charged ovalbumin-DOTAC and BSA-DOTAC, and similarly charged ovalbumin-SDS, BSA-SDS, lysozyme-DOTAC, and BLG-SDS systems within the concentration range of 20 wt% of both protein and surfactant are examined in water. Aqueous solutions of ovalbumin yield, in succession, precipitation, gel, and solution with increased addition of the surfactant dodecyltrimethylammonium chloride (DOTAC). The stability range of each region is determined. Both isotropic and anisotropic gels are detected. Solutions of bovine serum albumin (BSA) form only a solution phase with oppositely charged DOTAC. One solution phase is also obtained with all similarly charged protein-surfactant systems except the BLG-SDS-water system, which produces a gel phase in addition to a large solution phase. (2)H NMR longitudinal (R(1)) and transverse (R(2)) relaxation rates are determined in solution and gel by following the behavior of selectively deuterated surfactant at the alpha-methylene group next to the surfactant head group for the oppositely charged systems ovalbumin-DOTAC and BSA-DOTAC. Large R(2)-values proved the existence of large protein-surfactant aggregates in both systems. Copyright 1999 Academic Press.

Journal Article↗