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Biomedical subjects

A Mahmood

Publications and source records attributed to A Mahmood.

At least 19 recordsLinked to original sources
PubMed2001

[99mTc]oxotechnetium(V) complexes amine-amide-dithiol chelates with dialkylaminoalkyl substituents as potential diagnostic probes for malignant melanoma.

[99mTc]oxotechnetium(V) complexes of amine-amide-dithiol (AADT) chelates containing tertiary amine substituents were synthesized and shown to have affinity for melanoma. For complexation the AADT-CH2[CH2]nNR2 (n = 1, 2; R = Et, n-Bu) ligand was mixed with a [99mTc]oxotechnetium(V)-glucoheptonate precursor to make the AADT-[99mTc]oxotechnetium(V) complexes in nearly quantitative yield. Structurally analogous nonradioactive oxorhenium(V) complexes were also synthesized and characterized. In vitro sigma-receptor affinity measurements indicate these complexes to possess sigma-affinity in the low micromolar range with K(i) values in the 7.8-26.1 and 0.18-2.3 microM range for the sigma1- and sigma2-receptors, respectively. In vitro cell uptake of the 99mTc complexes in intact B16 murine melanoma cells at 37 degrees C after a 60-min incubation ranged from 12% for complex 2 (n = 1, R = n-Bu) to 68% for complex 4 (n = 2, R = n-Bu). In vivo evaluation of complexes 1-Tc-4-Tc in the C57Bl/B16 mouse melanoma model demonstrated significant tumor localization. Complex 1-Tc (n = 1, R = Et) displayed an in vivo tumor uptake of 7.6% ID/g at 1 h after administration with initial melanoma/blood (M/B), melanoma/spleen (M/S), and melanoma/lung (M/L) ratios >4; these ratios increased to 10.8, 10.1, and 7.3, respectively, at 6 h. While complex 3-Tc (n = 3, R = Et) had an initial tumor uptake of 3.7% ID/g 1 h after administration with M/B, M/S, and M/L ratios >2, a greater tumor retention and slightly faster clearance from nontumor-containing organs resulted in M/B, M/S, and M/L ratios of 19.1, 19.1, and 12.7, respectively, at 6 h. The high tumor uptake and significant tumor/nontumor ratios indicate that such small technetium-99m-based molecular probes can be developed as in vivo diagnostic agents for melanoma and its metastases.

Animals↗
PubMed2001

Regulation of surfactant-like particle secretion by Caco-2 cells.

Surfactant-like particle (SLP) is a phosphatidylcholine (PC)-rich membrane produced in the small intestine, and its secretion is increased by fat feeding. In Caco-2 cells known to produce SLP, preincubation with [(3)H]palmitate labelled the SLP and was used as a marker for newly secreted membrane. SLP-associated PC and protein (d=1.07-1.08 g/ml in a linear non-equilibrium NaBr gradient) were secreted in parallel with triacylglycerols (TG) and at a rate about twice the control rate in response to feeding cells with an oleate/egg PC mixture. Cholesterol and apolipoprotein A-I identified only a small peak corresponding to high-density lipoprotein (HDL), but the largest peak corresponded with SLP (d=1.07-1.08). Palmitate incorporation into PC showed a similar small peak migrating at the density of HDL, but most labelled PC secreted from the cells was due to SLP. PC secretion, alkaline phosphatase activity, and newly synthesized immunoprecipitated SLP proteins from conditioned serum-free media migrated together at a density of >/=1.21 g/ml in a lipoprotein NaBr step gradient, and represented SLP. Glycerol incorporated into TG migrated at a peak density of 1.12 g/ml, consistent with HDL secretion from cells incubated in serum-free media. These data confirm that the secreted PC in SLP is distinct from lipoprotein particles. Incorporation of [(3)H]palmitate into the PC fraction of either whole cell homogenate or isolated brush border membranes was not affected by oleate/egg PC feeding. Both Pluronic L-81, an inhibitor of chylomicron secretion, and BMS-197636-02, a microsomal triglyceride transfer protein inhibitor, blocked the secretion of both TG and PC. Elevation of intracellular cAMP levels that stimulate surfactant secretion from type II pneumocytes caused a 50% reduction in SLP and TG secretion from Caco-2 cells. These results confirm the SLP response to fat feeding found in vivo, further supporting a role for SLP in TG secretion from the enterocyte, and show that the regulation of SLP secretion differs from that of pulmonary surfactant.

Biological Factors↗
PubMed2001

Adult bone marrow stromal cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome.

To measure effect of bone marrow stromal cells (MSCs) administered i.v. on rats subjected to traumatic brain injury (TBI), we injected MSCs labeled by BrdU into the tail vein 24 h after TBI and sacrificed rats 15 days later. The neurological severity score (NSS) and the Rotarod test were used to evaluate neurological function. The distribution of the donor cells in brain, heart, lung, kidney, liver and spleen were analyzed in recipient rats using immunohistochemical staining. MSCs injected i.v. significantly reduced motor and neurological deficits compared with control groups by day 15 after TBI. The cells preferentially entered and migrated into the parenchyma of the injured brain and expressed the neuronal marker NeuN and the astrocytic marker GFAP. MSCs were also found in other organs and primarily localized to the vascular structures, without any obvious adverse effects. Our data suggest that i.v. administration of MSCs may be useful in the treatment of TBI.

Age Factors↗
PubMed2001

TmDOTA-: a sensitive probe for MR thermometry in vivo.

The lanthanide complex, thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (TmDOTA-), has been investigated as an agent for MR thermometry in vivo. The chemical shifts of the TmDOTA- protons were highly sensitive to temperature at a clinically relevant field strength, yet insensitive to pH and the presence of Ca2+. Given the excellent stability of lanthanide-DOTA complexes and high thermal sensitivity, TmDOTA- is expected to be a good candidate for MR thermometry in vivo.

Animals↗
PubMed2001

Activity of brush border membrane enzymes in proximal jejunum of portal hypertensive rats.

PURPOSE: Malabsorption accompanies portal hypertension, especially when associated with chronic liver disease. The development of portal hypertension is accompanied by significant alterations in the splanchnic microcirculation. In this study, the effect of extrahepatic and intrahepatic portal hypertension on brush border membrane enzymes was estimated. METHODS: Portal hypertension was induced in rats by partial portal vein ligation (PPVL) (n = 6) and common bile duct ligation (CBDL) (n = 6), and the activity of sucrase, lactase, alkaline phosphatase, and leucine aminopeptidase (LAP) in the intestinal homogenate was measured. RESULTS: Intrasplenic pulp pressure (ISPP) (in cm of saline) was found to be elevated in PPVL (21.3 +/- 1.47) and CBDL animals (21.5 +/- 1.79) as compared with findings in their respective sham-operated controls (12.74 +/- 0.86, 11.83 +/- 1.04). Only sucrase and LAP activity was significantly elevated (P < 0.05) in the PPVL group. No changes were observed in the CBDL group. CONCLUSION: Only sucrase and LAP activities were increased in PPVL rats.

Animals↗
PubMed2001

The Cardiff Depression Study: a sib-pair study of dysfunctional attitudes in depressed probands and healthy control subjects.

BACKGROUND: Current cognitive theories propose that depression develops as a result of the interaction between dysfunctional cognitive schemata and environmental stressors. There is also consistent evidence of a substantial genetic contribution to depression. This study examines the familiality and stability of dysfunctional attitudes and attempts to distinguish whether they reflect trait vulnerability to depression or the state of being depressed. METHOD: The 24-item Dysfunctional Attitude Scale (DAS-24) was completed by 108 depressed probands and their nearest-aged siblings and 105 healthy control probands and their nearest-age siblings, at the time of a semi-structured clinical interview and 10-12 months later. Subjects also completed self-report measures of depressed mood on both occasions. RESULTS: Measures of clinical depression were significantly correlated with DAS scores. At retest, DAS scores remained elevated despite improvement in mood, giving support for earlier findings, that dysfunctional attitudes remain active following recovery. The dependency subscale (DAS-D) of the DAS showed modest familiality, although there were no significant differences for DAS-D scores between the two groups of siblings. In a multiple regression analysis, current mood-state was the overwhelming predictor of DAS scores. However for DAS-D, gender as well as current mood influenced scores on this subscale. CONCLUSION: Although there was modest evidence for temporal stability and familiality for some DAS-24 subscale scores, dysfunctional attitudes were predominantly influenced by current low mood, and therefore reflect the state of being depressed rather than a familial vulnerability trait underpinning depression.

Adolescent↗
PubMed2001

The Cardiff sib-pair study: suicidal ideation in depressed and healthy subjects and their siblings.

Depression is associated with high rates of suicidal ideation, which varies in intensity from transient thoughts of wishing to be dead to the making of plans and, Finally, to attempts to kill oneself. There is limited evidence from family, twin, and adoption studies that completed suicide is familial and has a genetic etiological component. However, it is unclear whether suicidal ideation is also familial. The familiality of suicidal ideation has been examined in the subjects who participated in the Cardiff Depression Study, namely, 108 depressed probands. their nearest-aged siblings, and 105 healthy control subjects and their siblings. The study showed that 66% of depressed subjects had experienced suicidal ideation in the week prior to the interview, and that this was significantly associated with recurrent illness. Suicidal ideation was not shown to be familial. However, somewhat surprisingly, 6% of healthy, never-depressed subjects admitted to having had transient suicidal thoughts. Suicidal ideation was significantly associated with high neuroticism and psychoticism scores and severe threatening life events.

Adult↗
PubMed2001

In vivo near-infrared fluorescence imaging of osteoblastic activity.

In vertebrates, the development and integrity of the skeleton requires hydroxyapatite (HA) deposition by osteoblasts. HA deposition is also a marker of, or a participant in, processes as diverse as cancer and atherosclerosis. At present, sites of osteoblastic activity can only be imaged in vivo using gamma-emitting radioisotopes. The scan times required are long, and the resultant radioscintigraphic images suffer from relatively low resolution. We have synthesized a near-infrared (NIR) fluorescent bisphosphonate derivative that exhibits rapid and specific binding to HA in vitro and in vivo. We demonstrate NIR light-based detection of osteoblastic activity in the living animal, and discuss how this technology can be used to study skeletal development, osteoblastic metastasis, coronary atherosclerosis, and other human diseases.

Animals↗
PubMed2001

Intraarterial administration of marrow stromal cells in a rat model of traumatic brain injury.

To test the efficacy of various delivery routes of stem cells to treat cerebral injury, we investigated the parenchymal distribution of marrow stromal cells (MSCs) injected into the internal carotid artery (ICA) of the adult rat after traumatic brain injury (TBI). Bromodeoxyuridine (BrdU)-labeled MSCs were injected via the ipsilateral ICA at 24 h after TBI. Using histology and immunohistochemistry, the distribution of implanted MSCs was analyzed at 7 days after transplantation. Four groups (n = 4/group) were studied: group 1, animals transplanted with MSCs cultured with NGF and BDNF at 24 h after TBI; group 2, animals transplanted with MSCs cultured without NGF and BDNF; group 3, animals injected with a placebo, phosphate buffered saline into the ICA at 24 h after TBI; and group 4, rats subjected to TBI only. In groups 1 and 2, BrdU-positive cells were localized to the boundary zone of the lesion, corpus callosum and cortex of the ipsilateral hemisphere. The number of BrdU-positive cells was significantly higher in the ipsilateral hemisphere than in the contralateral hemisphere. More MSCs infused intraarterially engrafted in group 1 (18.9%) than in group 2 (14.4%, p < 0.05). Using double staining, BrdU-positive cells expressed MAP-2, NeuN, and GFAP in both groups 1 and 2, with this expression being greater in group 1 and the difference between two groups reaching statistical significance in case of MAP-2. Our data suggest that intraarterial transplantation of MSCs is a viable route for the intracerebral administration of MSCs for the treatment of TBI, since MSCs infused intraarterially after TBI survive and migrate into the brain. Some implanted MSCs express proteins specific to neurons and astrocytes. The addition of NGF and BDNF promote migration of MSCs into the brain and subsequent expression of neuronal protein MAP-2.

Animals↗
PubMed2001

Sensation-seeking, life events and depression. The Cardiff Depression Study.

BACKGROUND: The relationship between adversity and genetic risk factors in depression could be mediated by familial 'hazard prone' traits, as reflected in high levels of sensation-seeking. AIMS: To examine whether high sensation-seeking scores are associated with more adverse life events resulting in depression. METHOD: In a sib-pair design, 108 probands with depression and their siblings and 105 healthy control subjects and their siblings were compared for psychopathology, life events and scores on the Sensation-Seeking Questionnaire (SSQ). RESULTS: The SSQ scores were correlated negatively with depression, were familial and were correlated positively with less severe events, but not the severe events typically associated with depressive onsets. CONCLUSIONS: The SSQ measures a familial personality trait and depression is associated with lower scores. Although high sensation-seeking is associated with a higher rate of life events, these carry little threat.

Adolescent↗
PubMed2001

Intracranial bone marrow transplantation after traumatic brain injury improving functional outcome in adult rats.

OBJECT: The authors tested the hypothesis that intracranial bone marrow (BM) transplantation after traumatic brain injury (TBI) in rats provides therapeutic benefit. METHODS: Sixty-six adult Wistar rats, weighing 275 to 350 g each, were used for the experiment. Bone marrow prelabeled with bromodeoxyuridine (BrdU) was harvested from tibias and femurs of healthy adult rats. Other animals were subjected to controlled cortical impact, and BM was injected adjacent to the contusion 24 hours after the impact. The animals were killed at 4, 7, 14, or 28 days after transplantation. Motor function was evaluated both before and after the injury by using the rotarod test. After the animals had been killed, brain sections were examined using hemotoxylin and eosin and immunohistochemical staining methods. Histological examination revealed that, after transplantation, BM cells survived, proliferated, and migrated toward the injury site. Some of the BrdU-labeled BM cells were reactive, with astrocytic (glial fibrillary acid protein) and neuronal (NeuN and microtubule-associated protein) markers. Transplanted BM expressed proteins phenotypical of intrinsic brain cells, that is, neurons and astrocytes. A statistically significant improvement in motor function in rats that underwent BM transplantation, compared with control rats, was detected at 14 and 28 days posttransplantation. CONCLUSIONS: On the basis of their findings, the authors assert that BM transplantation improves neurological outcome and that BM cells survive and express nerve cell proteins after TBI.

Animals↗
PubMed2001

Ossification of autologous pericranium used in duraplasty. Case report.

Pericranium is frequently used in duraplasty and is considered superior to the many other alternatives because of its easy availability and because it offers a watertight dural closure while minimizing the problems of adhesion, infection, and rejection. Although the osteogenic potential of all periosteal tissues is recognized, a review of the literature did not reveal a reported case of osseous formation following use of pericranium for duraplasty. The authors report the case of a 17-year-old man who presented with a self-inflicted gunshot wound to the head. He was obtunded, but moving all extremities purposefully. Computerized tomography scanning demonstrated bifrontal injury. A bicoronal craniotomy with debridement was performed on an emergency basis, with vascularized pericranium used for a duraplasty. Follow-up cranioplasty demonstrated significant ossification of the pericranium 5 months after the original surgery. Pericranium is an attractive material for duraplasty; however, its osteogenic potential may interfere with future cranioplasty and cosmesis. This may be especially relevant in young persons.

Adolescent↗
PubMed2001

The use of general anaesthesia for orthodontic extractions.

AIM: The aims of the study were to evaluate 1) the uptake of general anaesthesia 2) the dental factors influencing use of general anaesthesia for routine orthodontic extractions. RESEARCH DESIGN: Retrospective cross-sectional. PARTICIPANTS: All patients, aged 16 years and under (n=145), currently undergoing orthodontic treatment at the University Dental Hospital of Manchester, who had received extractions, for their current course of treatment. METHOD: Patients were asked to complete a questionnaire after appliance adjustment. MAIN OUTCOME MEASURES: 1) type of anaesthesia received for the most recent orthodontic extractions 2) whether a choice of anaesthesia was given 3) number of permanent teeth removed for the current course of orthodontic treatment 4) previous experience of general anaesthesia. RESULTS: The response was 87%. Twenty-two per cent of patients received general anaesthesia, 64% local anaesthesia and 14% inhalation sedation. Sixty-five per cent of patients were not given a choice of anaesthesia for extractions. Stepwise logistic regression analysis revealed that a patient was more likely to receive a general anaesthetic if: 1) they had received a GA in the past (for fillings or extractions) 2) more than four teeth were extracted. CONCLUSIONS: Local anaesthesia was predominantly used for orthodontic extractions although the use of general anaesthesia was still quite high. The majority of patients were not given a choice of anaesthesia for routine extractions. Previous exposure to general anaesthesia and removal of more than four teeth increased the likelihood of a patient receiving general anaesthesia.

Adolescent↗
PubMed2001

Blood stream infections in a medical intensive care unit: spectrum and antibiotic susceptibility pattern.

OBJECTIVE: To determine the type and sensitivity pattern of causative organisms of septicaemia in intensive care unit, to prepare a guideline for empirical antibiotic therapy. SETTING: Department of pathology and adult medical intensive care unit, PNS SHIFA (Naval Hospital), Karachi. METHODS: The study was conducted from January 1997 to June 1999. Blood specimens for culture were drawn from patients who developed symptoms/signs of bacteraemia/septicaemia 48 hours or more after admission in medical ICU. The specimens were inoculated into Brain Heart Infusion broth. Subcultures were done on days 1,2,3,5,7 and 10. The isolates were identified by standard biochemical tests. Antibiotic susceptibility pattern of the isolates was studied by Modified Kirby Baur method. RESULTS: Eighty-six aerobic organisms were isolated. They included Staphylococcus aureus(n = 34), Pseudomonas aeruginosa (n = 13), Escherichia coli and Enterobacter spp(n = 9 each), Klebsiella pneumoniae(n = 8), Acinetobacter spp and Serratia spp(n = 5 each), Citrobacter diversus(n = 2) and Proteus vulgaris(n = 1). On antibiotic susceptibility testing, 48.18% Staphylococcus aureus isolates were methicillin resistant. Susceptibility to other common drugs was also quite low while 100% of these were susceptible to vancomycin and amikacin. In case of gram negative rods more than 80% were resistant to ampicillin and cotrimoxazole. Susceptibility to gentamicin was as low as 25% for Klebsiella pneumoniae to 44.4% in case of Escherichia coli. Susceptibility to the third generation cephalosporins and the quinolone tested (ciprofloxacin) varied between 50-75%. All these isolates except Pseudomonas aeruginosa were susceptible to imipenem and amikacin. CONCLUSION: In view of the isolation of antibiotic resistant organisms, vancomycin in combination with amikacin or imipenem are the drugs of choice for empirically treating blood stream infections in ICU. Infection control procedures and antibiotic control policies can help to tackle this problem.

Adolescent↗