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Biomedical subjects

K M Khan

Publications and source records attributed to K M Khan.

At least 91 records · Page 5Linked to original sources

Role of laminin in matrix induction of macrophage urokinase-type plasminogen activator and 92-kDa metalloproteinase expression.

Urokinase-type plasminogen activator (uPA) and 92-kDa matrix metalloproteinase (MMP-9) expression by RAW264.7 macrophages were up-regulated when plated on extracellular matrices. Collagen IV, fibronectin, and tenascin stimulated macrophages' MMP-9 expression. In contrast, laminin stimulated both uPA and MMP-9 expression in a dose- and time-dependent manner. The increase in macrophage uPA activity was preceded by an increase in their steady state levels of uPA mRNA. Laminin-induced uPA expression was most pronounced in RAW264.7 macrophages followed by THP-1 monocytes, J774A.1 macrophages, and bone marrow-derived macrophages. Neither laminin nor matrix induced alterations in THP-1 monocyte expression of plasminogen activator inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 or TIMP-2. Synthetic laminin peptides were utilized to identify the laminin domain(s) responsible for induction of uPA expression. Peptides derived from the beta1 chain of laminin had no effect on macrophage uPA expression, whereas SIKVAV, derived from alpha1 chain, stimulated uPA expression 20-fold. Preincubation of THP-1 monocytes with a monoclonal antibody directed against the alpha6 subunit of the alpha6beta1 laminin receptor blocked matrix induction of uPA without affecting the induction of MMP-9. These results demonstrate that macrophage binding to laminin plays an important role in the regulation of their degradative phenotype via the up-regulation of uPA and MMP-9.

Animals↗

Quantitative analysis of dopamine receptor messages in the mouse cochlea.

Dopamine receptor isoforms were examined in the cochlea of the CBA(J) mouse by RT-PCR analysis and nucleotide sequencing, utilizing primers specific for known dopamine receptor isoforms. Cochlear cDNA sequences corresponding to dopamine D2(long) and D3 receptors were amplified, whereas those representing D1A, D1B, D2(short), and D4 were not detected. Utilizing quantitative competitive PCR analysis, relative levels of dopamine receptor transcripts were found to be 0.002, 0.014, 0.016, and 1.000 for D2(long) cochlea, D3 cochlea, D3 brain, and D2(long) brain, respectively. In the context of previously published findings, the current work provides key quantitative evidence necessary to establish that dopamine is a neurotransmitter in the auditory inner ear.

Animals↗

Expression of adenylyl cyclase type I in cochlear inner hair cells.

Expression of calcium/calmodulin-activated adenylyl cyclase type I (ACI) mRNA has been determined in the cochlea and in an organ-of-Corti subdissected tissue fraction by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Amplification products of predicted size were obtained from the mouse cochlea and rat organ of Corti with nucleotide sequences corresponding to respective ACI brain transcripts. In addition, ACI template was detected in a rat inner hair cell cDNA library by PCR. Immunoreactivity to ACI has been localized within the organ of Corti to the inner hair cell, with diaminobenzidine staining found in both the cell body and in the stereocilia. Evidence, thus, has been obtained that both ACI transcript and protein are expressed in the inner hair cell, the primary mechanosensory receptor cell of the cochlea. We hypothesize that ACI is activated by calcium influx through a calcium/calmodulin interaction and that this adenytyl cyclase isoform may have a role in modulation of receptoneural afferent transmission and/or mechanosensory transduction in the cochlea.

Adenylyl Cyclases↗

Bone mass and bone turnover in power athletes, endurance athletes, and controls: a 12-month longitudinal study.

Strain magnitude may be more important than the number of loading cycles in controlling bone adaptation to loading. To test this hypothesis, we performed a 12 month longitudinal cohort study comparing bone mass and bone turnover in elite and subelite track and field athletes and less active controls. The cohort comprised 50 power athletes (sprinters, jumpers, hurdlers, multievent athletes; 23 women, 27 men), 61 endurance athletes (middle-distance runners, distance runners; 30 women, 31 men), and 55 nonathlete controls (28 women, 27 men) aged 17-26 years. Total bone mineral content (BMC), regional bone mineral density (BMD), and soft tissue composition were measured by dual-energy X-ray absorptiometry. Bone turnover was assessed by serum osteocalcin (human immunoradiometric assay) indicative of bone formation, and urinary pyridinium crosslinks (high-performance liquid chromatography) indicative of bone resorption. Questionnaires quantified menstrual, dietary and physical activity characteristics. Baseline results showed that power athletes had higher regional BMD at lower limb, lumbar spine, and upper limb sites compared with controls (p < 0.05). Endurance athletes had higher BMD than controls in lower limb sites only (p < 0.05). Maximal differences in BMD between athletes and controls were noted at sites loaded by exercise. Male and female power athletes had greater bone density at the lumbar spine than endurance athletes. Over the 12 months, both athletes and controls showed modest but significant increases in total body BMC and femur BMD (p < 0.001). Changes in bone density were independent of exercise status except at the lumbar spine. At this site, power athletes gained significantly more bone density than the other groups. Levels of bone formation were not elevated in athletes and levels of bone turnover were not predictive of subsequent changes in bone mass. Our results provide further support for the concept that bone response to mechanical loading depends upon the bone site and the mode of exercise.

Adolescent↗

Patellar tendon ultrasonography and jumper's knee in female basketball players: a longitudinal study.

OBJECTIVE: To compare patellar tendon sonographic findings at baseline and at follow-up in active female basketball players with and without symptoms of jumper's knee. We hypothesized that baseline sonographic morphology would not reliably predict prognosis and, in particular, that it would not predict the need for surgery. DESIGN: Prospective longitudinal study with 12-month minimum follow-up. SETTING: Institutional elite athlete study group in Australia (Victorian Institute of Sport Tendon Study Group). PATIENTS AND PARTICIPANTS: A total of 15 female elite basketball players with 23 sonographically abnormal tendons and 15 matched control basketball players with 23 sonographically normal tendons. MAIN OUTCOME MEASURES: Sonographic patellar tendon appearance and clinical assessment of symptoms of jumper's knee at baseline and follow-up. Dimensions of abnormal regions were measured. RESULTS: At baseline, the 23 subject tendons contained sonographic hypoechoic regions (six currently symptomatic, eight previously symptomatic only, and nine never symptomatic). At follow-up, the hypoechoic areas in seven tendons had resolved (and caused no symptoms), the hypoechoic areas in 11 tendons had remained essentially the same size (five were symptomatic), and the hypoechoic areas in five tendons had expanded (three symptomatic). At baseline, there were no differences between the mean +/- SD cross-sectional areas of the abnormalities in the tendons that subsequently resolved (15.9 +/- 10.1 mm2) and those that remained unchanged (39.3 +/- 25.8) or expanded (25.3 +/- 12.5). The presence of a baseline sonographic abnormality predicted symptoms of jumper's knee at follow-up (p < 0.05), but the presence of symptoms of jumper's knee at baseline also predicted symptoms at follow-up (p < 0.05). No subject or control missed any games or underwent surgical treatment. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas can resolve, remain unchanged, or expand in active sports-women without predicting symptoms of jumper's knee. Thus, symptoms were not directly related to sonographic tendon morphology. Sonographic hypoechoic regions ought not to constitute per se an indication for surgery.

Analysis of Variance↗

Instrument performance in bone density testing at five Australian centres.

AIMS: To assess the in vitro precision and accuracy of bone mineral densitometry (BMD) within and between locations at five Australian centres. METHODS: Using a multicentre reliability study the accuracy and short- and long-term precision of dual-energy X-ray absorptiometry (DXA) in vitro was compared on five instruments. Measures were performed using pencil beam mode on four Hologic QDR-2000 densitometers and one Hologic QDR-1000/W (Hologic Inc, Waltham, MA). RESULTS: Short-term precision of bone mineral density measurement was less than 0.5% for spine phantoms (n = 10 for each centre, mean intrasite coefficient of variation [CV] 0.39 +/- 0.09% [SD]) and for hip phantoms (n = 10 for each centre, mean intrasite coefficient of variation [CV] 0.34 +/- 0.10% [SD]). Between-centre measurement (n = 10 for each phantom) of a single spine phantom and a single hip phantom (specified mineral contents-58.5 g and 38.6 g, respectively) revealed ranges of bone mineral content of 57.7-58.1 g (all-point CV = 0.52%) and 37.1-37.8 g (all-point CV = 0.70%), respectively. When results from pairs of machines were compared there were statistically different mean BMD results for the majority of the ten possible pairings for both spine and hip measurements. Each study centre measured in vitro stability of phantom BMD measurements over a one year period (n = 45-283, median 157 for spine; and n = 0-262, median 38, for hip); CVs ranged from 0.38 to 0.53% for the spine measurements and from 0.38 to 0.54% for the hip measurements. The mean all-point accuracy of the spine phantom measurements was 99.1% and the hip phantom measurements was 96.7%. CONCLUSIONS: Across a number of instruments DXA demonstrates in vitro all-point precision of 0.5% for the spine phantom and 0.7% for the hip phantom. The instrument demonstrates accuracy of greater than 99% at the spine and 96% at the hip. This finding has clinical, research and quality control implications.

Absorptiometry, Photon↗

A cross sectional study of 100 athletes with jumper's knee managed conservatively and surgically. The Victorian Institute of Sport Tendon Study Group.

OBJECTIVES: Jumper's knee causes significant morbidity in athletes of all standards. However, there are few reference data on the clinical course of this condition in a large number of patients, and the aim of this study was to rectify this. METHODS: A retrospective study of the course of jumper's knee in 100 athletes who presented to a sports medicine clinic over a nine year period was carried out. Subjects completed a questionnaire designed to collect details of sport participation, symptoms, and time out of sport. Ultrasonographic results were recorded from the radiologists' reports. Histopathological results were obtained for patients who had surgery. RESULTS: Forty eight subjects recalled that symptoms of jumper's knee began before the age of 20 years. Symptoms prevented 33 from participating in sport for more than six months, and 18 of these were sidelined for more than 12 months. Forty nine of the subjects had two or more separate episodes of symptoms. Ultrasonography showed a characteristics hypoechoic region at the junction of the inferior pole of the patella and the deep surface of the patellar tendon. Histopathological examination showed separation and disruption of collagen fibres on polarisation light microscopy and an increase in mucoid ground substance consistent with damage of tendon collagen without inflammation. CONCLUSIONS: Jumper's knee has the potential to be a debilitating condition for a sports person. About 33% of athletes presenting to a sports medicine clinic with jumper's knee were unable to return to sport for more than six months.

Adolescent↗

Retired elite female ballet dancers and nonathletic controls have similar bone mineral density at weightbearing sites.

Elite female ballet dancers exhibit several risk factors for osteoporosis during their performing years. To study the long-term effect of this lifestyle, we compared the bone mineral density (BMD) of 101 retired elite female ballet dancers (mean age 51 years, SD = 14 years) and 101 normal controls, derived from a twin study, matched hierarchically for age, height, weight, and menopausal status. The dancers, who had been retired for a mean of 25.6 years (range 1-53 years) reported a greater prevalence of previous menstrual disturbance, greater lifetime alcohol intake and smoking, and a lower dietary milk intake in adolescence than controls (all p < 0.05). However, current exercise in the dancers was twice that of the controls (p < 0.01). The BMD of retired dancers did not differ from that of the controls at weightbearing sites. The mean +/- SE difference in BMD (dancers minus controls) was 0.009 +/- 0.013 at the total body, -0.009 +/- 0.018 at the total hip, 0.005 +/- 0.017 at the femoral neck, 0.014 +/- 0.018 at the femoral trochanter, 0.036 +/- 0.022 at the femoral intertrochanter and -0.017 +/- 0.021 at the lumbar spine. Retired dancers had lower mean (+/- SE) BMD at the nonweightbearing sites: ultradistal radius (-0.029 +/- 0.008) (p < 0.01) and at the midthird radius (-0.019 +/- 0.011) (p < 0.05). There was no difference in the proportion in each of the World Health Organization (WHO) categories of osteopenia (t score -1.0 to -2.5) and osteoporosis (t score < -2.5) at any of the measured sites. Regression analysis revealed that menstrual disturbance was negatively associated with BMD at the lumbar spine and the ultradistal radial sites, but not at the weightbearing femoral sites. This sample of retired elite ballet dancers who had multiple historical risk factors does not appear to have an increased risk for future hip or vertebral fracture based on WHO standards.

Absorptiometry, Photon↗

Calcium channel subunits in the mouse cochlea.

Messages for subunits of voltage-gated calcium channels were examined in the cochlea of the CBAJ mouse by PCR analysis. Total RNA was extracted from the auditory organs of 16-18-day-old animals. After reverse transcription, resulting cDNA was amplified by PCR with primers targeted to nucleotide sequences corresponding to 12 different calcium channel subunits. PCR products representing subunit gene expression were strongly and consistently amplified for alpha1C, alpha1D, alpha1E, alpha2delta, beta1, beta3, and beta4 but not for alph1A, alpha1B, alpha1S, beta2, or gamma. The chosen primers amplified cochlear cDNA to yield an overall pattern of bands different from that of any tissue studied thus far, in particular with respect to the alpha2delta and beta1 subunits; the alpha2delata product was found to be significantly shorter than the corresponding brain and skeletal muscle isoforms. Nucleotide sequencing confirmed the identity of mouse cochlear subunit cDNAs. The results suggest that L-type and presumptive R-type calcium channels are expressed in the mammalian cochlea and that the alpha2delta subunits may be coded by a characteristic splice-variant mRNA.

Animals↗

Patellar tendinosis (jumper's knee): findings at histopathologic examination, US, and MR imaging. Victorian Institute of Sport Tendon Study Group.

PURPOSE: To determine the histopathologic findings of patellar tendinosis ("jumper's knee") demonstrated with ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-four athletes (28 knees) with jumper's knee (23 men, one women; mean age, 30.9 years) scheduled to undergo open tenotomy underwent US patellar tendon examination. Seventeen patients (19 knees) also underwent MR imaging. Tissue was obtained for histopathologic examination in all 28 cases. Eleven age-, height-, and weight-matched athletes (22 knees) without previous knee symptoms served as control subjects for the US examination. Control material for histopathologic examination was obtained in 20 cadavers (39 knees). Data were analyzed with standard statistical methods. RESULTS: MR imaging and US both revealed an abnormal zone at the proximal patellar tendon attachment. Histopathologic examination revealed mucoid degeneration in all tendons in patients and in 8% (three of 39) of tendons in cadavers (P < .01). CONCLUSION: Jumper's knee is characterized by consistent changes at MR imaging, US, and histopathologic examination and is appropriately described as patellar tendinosis.

Adult↗

Stress fractures: a review of 180 cases.

OBJECTIVE: To review the cases of stress fracture seen over a 2-year period at a sports medicine clinic. DESIGN: One hundred and eighty cases diagnosed as stress fractures on the basis of clinical picture and radiological evidence were reviewed. The following features of each stress fracture were noted: age, sex, site, sport/activity. SETTING: A sports medicine centre in Melbourne, Australia. PATIENTS: The average age was 21.8 years. Seventy eight of these stress fractures were seen in women, 102 in men. RESULTS: The most common sites of stress fractures were the metatarsal bones (n = 42), tibia (n = 36), fibula (n = 30), tarsal navicular (n = 26) and pars interarticularis (n = 17). The most common sport was track (n = 54). Other common sports activities were jogging/distance running (n = 35), dance (n = 32) and Australian football (n = 14). The distribution of sites of stress fractures varied from sport to sport. Among the track athletes (n = 54), navicular (n = 19), tibia (n = 14) and metatarsal (n = 9) were the most common stress fracture sites. The distance runners (n = 35) predominantly sustained tibia (n = 15), and fibula (n = 8) stress fractures, while metatarsal stress fractures (n = 18) were the most common among dancers. The distribution of sports varied with the site of the stress fracture. In the metatarsal stress fractures (n = 42), dance was the most common activity. Distance running (n = 15) and track (n = 14) were the most common sports in the group to have sustained tibia stress fractures (n = 36). Track athletes (n = 14) were particularly prevalent in the navicular stress fracture group (n = 26). CONCLUSION: The distribution of sites of stress fractures in this study shows some differences from previously published studies.

Adult↗

Abnormal acid phosphatases in neuronal ceroid-lipofuscinoses.

Acid phosphatases in brain and cultured lymphoblasts from patients affected with neuronal ceroid-lipofuscinoses (NCL) were studied by starch gel electrophoresis. After electrophoresis the gel was incubated with 4-methyl umbelliferyl phosphate at pH 4.5 and the fluorescent reaction product was visualized under ultraviolet light. Control brain showed a single band with mobility of about 1 cm while NCL patients showed two additional fast moving bands. In the late-infantile, and in the adult form (Kufs disease), the middle band was prominent while the fast moving band was predominant in juvenile NCL. In long-term lymphoblasts, controls showed a single band of acid phosphatase activity while both juvenile and late-infantile NCL showed two additional fast moving bands. Obligate heterozygotes showed reduced levels of the fast moving bands. Fluorometric assay of acid phosphatase using 4-methylumbelliferyl phosphate as substrate showed a 2-fold increase in activity in the patients. The increased acid phosphatase activity is completely inhibited by tartrate. Lymphocyte hexosamnidase activities were unchanged in NCL patients lymphoblasts. Studies on brains of NCL patients and on cultured lymphoblasts from families with late-infantile and juvenile form of NCL showed that abnormal acid phosphatase is characteristic of NCL.

Acid Phosphatase↗

Analysis of nicotinic acetylcholine receptor subunits in the cochlea of the mouse.

The present study was designed to catalogue and compare nicotinic receptor subunit messages in the mammalian cochlea. Fourteen nicotinic acetylcholine receptor subunit messages were examined by polymerase chain reaction (PCR) analysis and nucleotide sequencing. Total RNA was extracted from the auditory organs of 14- to 18-day-old CBAJ mice, and mRNA was purified using oligo-dT cellulose. After reverse transcription, resulting cDNA was amplified by PCR with the use of primers specific for the nucleotide sequences representing the following nicotinic receptor subunits: muscle types alpha 1, beta 1, gamma, delta and epsilon and neuronal types alpha 2,3,4,5,6,7 and beta 2,3,4. cDNA from cochlear tissue corresponding to the muscle-type receptor subunit beta 1 and to neuronal-type receptor subunits alpha 2,4,5,6 and beta 2,3 was amplified, whereas cDNA for muscle types alpha 1, gamma, delta and epsilon and neuronal types alpha 3,7 and beta 4 was not. All PCR products were homologous in nucleotide sequence to the corresponding reference cDNAs from which the primers were designed. The current results indicate that nicotinic acetylcholine receptor (nAChR) subunits that are similar or identical to the stated muscle and neuronal types are expressed in the murine cochlea. The presence of messages corresponding to the muscle-type beta 1 and neuronal-type nAChR subunits may be correlated with the atypical cholinergic response of cochlear hair cells to agonists and antagonists.

Animals↗

Tarsal navicular stress fracture in athletes.

Stress fracture of the tarsal navicular bone is now frequently recognised. The majority of navicular stress fractures are partial fractures in the sagittal plane. They occur mainly in track and field athletes. A number of theories regarding the aetiology of this fracture have been proposed. Athletes with a history of vague, activity-related midfoot pain, with associated tenderness over the dorsal proximal navicular ('N' spot) should be suspected of having a navicular stress fracture. Plain radiography frequently fails to demonstrate the fracture, thus radionuclide scanning is the investigation of choice to detect navicular stress injury. A computed tomography (CT) scan should be performed to confirm the presence of the fracture. Various methods of treatment have been employed. A minimum of 6 weeks of strict non-weightbearing cast immobilisation is the treatment of choice. After removal of the cast, a further 6 week programme of rehabilitation with a graduated return to activity, joint mobilisation and soft tissue massage is required. Surgery for nonunion or delayed union is rarely required if initial treatment is appropriate.

Athletic Injuries↗

Acetylcholinesterase activity is associated with efferent endings in the sensory epithelia of the utricle and semicircular canals of the rainbow trout inner ear.

The mechanosensory hair cells of the utricle and semicircular canals of the trout inner ear are morphologically similar to type II hair cells of the avian and mammalian vestibular end organs. These cells are innervated by two types of nerve terminals. The nonvesiculated terminals are considered to be afferent, and the vesiculated endings are presumed to be efferent. The presumptive efferent endings contain numerous clear, round vesicles and a few that are dense-cored. Histocytochemical, electron microscopic analysis has localized acetylcholinesterase activity to plasma membranes of vesiculated, presumptive efferent nerve terminals in sensory epithelia of the utricle and semicircular canals. No reaction product was observed at the receptoneural synapse or found in nonvesiculated, presumptive afferent endings. Control specimens incubated in the presence of eserine sulfate, an inhibitor of acetylcholinesterase, were devoid of reaction product. These results support the tenet that vesiculated nerve endings in the sensory epithelia of the utricle and semicircular canals of the trout are cholinergic.

Acetylcholinesterase↗