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Biomedical subjects

J C Lee

Publications and source records attributed to J C Lee.

At least 19 recordsLinked to original sources

Imaging the infrapatellar tendon in the elite athlete.

Extensor mechanism injuries constitute a major cause of anterior knee pain in the elite athlete. Sonography and magnetic resonance imaging (MRI) are the imaging methods of choice when assessing the infrapatellar tendon. A comprehensive imaging review of infrapatellar tendon normal anatomy, tendinopathy, and partial/full-thickness tendon tears is provided. The value of imaging the infrapatellar tendon in clinical practice, including whether sonography can predict symptoms in asymptomatic athletes, is discussed. Acute avulsion fractures, including periosteal sleeve avulsion, and chronic avulsion injuries, including Sinding-Larsen-Johansson and Osgood-Schlatter syndromes, are shown. Mimics of infrapatellar tendon pathology, including infrapatellar plica injury, patellar tendon-lateral femoral condyle friction syndrome, and Hoffa's syndrome, are illustrated.

Athletic Injuries↗

Hibernoma: MRI features in eight consecutive cases.

AIM: To describe the preoperative magnetic resonance imaging findings of eight histologically-proven cases of hibernoma. MATERIALS AND METHODS: The site, size, and signal characteristics of eight consecutive hibernomas were retrospectively assessed on T1-weighted spin-echo and short T1 inversion recovery (STIR)/fat-saturated T2-weighted fast spin echo magnetic resonance images. Four patients also had gadolinium-enhanced fat-saturated T1-weighted spin echo imaging. Patient age and sex, and duration of symptoms were recorded. RESULTS: Three female and five male patients with an average age 36 years (range 16-53 years) were included. Seven lesions occurred in the thigh, four in the anterior compartment and three in the posterior compartment. One lesion occurred superficial to the scapula. All cases demonstrated common magnetic resonance imaging findings of a well-defined, heterogeneous mass, slightly or clearly hypo-intense to subcutaneous fat on T1-weighted spin-echo images, with prominent thin low signal bands throughout the tumour. The lesions failed to fully suppress on STIR or fat-saturated T2-weighted images. Only one of the four contrast-enhanced studies demonstrated increased vascularity in the tumour. CONCLUSION: The MRI findings of a lesion that is diffusely slightly hypointense to surrounding subcutaneous fat, should prompt the operator to consider hibernoma in the differential diagnosis.

Adipocytes, Brown↗

Livedoid vasculopathy: long-term follow-up results following hyperbaric oxygen therapy.

BACKGROUND: Livedoid vasculopathy, also known as atrophie blanche, is a recurrent painful vasculopathy appearing mostly on the lower limbs. Treatment is challenging and relapses are frequent. OBJECTIVES: To analyse the long-term effect and safety of hyperbaric oxygen (HBO) therapy in treating livedoid vasculopathy. METHODS: Twelve patients with active livedoid vasculopathy were included in this study. All patients underwent HBO therapy five times a week. Each week photographs were taken and the total dose of analgesics was recorded. Side-effects were documented and assessed. Recurrence was defined as the presence of skin ulceration. RESULTS: Of the eight patients who completed the treatment, resumption of ambulation and reduction of analgesics were achieved at an average of 4.9 HBO therapy sessions. Leg ulcers in all eight patients healed completely at a mean of 3.4 weeks (range 2-5 weeks). Six patients suffered relapses of ulceration and responded to additional HBO therapy. No significant side-effects were found. CONCLUSIONS: HBO is a relatively safe, fast and effective method to treat patients with livedoid vasculopathy.

Adolescent↗

Immunohistochemical localization of glutamate in the gerbil main olfactory bulb using an antiserum directed against glutamate.

Information on the localization and the roles of glutamate in the nervous system is becoming valuable because the axon terminals of the olfactory sensory neurons and the synapses of the mitral and tufted output cells appear to be glutamatergic. In this study, we have analysed the distribution of glutamate immunoreactivity in the main olfactory bulb (MOB) of the Mongolian gerbil using an antiserum directed against glutamate. Glutamate immunoreactivity in the MOB was present in the olfactory nerve layer (Onl), glomerular layer (GL), external plexiform layer (EPL) and mitral cell layer (ML), but not in the granule cell layer (GCL). Glutamate immunoreactivity detected in the Onl was thought to be terminal ramifications of glomeruli. Some neurons in the periglomerular region showed glutamate immunoreactivity. In the EPL, glutamate immunoreactivity was found in some neuronal somata (tufted cells) and processes. In addition, mitral cells in the ML were labelled by the glutamate antibody. The pattern of glutamate immunoreactivity in the mitral cells was similar to that in the tufted cells. In brief, glutamate in the gerbil MOB is the neurotransmitter used by primary afferents and output neurons.

Animals↗

Design of a subcutaneous vascular access device using Ni-Ti SMA clamps for hemodialysis.

A subcutaneous vascular access device which utilizes an Ni-Ti shape memory alloy (Ni-Ti SMA) spring, has been developed as a new method for subcutaneous vascular access in the treatment of hemodialysis patients. Until now, the connection between the SVAD and needle cannot be externally monitored, and the clamp must be opened and closed with a percutaneous needle by a nephrologist. The SMA-SVAD accomplishes the opening and closing of its clamp using two Ni-Ti SMA springs, and a transcutaneous energy transmission system (TET) transmits energy to the Ni-Ti SMA springs without the need for percutaneous wires. Two SMA springs open and close the clamp of the SMA-SVAD, without affecting any of the other parts of the system. Wasted thermal energy is reduced to minimal values via electrical regional heating methods. The state of the SMA-SVAD can be monitored according to the amount of power consumed by the external energy transmitter. In in-vitro experiments, when the clamp was opened and the pressure difference in the hemodialysis machine was set to 50 mmHg, water flow through SMA-SVAD reached 500 ml/min. The maximal surface temperatures of the SVAD and catheter were successfully maintained at proper levels (approximately 38-39 degrees C), approximately 2-3 degrees higher than the temperature of the surrounding tissues. The time elapsed from the initiation of energy transmission until the opening of the SMA clamp was 5 seconds.

Catheters, Indwelling↗

Development of a new pulsatile extracorporeal life support device incorporating a dual pulsatile blood pump.

A new pulsatile extracorporeal life support device (ECLS) has been developed, designed to sustain pulsatile blood flow during emergency cardiopulmonary resuscitations and cardiopulmonary operations. This device features two identical pulsatile pumps that operate alternately and can therefore provide blood inflow in a more uniform manner than similar systems featuring a single-pump configuration. In order to confirm the presumed benefits of this newly-developed dual pulsatile pump configuration, we have conducted a series of in vitro experiments designed to compare the properties of the new system with a single pump system, specifically with regard to pump delivery rate and active filling efficiency. Our results reveal that the dual pump configuration can, indeed, deliver a higher flow than can the single-pump system, and exhibits an active filling efficiency superior to that of the single-pump configuration. We performed a series of animal experiments to measure the pulsatility of the dual-pump configuration in terms of equivalent energy pressure (EEP). In order to measure EEP, we measured femoral arterial pressure and pump outflow. The results of our animal experiments revealed that the newly-developed pulstile ECLS exhibits sufficient pulsatility in terms of the EEP considerations.

Advanced Cardiac Life Support↗

Complex presentation of intussusception in childhood.

The simultaneous occurrence of intussusception and volvulus in the paediatric age group is rare. We report the case of a volvulus of an ileoileal intussusception in an 8-year-old boy. This is the first time that computerised tomography (CT) images of a volvulus of an ileoileal intussusception have been published, and they clearly demonstrate both pathologies. This case highlights the use of CT in determining the nature of an abdominal mass and demonstrates how helpful it can be in diagnosing the cause of small bowel obstruction in children.

Anastomosis, Surgical↗

Adhesive capsulitis: sonographic changes in the rotator cuff interval with arthroscopic correlation.

OBJECTIVE: To evaluate the sonographic findings of the rotator interval in patients with clinical evidence of adhesive capsulitis immediately prior to arthroscopy. DESIGN AND PATIENTS: We prospectively compared 30 patients with clinically diagnosed adhesive capsulitis (20 females, 10 males, mean age 50 years) with a control population of 10 normal volunteers and 100 patients with a clinical suspicion of rotator cuff tears. Grey-scale and colour Doppler sonography of the rotator interval were used. RESULTS: Twenty-six patients (87%) demonstrated hypoechoic echotexture and increased vascularity within the rotator interval, all of whom had had symptoms for less than 1 year. Three patients had hypoechoic echotexture but no increase in vascularity, and one patient had a normal sonographic appearance. All patients were shown to have fibrovascular inflammatory soft-tissue changes in the rotator interval at arthroscopy commensurate with adhesive capsulitis. None of the volunteers or the patients with a clinical diagnosis of rotator cuff tear showed such changes. CONCLUSIONS: Sonography can provide an early accurate diagnosis of adhesive capsulitis by assessing the rotator interval for hypoechoic vascular soft tissue.

Adult↗

Exogenous Bcl-xL fusion protein spares neurons after spinal cord injury.

Spinal cord injury (SCI) induces neuronal death, including apoptosis, which is completed within 24 hr at and around the impact site. We identified early proapoptotic transcriptional changes, including upregulation of proapoptotic Bax and downregulation of antiapoptotic Bcl-xL, Bcl-2, and Bcl-w, using Affymetrix DNA microarrays. Because Bcl-xL is the most robustly expressed antiapoptotic Bcl-2 molecule in adult central nervous system, we decided to characterize better the effect of SCI on Bcl-xL expression. We found Bcl-xL expressed robustly throughout uninjured spinal cord in both neurons and glia cells. We also found Bcl-xL localized in different cellular compartments: cytoplasmic, mitochondrial, and nuclear. Bcl-xL protein levels decreased in the cytoplasm and mitochondria 2 hr after SCI and persisted for 24 hr. To test the contribution of proapoptotic decreases in Bcl-xL to neuronal death, we augmented endogenous Bcl-xL levels by administering Bcl-xL fusion protein (Bcl-xL FP) into injured spinal cords. Bcl-xL FP significantly increased neuronal survival, suggesting that SCI-induced changes in Bcl-xL contribute considerably to neuronal death. Because Bcl-xL FP increases survival of dorsal horn neurons and ventral horn motoneurons, it could become clinically relevant in preserving sensory and motor functions after SCI.

Animals↗

Fusing DEDD with ubiquitin changes its intracellular localization and apoptotic potential.

DEDD, a highly conserved and ubiquitous death effector domain containing protein, exists in non, mono, and diubiquitinated forms. We previously reported that endogenous unmodified DEDD is only found in nucleoli and that mono- and diubiquitinated DEDD associate with caspase-3 in the cytosol suggesting that ubiquitination may be important to the apoptosis regulating functions of DEDD in the cytosol. We now demonstrate that many of its 16 lysine residues can serve as alternative acceptors for ubiquitination to maintain the monoubiquitination status of DEDD. A central region in DEDD (amino acids 109-305) outside the death effector domain was found to be essential for ubiquitination and/or the docking of the ubiquitination machinery. Fusion of ubiquitin to the C-terminus of DEDD to mimic monoubiquitinated DEDD relocated DEDD from nucleoli to the cytosol. This fusion protein also demonstrated a greater apoptosis potential than unmodified DEDD. Finally, we show that both mono- and polyubiquitination of DEDD can be achieved by the cellular inhibitor of apoptosis proteins 1 and 2 (cIAP-1/2). In addition, the cotransfection of DEDD with cIAP-1 or cIAP-2 results in the relocalization of the IAPs to the nucleoli. Our data suggest that monoubiquitination of DEDD regulates both its cytoplasmic localization and its proapoptotic potential and that IAP proteins can regulate DEDD's ubiquitination status.

Apoptosis↗

Postmastectomy radiotherapy reduces locoregional recurrence in elderly women with high-risk breast cancer.

AIMS: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out. RESULTS: Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival. CONCLUSIONS: In women aged 70 years or over with tumours greater than 5 cm or four or more positive nodes, significantly lower LRR was observed in women treated with radiotherapy compared with women treated without radiotherapy. PMRT should be considered in the management of elderly women with these high-risk characteristics.

Aged↗

Detection of oncogenic mutations in the EGFR gene in lung adenocarcinoma with differential sensitivity to EGFR tyrosine kinase inhibitors.

The complete sequencing of the human genome and the development of molecularly targeted cancer therapy have promoted efforts to identify systematically the genetic alterations in human cancer. By high-throughput sequencing of tyrosine kinase genes in human non-small-cell lung cancer, we identified somatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene (EGFR) that are correlated with clinical response to EGFR tyrosine kinase inhibitors (TKIs). We have shown that these mutant forms of EGFR induce oncogenic transformation in different cellular systems. Cells whose growth depends on EGFR with mutations in exons 19 and 21 are sensitive to EGFR-TKIs, whereas cells expressing insertion mutations in exon 20 or the T790M point mutant, found in tumor biopsies from patients that relapsed after an initial response to EGFR-TKIs, are resistant. Furthermore, by applying a novel, massively parallel sequencing technology, we have shown that clinically relevant oncogene mutations can be detected in clinical specimens with very low tumor content, thereby enabling optimal patient selection for mutation-directed therapy. In summary, by applying high-throughput genomic resequencing, we have identified a novel therapeutic target, mutant EGFR, in lung cancer and evaluated its role in predicting response to targeted therapy.

Adenocarcinoma↗

Carcinoma erysipelatoides from squamous cell carcinoma of unknown origin.

Carcinoma erysipelatoides, also known as inflammatory metastatic carcinoma, is a rare form of cutaneous metastasis from a malignancy. The characteristic histopathological finding is metastatic tumour cells inside the dermal lymphatic ducts. It is frequently observed in patients with breast carcinoma as well as adenocarcinoma of pancreas, rectum, lung, ovary and parotid gland. We present a 66-year-old man diagnosed to have metastatic squamous cell carcinoma by aspiration cytology from an enlarged neck lymph node and a core biopsy of a left axillary mass. He subsequently received radiotherapy; however, due to intolerance to erythema and swelling on local irradiated skin, radiotherapy was deferred. Skin lesions on upper chest and neck area, consisting of erythematous induration with telangiectasia and tenderness, progressed slowly and were treated as cellulitis. The erythema remained stationary with antibiotic treatment. Skin biopsy shows poorly differentiated squamous carcinoma cells within dermis and dilated dermal vessels.

Aged↗

Longitudinal single-cell cytokine responses reveal recurrent autoimmune myelin reactivity in relapsing--remitting multiple sclerosis patients.

The relationship between multiple sclerosis (MS) disease activity and myelin protein-induced cytokine responses over time is not elucidated. We addressed this relationship by examining longitudinal cytokine responses to myelin proteins every three months for one year, in the context of gadolinium (gad)-enhancing brain lesions and of clinical relapses. The ELISPOT assay was used to determine the ex vivo cytokine production in response to nine amino acid long peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in relapsing-remitting (RR) MS patients and matched healthy controls. We identified three longitudinal levels of myelin-induced cytokine secretion by adding up the positive responses for all PLP or MBP peptides obtained for five timepoints, at three-month intervals: low reactivity (< 200 cumulative cytokine-secreting cells), isolated peptide reactivity (201-450 cumulative cytokine-secreting cells) and recurrent protein-wide bursts of cytokine reactivity (> 451 cumulative cytokine-secreting cells). The majority of MS patients showed recurrent bursts to PLP and MBP. In contrast, controls showed a more even distribution between all levels of cytokine reactivity. The majority of patients with gad-enhancing lesions showed PLP/IFN gamma and MBP/IFN gamma recurrent burst responses. This is the first longitudinal study on MS patients in which nine amino acid long myelin peptides are used to reveal the broad range of PLP- and MBP-peptide cytokine reactivity across the whole molecule of these two major myelin proteins. This study also reveals the extremely dynamic nature of the immune reactivity to numerous regions of myelin, which can fluctuate dramatically over time. Such fluctuation could hamper the efficacy of antigen-based therapies for MS.

Adolescent↗

Seeing the gene therapy: application of gene gun technique to transfect and decolour pigmented rat skin with human agouti signalling protein cDNA.

We developed a gene gun method for the transfer of human agouti signalling protein (ASP) cDNA to alter rat skin colour in vivo. Human ASP cDNA was cloned into a modified cytomegalovirus plasmid and delivered to the skin of Long-Evans rats by gene gun bombardment. Skin pigmentation, body weight and blood sugar of ASP cDNA-transfected rats were recorded against the control group, which were injected with plasmids encoding for green fluorescent protein. The treated skin showed lighter skin colour after 3 days of ASP gene transfection. This depigmentation effect was most prominent on day 14 and the skin gradually returned to its original pigmentation by day 28. Successful transfection of ASP gene in skin and hair follicles, as well as downregulation of melanocortin-1 receptor (MC1R) and tyrosinase expression upon treatment, was confirmed using immunohistochemistry and Western blot analysis. Body weight and blood sugar in the treated rats did not show statistically significant differences as compared to control groups. These observations demonstrate that gene transfer using the gene gun method can induce high cutaneous ASP production and facilitate a switch from dark to fair colour without systemic pleiotropic effects. Such a colour switch may be that ASP is acting in a paracrine fashion. In addition, this study verifies that ASP exerts its functions by acting as an independent ligand that downregulates the melanocyte MC1R and tyrosinase protein in an in vivo system. Our result offers new, interesting insights about the effect of ASP on pigmentation, providing a novel approach to study the molecular mechanisms underlying skin melanogenesis.

Agouti Signaling Protein↗

Age-related change of somatostatin-immunoreactive neurones in the main olfactory bulb of the rat.

Somatostatin is found in the olfactory system, including the main olfactory bulb (MOB), and is thought to be one of the neuroactive substances for olfaction. However, somatostatin immunoreactivity in the olfactory system has not been determined during ageing. Hence, we examined the age-related changes of somatostatin-immunoreactive (IR) neurones in the rat MOB over a period of 2 years, at the following various ageing stages: post-natal month 1 (PM 1), PM 3, PM 6, PM 12 and PM 24. In PM 1 group, a few somatostatin-IR neurones were detected in the granule cell layer (GCL), and had slender or oval somata and short processes. At PM 3, somatostatin-IR neurones were observed in the glomerular, external plexiform and GCL. The size of somatostatin-IR somata was larger than that at PM 1. In PM 6 group, the number and size of somatostatin-IR neurones increased, and their processes became longer while running in various directions. At PM 12, somatostatin-IR neurones increased in number, and their processes became markedly longer than those at PM 6. At this stage, somatostatin-IR neurones had multipolar somata, and were the largest in size. In PM 24 group, somatostatin-IR neurones were most numerous. However, the processes of somatostatin-IR neurones were shorter than those at PM 12. This study suggests that the increased number of somatostatin-IR neurones in the MOB of aged rats may play a role to compensate for any decrease of olfactory function.

Aging↗

Histochemical study on neurodegeneration in the olfactory bulb after transient forebrain ischaemia in the Mongolian gerbil.

In the present study, we investigated the ischaemia-related neurodegeneration in the main and accessory olfactory bulb (AOB) after 5 min transient forebrain ischaemia in the Mongolian gerbil using the acid fuchsin staining method. Between 5 and 15 days after ischaemia, acid fuchsin positive cells markedly increased in the external plexiform layer (EPL), mitral cell layer (ML) and glomerular layer (GL) of the main olfactory bulb (MOB), and in the mixed cell layer (MCL) and GL of the AOB. By 30 days after ischaemia reperfusion, acid fuchsin positive neurons were shrunken and showed low acidophilia in somata. Many necrotic vacuoles were found in the EPL and GL of the MOB 30 days after ischaemia. At this time, necrotic vacuoles were very few in the AOB. Therefore, our results suggest that the GL and EPL of the MOB are vulnerable to ischaemic damage at a later time after ischaemic insult, and that the AOB is more resistant to ischaemic damage as compared with the MOB.

Animals↗