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Biomedical subjects

L Lee

Publications and source records attributed to L Lee.

At least 127 records · Page 7Linked to original sources
PubMed1998

Scapulothoracic dissociation.

Scapulothoracic dissociation is an uncommon and devastating traumatic injury. A review of 72 cases in the English literature shows that a broad range of musculoskeletal and neurovascular injuries resulting from blunt trauma have been classified as scapulothoracic dissociation since the term was first used in 1984. A review of the current clinical signs and radiographic findings that define scapulothoracic dissociation, as well as a brief description of treatment options and outcomes, is presented.

Acromioclavicular Joint↗
PubMed1998

Human immunodeficiency virus-related progressive multifocal leukoencephalopathy with a CD4+ of 444 per mm3: a case report.

A 47-year-old homosexual man with human immunodeficiency virus infection and CD4+ cell count of 444 per mm3, and with a viral load of 95,720 copies per mL, developed a rapidly progressive cerebellar lesion one month after undergoing coronary artery bypass graft. Diagnostic data were unremarkable with the exception of the magnetic resonance imaging that revealed multiple subcortical and cerebellar lesions consistent with a demyelinating process. The patient died within two months. Postmortem examination of the cerebellum revealed acute phase progressive multifocal leukoencephalopathy. This case demonstrates that multifocal leukoencephalopathy must be considered in HIV+ patients in the setting of neurologic deterioration with radiographic evidence of demyelination regardless of CD4+ count.

AIDS-Related Opportunistic Infections↗
PubMed1997

The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans.

In mammals, insulin signalling regulates glucose transport together with the expression and activity of various metabolic enzymes. In the nematode Caenorhabditis elegans, a related pathway regulates metabolism, development and longevity. Wild-type animals enter the developmentally arrested dauer stage in response to high levels of a secreted pheromone, accumulating large amounts of fat in their intestines and hypodermis. Mutants in DAF-2 (a homologue of the mammalian insulin receptor) and AGE-1 (a homologue of the catalytic subunit of mammalian phosphatidylinositol 3-OH kinase) arrest development at the dauer stage. Moreover, animals bearing weak or temperature-sensitive mutations in daf-2 and age-1 can develop reproductively, but nevertheless show increased energy storage and longevity. Here we show that null mutations in daf-16 suppress the effects of mutations in daf-2 or age-1; lack of daf-16 bypasses the need for this insulin receptor-like signalling pathway. The principal role of DAF-2/AGE-1 signalling is thus to antagonize DAF-16. daf-16 is widely expressed and encodes three members of the Fork head family of transcription factors. The DAF-2 pathway acts synergistically with the pathway activated by a nematode TGF-beta-type signal, DAF-7, suggesting that DAF-16 cooperates with nematode SMAD proteins in regulating the transcription of key metabolic and developmental control genes. The probable human orthologues of DAF-16, FKHR and AFX, may also act downstream of insulin signalling and cooperate with TGF-beta effectors in mediating metabolic regulation. These genes may be dysregulated in diabetes.

Alternative Splicing↗
PubMed1997

Covalent cross-linking of fibronectin to fibrin is required for maximal cell adhesion to a fibronectin-fibrin matrix.

In a blood clot, fibrin and plasma fibronectin (pFN) are covalently cross-linked by activated factor XIII (factor XIIIa) to form pFN-fibrin multimers. To determine the functional significance of covalent pFN-fibrin interactions, we have developed an in vitro model which allows the incorporation of recombinant FN (recFN) molecules into a covalently cross-linked recFN-fibrin matrix. Using the baculovirus expression system, we have expressed recFN monomers composed of the amino-terminal 70-kDa region and the first 11 type III repeats (WT) with mutations in the glutamines at positions 3 and 4 (Q2) or at 3, 4, and 16 (Q3). Examination of the covalent incorporation of these recFNs into fibrin clots confirms that glutamines 3 and 4 are major participants in FN-fibrin cross-linking as the mutation of these sites reduces cross-linking efficiency by 65%. Additional mutation of the glutamine at position 16, however, eliminates >99% of cross-linking suggesting that it also may be factor XIIIa reactive. When the Q3 recFN-fibrin clots were used as substrates for cell adhesion, there was a decrease in both cell attachment and spreading when compared with the WT recFN-fibrin clots. These data demonstrate that for maximal cell attachment to a FN-fibrin clot, FN must be cross-linked to fibrin by factor XIIIa.

3T3 Cells↗
PubMed1997

The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export.

BACKGROUND: The human immunodeficiency virus (HIV-1) uses the viral protein Rev to regulate gene expression by promoting the export of unspliced and partially spliced viral transcripts. Rev has been shown to function in a variety of organisms, including Saccharomyces cerevisiae. The export activity of Rev depends on a nuclear export signal (NES), which is believed to interact either directly or indirectly with the nuclear pore complex to carry out its export function. Crm1p is a member of the importin-beta protein family, other members of which are known to be directly involved in nuclear import. Crm1p has recently been shown to contribute to nuclear export in vertebrate systems. Here, we have studied this mechanism of nuclear to cytoplasmic transport. RESULTS: Viable mis-sense mutations in the CRM1 gene substantially reduced or eliminated the biological activity of Rev in S. cerevisiae, providing strong evidence that Crm1p also contributes to transport of Rev NES-containing proteins and ribonucleoproteins in this organism. Crm1p interacted with FG-repeat-containing nuclear pore proteins as well as Rev, and we have demonstrated that the previously described two-hybrid interaction between Rev and the yeast nuclear pore protein Rip1p is dependent on wild-type Crm1p. CONCLUSIONS: We conclude that Crm1p interacts with the Rev NES and nuclear pore proteins during delivery of cargo to the nuclear pore complex. Our findings also agree well with current experiments on Crm1p orthologs in Schizosaccharomyces pombe and in vertebrate systems.

Biological Transport↗
PubMed1997

Regimens of IGF-I treatment in fetal pancreas transplantation.

Transplantation of fetal pancreas (FP) is a potential treatment for diabetes mellitus. FP has remarkable proliferative capacity and may be induced to expand sufficiently to provide a functional beta cell mass in adult recipients. We have demonstrated that local delivery of recombinant insulin-like growth factor-I (IGF-I) onto FP isografts is sufficient to reverse streptozotocin-induced diabetes in animals receiving as few as 4 fetal pancreata. In this current study we investigated other regimens of IGF-I delivery in an attempt to define whether its effects on FP required local delivery or whether other, more clinically feasible, forms of treatment would suffice. In our model, diabetic Lewis rats received isografts of 16 FP into the anterior thigh intramuscular (IM) site. In the group of FP recipients treated with vehicle alone, no animals converted to euglycemia (0/8). When the IM site was pretreated locally with 14 days of continuous IGF-I administration (69 micrograms/kg per day) prior to FP transplantation, 100% of the recipients (10/10) became euglycemic with a mean interval from transplant to euglycemia of 35 +/- 15 days (P < 0.001 when compared to vehicle alone). No significant advantage over the vehicle alone group was gained either when the FP tissue was cultured for 48 hr in the presence of IGF-I (100 micrograms/ml) and then implanted (27% conversion to euglycemia, 3/11) or when FP isografts were treated with continuous subcutaneous delivery of IGF-I (69 micrograms/kg per day over 14 days) distant from the transplant site (0% conversion to euglycemia, 0/6). IGF-I increased the rate of conversion to euglycemia either when delivered locally to FP isografts or when delivered to the transplant bed prior to transplantation. This suggests an active role of the IGF-I-treated transplant bed in the success of FP transplantation.

Animals↗
PubMed1997

Classifying sub-acute and non-acute patients: results of the New South Wales Casemix Area Network study.

In 1994 the New South Wales Casemix Area Network initiated a study to develop a classification and funding model for sub-acute and non-acute care. Thirty-five rehabilitation, geriatric, psychogeriatric and palliative care services were recruited into the study throughout eight area health services. The aim of the first phase, summarised here, was to capture and analyse a sufficiently large quantity of data to select those variables most likely to predict resource utilisation, for subsequent use in a detailed costing study. It is known that acute care diagnosis related groups are not predictive of costs in sub-acute care. This phase of the project confirmed that, in New South Wales, the most predictive variables were case type, functional status measures, impairment type for rehabilitation, phase for palliative care and severity of symptoms for palliative care. The resultant Phase 1 casemix classification, which has built on recent United States experience and studies in other Australian States, has been termed the New South Wales Sub-Acute and Non-Acute Patient (SNAP) Version 1 classification.

Activities of Daily Living↗
PubMed1997

Modified barium swallow does not affect how often PEGs are placed after stroke.

Dysphagia frequently follows stroke, but often resolves quickly. Percutaneous endoscopic gastrostomy (PEG) or other feeding tubes are placed to improve nutrition and hydration, and reduce the risk of aspiration pneumonitis. We evaluated the impact of modified barium swallow in determining PEG placements and the influence of specific swallowing abnormalities on PEG placement. The abnormalities assessed were presence of pharyngeal stasis and/or visualization of posterior pharyngeal transfer problems and aspiration of liquid or solids. A total of 302 patients with stroke were admitted to our hospital between 1989 and 1993, but only those with hemorrhagic or nonhemorrhagic stroke by computed tomographic (CT) scans or magnetic resonance imaging (MRI) or autopsy were included in our study. Patients with transient ischemic attacks (TIAs), central nervous system tumors, and traumas were excluded. Barium swallow studies were performed on 69 (23%) of patients; 49 (71%) were abnormal, based on aspiration of barium, pharyngeal stasis, or postpharyngeal transfer dysphagia. PEGs were placed in only 18% of those with abnormal studies. Of the patients with normal barium swallow studies, 25% had a PEG placed. Two hundred thirty-three patients underwent no barium swallow studies, but 11 (4.72%) of these had PEG placed. The rate of PEG placement was not related to any one of the abnormalities noted on the modified barium swallow. Rather, patients who received PEG had significant neurological deficits and increased prevalence of aspiration pneumonitis. The decision to insert PEG was made on clinical grounds and not on abnormal barium studies alone.

Aged↗
PubMed1997

Inhibition effect of shengma-gegen-tang on measles virus in Vero cells and human peripheral blood mononuclear cells.

Shengma-Gegen-Tang has long been used against measles virus in human peripheral blood mononuclear cells (PBMC) as well as in Vero cells. One hundred micrograms/ml Shengma-Gegen-Tang in PBMC displays significant anti-measles activity, whereas the same concentration in Vero cells does not. After eight days of infection, the release of virus is significantly suppressed by Shengma-Gegen-Tang in the case of PBMC. In addition, Shengma-Gegen-Tang has a selective stimulation to the secretion of cytokine TNF-alpha in PBMC. Time kinetic analysis indicated that the stimulation of secretion was rapid and could be detected only 2 hrs following the treatment of the PBMC. It rose to an optimal level in 8-12 hrs. These findings suggest that the magnification of anti-measles virus activity of this agent is lymphocyte dependent and may well be mediated by TNF-alpha.

Animals↗
PubMed1997

Superoxide production and antioxidant enzymes in ammonia intoxication in rats.

Injection of large doses of ammonium salts lead to the rapid death of animals. However, the molecular mechanisms involved in ammonia toxicity remain to be clarified. We have tested the effect of injecting 7 mmol/kg of ammonium acetate on the production of superoxide and on the activities of some antioxidant enzymes in rat liver, brain, erythrocytes and plasma. Glutathione peroxidase, superoxide dismutase and catalase activities were decreased in liver and brain (both in cytosolic and mitochondrial fractions) and also in blood red cells, while glutathione reductase activity remained unchanged. Superoxide production in submitochondrial particles from liver and brain was increased by more than 100% in both tissues. Both diminished activity of antioxidant enzymes and increased superoxide radical production could lead to oxidative stress and cell damage, which could be involved in the mechanism of acute ammonia toxicity.

Ammonia↗
PubMed1997

A study of the effects of bowel preparation on CEA levels in patients undergoing surveillance colonoscopy.

Mechanical bowel preparation has been postulated to be another cause of "false rise' of serum carcinoembryonic antigen (CEA) levels. Furthermore, it was shown that high-risk patients for colorectal cancer had a greater rise in serum CEA after bowel preparation. To verify these findings, a prospective study of 24 consecutive patients in our surgical endoscopic unit on the effect of mechanical bowel preparation of serum CEA level as carried out from January to March 1994. Blood samples were taken before and after bowel preparation for patients undergoing surveillance colonoscopy for various reasons. Our study did not show any relationship between serum CEA levels and bowel preparation. No rise of serum CEA was found even in high-risk patients after bowel preparation.

Adult↗
PubMed1997

Effects of a pre-training conditioning programme on basic military training attrition rates.

The medical attrition rates of 4 cohorts of recruits undergoing basic military training (BMT) were studied. They were grouped as follows: Group A (n = 3475), a mixture of fit and unfit recruits; Group B (n = 2081), consisting only of fit recruits; Group C (n = 940) comprising only unfit recruits who underwent a 4 to 6 weeks conditioning programme prior to being subjected to a similar 3-month BMT for all 3 groups and Group D (n = 2613) comprising unfit recruits who underwent an extended 4-month BMT. It was found that Group B [Relative risk (RR) = 0.26 95% confidence interval (CI) = 0.21, 0.33] and Group C (RR = 0.45 95% CI = 0.38, 0.62) had significantly lower medical attrition rates compared with Group A (RR = 1). Group D, however, did not show significantly lower attrition rates in spite of a more gradual training pace. When the unfit cohorts were compared, Group C (RR = 0.52 95% CI = 0.40, 0.67) had significantly lower attrition rates than Group D (RR = 1). The major cause of medical attrition in all groups was musculo-skeletal injuries sustained during training. Our results showed that a formal pre-training conditioning programme resulted in lower attrition during BMT and this reduction was more effective than training the recruits at a slower pace by extending the BMT by one month.

Adult↗
PubMed1997

Avian leukemias and lymphomas: interplay between retroviruses and herpesviruses.

Avian leukemias and lymphomas are caused primarily by retroviruses and herpesviruses. The protooncogenes activated by avian retroviral insertions in B & T-cell lymphomas will be summarized, with discussion on a new common insertion site, bravo, associated with RAV-O LTR insertion. Two novel interactions between avian retroviruses and Marek's disease herpesvirus (MDV) will be described: one involves direct interactions between putative viral oncoproteins and the other integrative recombination between these two viruses.

Alpharetrovirus↗
PubMed1997

Streptokinase entrapment in interdigitation-fusion liposomes improves thrombolysis in an experimental rabbit model.

The successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis. First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase+empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p < 0.05) in the percent clot lysis were observed between saline control (22.4 +/- 3.3%; mean +/- S.E.), free streptokinase (36.3 +/- 3.4%), and liposomal streptokinase (47.4 +/- 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 +/- 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 +/- 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets. When tested in rabbits immunized against streptokinase, liposomal (33.8 +/- 1.5%) but not free streptokinase (29.3 +/- 2.1%) showed significant thrombolytic activity compared to saline (22.4 +/- 3.3%) (p < 0.05). The thrombolytic activity was comparable to free streptokinase in non-immunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase.

Animals↗
PubMed1997

Closed head injuries in children following the use of a sarong cradle.

INTRODUCTION: Sarong cradles are unique to South-East Asian culture. Their use can lead to injuries from falls, over-enthusiastic rocking and defective equipment. We present 19 children who attended the Accident and Emergency (A&E) Department of a general hospital and who sustained injuries while in a sarong cradle. All had closed head injuries. METHODS AND MATERIALS: The data was collected over a 9-month period from September 1992 to May 1993. All patients with a documented history of fall following the use of a sarong cradle, were recruited into the study. The adults accompanying the patients were interviewed with a structured questionnaire. The information was recorded by the doctor in attendance. RESULTS: The ages of the 19 patients ranged from 13 days to 29 months. There were 17 Chinese, 1 Malay and 1 Indian. The types of closed head injuries included minor head injury with no external signs of injury, scalp lacerations, scalp haematomas and severe head injury with an extradural haematoma. The majority (14) were discharged from the A&E Department with head injury advice, 4 were admitted to the General Neurosurgical ward and one, to the Neurosurgical Intensive Care Unit. There were no fatalities in this group. The accidents happened while the children were either sleeping (14), playing (4) or feeding (1). CONCLUSIONS: While most head injuries sustained in this manner are usually mild, there is a potential that such injuries may lead to more serious injuries. Care givers who use the sarong cradle should be aware of the dangers and exercise due care during use.

Accidental Falls↗
PubMed1996

Regulation of interleukin-2 transcription by inducible stable expression of dominant negative and dominant active mitogen-activated protein kinase kinase kinase in jurkat T cells. Evidence for the importance of Ras in a pathway that is controlled by dual receptor stimulation.

Engagement of the T cell receptor induces the activation of several mitogen-activated protein kinase modules, including the extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK) cascades. Whereas extracellular signal-regulated kinase is activated by T cell receptor/CD3 ligation alone, activation of JNK requires co-stimulation by the CD28 receptor. Activation of MEKK-1, which acts as a mitogen-activated protein kinase kinase kinase in the JNK pathway, was also induced by CD3 plus CD28 (CD3/CD28) ligation in Jurkat cells. To study the significance of the JNK cascade in T lymphocytes, we established stable Jurkat cell lines that inducibly express dominant active (DA) or dominant negative (DN) MEKK-1. Whereas expression of DA-MEKK-1 resulted in the constitutive activation of JNK along with the transcriptional activation of the minimal interleukin-2 (IL-2) promoter, DN-MEKK-1 inhibited JNK responsiveness during CD3/CD28 co-stimulation. In addition to inhibiting CD3/CD28-induced IL-2 mRNA expression, DN-MEKK-1 abrogated the transcriptional activation of the IL-2 promoter and the distal nuclear factor of activated T cells (NFAT)-activating protein 1 (AP-1) response element in that promoter. A c-Jun mutant lacking activation sites for JNK also interfered with the activation of the distal NFAT/AP-1 complex, suggesting that the JNK pathway functions by controlling AP-1 response elements in the IL-2 promoter. Using inducible stable expression of DA- and DN-Ras in Jurkat cells, we found that Ras regulates JNK activation in these cells. Our results suggest that the dual ligation of CD3 and CD28 in T cells triggers a cascade of events that involve Ras, the JNK cascade, and one or more AP-1 response elements in the IL-2 promoter.

Base Sequence↗