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Biomedical subjects

G Ho

Publications and source records attributed to G Ho.

At least 37 records · Page 2Linked to original sources
PubMed1996

Receptor-mediated endocytosis of coagulation factor Xa requires cell surface-bound tissue factor pathway inhibitor.

Coagulation factor Xa is a plasma serine protease that catalyzes prothrombin to thrombin conversion, which, in turn, leads to the generation of the fibrin clot. Of the several parameters that govern the plasma level of factor Xa, control of its catabolism is of crucial importance. However, little is known regarding the mechanisms by which factor Xa is catabolized. In the present study we examine the cellular basis for the uptake and degradation of factor Xa. 125I-Factor Xa was degraded by hepatoma cells and embryonic fibroblasts via a process which required cell surface-bound tissue factor pathway inhibitor (TFPI), a potent inhibitor of factor Xa. Uptake and degradation of cell surface-bound 125I-TFPI was also markedly stimulated in response to factor Xa binding. The intracellular kinetics of 125I-factor Xa and cell surface-bound 125I-TFPI display a strikingly similar pattern, suggesting that factor Xa and cell surface-bound TFPI are taken up as a bimolecular complex. Using cell lines either deficient in low density lipoprotein receptor-related protein, an endocytic receptor that mediates the degradation of uncomplexed TFPI (Warshawsky, I., Broze, G.J., Jr., and Schwartz, A.L. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 6664-6668), or deficient in tissue factor (TF), an integral membrane protein capable of forming quarternary complexes with factor Xa, TFPI, and factor VIIa, we demonstrated that the receptor that mediates the uptake and degradation of factor Xa-TFPI complex was neither low density lipoprotein receptor-related protein nor TF. As the vascular endothelial cell surface retains a substantial pool of TFPI (Sandset, P.M., Alildgaard, U., and Larsen, M.L. (1988) Thromb. Res. 50, 803-813; Novotny, W.F., Brown, S.G., Miletich, J.P., Rader, D.J., and Broze, G.J., Jr. (1991) Blood 78, 387-393), our data suggest that endothelial cell surface TFPI may be actively involved in the clearance of factor Xa from the circulation via mediated uptake and degradation.

Cell Line↗
PubMed1996

Automated system for detailed measurement of respiratory mechanics.

OBJECTIVE: The mechanical properties of the respiratory system (i.e., elastance and resistance) depend on the frequency, tidal volume, and shape of the flow waveform used for forcing. We developed a system to facilitate accurate measurements of elastance and resistance in laboratory and clinical settings at the frequencies and tidal volumes in the physiologic range of breathing. METHODS: A personal computer (PC) is used to drive a common clinically used ventilator while simultaneously collecting measurements of airway flow, airway pressure, and esophageal pressure from the experimental subject or animal at different frequencies and tidal volumes. Analysis analogous to discrete Fourier transform at the fundamental frequency (i.e., ventilator setting) is used to calculate elastances and resistances of the total respiratory system and its components, the lungs and the chest wall. We have shown that this analysis is independent of the high-frequency harmonics that are present in the waveform from clinical ventilators. RESULTS: The system has been used successfully to make measurements in anesthetized/paralyzed dogs and awake or anesthetized human volunteers in the laboratory, and in anesthetized human volunteers in the laboratory, and in anesthetized humans in the operating room and intensive care unit. Elastances and resistances obtained with this approach are the same as those obtained during more controlled conditions, e.g., sinusoidal forcing. CONCLUSIONS: Accurate, standardized measurements of lung and chest wall properties can be obtained in many settings with relative ease with the system described. These properties, and their frequency and tidal volume dependences in the physiologic range, provide important information to aid in the understanding of changes in respiratory function caused by day-to-day conditions, clinical intervention and pathologies.

Airway Resistance↗
PubMed1995

Both the amino and carboxyl termini of Dictyostelium myosin essential light chain are required for binding to myosin heavy chain.

Dictyostelium myosin deficient in the essential light chain (ELC) does not function normally either in vivo or in vitro (Pollenz, R. S., Chen, T. L., Trivinos-Lagos, L., and Chisholm, R. L. (1992) Cell 69, 951-962). Since normal myosin function requires association of ELC, we investigated the domains of ELC that are necessary for binding to the myosin heavy chain (MHC). Deleting the NH2-terminal 11 or 28 amino acid residues (delta N11 or delta N28) or the COOH-terminal 15 amino acid residues (delta C15) abolished binding of the ELC to the MHC when the mutants were expressed in wild-type (WT) cells. In contrast, the ELC carrying deletion or insertion of four amino acid residues (D4 or I4) in the central linker segment bound the MHC in WT cells, although less efficient competition with WT ELC suggested that the affinity for the MHC is reduced. When these mutants were expressed in ELC-minus (mlcE-) cells, where the binding to the heavy chain is not dependent on efficient competition with the endogenous ELC, delta N28 and delta N11 bound to the MHC at 15% of WT levels and delta C15 did not bind to a significant degree. I4 and D4, however, bound with normal stoichiometry. These data indicate that residues at both termini of the ELC are required for association with the MHC, while the central linker domain appears to be less critical for binding. When the mutants were analyzed for their ability to complement the cytokinesis defect displayed by mlcE- cells, a correlation to the level of ELC carried by the MHC was observed, indicating that a stoichiometric ELC-MHC association is necessary for normal myosin function in vivo.

Animals↗
PubMed1995

Septic bursitis.

Nine cases of septic bursitis are presented, and the literature on the subject comprehensively reviewed, with an emphasis on the clinical manifestations of septic bursitis in various anatomic locations. Physical activities associated with increased susceptibility to septic bursitis and systemic conditions that increase the severity of septic bursitis are catalogued. Analysis of the microbiology of cases reported in the literature demonstrates that greater than 80% of cases of septic bursitis are caused by Staphylococcus aureus and other gram-positive organisms. However, a wide variety of gram-negative microorganisms, fungi, and other infectious agents have been reported to cause septic bursitis and may lead to complications in diagnosis and treatment. The nine cases reported here demonstrate the potential severity of septic bursitis and emphasize that significant systemic complications may result from this common musculoskeletal infection. Indications for hospitalization and/or intravenous antibiotic therapy for septic bursitis include the presence of fulminant local infection, evidence for systemic toxicity, or infection in an immunocompromised patient. Patients who fail to respond to intravenous antibiotics and percutaneous aspiration of the bursa may require surgical drainage or bursectomy by one of several methods that have been proposed. There is some recent evidence that intrabursal corticosteroid injection for therapy of nonseptic subcutaneous bursitis may be more effective than systemic antiinflammatory medication or simple bursa aspiration.

Adult↗
PubMed1995

Targeted disruption of the Dictyostelium myosin essential light chain gene produces cells defective in cytokinesis and morphogenesis.

We have previously demonstrated that the myosin essential light chain (ELC) is required for myosin function in a Dictyostelium cell line, 7-11, in which the expression of ELC was inhibited by antisense RNA overexpression. We have now disrupted the gene encoding the ELC (mlcE) in Dictyostelium by gene targeting. The mlcE- mutants provide a clean genetic background for phenotypic analysis and biochemical characterization by removing complications arising from the residual ELC present in 7-11 cells, as well as the possibility of mutations due to insertion of the antisense construct at multiple sites in the genome. The mlcE- mutants, when grown in suspension, exhibited the typical multinucleate phenotype observed in both myosin heavy chain mutants and 7-11 cells. This phenotype was rescued by introducing a construct that expressed the wild-type Dictyostelium ELC cDNA. Myosin purified from the mlcE- cells exhibited significant calcium ATPase activity, but the actin-activated ATPase activity was greatly reduced. The results obtained from the mlcE- mutants strengthen our previous conclusion based on the antisense cell line 7-11 that ELC is critical for myosin function. The proper localization of myosin in mlcE- cells suggests that its phenotypic defects primarily arise from defective contractile function of myosin rather than its mislocalization. The enzymatic defect of myosin in mlcE- cells also suggests a possible mechanism for the observed chemotactic defect of mlcE- cells. We have shown that while mlcE- cells were able to respond to chemoattractant with proper directionality, their rate of movement was reduced. During chemotaxis, proper directionality toward chemoattractant may depend primarily on proper localization of myosin, while efficient motility requires contractile function. In addition, we have analyzed the morphogenetic events during the development of mlcE- cells using lacZ reporter constructs expressed from cell type specific promoters. By analyzing the morphogenetic patterns of the two major cell types arising during Dictyostelium development, prespore and prestalk cells, we have shown that the localization of prespore cells is more susceptible to the loss of ELC than prestalk cells, although localization of both cell types is abnormal when developed in chimeras formed by mixing equal numbers of wild-type and mutant cells. These results suggest that the morphogenetic events during Dictyostelium development have different requirements for myosin.

Animals↗
PubMed1994

Bacterial endocarditis and septic arthritis presenting as polymyalgia rheumatica.

We describe a case of enterococcus endocarditis in a 74-year-old woman with hypercholesterolemia, porcine aortic valve, and osteoarthritis. She presented with the abrupt onset of severe back pain, proximal myalgia, and left knee synovitis, associated with an anemia and marked elevation of ESR. She was misdiagnosed as having polymyalgia rheumatica until both the synovial fluid and blood cultures grew enterococcus. Her musculoskeletal symptoms totally resolved with antibiotic treatment. Septic arthritis is a rare manifestation of bacterial endocarditis. However, one-third of all cases of bacterial endocarditis have musculoskeletal symptoms. These include backache, arthritis of the peripheral joints, and diffuse myalgia and arthralgia. Unexplained rheumatic complaints should alert us to the possibility of bacterial endocarditis.

Aged↗
PubMed1993

Gout and pseudogout in hospitalized patients.

BACKGROUND: We determined the clinical characteristics of acute gout and pseudogout in hospitalized patients and examined the morbidity of inappropriate treatment and misdirected investigation when the diagnosis of acute crystal-induced synovitis was delayed. PATIENTS AND METHODS: We reviewed the medical records of 67 hospitalized adults seen in consultation consecutively by one hospital-based rheumatologist during a 64-month period between 1986 and 1991 with the diagnosis of acute gout or pseudogout. RESULTS: Gout was diagnosed in 41 patients, pseudogout in 24, and both crystal-induced diseases in two. The average age was 75.3 years. Polyarticular disease was common in both gout (49%) and pseudogout (42%). Fever attributable to synovitis was present in 34% of the patients and was more prevalent in patients with polyarticular (50%) than monoarticular (20%) inflammation. A quarter of the patients encountered errors in diagnosis, treatment, or both before rheumatologic consultation. Eleven patients experienced delays in diagnosis, and six patients had the correct diagnosis but received ineffective treatment. CONCLUSIONS: Fever and polyarticular arthritis are noteworthy features in the hospitalized patient with acute gout or pseudogout. When the diagnosis of crystal-induced synovitis is overlooked, misdirected investigation and inappropriate treatment compound the morbidity of continued pain.

Adult↗
PubMed1993

Hypoxic forebrain cholinergic neuron injury: role of glucose, excitatory amino acid receptors and nitric oxide.

Glucose depletion increased sensitivity to hypoxic insult in basal forebrain forebrain cultures in a dose-dependent manner as indicated by reduction of choline acetyltransferase (ChAT) activity, increased lactate dehydrogenase (LDH) release and disrupted morphology. The glutamate receptor antagonists 2-amino-5-phosphonovaleric acid (APV) and 6-cyano-2,3-nitroquinoxoline (CNQX) limited the degree of injury in combination and individually. The nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine (NNLA) also either completely protected against mild injury or attenuated severe injury.

2-Amino-5-phosphonovalerate↗
PubMed1993

Bacterial arthritis.

The 1992 literature on septic arthritis reiterated the factors that portend a poor outcome in septic arthritis. However, we still know very little about how to improve the outcome for such patients. Infections of the musculoskeletal system may be more common among patients with HIV than the reported cases indicate. Bacterial endocarditis is frequently associated with musculoskeletal complaints. Low back pain may be a presenting manifestation. Acute gout and septic arthritis can cause peripheral arthritis in some patients with bacterial endocarditis. Septic arthritis can present unusual manifestations and can occur as a complication of arthroscopic surgery; the risk factors for its development after arthroscopy have been identified. Arthroscopy as a therapeutic procedure to drain an infected joint is discussed.

Adult↗
PubMed1992

Effects of analysis method and forcing waveform on measurement of respiratory mechanics.

The respiratory system has been shown to exhibit nonlinear mechanical properties in the frequency (f) range of normal breathing, manifested by tidal volume (Vt) dependence. Calculations of respiratory system resistance (R) and elastance (E) from pressure-flow measurements during external forcing at a given f may be ambiguous, especially if non-sinusoidal forcing waveforms are used. We evaluated the degree to which R and E depended upon: (1) analysis method (Fourier transform, multiple regression and pressure-volume loop analysis) and; (2) shape of the forcing waveform (sinusoidal, quasi-sinusoidal and step). We measured pressure and flow at the mouth of 5 healthy, awake subjects, relaxed at functional residual capacity, during forcing with the three different waveforms in the normal range of f (0.2-0.6 Hz) and Vt (250-750 ml). During sinusoidal forcing, E and R were not affected by analysis method (P greater than 0.2). With Fourier transform and multiple regression, E was not affected by waveform shape (P greater than 0.05); with loop analysis, E was slightly (less than 10%) higher during quasi-sinusoidal and step forcing than during the sine (P less than 0.05). R was least affected by waveform shape with Fourier transform. We conclude that, in the f and Vt range of normal breathing: (1) respiratory system impedance is 'quasi-linear,' i.e. despite dependencies of R and E on Vt, non-linearities are not large enough to restrict interpretation of R and E at a given f and Vt; (2) it may be possible to measure R and E using non-sinusoidal forcing waveforms available on most clinical ventilators, incurring only modest error.

Adult↗
PubMed1992

Bacterial arthritis.

The 1991 literature on septic arthritis included a concise review of adult septic arthritis, examples of pseudoseptic arthritis, and two interesting animal studies. One animal study examined the induction of acute synovitis by the intra-articular injection of bacterial endotoxin and the cytokines tumor necrosis factor-alpha, and interleukin-1 beta; and the other studied the effects of early and delayed synovectomy in the management of septic arthritis. The predispositions to septic arthritis can be divided into local joint abnormalities, systemic factors, or both. Examples of the local joint abnormalities include osteoarthritis of the hip and apatite-associated arthropathy. Septic arthritis in a patient with rheumatoid arthritis, in a patient with diabetes mellitus and hip arthropathy associated with hemochromatosis, or in a patient with acquired immunodeficiency syndrome and hemophilic arthropathy are examples of how systemic predisposition is coupled with local joint pathology to increase the vulnerability of the host to joint infection. Other examples of systemic disease that predispose to septic arthritis are systemic lupus erythematosus, hypogammaglobulinemia, and human immunodeficiency virus infection, as well as intravenous drug abuse. Unusual microorganisms causing septic arthritis in the adult include Achromobacter xylosoxidans, Moraxella catarrhalis, meningococci, and diphtheroids. Uncommon pathogenesis is represented by a case of intra-articular inoculation of Mycobacterium gastri into the small joint of the hand and a case of mixed bacterial infection of the hip resulting from an extension of a contiguous pelvic infection associated with trauma. Two cases of immune complex glomerulonephritis illustrate the extra-articular complications of septic arthritis: one due to group G streptococcus and the other due to pneumococcus. Finally, septic bursitis is reviewed from the community practice perspective.

Animals↗
PubMed1991

Bacterial arthritis.

In this review of the 1990 septic arthritis literature, we revisit synovial fluid leukocytosis, examine the utility of synovial fluid glucose and protein measurements, and look at the levels of two cytokines, tumor necrosis factor and interleukin-1, in infected joint fluids. We see the many faces of gonococcal arthritis and the ravages of septic arthritis when the host has rheumatoid arthritis. Should we recommend antibiotic prophylaxis for the rheumatoid patient with a prosthetic joint who is undergoing a procedure that leads to transient bacteremia? What are some of the salient features of septic arthritis when it involves the sternoclavicular or sacroiliac joints? We also look at some unusual microorganisms, eg, group C Streptococcus, Streptococcus viridans, Listeria monocytogenes, Pseudomonas cepacia, Pseudomonas maltophilia, and Neisseria sicca. In patients with acquired immunodeficiency syndrome, we encounter reports of septic arthritis, osteomyelitis, and spinal epidural abscess caused by opportunistic microorganisms. Two unusual sites of infection include the C1-2 lateral facet joint and subacromial bursa without involvement of the glenohumeral joint. Finally, we examine how to drain a septic knee: the orthopedic point of view.

Arthritis, Infectious↗