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Biomedical subjects

L Wong

Publications and source records attributed to L Wong.

At least 55 records · Page 3Linked to original sources

Needle-tract implantation from hepatocellular cancer: is needle biopsy of the liver always necessary?

Percutaneous needle biopsies are frequently used to evaluate focal lesions of the liver. Needle-tract implantation of hepatocellular cancer has been described in case reports, but the true risk for this problem has not been clearly defined. We retrospectively reviewed 91 cases of hepatocellular cancer during a 4-year period from 1994 to 1997. Data on diagnostic studies, therapy, and outcome were noted. Of 91 patients with hepatocellular cancer, 59 patients underwent percutaneous needle biopsy as part of their diagnostic workup for a liver mass. Three patients (5.1%) were identified with needle-tract implantation of tumor. Two patients required en bloc chest wall resections for implantation of hepatocellular cancer in the soft tissues and rib area. The third patient, who also received percutaneous ethanol injection of his tumor, required a thoracotomy and lung resection for implanted hepatocellular cancer. Percutaneous needle biopsy of suspicious hepatic lesions should not be performed indiscriminately because there is a significant risk for needle-tract implantation. These biopsies should be reserved for those lesions in which no definitive surgical intervention is planned and pathological confirmation is necessary for a nonsurgical therapy.

Adult↗

Development of multi-species consortia biofilms of oral bacteria as an enamel and root caries model system.

The aim was to establish defined-species consortium plaque biofilms to investigate enamel and root caries in an artificial mouth. Strains of the putative enamel and root caries pathogens, Streptococcus mutans, Strep. sobrinus, Actinomyces naeslundii and Lactobacillus rhamnosus, were screened in batch culture for potential cariogenic properties: a low terminal pH, ability to aggregate, and catabolic diversity. The strains selected were grown as monoculture biofilms and as consortium plaque biofilms in a multiplaque artificial mouth. The biofilms were supplied with a constant flow of a simulated oral fluid and were given periodic sucrose (and in some instances glucose) to simulate meals. All the bacteria except L. rhamnosus formed large, monospecies biofilms with resting pH in the range 5.3-5.8. The consortia biofilms were larger and had a resting pH of 4.9-5.3. The consortia biofilms supplied with 8-hourly carbohydrate comprised mainly 'mutans' streptococci (58, SD 5.5%) and L. rhamnosus (42, SD 5.7%). A. naeslundii characteristically was absent or present in a low percentage (up to 4% colony-forming units). All biofilms demineralized polished bovine enamel and dentine blocks, as assessed by microradiography and enamel-surface microhardness measurement. The consortia also demineralized intact enamel and tooth roots; they were more cariogenic to enamel than any of the monoculture biofilms, as measured by enamel-surface softening, but variation in lesion depth was proportional to biofilm wet weight irrespective of acidogen composition (r = 0.93, p < 0.05). Enamel lesions had a well-mineralized intact surface and a zone of subsurface demineralization, typical of early natural lesions. Dentine and root lesions showed extensive demineralization but lacked a pronounced surface mineralized zone. Substitution of glucose for sucrose had no effect on the cariogenicity of the consortium to bovine enamel or human roots and had no major effect on the plaque composition. Continuously supplied fluoride (19 parts/10(6)) resulted in a substantially reduced enamel surface softening and subsurface demineralization of intact roots. It was concluded that consortia biofilms of selected caries pathogens generate realistic caries lesions in all tooth hard tissues under controlled growth conditions in the artificial mouth. This in vitro caries experimental model may prove useful for the study of interrelations between the plaque biofilm, tooth tissues and the oral environment, and for the development of procedures to modify the course of caries development.

Actinomyces↗

Progressive supranuclear palsy.

Here we describe the case of a 69-year-old Caucasian male who presented complaining of frequent diplopia (horizontal and vertical), as well as transient blurry vision. The subsequent findings were most consistent with a progressive supranuclear palsy (PSP).

Journal Article↗

Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator.

BACKGROUND: Urokinase-type plasminogen activator (uPA) is a protease associated with tumor metastasis and invasion. Inhibitors of uPA may have potential as drugs for prostate, breast and other cancers. Therapeutically useful inhibitors must be selective for uPA and not appreciably inhibit the related, and structurally and functionally similar enzyme, tissue-type plasminogen activator (tPA), involved in the vital blood-clotting cascade. RESULTS: We produced mutagenically deglycosylated low molecular weight uPA and determined the crystal structure of its complex with 4-iodobenzo[b]thiophene 2-carboxamidine (K(i) = 0.21 +/- 0.02 microM). To probe the structural determinants of the affinity and selectivity of this inhibitor for uPA we also determined the structures of its trypsin and thrombin complexes, of apo-trypsin, apo-thrombin and apo-factor Xa, and of uPA, trypsin and thrombin bound by compounds that are less effective uPA inhibitors, benzo[b]thiophene-2-carboxamidine, thieno[2,3-b]-pyridine-2-carboxamidine and benzamidine. The K(i) values of each inhibitor toward uPA, tPA, trypsin, tryptase, thrombin and factor Xa were determined and compared. One selectivity determinant of the benzo[b]thiophene-2-carboxamidines for uPA involves a hydrogen bond at the S1 site to Ogamma(Ser190) that is absent in the Ala190 proteases, tPA, thrombin and factor Xa. Other subtle differences in the architecture of the S1 site also influence inhibitor affinity and enzyme-bound structure. CONCLUSIONS: Subtle structural differences in the S1 site of uPA compared with that of related proteases, which result in part from the presence of a serine residue at position 190, account for the selectivity of small thiophene-2-carboxamidines for uPA, and afford a framework for structure-based design of small, potent, selective uPA inhibitors.

Amidines↗

Assessing the in vitro cell based ocular compatibility of contact lens materials.

A series of in vitro assays for determining the biocompatibility of ocular biomaterials have been developed and used to assess the differences in performance of omafilcon A, etafilcon A and nelfilcon A contact lens materials. The assays assessed bacterial attachment, macrophage adhesion, granulocyte adhesion and activation, epithelial cell adhesion and corneal cell contact damage. Overall, omafilcon A was found to be more biocompatible than the other materials although there was no significant difference between the epithelial cell adhesion and granulocyte adhesion and activation on any of the hydrogels. Etailcon A performed less well compared to nelfilcon A and omafilcon A with respect macrophage adhesion and bacterial adhesion. The results indicate that these biological assays can be successfully applied for the testing of contact lens materials and may be particularly useful in the in vitro screening of new extended wear contact lens materials where cell adhesion and activation may have a greater influence on clinical performance.

Journal Article↗

Autonomously replicating macronuclear DNA pieces are the physical basis of genetic coassortment groups in Tetrahymena thermophila.

The macronucleus of the ciliate Tetrahymena thermophila contains a fragmented somatic genome consisting of several hundred identifiable chromosome pieces. These pieces are generated by site-specific fragmentation of the germline chromosomes and most of them are represented at an average of 45 copies per macronucleus. In the course of successive divisions of an initially heterozygous macronucleus, the random distribution of alleles of loci carried on these copies eventually generates macronuclei that are pure for one allele or the other. This phenomenon is called phenotypic assortment. We have previously reported the existence of loci that assort together (coassort) and hypothesized that these loci reside on the same macronuclear piece. The work reported here provides new, rigorous genetic support for the hypothesis that macronuclear autonomously replicating chromosome pieces are the physical basis of coassortment groups. Thus, coassortment allows the mapping of the somatic genome by purely genetic means. The data also strongly suggest that the random distribution of alleles in the Tetrahymena macronucleus is due to the random distribution of the MAC chromosome pieces that carry them.

Alleles↗

Reconstruction of complex cranial wounds with demineralized bone matrix and bilayer artificial skin.

Complex wounds involving loss of both cranium and scalp are difficult to reconstruct. Current solutions include both autogenous and alloplastic materials. Tissue engineering provides interesting alternatives for reconstruction of missing bone and soft tissue. Demineralized bone matrix and Integra, artificial bilayer skin substitute, have been used successfully to reconstruct bone and skin as isolated defects, but never in combination. This study investigates the possibility of using demineralized bone matrix in a gel carrier and Integra for combined cranial and scalp defects. The study was divided into two parts. In the first, demineralized bone matrix in the forms of Grafton Flex (n = 12) and Grafton putty (n = 12) was used to reconstruct 15-mm critical size cranial defects in female adult New Zealand White rabbits. In the control group (n = 6), the defect was left empty. The second part of the study investigated the use of Integra and Grafton Flex to reconstruct a 15-mm cranial defect with an overlying full-thickness scalp defect (n = 6). The first study revealed bony healing of the critical-size cranial defect with demineralized bone matrix. The second study demonstrated successful reconstitution of scalp and cranium with both demineralized bone matrix and Integra. We conclude that complex cranial defects involving bone and soft tissue may be successfully reconstructed with their tissue-engineered substrates, demineralized bone matrix (Grafton) and Integra artificial skin.

Absorptiometry, Photon↗

Efficacy and cognitive effects of right unilateral electroconvulsive therapy.

The efficacy, memory, and cognitive effects of right unilateral (RUL) electroconvulsive therapy (ECT) at 2.5 times threshold in 32 inpatients with moderate to severe major depressive disorder were evaluated at baseline, during the course of treatment, and 1 month after treatment. Neuropsychological assessment included the Randt Memory Test, Personal Memory Test, short-version Wechsler Adult Intelligence Scale-Revised, and Self-Rating Scale of Memory Functions. At the treatment end point, although the Hamilton Depression Rating Scale mean score was decreased by 54.2%. the response rate of 2.5 times threshold RUL ECT using stringent criteria was only 31.2%. Treatment was associated with significant anterograde memory impairment in the short term. Mean total scores of the Randt Memory Test and Personal Memory Test were decreased from baseline by 14.8% and 32.5%, respectively, after six sessions of ECT. These memory deficits were significantly improved by the 1 month follow-up examination. Subjective memory scores increased consistently during treatment, correlating with improvements in mood. No adverse effects on nonmemory cognition were found. Although RUL ECT at 2.5 times threshold is not associated with marked or persistent cognitive disturbances, its efficacy may be insufficient in clinical practice.

Adult↗

Carboxy terminus of human herpesvirus 8 latency-associated nuclear antigen mediates dimerization, transcriptional repression, and targeting to nuclear bodies.

Human herpesvirus 8 (HHV-8; also known as Kaposi's sarcoma-associated herpesvirus) is the causative agent of Kaposi's sarcoma and certain B-cell lymphomas. In most infected cells, HHV-8 establishes a latent infection characterized by the expression of latency-associated nuclear antigen (LANA) encoded by open reading frame 73. Although unrelated by sequence, there are functional similarities between LANA and the EBNA-1 protein of Epstein-Barr virus. Both accumulate as subnuclear speckles and are required for maintenance of the viral episome. EBNA-1 also regulates viral gene expression and is required for cell immortalization, suggesting that LANA performs similar functions in the context of HHV-8 infection. Here we show that LANA forms stable dimers, or possibly higher-order multimers, and that this is mediated by a conserved region in the C terminus. By expressing a series of truncations, we show that both the N- and C-terminal regions localize to the nucleus, although only the C terminus accumulates as nuclear speckles characteristic of the intact protein. Lastly, we show that LANA can function as a potent transcriptional repressor when tethered to constitutively active promoters via a heterologous DNA-binding domain. Domains in both the N and C termini mediate repression. This suggests that one function of LANA is to suppress the expression of the viral lytic genes or cellular genes involved in the antiviral response.

Amino Acid Sequence↗

Differential response to low-fat diet between low and normal HDL-cholesterol subjects.

Heart attacks frequently occur in normolipidemic subjects with low concentration of high density lipoproteins (</=35 mg/dL). A low-fat diet is generally recommended to patients with coronary heart disease. A low-fat diet decreases both low density (LDL) and high density lipoproteins (HDL). We have shown that on an Average American Diet, subjects with different HDL-cholesterol (HDL-C) levels have different HDL subpopulation profiles. In low HDL-C subjects (</=35 mg/dL), the apoA-I-only subpopulation alpha(1) is significantly decreased compared to individuals with normal HDL-C levels (>35 mg/dL). We hypothesized that as subjects with low HDL-C already have low HDL concentrations, the major decrease of HDL-C will occur in subjects with normal HDL-C when a low-fat diet is consumed. Normolipidemic male subjects consumed three diets differing in total fat and saturated fat composition (AAD: 37%, Step-1: 28%, Step-2: 24% total fat) for 6 weeks in a three-period double-blind randomized crossover design. Plasma lipids and apolipoproteins were determined and changes in distribution of HDL subpopulations were evaluated. As a result of a low-fat diet, low HDL-C individuals slightly decreased their HDL-C, but substantially decreased their LDL-C resulting in a significant improvement in the LDL-C/HDL-C ratio. However, subjects with normal HDL-C levels decreased both their LDL-C and HDL-C resulting in an unchanged LDL-C/HDL-C ratio. We also observed significant differences in response to low-fat diets in HDL-C and alpha(1) concentrations between low and normal HDL-C subjects. In the normal HDL-C group, consumption of a low-fat diet also resulted in redistribution of apoA-I-containing HDL subpopulations, indicated by a decrease in the large apoA-I-only alpha(1) subpopulation. These data demonstrate that male subjects with low HDL-C respond to a low-fat diet differently than individuals with normal HDL-C.

Adult↗

Escharotomy and fasciotomy of the burned upper extremity.

Escharotomy and fasciotomy are performed in the burned upper extremity to prevent and treat the sequelae of circumferential full-thickness burns and high-voltage electrical burns. Indications to perform these procedures are determined primarily by clinical examination but can be supplemented by measurements of subfascial pressures. The techniques are designed to avoid further complications. Options for wound closure are discussed. The use of allograft as temporary coverage of fasciotomy incisions may allow delayed primary closure.

Arm Injuries↗

Microdochectomy for single-duct nipple discharge.

INTRODUCTION: Isolated single-duct nipple discharge is worrying and poses a surgical dilemma. Factors predicting malignancy are controversial. MATERIALS AND METHODS: Retrospective review of 92 consecutive microdochectomies for single-duct nipple discharge in a tertiary referral centre over 8 years. RESULTS: The commonest causes were ductal papilloma (52%) and fibrocystic diseases of the breast (21%). Five (5%) patients had breast carcinoma, of whom only 1 had an invasive component. The median age of these patients was 43 years (range 26 to 72 years) which was similar to median age of the whole cohort. Sixty-seven (73%) patients presented with blood-stained nipple discharge. The 5 patients with breast carcinoma had blood-stained discharge. Mammography was abnormal in 1 out of 4 patients in the carcinoma group. CONCLUSIONS: The incidence of breast carcinoma in patients presenting with isolated single-duct nipple discharge was low (5%) among Singaporean women. There was no reliable predictors of malignancy, though all patients with carcinoma presented with blood-stained discharge. Microdochectomy still remains an effective treatment for nipple discharge both for cure and diagnosis.

Adolescent↗

Attitudes on organ donation among Hawaii physicians.

A survey of physicians attending the recent Hawaii Medical Association meeting was conducted in order to assess physician attitudes on organ donation. Physicians were asked 6 questions and demographics were collected. Results indicate that Hawaii physicians generally support organ donation and are aware of some of the current federal legislation regarding donation.

Attitude of Health Personnel↗

Effects of a hemoglobin-based oxygen carrier (HBOC-201) on coagulation testing.

Polymerized bovine hemoglobin (HBOC-201) is currently under investigation as an alternative to blood banked human red cells. Due to the dark red, hemolyzed appearance of HBOC-201, we sought to describe the effects of HBOC-201 on coagulation analyzers that perform prothrombin times (PT), activated partial thromboplastin times, fibrinogen, and antithrombin. Pooled normal plasma was combined with HBOC-201 to achieve plasma hemoglobin levels of 1.4, 2.6 3.8, 4.8, and 6.2 g/dL. Results for each test from HBOC-201 prepared plasmas were compared to saline matched controls. Two consecutive absolute result differences of > 10% between saline controls and HBOC-201 samples were used for determining interference on test accuracy by the concentration of HBOC-201. Mechanical detection methods (fibrometer, STA, CS-190) and the MDA-180 were less affected by increasing levels of HBOC-201 than optical detection devices for all test parameters.

Blood Coagulation Tests↗

Visualization and manipulation of pedigree diagrams.

The Pedigree Visualizer is a system for visualization of pedigree diagrams. It accepts a simple text-based specification of a pedigree diagram. The pedigree diagram is then layout automatically. Both GIF- and PS-formatted output files are produced. In addition, the Pedigree Visualizer also provides a rich set of functions for the manipulation and management of large pedigree files.

Computational Biology↗

Cyclic 3-deaza-adenosine diphosphoribose: a potent and stable analog of cyclic ADP-ribose.

Cyclic 3-deaza-adenosine diphosphoribose (3-deaza-cADPR), an analog of cyclic adenosine diphosphoribose (cADPR) was synthesized. 3-deaza-cADPR differs from cADPR by only the substitution of carbon for nitrogen at the 3-position of the purine ring. Similar to cADPR, the analog has potent calcium releasing activity in sea urchin egg homogenates and was able to induce calcium release at concentrations as low as 0.3 nM. The EC(50) value for 3-deaza-cADPR-induced calcium release was 1 nM, which is about 70 times more potent than cADPR. The properties of calcium release induced by 3-deaza-cADPR in all other respects were similar to those of cADPR. Thus, 3-deaza-cADPR and cADPR were capable of cross-desensitizing each other and their calcium releasing activities were potentiated by Sr(2+) as well as caffeine. 8-amino-cADPR, a selective antagonist of cADPR, was also able to inhibit 3-deaza-cADPR induced calcium release. Taken together, these data suggest that 3-deaza-cADPR releases calcium through the same mechanism as cADPR. 3-deaza-cADPR was found to be resistant to both heat and enzymatic hydrolysis. Only 15% of 3-deaza-cADPR was destroyed after boiling this compound for 2 h. No loss of 3-deaza-cADPR was observed when treated with CD38 under conditions where cADPR was completely hydrolyzed. Thus, 3-deaza-cADPR is a potent and stable analog of cADPR. These properties should make 3-deaza-cADPR a useful probe in studies focused on the mechanism of cADPR action.

Adenosine Diphosphate Ribose↗