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Biomedical subjects

K Lam

Publications and source records attributed to K Lam.

At least 55 records · Page 3Linked to original sources

Regression estimator in ranked set sampling.

Ranked set sampling (RSS) utilizes inexpensive auxiliary information about the ranking of the units in a sample to provide a more precise estimator of the population mean of the variable of interest Y, which is either difficult or expensive to measure. However, the ranking may not be perfect in most situations. In this paper, we assume that the ranking is done on the basis of a concomitant variable X. Regression-type RSS estimators of the population mean of Y will be proposed by utilizing this concomitant variable X in both the ranking process of the units and the estimation process when the population mean of X is known. When X has unknown mean, double sampling will be used to obtain an estimate for the population mean of X. It is found that when X and Y jointly follow a bivariate normal distribution, our proposed RSS regression estimator is more efficient than RSS and simple random sampling (SRS) naive estimators unless the correlation between X and Y is low (/rho/ < 0.4). Moreover, it is always superior to the regression estimator under SRS for all rho. When normality does not hold, this approach could still perform reasonably well as long as the shape of the distribution of the concomitant variable X is only slightly departed from symmetry. For heavily skewed distributions, a remedial measure will be suggested. An example of estimating the mean plutonium concentration in surface soil on the Nevada Test Site, Nevada, U.S.A., will be considered.

Biometry↗

Reversible Ca2+-dependent translocation of protein kinase C and glucose-induced insulin release.

It has been reported that protein kinase C (PKC) interacts at multiple sites in beta-cell stimulus-secretion coupling. Nevertheless, there is still controversy concerning the importance of this enzyme in glucose-induced insulin release. The present study was undertaken to clarify whether glucose, directly, or through changes in cytoplasmic free Ca2+ concentration, [Ca2+]i, could promote translocation of PKC from the soluble to the membrane compartment. Whereas glucose, which increases [Ca2+]i, did not affect long-term distribution of PKC activity between soluble and membrane fractions, this distribution was reversibly affected acutely by the Ca2+ concentration in the extraction media. Translocation of PKC to the membrane by incubation of HIT cells for 10 min in the presence of 20 nM phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a 5-fold increase in glucose-induced insulin release. This was prevented by 50 nM concentration of the PKC inhibitor staurosporine, provided that the cells were exposed to the inhibitor before the phorbol ester. Cells pretreated with TPA demonstrated increased insulin secretion in response to glucose for several hours. This time course extended beyond the disappearance of [3H]TPA from the cells, which was complete after 1 h. Activation of PKC increased both average insulin release and the amplitude of oscillations 2-fold, but did not affect oscillation frequency. The stimulatory effect of increased PKC activity on insulin release was not matched by changes in [Ca2+]i. We suggest that stimulation of the pancreatic beta-cell with glucose promotes transient translocation of certain PKC isoforms from the cytoplasm to the plasma membrane as a direct consequence of the increase in [Ca2+]i. Such a translocation may promote phosphorylation of one or several proteins involved in the regulation of the beta-cell stimulus-secretion coupling. This results in potentiation of glucose-induced activation of insulin exocytosis, an effect then not mediated by an increase in [Ca2+]i per se. Hence, pulsatile insulin release can be obtained under conditions where overall [Ca2+]i does not change, challenging the view that oscillations in [Ca2+ ]i are indeed driving the oscillations in hormone release.

Animals↗

Expression of A-myb, but not c-myb and B-myb, is restricted to Burkitt's lymphoma, sIg+ B-acute lymphoblastic leukemia, and a subset of chronic lymphocytic leukemias.

The A-myb gene encodes a transcription factor that is related both functionally and structurally to the v-myb oncogene. Following our observations that A-myb is expressed in a restricted subset of normal mature human B lymphocytes, with the phenotype CD38+, CD39-, slgM-, we have now investigated the pattern of A-myb expression in neoplastic B cells representating the whole spectrum of B-cell differentiation and compared it to that of c-myb and B-myb. In a panel of 32 B-cell lines, A-myb was very strongly expressed in most Burkitt's lymphoma (BL) cell lines, but weak or negative in 2 pre-B acute lymphoblastic leukemia (ALL), 4 non-Hodgkin's lymphoma (NHL), 6 Epstein-Barr virus-immortalized lymphoblastoid cell lines, and 6 myeloma lines. Protein expression paralleled that of the RNA. We have also investigated A-myb expression in 49 fresh cases of B leukemias. Among 24 ALL, 6 were of the null and 11 of the common type and all these were negative for A-myb expression; on the other hand, all 7 B-ALL cases (slg+), as well as one fresh BL case with bone marrow infiltration, expressed A-myb. A-myb was undetectable in 4 prolymphocytic leukemias (PLL) but was strongly expressed in 5/20 (25%) of chronic lymphocytic leukemia (CLL) samples. In the latter A-myb did not correlate with phenotype or clinical stage. Finally, we have studied the progression of one case of CLL into Richter's syndrome and have found that the Richter's cells expressed about 25-fold less A-myb RNA than the CLL cells from the same patient. The pattern of c-myb and B-myb was clearly distinct from that of A-myb. C-myb and B-myb were expressed in all neoplastic groups, except in CLL cells. Thus, A-myb expression, unlike that of c-myb and B-myb, is restricted to a subset of B-cell neoplasias (in particular BL and slg+B-ALL) representative of a specific stage of B-cell differentiation. This expression may in part reflect expression of A-myb by the normal germinal center B cells that are the normal counterpart of these transformed B cells. The data presented strongly support a role for this transcription factor in B-cell differentiation and perhaps in B-cell transformation in some neoplasias.

B-Lymphocytes↗

Aging impairs afferent nerve function in rat intestine. Reduction of mesenteric hyperemia induced by intraduodenal capsaicin and acid.

The high incidence of peptic ulcer disease despite decreased acid secretion in the elderly suggests an impairment of mucosal defense mechanism with aging. Stimulation of the intestinal mucosal afferent nerves by intraduodenal application of capsaicin or hydrochloric acid (HCl) increases superior mesenteric artery (SMA) blood flow and protects the duodenal mucosa against deep damage. We tested the hypothesis that the intestinal hyperemia induced by intraduodenal capsaicin or HCL is significantly reduced in older (12 months) rats compared with younger (2 months) rats. Mesenteric blood flow was measured by pulsed Doppler flowmetry in anesthetized rats with the flow probe around the SMA. Two milliliters per kilogram of 160 microM capsaicin or 0.1 N HCl administered intraduodenally increased SMA blood flow significantly in both age groups. The peak response in SMA blood flow, however, was significantly smaller in the older rats than in the younger rats. These observations support the hypothesis that impairment of afferent nerve function occurs with aging in the rat intestine.

Afferent Pathways↗

Primary afferent nerves mediate in part beta-adrenoceptor stimulation-induced mesenteric hyperemia in rats.

We tested the hypothesis that in the rat duodenum and intestine the mesenteric hyperemia due to beta-adrenoceptor stimulation is mediated by capsaicin-sensitive afferent nerves. Superior mesenteric artery blood flow was measured by pulsed Doppler flowmetry in the anesthetized rat. Functional ablation of afferent nerves was accomplished by subcutaneous 125 mg/kg capsaicin pretreatment 10 to 14 days before blood flow studies. Blockade of capsaicin-sensitive cation-selective ion channels of the duodenal and intestinal mucosal afferent nerves was achieved by intraduodenal 0.1% ruthenium red given 15 min prior to the intraduodenal administration of 5 mg/kg isoproterenol. Functional ablation of the afferent nerves and blockade of the capsaicin-sensitive cation-selective ion channels alone or in combination resulted in a significant reduction of mesenteric hyperemia induced by intraduodenal isoproterenol. These data support the hypothesis that beta-adrenoceptor stimulation by intraduodenal isoproterenol induces mesenteric hyperemia in part through afferent nerves in the rat duodenal and intestinal mucosa. The results suggest for the first time a link between beta-adrenoceptor function and peripheral capsaicin-sensitive afferent nerve-mediated mechanism in the rat gut.

Afferent Pathways↗

Instructional technology in schools educating deaf and hard of hearing children: a national survey.

A survey on the availability of technology for instructional use was conducted by means of a mail questionnaire sent to schools that participate in the Annual Survey of Deaf and Hard of Hearing Children and Youth. Responses from 546 schools indicated that computers and printers are now commonplace, but inventories remain low for a sizable minority (42%) of schools. Center schools reported larger inventories of computers, printers, closed-caption decoders, and VCRs than were reported by local schools, but inventories of newer technologies such as CD-ROMs, videodiscs, and computer projection systems were low among both types of schools. The top needs indicated by schools were more equipment; more software, videocassettes, and other supporting materials; more teacher training; and more time for teachers to devote to instructional technology.

Child↗

Measurement of prostate movement over the course of routine radiotherapy using implanted markers.

PURPOSE: To measure the range and frequency of occurrence of intertreatment movement of the prostate gland over the course of radiotherapy, and to demonstrate that the prostate may move independently of the surrounding bones of the pelvis. METHODS AND MATERIALS: Ten patients underwent implantation of radiopaque markers around the prostate. Orthogonal portal films were taken at multiple stages during the course of treatment and digitized. An image registration tool was used to solve for film detector placement and, subsequently, to determine positional changes between structures on a reference portal image pair and all subsequent pairs for each patient. Transformations describing prostate movement were measured independently of those describing setup variations of the pelvic girdle. RESULTS: Translation and/or rotation of the prostate was detected in 70% of the treatments for which films were taken. The maximum measured displacement was 7.5 mm along a major axis. Typical translations of the prostate were between 0-4 mm. The translation and rotation had a predominant direction, suggesting a natural axis for prostate movement. CONCLUSION: Although significant prostate displacement can occur between treatments, the typical range of movement seen along a major axis was less than 5 mm. Proper treatment planning should consider the movement of the target independent of surrounding bony anatomy. Advances in online portal imaging, image registration, and dynamic field shaping may permit shaped fields that encompass the prostate gland in its position at the time of treatment, allowing for the use of smaller fields while ensuring proper target coverage.

Humans↗

Electron microscopy study of the mode of growth of Pseudomonas pseudomallei in vitro and in vivo.

The mode of growth of Pseudomonas pseudomallei in culture media and in the lung tissue of infected humans and animals was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). In culture media, P. pseudomallei cells were seen to be entrapped in microcolonies within large amounts of intercellular fibrous material. The lung tissue of infected humans and animals showed that bacterial cells growing in lung tissue were surrounded by radially arranged fibres that constitute a very well defined glycocalyx structure. In the infected areas of the animal lung tissue, bacterial cell could be seen to have formed glycocalyx enclosed microcolonies that displaced host cell components, e.g. the nucleus of a phagocyte. The presence of bacteria in unusual locations indicated that effective phagocytosis was not occurring. The demonstration that cells of P. pseudomallei produce exopolysaccharide glycocalyces and form glycocalyx enclosed microcolonies in laboratory media and in lung tissue of infected humans and animals and the presence of bacteria in unusual locations contribute to a new understanding of the mechanism whereby this organism can cause persistent chronic infections.

Animals↗

The phosphatidylinositol 3-kinase serine kinase phosphorylates IRS-1. Stimulation by insulin and inhibition by Wortmannin.

Phosphatidylinositol 3-kinase (PI 3-kinase) is a heterodimer composed of an 85-kDa subunit that binds tyrosyl-phosphorylated proteins via its SH2 domains and a 110-kDa catalytic subunit. Expression and mutagenesis experiments have shown that the 110-kDa subunit is a dual specificity kinase that possesses both lipid and serine kinase activities. Except for the 85- and 110-kDa subunits of PI 3-kinase, however, no endogenous substrates for the serine kinase have been identified. The results of the present study show that another target of this kinase is the insulin receptor substrate, IRS-1. Serine phosphorylation of IRS-1 as well as the 85-kDa subunit of PI 3-kinase was demonstrated in immunoprecipitates of PI 3-kinase and IRS-1 isolated from rat adipocytes incubated with insulin. In adipocytes incubated in the absence of insulin, only the serine phosphorylation of p85 was observed in immunoprecipitates of PI 3-kinase. Both the serine and lipid kinase activities of PI 3-kinase were abolished by the fungal metabolite Wortmannin. Wortmannin also partially inhibited the ability of insulin to stimulate glucose transport and inhibit lipolysis in fat cells. These data raise the possibility that the serine kinase activity of PI 3-kinase is involved in insulin signaling. They also suggest that inhibition of the lipid or serine kinase activities of PI 3-kinase could explain the effect of Wortmannin to diminish insulin action.

Adipocytes↗

Hydrophobic bile salt inhibits bacterial adhesion on biliary stent material.

Blockage of indwelling biliary stents is caused by biliary sludge, which forms as a result of bacteria adhering to the surface of the stent material and forming adherent biofilm. As the adherence of bacteria on plastic surface involves hydrophobic interaction of the plastic polymer and the bacterial cell wall, we tested if the detergent property of bile salts might retard bacterial adherence. Three common biliary pathogens isolated from the bile of patients suffering from acute suppurative cholangitis were used in this experiment: E. coli (O21:H25) which form pili and a glycocalyx; E. coli (O101:H9), non-piliated but with a glycocalyx, and Enterococcus fecalis without either pili or a glycocalyx. Polyethylene disks (1 cm2 diameter) were used for the in vitro adhesion study. They were continuously perfused by the bacterial suspension, flowing at 50 ml/hr at 37 degrees C for 24 hr. The suspending media used were sterile human bile and tryptic soy broth. Two different bile salts, taurocholate and taurodeoxycholate, were added to the perfusion media. The number of bacteria adhering to the surface was assessed by viable bacterial count, epifluorescence microscopy, and scanning electron microscopy. The results showed that E. coli (O21:H25) exhibited better adherence than the nonpiliated E. coli (O101:H9), which in turn was better than the non-pili-, non-glycocalyx-producing Enterococcus fecalis. When a more hydrophobic bile salt, taurodeoxycholate, was added at 25 or 50 mM to the tryptic soy broth or to the human bile, the adherence of the two E. coli strains were reduced 100- to 1000-fold (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Adhesion↗

Mechanism of electrical enhancement of efficacy of antibiotics in killing biofilm bacteria.

The bioelectric effect, in which electric fields are used to enhance the efficacy of biocides and antibiotics in killing biofilm bacteria, has been shown to reduce the very high concentrations of these antibacterial agents needed to kill biofilm bacteria to levels very close to those needed to kill planktonic (floating) bacteria of the same species. In this report, we show that biofilm bacteria are readily killed by an antibiotic on all areas of the active electrodes and on the surfaces of conductive elements that lie within the electric field but do not themselves function as electrodes. Considerations of electrode geometry indicate that very low (< 100 microA/cm2) current densities may be effective in this electrical enhancement of antibiotic efficacy against biofilm bacteria, and flow experiments indicate that this bioelectric effect does not appear to depend entirely on the possible local electrochemical generation of antibacterial molecules or ions. These data are expected to facilitate the use of the bioelectric effect in the prevention and treatment of device-related bacterial infections that are caused by bacteria that grow in biofilms and thereby frustrate antibiotic chemotherapy.

Anti-Bacterial Agents↗

Decreased bone mineral density in premenopausal asthma patients receiving long-term inhaled steroids.

Inhaled corticosteroids have become a key element in the maintenance treatment of bronchial asthma. It is well-known that long-term systemic steroid use causes osteoporosis, whereas its inhaled counterpart has been believed to be devoid of such a side-effect. However, recent studies showed that administration of inhaled corticosteroids was associated with biochemical evidence of derangement in bone turnover. We therefore studied bone mineral density (BMD) by dual energy x-ray absorptiometry in 30 patients (18 females, 12 males) with bronchial asthma treated with steroids, essentially by the inhaled route only (both nasal and tracheobronchial), and compared them with healthy subjects individually matched for age, sex, menopausal status, and body mass index (BMI). There was a significant decrease in BMD in the patient group at the hip (neck of femur, p = 0.007; trochanter of femur, p = 0.034; Ward's triangle, p = 0.016) and the lumbar area of the spine (L2-4, p = 0.041). Further analysis showed that this difference from control subjects was mainly seen in the female patients and not in the male patients (neck of femur, p = 0.049; Ward's triangle, p = 0.025; lumbar spine, p = 0.039). In the female patients, there was significant negative correlation of BMD of the lumbar area of the spine and the trochanter of femur with daily inhaled steroid dose and positive correlation of BMD of the trochanter with BMI.

Absorptiometry, Photon↗

Outmigration of foreign-born members in Canada.

"This paper studies the partial effect of various socio-economic characteristics on the rate of outmigration of the foreign-born from the Canadian population. The data sets used are based on the microdata of the 1971 and 1981 censuses of population. It is found that migrants with high school education have the highest propensity to outmigrate, while those with less than high school education have the lowest. The propensity to outmigrate is positively related to the age of the migrant. Males tend to have a higher propensity to outmigrate, while having a command of official languages reduces the propensity to outmigrate." (SUMMARY IN FRE)

Age Factors↗

Therapeutic efficacy of fleroxacin for eliminating catheter-associated urinary tract infection in a rabbit model.

The efficacy of fleroxacin as therapy for experimentally induced catheter-associated urinary tract infection (CAUTI) was examined. A rabbit model of CAUTI using a closed urinary catheter drainage system and the mutant strain of Escherichia coli (WE 6933) were used to examine three dosage regimens (30 mg/kg q8h i.v.; 20 mg/kg q8h i.v.; and 10 mg/kg q8h++i.v.) of fleroxacin administered intravenously for 4 days. Quantitative bacterial counts, urinary concentrations of fleroxacin and desmethylferoxacin, histopathologic changes, and electron microscopic evaluation of catheter-associated biofilm and mucosal biofilm were performed. The results indicated that the bacterial biofilm on the urinary catheter could be eliminated by fleroxacin at 30 mg/kg q8h i.v. and 20 mg/kg q8h i.v. Fleroxacin concentrations in urine exceeded the levels necessary to destroy E. coli. Viable bacteria were eliminated with the third regimen (10 mg/kg q8h i.v.), but electron microscopy demonstrated remnants of bacterial biofilm. Histopathologic changes were significantly reduced in all fleroxacin-treated rabbits, and scanning electron microscopy showed deterioration of the bacterial biofilm on the surface of the Foley catheter in treated animals. These data suggest that fleroxacin may be useful for treating catheter-related infections because these therapeutic dosages limited ascending infections of the urethra and bladder, eliminated catheter-associated biofilms, and killed planktonic bacteria in urine.

Animals↗

Presence of multiple forms of peptidase inhibitors in rat milk.

Peptides such as somatostatin (SS14), epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulin-like growth factors (IGF-I and IGF-II) are present in breast milk from various species, and their significance in the developing gastrointestinal tract has been suggested. Our recent studies have indicated that rat milk soluble fraction (RMSF) protects SS14 in the gastrointestinal lumen by inhibiting in vitro the luminal peptidolysis. In the present studies, we have shown that RMSF inhibited in vitro degradation by midjejunal luminal flushings of suckling rats of 125I-labeled somatostatin 14[Tyr11], EGF, TGF alpha, IGF-I and IGF-II, as well as trypsin activity in vitro against benzoyl-L-arginyl-p-nitroanilide. The inhibitory factors present in the RMSF were further fractionated by gel filtration on Sephadex G100, ion-exchange chromatography on DEAE-Sephadex, and fast protein liquid chromatography (FPLC). Gel filtration of Sephadex G100 separated RMSF into three peaks of proteins: G1, G2, and G3; peptidase inhibitor activities were present exclusively in G1. Ion-exchange chromatography on DEAE-Sephadex column resolved peptidase inhibitory activity (G1) into three different peaks, D1, D2, and D3, eluted at sodium chloride concentrations of 0.05 M, 0.1 M, and 0.2 M, respectively. Further purification of D2 by FPLC resulted in a fraction rich in peptidase inhibitory activity, which was essentially free of trypsin inhibitory activity. Results indicate the presence of at least three peptidase inhibitors in rat milk, which may play a role in the protection of milk-borne peptides in the gastrointestinal lumen.

Animals↗

Resistance of Pseudomonas pseudomallei growing as a biofilm on silastic discs to ceftazidime and co-trimoxazole.

We have examined the resistance of Pseudomonas pseudomallei biofilm cells to ceftazidime and cotrimoxazole. A large number of these biofilm cells remained viable at 12 and at 24 h, except in the biofilm treated with 200 times the MIC of ceftazidime. The inherent resistance of P. pseudomallei biofilms to conventional antibiotics may explain the lack of success in the treatment of the chronic manifestations of this bacterial infection.

Burkholderia pseudomallei↗

Biofilms on indwelling vascular catheters.

BACKGROUND AND METHODS: Some bacteria have a natural tendency to adhere to available surfaces and to form biofilms. Biofilms have been demonstrated on right heart flow-directed catheters, endocardial pacemaker leads, urinary catheters, and other medical devices. In this study, we examined arterial and central venous catheters that had been in place in ICU patients between 1 and 14 days for the presence of bacterial biofilms by scanning electron microscopy, transmission electron microscopy, and a special scraping/sonication bacterial recovery technique. The data taken from these processes were compared with skin entry site swabs and blood cultures and correlated with patient data on infection, bacterial colonization, and antibiotic use. RESULTS: Extensive biofilm formation was demonstrated by scanning electron microscopy on all 42 arterial and 26 central venous catheters. Bacteria were seen within the biofilms on 69% (29/42) of the arterial and 88% (23/26) of the central venous catheters. These two direct methods for the detection of biofilm bacteria on the catheter surfaces demonstrated the presence of adherent organisms on 81% of devices examined. Some catheters that had been in place for only 1 day were colonized by bacterial biofilms. Biofilm scraped from catheter surfaces and dispersed by mixing and sonication yielded cultures (32% of catheters) of predominantly skin bacteria. In a few instances, the recovery of bacteria from biofilms on vascular catheters coincided with positive cultures from skin entry site swabs and/or from the blood of the patient, but there was no significant correlation between bacterial recovery from the catheter surface, entry site, and/or patients' blood. CONCLUSIONS: Direct microscopic examination of 68 vascular catheters that had been in place 1 to 14 days showed that most (81%) were colonized by bacteria growing in slime-enclosed biofilms. In many cases, this colonization of catheter surfaces could be confirmed by special biofilm culture recovery methods. Although the clinical importance of bacterial biofilms on catheter surfaces is speculative, their presence and potential to serve as a nidus for infection and bacteremia in critically ill immunocompromised hosts are cause for concern.

Alberta↗