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Biomedical subjects

P Lau

Publications and source records attributed to P Lau.

At least 55 records · Page 3Linked to original sources

Murine IL-10 fails to reduce GVHD despite inhibition of alloreactivity in vitro.

Graft-versus-host disease (GVHD) is a serious complication following allogeneic bone marrow transplantation (BMT). Initial immunologic events that are thought to lead to clinical GVHD include allogeneic antigen presentation, CD4+ T cell proliferation and eventually generation of specific cytotoxic lymphocytes. Interleukin-10 (IL-10) has been shown to inhibit the function of antigen presenting cells (APC) and to reduce lymphocyte proliferation. In this study we investigated the possible role of recombinant murine IL-10 (rmIL-10) as prophylactic treatment of GVHD in a murine BMT model involving B10.BR donor mice (H-2k) and AKR recipients (H-2k). In particular, we wished to determine whether early post-BMT administration of IL-10 would suppress GVHD by interfering with macrophage function and inflammatory cytokine production during the proposed "afferent' phase of GVHD. In MLR assays, rmIL-10 significantly inhibited the proliferation of donor spleen cells when stimulated by irradiated recipient spleen cells in a dose-dependent manner. In murine BMT, rmIL-10 was administered exogenously by intraperitoneal injection of 100 U daily in two different dosage schedules, on days-1, 0, 1, 2, 3, 6 to target the early post-BMT phase, and days-1, 0, 3, 5, 7, 10 after BMT, to administer the same total dose throughout the engraftment period. IL-10 injected mice had lower plasma IL-1 alpha levels on day 3 (12 pg/ml vs 64 pg/ml in controls, P < 0.05), suggesting that both macrophage function and inflammatory cytokine production were inhibited. In contrast to the MLR data, no significant improvement in morbidity and mortality from GVHD was observed. Therefore, IL-10 does not appear to be useful in GVHD prophylaxis.

Animals↗

Cholesteryl ester transfer protein (CETP) mRNA abundance in human adipose tissue: relationship to cell size and membrane cholesterol content.

Cholesteryl ester transfer protein (CETP) has a well-defined role in plasma neutral lipid transport. CETP synthesized by human adipose tissue may contribute to the plasma CETP pool. CETP mRNA abundance increases in subcutaneous adipose tissue in response to cholesterol feeding and we have hypothesized that CETP gene expression is regulated by a specific pool of cellular sterol. In the present study, we have quantified CETP mRNA levels in subcutaneous adipose tissue of 10 female subjects using a solution hybridization RNase protection assay. Particulate (membrane cholesterol) and lipid droplet cholesterol (core cholesterol) were determined by gas chromatography. CETP mRNA abundance in these adipose tissue specimens correlated significantly with membrane cholesterol expressed as a fraction of membrane protein (r = 0.67, P = 0.031). There was also a linear relationship between CETP mRNA abundance and membrane cholesterol to core triglyceride ratio (r = 0.77, P = 0.009) and a strong correlation between the percentage of cellular cholesterol in the membrane fraction (ratio of membrane to core cholesterol) and CETP mRNA abundance (r = 0.91, P = 0.0002). In contrast, there was a negative relationship between each of lipid droplet cholesterol and triglyceride and CETP mRNA levels. Human adipose tissue maintained in organ culture for several days was shown to secrete CETP into the culture medium. Incubation with cholesterol-rich chylomicron remnants elicited a dose-dependent increase in both membrane and core cholesterol and a concomitant increase in the level of CETP mRNA. These studies demonstrate that adipose tissue CETP mRNA abundance is a function of membrane cholesterol concentration rather than lipid droplet cholesterol and that CETP mRNA increases with adipocyte cholesterol enrichment via chylomicron remnants. CETP gene expression is highest in small lipid-poor adipocytes, suggesting that CETP synthesized and secreted by adipocytes may have a role in promoting cellular cholesterol accumulation.

Adipose Tissue↗

A novel haemophilia B defect due to partial duplication of the factor IX gene.

A patient with mild FIX deficiency was found to have partial duplication of the 3' region of the gene, giving, in addition to the a normal gene, another piece of DNA containing exons 5', 6', 7' and 8' and the intervening sequences. Cloning and sequencing of the junction region revealed that crossover occurred at nt 31927 in the 3' untranslated region of one chromosome/chromatid and nt 10640 in intron 4 of the other. No homology or topoisomerase specific sequences were observed in the crossover region. PCR and sequencing of illegitimate FIX transcripts from the patient's lymphocytes showed at least three different species of mRNAs. Translation of two of these 'novel' mRNAs should result in truncated proteins. Possibilities for the splicing of the mature mRNA are offered to explain the translation of a normal-size FIX protein, which was the only product demonstrated on Western blot analysis.

Base Sequence↗

Prevalence of human papillomavirus types 16 and 18 in penile carcinoma: a study of 41 cases using PCR.

AIMS: To determine retrospectively the prevalence of human papillomavirus (HPV) types 16 and 18 in penile carcinomas. METHODS: Forty one surgically resected penile carcinomas from the archives at Queen Mary Hospital, Hong Kong, were reviewed and classified into verrucous carcinoma, and well, moderately, and poorly differentiated squamous cell carcinomas. Paraffin wax embedded tumour tissue was sectioned and analysed for HPV 16 and HPV 18 using the polymerase chain reaction with type specific internal probes. RESULTS: There were seven verrucous carcinomas, and 11 well, 17 moderately, and six poorly differentiated squamous cell carcinomas. Six of the 41 (15%) patients had penile carcinoma containing HPV 16 or HPV 18 DNA, or both, with HPV 16 found in four (10%) and HPV 18 in four (10%). The mean ages of HPV positive and HPV negative groups of patients were 68.5 and 57.6 years, respectively (p < 0.05). None of the seven verrucous and 11 well differentiated squamous cell carcinomas was positive for HPV. The mean age of patients who had these carcinomas was 52.4 years. As a group, these low grade carcinomas occurred in patients younger by more than a decade than those who had carcinomas of the higher grades (mean age 64.4 years; p < 0.01). CONCLUSIONS: Penile carcinomas had much lower rates of infection by HPV 16 or HPV 18 than cervical carcinomas in this Hong Kong population. Based on our findings and on data collated from published findings, it is concluded that penile verrucous carcinomas are not associated with HPV 16 and HPV 18. The overall low prevalence of HPV 16 and HPV 18 in penile carcinomas suggests that other HPV types might be important in the pathogenesis of these tumours.

Aged↗

Unusual presentations of advanced prostate cancer.

With the advent of prostatic-specific antigen, transrectal ultrasound and an increasing awareness of prostate cancer among the population, prostate cancer is being detected at an increasingly early stage. Despite this, it is estimated that up to 40% of the patients present with manifestations of metastatic prostate cancer. Although the most common sites for metastases at presentation are the obturator lymph nodes and the bony skeleton, advanced prostate cancer may produce a variety of clinical scenarios by involving contagious and distant organs. Such presentations of advanced prostate cancer can add significantly to the morbidity and mortality of this disease. In brief review, we will focus on uncommon presentations of advanced prostate cancer.

Journal Article↗

Absorption of intranasal salmon calcitonin in normal subjects and hypogonadic men.

The absorption kinetics of intranasal salmon calcitonin were assessed in 4 normal subjects and 9 patients with Klinefelter's syndrome. After administration, absorption occurred within 5 minutes. There was a highly significant correlation between the amount administered and the amount absorbed (r = -0.83, P less than 0.0005).

Administration, Intranasal↗

Vitamin D status among patients with fractured neck of femur in Hong Kong.

Vitamin D deficiency leads to secondary hyperparathyroidism initially and then to mild osteomalacia, both of which conditions may be aymptomatic and may predispose to bone fracture. To assess the importance of vitamin D deficiency in predisposing to fractured neck of femur, we studied the vitamin D status, dietary intake and socio-economic characteristics in 69 patients with fractured neck of femur (group A), 28 normal subjects with age above 60 (group B), and 101 normal volunteers (group C). Patients with fractured neck of femor had significantly lower levels of serum 25-hydroxy-cholecalciferol compared with subjects of groups B and C. There is no statistically significant difference in other biochemical parameters, including calcium, phosphate, and alkaline phosphatase. Patients with fractured neck of femur and with 25-hydroxycholecalciferol below 20 ng/mL were characterized by a home-bound and/or institutionalized life-style, smaller living place, and limited access to open space. To conclude, hypovitaminosis D is a common problem among elderly patients with fractured neck of femur in Hong Kong. The fact that such vitamin D deficiency is associated with muscle weakness may contribute to falls, and thus indirectly account for an increased rate of hip fractures over the normal control.

Aged↗

25-Hydroxycholecalciferol and insulin-like growth factor I are determinants of serum concentration of osteocalcin in elderly subjects with and without spinal fractures.

Osteocalcin is one of the major proteins in the osseous matrix. To evaluate the determinants and thus the physiological control of osteocalcin production in normal and osteoporotic subjects, the serum levels of osteocalcin, 25-hydroxycholecalciferol (25-OH-D3), and insulin-like growth factor I (IGFI) were measured by radioimmunoassay in 44 subjects over 60 years old. Circulating osteocalcin, 25-OH-D3, and IGFI were 0.28 +/- 0.10 nmol/L (1.65 +/- 0.96 ng/mL), 70.5 +/- 25.1 nmol/L (28.3 +/- 10.1 ng/mL), and 23.8 +/- 12.0 nmol/L in 27 healthy controls respectively, as compared with 0.09 +/- 0.09 nmol/L (0.52 +/- 0.52 ng/mL), 48.2 +/- 19.9 nmol/L (19.35 +/- 7.91 ng/mL), and 16.56 +/- 6.96 nmol/L in 17 patients with spinal fractures. Significant correlation was found between osteocalcin and 25-OH-D3 level, as well as between osteocalcin and IGFI. The results show that IGFI and 25-OH-D3 are important determinants for serum concentration of osteocalcin in elderly subjects with and without spinal fractures.

Aged↗

Effects of aluminum on the parathyroid hormone receptors of bone and kidney.

Aluminum intoxication is associated with low osseous remodeling rate and peripheral resistance to parathyroid hormone (PTH). The pathophysiological mechanism of these aluminum induced changes was investigated using cultured clonal osteoblastic UMR-106 cells as well as dog renal cortical membrane. Both systems possess high-affinity PTH receptors that are coupled to adenylate cyclase. The UMR-106 cells have typical osteoblastic features, including receptors for the tissue-specific hormones, formation and mineralization of a bone-like ground substance and exclusive synthesis of type 1 collagen. The results show that aluminum at a concentration of 4 microM and 40 microM significantly inhibits the cyclic AMP responses to PTH challenge in UMR-106 cells, and this is associated with significant decrease in the binding to the PTH receptor. At 200 microM, no PTH-responsive adenylate cyclase or binding to receptor can be demonstrated. The effect of aluminum on UMR-106 rat osteosarcoma cells is not due to changes in cell number, cell viability or rate of mitogenesis. Similar results are obtained with dog kidney membrane. At a concentration of 10 microM and 400 microM, there is significant inhibition of the binding of PTH to kidney membrane and proportional decrease in PTH-stimulated adenylate cyclase. With higher concentration of aluminum, no response or binding can be demonstrated. In conclusion, aluminum at concentrations of 4 to 400 microM is associated with a decrease in affinity of PTH receptor and concomitant suppression of PTH-stimulated adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

Group A variants defined with a monoclonal anti-A reagent.

Unusual serologic findings mimicking the B(A) phenomenon were noted in two group B blood donors using blended murine monoclonal anti-A reagent. With additional studies, including a binding experiment using affinity chromatography, the presence of aberrant group A activities was confirmed. This observation suggests that persons with atypical B(A) phenotype may warrant further investigation to delineate the ABO blood group.

ABO Blood-Group System↗

Eight-month longitudinal study of urinary excretion of albumin and tubular proteins in diabetic subjects.

To evaluate the importance of tubular proteinuria in diabetic nephropathy, we studied the serial changes of micro-albuminuria, microproteinuria and protein patterns by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in 38 diabetic patients over 8 months. There was a significant correlation between the amount of micro-albuminuria measured by radio-immunoassay and the amount of microproteinuria quantitated by the Coomassie brilliant blue dye binding method (r = 0.976; p less than 0.0001). Micro-albuminuria of 50 mg/day was equivalent to microproteinuria of 190 mg/day. Among the 38 diabetic patients, 26 had micro-albuminuria above 50 mg/day, while 12 had micro-albuminuria below this level. There was a significant correlation between the amount of microproteinuria and haemoglobin A1, showing that the quantity of microproteinuria was affected by metabolic control. Diabetic patients with micro-albuminuria of above 50 mg/day have a significantly higher diastolic blood pressure than those below this level. Among the diabetic patients with micro-albuminuria of less than 50 mg/day, the amount of micro-albuminuria and microproteinuria remained constant, whereas progressive increases in micro-albuminuria and microproteinuria were observed among the 12 diabetic subjects with micro-albuminuria above 50 mg/day. These support the prognostic importance of this quantity of micro-albuminuria. The protein patterns as revealed by SDS-PAGE with Coomassie blue staining show a significant loss of low-molecular-weight proteins in 7 patients, which may therefore suggest tubular damage. The loss of tubular proteins persisted over a period of 8 months in all 7 subjects, and the amount gradually increased over this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The characterization, regulation, and function of insulin receptors on osteoblast-like clonal osteosarcoma cell line.

The properties and regulation of insulin receptors on monolayers of cultured clonal osteoblastic rat osteosarcoma UMR-106 cells and human osteosarcoma U20S cells were studied. Confluent cultures of UMR-106 cells bound lactoperoxidase-labeled, HPLC-purified [125I]A-14-monoiodinated insulin in a reversible, saturable, and specific manner. Binding was related inversely to the incubation temperature. Prolonged period of steady-state binding was achieved at all temperatures studied. Competition curves demonstrated half-maximal inhibition of [125I]insulin binding at an unlabeled insulin concentration of about 1 nM. Scatchard analysis of the binding data was curvilinear, suggesting negative cooperativity, and revealed that UMR-106 osteoblasts contained about 87,000 receptor sites per cell according to a two-site model. Bound [125I]insulin dissociated from osteoblasts with a t1/2 of about 15 minutes at 22 degrees C. The dissociation curve was multiexponential, and the addition of native insulin accelerated the dissociation of intact but not degraded [125I]insulin. Preincubation with 125 nM insulin for 1 h induced 70% loss of binding sites and reduced total insulin bound by 30%. When monolayers were treated with the lysosomotropic agent chloroquine, a 40% increase in cell-associated radioactivity that could not be dissociable in fresh buffer was observed. The use of an energy depleter, sodium fluoride, completely inhibited the effects of chloroquine. Similar results were obtained for human osteosarcoma U20S cells except that the number of receptor sites was far less than that of UMR-106 cells. Insulin increased collagen synthesis at a half-maximal concentration of 1 nM. To conclude, cultured rat and human osteoblasts possess insulin receptors that exhibit kinetic properties and specificity similar to those of other insulin target cells. Receptor-bound insulin is internalized and degraded by a chloroquine-sensitive, energy-requiring reaction. Insulin receptor on bone cells modulates the synthesis of collagen and this role may be important in bone homeostasis.

Animals↗

Wound tension in rhytidectomy. A preliminary report.

In superficial musculoaponeurotic system (SMAs) suspension procedures in rhytidectomy, skin closing tension seems to be lower at the main anchor points than with non-SMAS procedures. To evaluate this clinical impression, a preliminary investigation into the effect of SMAS suspension on wound closing tension was undertaken. Intraoperatively, skin closing tension was compared with and without SMAS plication sutures at the two key anterior and posterior skin anchor points. Results confirmed decreased tension with SMAS plication. Anteriorly in the temporal part of the scalp, a significant difference of 87 g was demonstrated. Posteriorly in the occipital hairline, a significant difference of 96 g was demonstrated. Individual differences in tension were more pronounced in patients with prominent SMAS laxity than in those patients with mild laxity.

Aged↗

Evaluation of a prescreening blood donor program for prevention of perinatal transfusion-acquired cytomegalovirus (CMV) infection.

The purpose of this study was to evaluate the efficacy of a prescreened CMV seronegative blood donor group in preventing transfusion-acquired CMV infection in premature infants in the perinatal period. Group 0 donors with known CMV seronegative status were recruited to supply blood to the neonatal intensive care nurseries. One hundred and twenty-seven low birth weight infants born of CMV seronegative mothers remained seronegative when blood for transfusion was screened for CMV antibody. Twenty two infants shared six units of CMV seropositive blood due to technical errors or poor sensitivity of the test kit in the initial phase of the study. Fifteen of these patients were in the study group. One infant died of immaturity at four weeks of age and two of the remaining 14 showed asymptomatic CMV infection. Another infant who received granulocyte concentrates from CMV seropositive donors had symptomatic CMV infection. Throughout the 24 month study period, blood supply to the ICN was adequate and timely. The donor seroconversion rate was 0.7% per annum. Only one infant was exposed to the risk of CMV infection due to donor seroconversion. We conclude that the prescreening donor program is a sensible and efficient approach for providing CMV seronegative blood in neonatal transfusion therapy.

Antibodies, Viral↗

Sonographic renal parameters as related to age.

Four hundred and fifty-four kidneys were evaluated by real time ultrasound for appearance of renal cortical echogenecity, medullary pyramids and central sinus echoes. These renal parameters were correlated with age in 227 patients ranging in age from 0-15 years. The renal parenchymal echogenicity was observed to change not abruptly at a certain age but gradually over a period of years.

Adolescent↗

Cranial bone grafts for post-traumatic facial defects.

Recent interest in onlay cranial bone grafts has shown it to be a preferred technique in the reconstruction of facial defects. This paper reports seven patients in whom outer table cranial bone grafts were used to reconstruct post-traumatic facial deformities. These included orbital and zygomatic deformities (2 patients), maxillary defects (2 patients), mandibular defects (2 patients), and nasal deformity (1 patient). A brief review of the development of membranous bone grafting for maxillofacial reconstruction is given. Good cosmetic results were obtained in six of seven patients with no evidence of graft resorption. One patient required removal of the graft because of inadequate soft tissue coverage. No patient suffered any significant donor site morbidity. In summary, this technique is extremely useful in treating post-traumatic bony deformities of the facial skeleton. The excellent graft survival and ease in harvesting the graft make this technique preferable to traditional endochondral grafts taken from the iliac crest and rib.

Adult↗

Evaluation of cytomegalovirus (CMV) antibody screening tests for blood donors.

Four technics were compared to find the most suitable screening test for the cytomegalovirus (CMV) antibody status in blood donors. One hundred thirty-five donor samples were tested by two enzyme immunoassays, EIA(Litton) and EIA(Abbott), and by latex agglutination (LA) and complement fixation (CF). The seroreactivity of the tests were judged by concordance of three or more methods. The authors found that the test performance of the EIA(Litton) could be improved with adjustment of sample color variation, which increased the test sensitivity and specificity from 48.8% and 87.2% to 83.8% and 96.4%, respectively. Both the EIA(Abbott) and LA technics proved to be ideal screening tests with 100% sensitivity and negative predictive values. However, the rapid turnaround time and the simplicity in technics and equipment used with the LA test make it the test of choice for blood donor screening.

Antibodies, Viral↗