Biomedical subjects

K S Lam

Publications and source records attributed to K S Lam.

At least 73 records · Page 4Linked to original sources

PubMed1998

The effects of space flight on the production of monorden by Humicola fuscoatra WC5157 in solid-state fermentation.

The effect of space flight on the production of the antibiotic monorden on two types of agar media, T8 and PG, by Humicola fuscoatra WC5157 was examined on board the US Space Shuttle mission STS-77 in May 1996. Paired space-flight and ground control samples were prepared using identical hardware, protocol, media, and inoculum. Inoculation occurred simultaneously for both groups 2.5 after launch. The flight and ground samples were allowed to grow for the entire 10-day mission in a dark, thermally controlled (22 degrees C) environment. Post-flight HPLC analysis of the flight and ground sample extracts indicated that the production of monorden by H. fuscoatra WC5157 in the flight samples was higher than in the ground samples in both agar media. In the T8 medium, the production of monorden in the flight and ground samples was 11.6 +/- 3.5 micrograms and 8.9 +/- 1.1 micrograms respectively (30% increase). In the PG medium, the production of monorden in the flight and ground samples was 23.8 +/- 3.3 micrograms and 8.2 +/- 2.2 micrograms respectively (190% increase). The production of monorden in the flight and ground control samples was confirmed by HPLC-MS analysis.

Antifungal Agents↗

PubMed1998

Application of "one-bead one-compound" combinatorial library methods in signal transduction research.

Using a "split-synthesis" solid phase synthetic approach, bead libraries can be generated such that each bead displays only one chemical entity. This "one-bead one-compound" combinatorial library can then be assayed for specific biological properties using either a solid-phase on-bead binding or functional assay, or a releasable solution phase assay. Positive compound-beads can then be isolated for structure determination. Various assay systems to screen such a "one-bead one-compound" library are described. We have used this combinatorial library method to discover peptides that bind to the cell surface immunoglobulins of murine lymphoma cells. Such peptides, when presented in an oligomeric form to a lymphoma cell are able to induce signal transduction. Additionally, we have also applied the "one-bead one-compound" combinatory library approach to elucidate peptide substrate motifs for protein tyrosine kinases. Multiple distinct peptide motifs were identified for p60(c-src) protein tyrosine kinase. Using the identified peptide substrates as templates, potent and highly specific pseudosubstrate-based peptide inhibitors were developed.

Animals↗

PubMed1998

Antiresorptive therapy in asthmatic patients receiving high-dose inhaled steroids: a prospective study for 18 months.

BACKGROUND: Inhaled steroid therapy is an effective and well tolerated mode of therapy for asthma. Although systemic side-effects of inhaled steroids are much less common than those found with systemic steroids, the drugs may be absorbed through mucosal surfaces. Inhaled steroids have been reported to disturb normal bone metabolism, and they are associated with a decrease in bone mineral density. OBJECTIVE: We conducted this study to investigate bone density in asthmatic subjects receiving long-term high-dose inhaled steroids and the effects of supplementation with oral calcium with or without etidronate. METHODS: We evaluated thirty-eight Chinese subjects (24 men and 14 premenopausal women; 28 patients and 10 healthy control subjects) in this prospective study. Patients were randomized into three arms: those receiving no supplement, those receiving 1000 mg/day calcium supplement, and those receiving 400 mg/day cyclical sodium etidronate with 1000 mg/day calcium, respectively. The patients and control subjects were matched for age, sex, and dose of inhaled steroids. Bone density at lumbar spine and hip region was measured by dual energy x-ray absorptiometry with a densitometer at baseline and at 6, 12, and 18 months for the asthmatic groups and at baseline and at 12 and 18 months for the control group. Serum calcium, phosphate, alkaline phosphatase, osteocalcin, parathyroid hormone, 25-hydroxyvitamin D, and urinary hydroxyproline/creatine were measured simultaneous to bone density assessments. RESULTS: There were 10 control subjects, 10 asthmatic subjects receiving no supplement, eight asthmatic subjects receiving calcium supplement, and 10 asthmatic subjects receiving calcium and etidronate therapy, respectively. The mean (+/- SEM) dosages of beclomethasone or budesonide for the three groups of asthmatic subjects were 2.2 +/- 0.3, 2.0 +/- 0.2, and 2.0 +/- 0.2 mg/day, respectively. Mean dietary calcium intake of the study subjects was 766 +/- 39 mg/day. At baseline, bone mineral density of the spine in the group receiving no supplement was significantly lower than that found in the control group (p < 0.05). At 18 months, patients receiving no supplement had significantly greater bone loss at the lumbar spine than patients receiving etidronate plus calcium lactate-gluconate (CaLG) or CaLG alone (p < 0.05). The increase in bone mineral density versus baseline observed in patients receiving CaLG with or without etidronate (p < 0.05) probably did not result from increased bone formation because serum osteocalcin levels showed a significant reduction in all three groups of patients (p < 0.05). An increase in mean serum calcium (p < 0.05) was seen in patients receiving CaLG with or without etidronate. CONCLUSION: Our results suggest that long-term administration of high-dose inhaled steroid (>1.5 mg/day) induces bone loss that is preventable with calcium supplementation with or without cyclical etidronate. Long-term studies involving more patients should follow to confirm these preliminary findings.

Administration, Inhalation↗

PubMed1998

Baculoviral expressed HLA class I heavy chains used to screen a synthetic peptide library for allele-specific peptide binding motifs.

Recombinant baculoviruses encoding truncated HLA-A*0101 and HLA-A*0201 class I heavy chains have been isolated and used to infect lepidopteran cells. Proteins overexpressed in this system were glycosylated, and consisted of 282 amino acid residues after signal sequence cleavage. These class I heavy chains could fold into their native conformation in the presence of recombinant human beta2-microglobulin expressed in Escherichia coli and a synthetic peptide library of nonamers bound to resin-support beads. Reconstitution into native ternary complexes was detected using a conformation specific monoclonal antibody followed by isolation and sequencing of the bound peptides. The motifs obtained for HLA-A1.1 and HLA-A2.1 peptides are similar although more extensive than those derived from sequencing endogenous peptides. This approach selects peptides which form very stable complexes regardless of whether these peptides are generated under physiological conditions, thereby providing unique supplementary data for predicting and designing CTL epitopes. This method is based solely on peptide binding to the class I molecule and is therefore independent of any constraints imposed by endogenous intracellular processing or transport systems. A comparison of the two motifs provides an opportunity to distinguish between the requirements of binding from those arising as a function of intracellular processing or transport. Our findings are not consistent with a recent report suggesting that constraints on the COOH termini of these peptides can be attributed to the effects of either intracellular processing or transport. We find that the carboxy termini in the class I peptides analyzed to date mimic the endogenous data, suggesting that residues in this position contribute to binding affinity.

Alleles↗

PubMed1998

Changing prevalence of retinopathy in newly diagnosed non-insulin dependent diabetes mellitus patients in Hong Kong.

In this retrospective study, the prevalence of chronic microangiopathic complications was determined in 474 Chinese patients with non-insulin dependent diabetes mellitus (NIDDM) who presented within 1 year of diagnosis to the diabetes clinic from January 1990 to December 1996. Mean age (+/- S.E.) was 53.6 (+/- 0.6) years. The overall prevalence of retinopathy was 21.9%. A significant increase was observed from 1990 to 1994 (P < 0.005), with the prevalence being 14.8, 13.0, 24.5, 32.3 and 35.4%, respectively, in consecutive years. A decreasing prevalence was seen from 1994 to 1996 (P < 0.001), being 8.2 and 7.4% in 1995 and 1996, respectively. A total of 95% of patients had nonproliferative retinopathy--proliferative retinopathy was found in 5% only. The overall prevalence of clinical nephropathy (proteinuria > 0.5 g/day) was 3.7%. Clinical neuropathy (increased vibration perception threshold) was found in 12.8% of patients. Patients with retinopathy and neuropathy were older (P < 0.0001 and P < 0.005, respectively) than those without the complications and systolic hypertension was more prevalent in patients with retinopathy (P < 0.05). In conclusion, a high prevalence of diabetic microangiopathic complications, especially of retinopathy, is present in newly diagnosed NIDDM patients in our population. It remains to be determined whether the changing prevalence of retinopathy at diagnosis bears any relationship to the increasing public awareness of diabetes and its complications in Hong Kong in recent years. Examination for chronic microangiopathic complications should be carried out in all newly diagnosed NIDDM patients.

Asian People↗

PubMed1998

Adrenal extramedullary haemopoiesis: diagnosis by a non-invasive method.

Bilateral adrenal masses were discovered incidentally in a patient with beta-thalassaemia intermedia. Endocrine investigations showed that the adrenal lesion was hormonally inactive. Extramedullary haemopoiesis involving the adrenal glands was suggested by the presence of reticuloendothelial tissue as demonstrated by bone marrow scintigraphy using Technetium Tc-99m nanocolloid. This report illustrates the use of non-invasive functional imaging techniques in the management of adrenal 'incidentalomas', which in this case turned out to be a rare presentation of extramedullary haemopoiesis.

Adrenal Gland Neoplasms↗

PubMed1998

Strong association between DQA1/DQB1 genotype and early-onset IDDM in Chinese: the association is with alleles rather than specific residues.

We report on the role of HLA-DQA1 and DQB1 alleles in determining susceptibility to insulin-dependent diabetes mellitus (IDDM) in Hong Kong Chinese and investigate whether these alleles affect the age of onset of the disease. We studied 76 unrelated Chinese patients and 250 controls. There was no apparent predisposing effect of non-aspartic acid residues at position 57 of the DQ beta chain (Asp57-) but there was an excess of homozygous genotypes containing arginine at position 52 of the DQ alpha chain (Arg52+). This excess was mainly attributable to the genotype DQA1*0301/DQA1*05011 in early-onset disease. There was a significant excess of heterodimers of DQ alpha and DQ beta carrying Arg52+ and Asp57- in both early-onset and late-onset disease, but the excess in early-onset disease was mainly attributable to a single heterodimer formed by DQA1*05011 and DQB1*0201. Of three DQA1/DQB1 genotypes containing a double dose of Arg52+ and Asp57-, only one had a strong association with both early-onset and late-onset disease. We show that early-onset IDDM and late-onset IDDM in Chinese may be separated on the basis of their associated DQA1 and DQB1 genotypes and we conclude that previously reported associations of IDDM with Arg52+ and Asp57- residues in Chinese are secondary to specific combinations of DQA1 and DQB1 alleles. We also show that DRB1 molecules play a distinct role in determining susceptibility to early-onset IDDM but the greatest effect is exerted by specific DR/DQ genotypic combinations.

Adult↗

PubMed1998

A phase I/II trial of paclitaxel for non-Hodgkin's lymphoma followed by paclitaxel plus quinine in drug-resistant disease.

Patients with non-Hodgkin's lymphoma (NHL) recurrent after chemotherapy exhibit clinical characteristics compatible with the phenomenon of multidrug resistance (MDR) and frequently have detectable levels of P-glycoprotein (P-gp). Paclitaxel has been used in recurrent NHL with limited success. To test whether clinical resistance to paclitaxel can be reversed, we treated patients having paclitaxel-resistant NHL with paclitaxel plus quinine and measured the effects of quinine on paclitaxel pharmacokinetics. Eligible patients had recurrent and measurable NHL. Patients initially received paclitaxel, 120 mg/m2 (dose determined by a phase I trial of paclitaxel plus quinine), as a 20-24 h infusion every 3 weeks until there was evidence of clinical resistance. Patients then received paclitaxel at the same dose rate plus oral quinine at a fixed dose rate of 400 mg three times each day. Paclitaxel pharmacokinetics were studied in each patient using paired samples from plasma obtained at the end of the 24 h paclitaxel infusion as an estimate of the steady-state drug level. Of 14 patients treated with paclitaxel alone, one patient obtained a partial response (7%). At the time of disease progression, one patient (same patient) obtained a partial response with paclitaxel plus quinine (7%). Steady-state paclitaxel levels were obtained in 12 patients. In 11 of 12 patients the steady-state paclitaxel level was substantially lower with the addition of quinine. The average ratio of end of infusion plasma levels (paclitaxel alone/paclitaxel plus quinine) was 0.6 (range 0.31-0.97) indicating a 40% decrease in paclitaxel levels with the addition of quinine (p=0.001). We conclude that paclitaxel given by this dose and schedule has modest activity in recurrent NHL. The addition of quinine to paclitaxel also has limited activity, but the combination did reverse paclitaxel resistance in one patient, adding support to the hypothesis that clinical drug resistance can be overcome with chemosensitizers in individual patients. Pharmacokinetic studies indicate that the reversal of drug resistance in this study cannot be attributed to changes in clearance of paclitaxel (which appears to increase with quinine), but more likely to the sensitization of lymphoma cells.

Adolescent↗

PubMed1998