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Biomedical subjects

S Kwan

Publications and source records attributed to S Kwan.

At least 37 records · Page 2Linked to original sources

Incidence of ras oncogene activation in lung carcinomas in Hong Kong.

BACKGROUND: In Hong Kong, lung carcinomas contribute to the majority of cancer deaths among Chinese. Point mutational activation of ras oncogenes has been observed in several populations. The incidence of these mutations in Hong Kong lung carcinomas was investigated. METHODS: Lung resections obtained from 52 Chinese patients whose conditions were newly diagnosed as non-small cell lung cancer, paraffin sections from 29 Chinese patients with previously diagnosed adenocarcinoma of the lung, and paraffin sections from 49 squamous cell carcinomas were examined for the presence of point mutations in Ki-ras codon 12, N-ras codon 61, and Ha-ras codon 12 oncogenes by allele-specific hybridization after specific amplification of appropriate regions of the DNA using the polymerase chain reaction. RESULTS: Among the 130 lung carcinomas investigated, Ki-ras point mutations were detected in seven cases, of which six were adenocarcinomas and one a squamous cell carcinoma. No mutations were detected in the N-ras and Ha-ras codons. CONCLUSIONS: The incidence of Ki-ras codon 12 point mutational activation in Chinese patients with adenocarcinomas was 6 of 63 (9.5%). The incidence of Ki-ras 12 point mutational activation among men with lung adenocarcinomas in Hong Kong (6 of 32 patients, 18.8%) is significantly different from that in women in Hong Kong (0 of 31 patients, 0%). Although ras oncogenes are implicated as having a role in the development of lung adenocarcinomas, especially among smokers, it is clear from these data that they are not associated with the unusually high incidence of lung adenocarcinomas among women in Hong Kong.

Adenocarcinoma↗

Combined use of fine-needle aspiration cytologic examination and tuberculin skin test in the diagnosis of cervical tuberculous lymphadenitis. A prospective study.

A prospective study to evaluate the efficacy of combined use of fine-needle aspiration (FNA) cytologic examination and Mantoux test in the diagnosis of cervical tuberculous lymphadenitis was carried out. Tuberculin reactions were determined in 59 control subjects. Preoperative FNA cytologic examinations and Mantoux tests were performed on 74 patients with cervical lymphadenopathy. The lymph nodes were then excised and examined histologically and cultured for mycobacteria. Forty-eight, 22, and 4 patients had histologically confirmed tuberculous, non-specific, and malignant lymphadenopathy. Fine-needle aspiration cytologic examination alone could detect cervical tuberculous lymphadenitis in 37 patients (77%). The predictive value of a strong tuberculin reaction for mycobacterial infection was 100%. The combined use of a Mantoux test and FNA cytologic examination was able to diagnose 43 (90%) of 48 cases of tuberculous lymphadenitis cervical preoperatively. Combined use of FNA cytologic examination and Mantoux test was efficient in the diagnosis of tuberculous lymphadenitis.

Adolescent↗

Source of tubercle bacilli in cervical lymph nodes: a prospective study.

A prospective study searching for associated mycobacterial infection of the upper aerodigestive tract in patients with cervical tuberculous lymphadenitis (TBLN) was carried out. One hundred and thirteen patients with a clinical suspicion of cervical TBLN were included. All patients had a physical examination of the upper aerodigestive tract. Routine endoscopy and biopsy of the nasopharynx were performed. All of them had surgery to the cervical lymph node. Seventy-five patients had histologically confirmed cervical TBLN. Culture of the lymph node specimen showed Mycobacterium tuberculosis in 68 (90 per cent). In 45 (60 per cent) patients with cervical TBLN the primary foci of infection could not be found. Twenty-nine (39 per cent) had radiographic evidence of active or healed pulmonary tuberculosis. Sputum culture from two patients showed Mycobacterium tuberculosis. Five patients (six per cent) had tuberculous nasopharyngitis. In one of them (one per cent) the tuberculous nasopharyngitis was primary as no other evidence of mycobacterial infection was found. In the present study, mycobacterial infection of other parts of the upper aerodigestive tract was not found.

Adolescent↗

Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis.

In a randomised, controlled study alternate day prednisolone with an initial high dose phase ("prednisolone only series") has been compared with cyclophosphamide plus alternate day low dose prednisolone ("cyclophosphamide-prednisolone series") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed. Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two of the 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamide-prednisolone series (three of the seven had stopped treatment because of toxicity). Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive of outcome. Analyses of subgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment.

Adult↗

Clinical and histopathological predictors of progressive disease in IgA nephropathy.

The clinical course and biopsy findings of twenty-one patients with IgA nephropathy, followed up for a mean period of 37.4 mth (range 24-54 mth) after diagnosis, were reviewed retrospectively to determine whether the clinical presentations, the laboratory findings or histopathologic changes have prognostic implications. An age of 24 yr or above and a serum creatinine of 0.18 mmol/l or above at diagnosis correlated significantly with renal insufficiency at the end of the follow-up (P = 0.023 & 0.03). Proteinuria of 1.5 g/d or more and hypertension (systolic greater than 150 mmHg or diastolic greater than 100 mmHg) when well controlled, were not found to be significant. Asymptomatic proteinuria and gross hematuria, on the other hand, correlated negatively with renal insufficiency at the end of the follow up (P = 0.034). With respect to histopathological changes, greater than 30% global glomerular sclerosis and moderate or marked tubular atrophy correlated significantly with renal insufficiency (P = 0.005 and 0.005). However, less than 10% glomerular crescents, small amounts of mesangial electron dense deposits or absent ultrastructural peripheral glomerular capillary wall abnormalities correlated negatively with renal insufficiency (P = 0.017, 0.03 & 0.03).

Adolescent↗

Selective 5-HT2 receptor blockade in exercise-induced asthma.

Seven young extrinsic asthmatics participated in an open, pilot study to determine the protective effect of a selective 5-hydroxytryptamine (5-HT) blocking agent, ketanserin, on exercise induced asthma. Ketanserin in a dose of 10 mg given intravenously 20 min before exercise altered the basal bronchomotor tone in only 1 of 6 subjects and offered partial protection against exercise-induced bronchoconstriction in 1 of 5 asthmatics with no overall effect in the group. All patients experienced sleepiness after administration of ketanserin and one had bradycardia with hypotension. The ineffectiveness of ketanserin suggests indirectly that serotonin has a limited role in the pathogenesis of exercise-induced asthma.

Adolescent↗

Mapping of transfer regions within incompatibility group HI plasmid R27.

Plasmids of incompatibility group HI are large (greater than 150 kilobases [kb]) and possess an unusual thermosensitive mode of conjugative transfer. R27, the prototype IncHi1 plasmid, encodes resistance to tetracycline via a determinant which is related to transposon Tn10. A restriction endonuclease map of R27 (size, 182 kb) was recently constructed with ApaI, PstI, and XbaI. Transfer genes within R27 were mapped by insertion of Tn5 and Tn7. At least two different regions of the plasmid were concerned with transfer functions. Insertions into either region completely abolished transfer. None of the insertions had any effect on entry exclusion (Eex) of other IncH plasmids. However, a deletion mutant which lacked the Eex function was obtained, allowing us to map the probable site of the gene encoding Eex to one of the two transfer regions. The tetracycline resistance determinant in R27 was located within an 8-kb region between the two main transfer regions. The transfer genes, therefore, are not located together in R27 but are situated in at least two major widely separated transfer regions.

Chromosome Mapping↗

Resistance of Pseudomonas aeruginosa mutants with altered control of chromosomal beta-lactamase to piperacillin, ceftazidime, and cefsulodin.

Examination of beta-lactam susceptibility of mutants altered in the control of chromosomal beta-lactamase of Pseudomonas aeruginosa supports the view that a constitutive level of beta-lactamase is not an adequate explanation for resistance to cefsulodin and ceftazidime but could be for resistance to piperacillin which has an efficiency of hydrolysis ca. 10 times higher than does cefsulodin or ceftazidime.

Anti-Bacterial Agents↗

Peripheral glomerular capillary wall lesions in IgA nephropathy and their implications.

Peripheral glomerular capillary walls were studied in 26 cases of IgA nephropathy by means of the transmission electron microscope. Ultrastructural abnormalities were identified in 11 cases (42%). Abnormalities of the glomerular basement membrane (GBM) were the most frequent change which consisted of localized thinning, lamination, irregular thickening, disruption, membranolysis and aneurysmal dilatation of the GBM. Subendothelial electron dense deposits were seen. Necrosis and detachment of the podocytes from the GBM were also encountered. The changes were correlated with the clinical findings at the time of diagnosis which showed a significant correlation of these peripheral glomerular capillary wall lesions with proteinuria. With light microscopy, crescents were significantly more frequently seen in the cases showing the ultrastructural capillary wall abnormalities than those without. This observation suggested that local peripheral glomerular capillary wall damage was an important factor in the pathogenesis of the extracapillary lesions in IgA nephropathy.

Adult↗

Roles of ribosomal binding, membrane potential, and electron transport in bacterial uptake of streptomycin and gentamicin.

The effects of a set of conditions on aminoglycoside uptake were determined. Membrane vesicles either with a membrane potential (delta psi) of -125 mV (adequate to drive lysine uptake) or with succinate, lactate, or phenazine methosulfate did not accumulate gentamicin unless components of protein synthesis were included. Ribosomally resistant (rpsL) Escherichia coli cells demonstrated energy-dependent phase II uptake similar to that of a streptomycin-susceptible strain of E. coli when treated with 100 micrograms of puromycin per ml. Puromycin (100 micrograms/ml) also increased the uptake of the cationic compounds polyamine and arginine. These studies support a role of protein synthesis in aminoglycoside uptake and in the development of energy-dependent phase II. delta psi of cells did not increase either at the initiation of or during energy-dependent phase II, showing that energy-dependent phase II is not due to an elevation of delta psi. In a Bacillus subtilis system, significant streptomycin uptake requires a threshold value of delta psi which varies depending upon the concentration of streptomycin used. At 25 micrograms/ml, the uptake of streptomycin reached maximal levels after exceeding the threshold value, whereas at 100 micrograms/ml there was a gradual increase of the uptake to the maximal after the threshold value was exceeded. Several studies supported the view that electron transport has a specific role other than its requirement to produce the cellular delta psi. The uptake of gentamicin was stimulated to a greater extent by phenazine methosulfate-ascorbate than by the ionophore nigericin in strains of E. coli, although nigericin stimulated delta psi to a greater degree. Cells with 25% of the normal quinone concentration had delta psi values identical to cells with the normal quinone concentration, but the quinone-deficient cells had a significantly lower rate of gentamicin uptake. KCN prevented gentamicin uptake but did not prevent the development of delta psi. The effects of ubiquinone depletion in an E. coli strain were more evident on gentamicin uptake than on ATP-driven glutamine transport or proton motive force-driven proline transport, consistent with a specific requirement for quinones in aminoglycoside uptake. A detailed explanation of the mechanism of accumulation of streptomycin and gentamicin and a proposed mechanism for killing bacterial cells by these agents have been provided.

Bacteria↗

Differential effect of chronic desipramine and amitriptyline treatment on rat brain adrenergic and serotonergic receptors.

Serotonergic and adrenergic receptors were examine in rat brains by direct binding assays after chronic treatment with tricyclic antidepressants. Chronic amitriptyline (AMT) treatment (10 mg/kg/day i.p. for 21 days) decreased specific 3H-spiperone binding in the cortex and not in the caudate nuclei. Specific 3H-dihydroalprenolol (3H-DHA) binding was reduced in cerebellar but not in cerebral cortex. Chronic desipramine (DMI) treatment given in the same dose schedule, on the other hand, decreased specific 3H-DHA binding in both cerebellar and cerebral cortex. Specific 3H-spiperone binding in the cerebral cortex was also reduced but to a lesser extent than that in the AMT treated group. Scatchard analysis showed that reductions in 3H-spiperone or 3H-DHA binding in all cases were due to decreases in number of binding sites (Bmax) and not to changes in dissociation constants (KD). No change was observed in 3H-serotonin (3H-5HT), 3H-clonidine, or 3H-WB-4101 binding. The results show that there is no single common change in brain adrenergic and serotonergic receptors after chronic AMT and DMI treatment.

Amitriptyline↗