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Biomedical subjects

T Lee

Publications and source records attributed to T Lee.

At least 19 recordsLinked to original sources

Identification and biochemical characterization of human plasma neutrophil inhibitor in vitro.

In this study, assessment by a flow cytometric method using dichlorhydroxy fluorescin diacetate (DCFADH) in vitro revealed that human peripheral blood inhibits the production of active oxygen species by human peripheral neutrophils. It was also revealed that among the blood components, the plasma fraction inhibits active oxygen production most strongly. This plasma inhibitory activity was dose-dependent. Human serum also exerted an inhibitory activity; however, its activity was only one-third that of plasma. Moreover, when HL-60 human promyelocytic leukemic cells, with or without differentiation into the neutrophils by culturing with dimethyl sulfoxide (DMSO), active oxygen, which was also inhibited by plasma, was produced. Heat inactivation of the plasma did not alter the inhibitory activity, and gel filtration analysis showed that the peak activity was associated with a molecular mass of 70,000. The results of this study indicate that human plasma contains one or more substances that inhibit the active oxygen production of neutrophils, which may play an important role in inhibiting unneeded neutrophil activation in the bloodstream.

Cell Line

Indicators and research methods for rapid assessment of a tuberculosis control programme: case study of a rural area in South Africa.

SETTING: An evaluation of the Tuberculosis Control Programme (TBCP) of KaNgwane, a rural, previously designated 'homeland' of South Africa, was performed in 1990. OBJECTIVE: The evaluation is presented as a case study to illustrate a proposed methodology for rapid, comprehensive, management oriented TBCP research. DESIGN: The components of the TBCP were categorised into direct TBCP activities, management processes and integration of the TBCP into Primary Health Care (PHC). The methods used to evaluate indicators for each of these components included: policy analysis, interviews with staff and patients, observation of in-patient and ambulatory patient care, record reviews and a household survey. RESULTS: The regional scope of the study yielded a wealth of useful information at a managerial level. Detailed, quantitative information was obtained, allowing for the identification of weaknesses in the TBCP and the targeting of appropriate action. Particularly problematic aspects were: the health information collection, case-finding and case-holding, health education and coordination and supervision. Comparative analyses between different health wards helped identify particular areas of weakness. Both illustrative results and methodological limitations are presented. The methodology used is related to previous South African TB health service research and to the emerging field of rapid assessment methods. CONCLUSIONS: A rapid but comprehensive review of a TBCP can be done if indicators and research methods are carefully selected and record systems are functional. If record systems are not functional, the non-record review methods still offer substantial information on many indicators and one or two quantitative indicators (e.g. case holding) could be selectively measured through reviewing a sample of records.

Adult

Neuropsychological outcome from psychosurgery for obsessive-compulsive disorder.

Seventeen obsessive-compulsive disorder patients treated with psychosurgery were administered a comprehensive neuropsychological test battery. Their performance on neuropsychological testing was compared with that of an age and severity matched sample of 17 OCD sufferers who had not received psychosurgery. The psychosurgery and control groups did not differ in intellectual or memory functioning, consistent with earlier findings that psychosurgery does not reduce global ability estimates. The psychosurgery group performed more poorly than the control group on an adaptation of the Wisconsin Card Sorting Test, demonstrating the possible impact of frontal lobe lesions on the abilities underpinning the formation and shifting of response sets.

Adult

Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan.

Seventeen patients with papillary thyroid cancer whose serum thyroglobulin (Tg) levels were elevated when hypothyroid, but whose diagnostic whole body scans were negative, were treated with 150-300 mCi 131I. All patients had total thyroidectomy and 131I ablation for thyroid remnants. Before the study, 9 patients had 131I therapy for tumor recurrence and/or metastases, and 5 patients had excisions of nonfunctioning metastasis. Radiological studies did not reveal evidence of metastases. In the initial evaluation, Tg levels ranged from 8-480 ng/mL (24 pmol/L to 1.5 nmol/L), and posttherapy whole body scans (RxWBS) revealed undiagnosed local recurrence and/or metastases in 16 of 17 patients. Follow-up from 6 months to 5 yr is available in 16 patients. RxWBS after a second treatment was positive in 8 of 13 patients, and after a third treatment in 5 of 5 patients, although in 3 cases, uptake in distant metastasis had disappeared. In 8 patients, Tg fell to 5 ng/mL or less. In 1 patient, RxWBS became negative, but Tg remained elevated; subsequent treatment revealed local and mediastinal uptake, but previous lung uptake had disappeared. In 8 patients, RxWBS remains positive, and elevated Tg persists. A total of 35 RxWBS were performed; 29 were positive. Follow-up Tg concentrations decreased in 81% of patients after the first treatment, in 90% after the second treatment, and in 100% of the patients after the third treatment. Tg (mean +/- SE) decreased from 74 +/- 33 ng/mL in the first evaluation to 62 +/- 32 ng/mL in the second study and 32 +/- 20 ng/mL in the third study. The therapeutic effectiveness of 131I treatment in patients with elevated Tg and negative diagnostic whole body scans is indicated by the conversion to negative RxWBS, the statistically significant decrease in the mean Tg level, and the reduction of serum Tg to 5 ng/mL or less in 50% of patients. Further experience with this therapeutic approach is required to evaluate its effectiveness in improving prognosis and survival.

Adult

The breathless FGF receptor homolog, a downstream target of Drosophila C/EBP in the developmental control of cell migration.

To investigate the molecular mechanisms responsible for the temporal and spatial control of cell movements during development, we have been studying the migration of a small group of follicle cells, called the border cells, in the Drosophila ovary. Timely initiation of border cell migration requires the product of the slow border cells (slbo) locus, which encodes the Drosophila homolog of the transcription factor C/EBP. Here we report evidence that one target of C/EBP in the control of border cell migration is the FGF receptor homolog encoded by the breathless (btl) locus. btl expression in the ovary was border cell-specific, beginning just prior to the migration, and this expression was reduced in slbo mutants. btl mutations dominantly enhanced the border cell migration defects found in weak slbo alleles. Furthermore, C/EBP-independent btl expression was able to rescue the migration defects of hypomorphic slbo alleles. Purified Drosophila C/EBP bound eight sites in the btl 5' flanking region by DNAse I footprinting. Taken together these results suggest that btl is a key, direct target for C/EBP in the regulation of border cell migration.

Animals

Isoniazid prophylactic therapy for tuberculosis in HIV-seropositive patients--a least-cost analysis.

The expected upsurge in the number of new cases of tuberculosis resulting from the HIV/AIDS epidemic prompted an examination of the feasibility of prevention strategies to limit the increase in clinical tuberculosis. A computer spreadsheet model was developed to estimate the costs and benefits that would result from isoniazid chemoprophylaxis for tuberculosis in a hypothetical cohort of 100,000 HIV-seropositive people in South Africa over a period of 8 years. At a 50% prevalence of tuberculosis infection among those at high background risk, and 5-10% among those at low risk, there would have been 34,000 cases of active tuberculosis in the cohort and their contacts if no prophylactic therapy had been used. On the other hand, a chemoprophylaxis policy would have meant only 12,200 cases of tuberculosis, if a patient compliance rate of 68.5% had been assumed. Such a policy would have prevented 21,800 cases of active tuberculosis. The estimated total discounted cost of a chemoprophylaxis programme would have been R51.3 million. In the absence of preventive therapy the discounted cost of treating patients with active tuberculosis would have been R91.9 million over the 8-year period. Therefore, if the benefits of chemoprophylaxis were defined in terms of averted health care costs, such a policy would have resulted in net savings of R40.6 million. This study did not estimate losses in production associated with tuberculosis treatment or the value of preventing tuberculosis per se, though such indirect costs would have increased the benefit of the prevention programme.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care

Steroid and asparaginase-induced hyperlipidemia in leukemia.

A case presentation of a ten year old girl diagnosed with acute lymphoblastic leukemia is described. Following her combination chemotherapy regimen with steroids and asparaginase, a most interesting development of hyperlipidemia of the blood plasma and lipemia retinalis was noted.

Asparaginase

Ultrasonographic evaluation of multicystic dysplastic kidney.

Eleven cases of multicystic dysplastic kidney (MCDK) in children were diagnosed over an 11 year period. All underwent postnatal ultrasound (US) studies. Four different patterns of MCDK were recognized: (1) Six cases presented with the classic sonogram of multicystic components. (2) Three cases had hydronephrotic form; correct diagnosis between hydronephrotic form of MCDK and hydronephrosis was difficult as there was a medially-located, large, lobulated cyst and there was connection between the large cyst and neighboring small cysts. (3) One case initially presented with normal renal sonogram but a small cyst appeared on follow up sonogram and there was also decreased renal size and increased echogenecity. (4) One case had only two moderate-sized cysts but no identifiable renal parenchyma. Two cases had follow-up US examination and one dysplastic kidney decreased in renal size on follow-up sonogram. Intravenous urography and radionuclide study revealed both these dysplastic kidneys to be nonfunctioning. Nine children had surgical resection of the diseased kidneys. Contralateral renal anomalies were detected in five children, which included ureteropelvic junction stenosis, ureterovesical junction stenosis, distal ureteral stenosis and polycystic kidney disease. Two of three hydronephrotic forms of MCDK had contralateral ureteral stenosis. Two of six classic forms of MCDK had contralateral ureteral stenosis. The proportion of contralateral ureteral stenosis was higher in the group of hydronephrotic forms of MCDK. Ultrasonography is beneficial for conclusive diagnosis of MCDK; however, a differential diagnosis of simple hydronephrosis needs to be considered.

Female

Differences in haemagglutination activity and electrophoretic mobility of E protein between the parent SA14 and attenuated vaccine SA14-14-2 strains of Japanese encephalitis virus.

E protein characteristics of the attenuated Japanese encephalitis (JE) virus strain SA(A) derived from the live vaccine strain SA14-14-2 were compared with those of the virulent strain SA(V). SA(A) showed lower haemagglutination (HA) activity with broader optimum pH range of HA reaction than SA(V), and the E protein of SA(A) had slower electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) than that of SA(V). These properties of SA(A) E protein appear to be caused by eight amino acid changes found in the E protein coding region of the SA(A) virus genome.

Amino Acids

Well-differentiated hepatocellular carcinoma: clinicopathological features and results of hepatic resection.

OBJECTIVES: To clarify clinicopathological features and surgical results in patients with well-differentiated hepatocellular carcinoma (wd-HCC) corresponding to Edmondson's cell grading I/I-II. METHODS: The clinicopathological characteristics, diagnosis, and results of surgery were studied in 14 wd-HCC patients who underwent limited hepatic resection. RESULTS: All patients had liver cirrhosis and solitary tumors. The tumor sizes ranged from 10 to 25 mm. Serum alpha-fetoprotein levels were normal in 13 patients. The detection rates of sonography, computed tomography (CT), angiography, CT during arterial portography, 1-wk lipiodol CT, and 3-wk lipiodol CT were 100%, 43%, 36%, 69%, 57%, and 0%, respectively. High echoic pattern on sonography and disappearance of lipiodol 3 wk after injection were characteristic findings. There was no operative death. Although seven patients developed intrahepatic tumor recurrence, early treatment including ethanol injection therapy and arterial embolization/infusion therapy controlled the recurrences in five patients. Eleven patients are surviving 25-83 mo after surgery (mean, 44 mo); the remaining three died of pneumonia or hepatic insufficiency 44-62 mo after surgery. Eight patients received successful direct interruption surgery for concurrent esophagocardia varices. Pathological features of wd-HCCs included lack of tumor invasiveness or capsule, nuclear crowding, microacinar formation, fat deposition, presence of portal tracts, and surrounding adenomatous hyperplasia. CONCLUSION: Wd-HCCs present atypical findings in various imagings and histology because of the earlier developmental stage of HCCs. Hepatic resection for wd-HCCs provides excellent patient survival.

Carcinoma, Hepatocellular

Treatment response with transurethral radiofrequency thermotherapy for symptomatic benign prostatic hyperplasia.

One hundred and two patients with benign prostatic hyperplasia were treated by transurethral radio-frequency thermotherapy (TURT) device (Thermex-II, Direx, Israel) with 47.5 degrees C in single session for 2 hours and 30 minutes from November 1992 to October 1993. Among them, 83 patients, who were followed up for more than 3 months were included in this study. Twenty-seven (32.5%) patients had a history of acute retention. Pretreated values of the mean Madsen-Iversen symptom score, maximum urine flow rate, postvoiding residual urine volume, prostate volume and prostate specific antigen (PSA) were 15.4, 6.5 ml/sec, 61.3ml, 43.2ml and 0.77 ng/ml respectively. Madsen-Iversen symptom score, maximum urine flow rate were measured at 2 weeks, 1, 3 and 6 months after TURT. The residual urine volume, prostate volume and PSA level were measured at 3 and 6 months after TURT. During the follow up, the symptom score started to decrease significantly at 1 month (9.9, p < 0.01) after TURT, and gradually decreased up to 6.9 at 3 months. The maximum flow rate showed initial significant improvement at 2 weeks (8.1 ml/sec., p < 0.01), but no significant interval change was observed thereafter. The residual volume decreased significantly at 3 months (41.3 ml, p < 0.01) and no decrement was noted until 6 months. Neither the prostate volume nor PSA value changed significantly at 3 or 6 months after TURT. The improvement, which was defined as a change of 50% or more in at least one of subjective or objective symptoms showed in 63.9% (53/83) at 3 months and 57.1% (32/56) at 6 months. Both subjective and objective improvements at 3 and 6 months after treatment showed in 24.1% and 19.6%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

An index case of adrenomyeloneuropathy in a Chinese man.

X-linked adrenomyeloneuropathy (AMN) is a phenotypic variant of adrenoleukodystrophy (ADL) presenting in early adult life with progressive ataxia and spasticity, and on occasion with adrenal insufficiency. We describe a 26-year-old Chinese man with a 2-year history of gait difficulty due to spasticity, absent pattern shift visual evoked (VER) responses and posterior white matter lesions on T2 weighted brain magnetic resonance images. His parents are clinically normal and his 24-year-old brother has hyperreflexia in the legs but normal VER latencies. The patient's ACTH levels were elevated and the serum cortisol did not rise with either Synacthen or corticotropin releasing hormone. Assay of his plasma confirmed elevation of very long chain fatty acids (VLCFA) consistent with a defect in peroxisomal VLCFA metabolism. This is the first local report of a patient with AMN.

Adrenoleukodystrophy

A microdialysis study on striatal dopamine, 5-HT and metabolites in conscious rats after various treatments: evidence for extravesicular release of dopamine.

The effects of death and various treatments that affect the status of nigrostriatal neurones on striatal release of dopamine (DA) and 5-hydroxytryptamine (5-HT) and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylethylamine (3-MT), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were studied by in vivo microdialysis. In conscious rats, DA and 5-HT levels were very low compared with their metabolites except 3-MT which was rarely detectable. Upon death by pentobarbitone overdose, there was an immediate surge of the DA level reflecting massive release of the neurotransmitter. This increase was accompanied by a significant increase in 3-MT level but not the other two DA metabolites. Post mortem release of 5-HT was also observed but to a much smaller extent than that of DA. The amounts of amines released appeared to be proportional to the amine stores. When L-dihydroxyphenylalanine (DOPA) was administered to reserpinized rats, the extracellular levels of both DOPAC and HVA increased but not that of DA. However, marked release of DA occurred at death in contrast to reserpinized rats not injected with the precursor. It is evident that exogenous L-DOPA is taken up into the dopaminergic nerve endings and is converted to releasable extravesicular DA, and that this releasable DA is released, at least in part, in accordance with neuronal activities.

3,4-Dihydroxyphenylacetic Acid

Optimization of a recombinant von Willebrand factor fragment as an antagonist of the platelet glycoprotein Ib receptor.

The binding of von Willebrand factor (vWF) to platelet glycoprotein (GP) Ib receptor is one of the initial events in thrombus formation. Previous studies have shown that RG12986, a reduced and alkylated recombinant fragment of vWF (Ser445-Val733), can inhibit binding of native vWF to GP Ib and offers potential as an anti-thrombotic agent. We have now evaluated a series of deletion mutants of RG12986 and found that reduced and alkylated rvWF508-704 is close to the minimal sequence with optimal RG12986-like activity (IC50 for inhibition of GP Ib-dependent platelet aggregation in the absence of modulators: 0.022 microM +/- 0.01, n = 3) and that it too binds directly to GP Ib. Under in vitro conditions, with no exogenous modulators present and in the absence of shear stress, oxidized rvWF508-704 (containing a disulfide bond between Cys508 and Cys659) is approximately 5-fold less active than reduced and alkylated rvWF508-704; the two fragments, however, display comparable activity in the presence of the modulator botrocetin. The smaller rvWF508-704 fragment offers distinct advantages over RG 12986. In particular, removal of non-active NH2 and COOH terminal sequences may reduce the risk of antigenicity and may contribute to rendering the molecule mostly monomeric in solution, as opposed to the monomer-dimer equilibrium previously described for RG12986.

Chromatography, High Pressure Liquid