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Biomedical subjects

T Lee

Publications and source records attributed to T Lee.

At least 199 records · Page 11Linked to original sources
PubMed1996

Duodenum-preserving resection of the head of the pancreas: the significance as a diagnostic therapy of the lesion in the pancreatic head.

A 75-year-old man who was diagnosed as having mucin-producing pancreatic cystic lesion of the main pancreatic duct by duodenoscopic examination was reported. Because of the low malignant potential of such lesions, duodenum-preserving resection of the head of the pancreas was performed, and the intra-operative histological examination showed no malignancy of the resected pancreatic head and no other surgical procedures, such as lymph-adenectomy nor pancreato-duodenectomy were necessary. The significance of this case report lies in that a less invasive operation should be selected at first to diagnose whether the lesion is malignant or not, and also that the selected operation itself must be sufficient to resect an adequate part of the pancreatic tissue involving the cystic lesion, if not malignant. Here, we report the process to select the procedure and the surgical technique.

Aged↗
PubMed1996

Cladribine and mitoxantrone dose escalation in indolent non-Hodgkin's lymphoma.

PURPOSE: Since cladribine (2-chlorodeoxyadenosine [2-CdA]) and mitoxantrone both exhibit major activity against indolent lymphoid malignancies and have different mechanisms of action, we performed a dose-escalation study of 2-CdA and mitoxantrone in patients with alkylator-failed indolent lymphoma to determine the maximum-tolerated dose (MTD) of this combination and to make preliminary observations about efficacy. PATIENTS AND METHODS: Twenty-three patients were treated every 28 to 35 days, in cohorts of at least three patients, with stepwise dose escalations until dose-limiting toxicities (DLTs) were encountered. The initial dose levels were 2-CdA 0.1 mg/kg/d by continuous infusion for 7 days, mitoxantrone 5 mg/m2 intravenously (i.v.) on day 1, and prednisone 100 mg/d on days 1 to 5. Mitoxantrone was dose-escalated in increments of 2.5 mg/m2 i.v. on day 1. RESULTS: The MTD of the combination was 2-CdA 0.1 mg/kg/d for 7 days, mitoxantrone 7.5 mg/m2 i.v. on day 1, and prednisone 100 mg/d on days 1 to 5. Myelosuppression and infection were the DLTs. The recommended phase II doses were 2-CdA 0.075 mg/kg/d for 7 days mitoxantrone 5 mg/m2 i.v. on day 1; prednisone was omitted to decrease the risk of opportunistic infections. The overall response rate was 70%, with 22% complete responses (CRs) and 48% partial responses (PRs). The median duration of CR was 15 months and PR 5 months. CONCLUSION: These results demonstrate the feasibility and safety of combining 2-CdA and mitoxantrone in the treatment of indolent lymphoma, and appear to confirm clinically the mechanistic synergism and rationale for this combination regimen. Prednisone exacerbated the risk of opportunistic infection and was omitted. The overall response rate was high, including durable CRs. Further studies of this combination regimen are warranted in untreated and alkylator-failed indolent lymphoma.

Adult↗
PubMed1996

A disulfide bonding interaction role for cysteines in the extracellular domain of the thyrotropin-releasing hormone receptor.

The roles of disulfide and sulfhydryl groups in the specific binding of TRH to its receptor have been examined. In all TRH receptors (TRH-Rs) isolated from different species so far, there are only two extracellular cysteine residues (Cys98 in the extracellular loop between transmembrane helices 2 and 3 and Cys179 in the extracellular loop between transmembrane helices 4 and 5) that are in positions homologous to cysteine residues in other G protein-coupled receptors. Another Cys (Cys100) is located in close proximity to Cys98 at the interface between the first extracellular loop and third transmembrane domain. To assess the role of these TRH-R Cys residues in disulfide bonding interactions, they were mutated to either Ser or Ala. Six mutant receptors (Cys98Ser, Cys98Ala, Cys179Ser, Cys179Ala, Cys100Ser, and Cys100Ala) were expressed in COS-1 cells and tested for their ability to bind TRH and to activate total inositol phosphate (IP) formation. TRH-R mutants Cys100Ser and Cys100Ala showed TRH binding affinities and IP activation similar to the wild-type (WT). In contrast, mutants Cys98Ser, Cys98Ala, Cys179Ser, and Cys179Ala showed no high affinity TRH binding. The potencies of Cys98Ala and Cysl79Ala as measured by IP stimulation were decreased by four orders of magnitude when compared with WT. Cys98Ser potency decreased by five orders of magnitude, whereas Cys179Ser showed no IP production. Northern blotting confirmed expression of all the mutant TRH-Rs at the messenger RNA (mRNA) level. An epitope tag derived from the Haemophilus influenza hemagglutinin protein was incorporated at the NH2 termini of the TRH-R WT and TRH-R Cys mutants to allow the independent assessment of cell surface expression of receptor protein. TRH-R mutants that failed to show receptor binding (Cys98Ser, Cys98Ala, Cys179Ala) showed WT levels of cell surface receptor expression, indicating that loss of receptor binding in these mutants is not attributable to loss of receptor expression. In contrast, cell surface expression of Cysl79Ser, which showed no ligand induced IP stimulation, could not be detected. Dithiothreitol, a disulfide bond reducing agent, and p-chloromercuribenzoic acid (p-CMB), a sulfhydryl blocking compound, reduced specific TRH binding in a dose-dependent manner. The inhibition of binding by dithiothreitol implies that the integrity of a disulfide bond is important for TRH binding to its receptor. The dramatic inhibition of TRH binding by p-CMB indicates that free sulfhydryl groups are also associated with the binding of the ligand to its receptor. This study presents evidence that a disulfide bond exists between Cys98 and Cys179 which is essential for maintaining the receptor in the correct conformation for ligand binding. Cys100 is not thought to have a disulfide bonding interaction role. Results obtained after chemical modification have shown that free sulfhydryl groups within the TRH-R may also have a role in ligand interactions.

Amino Acid Sequence↗
PubMed1996

Function of the Drosophila POU domain transcription factor drifter as an upstream regulator of breathless receptor tyrosine kinase expression in developing trachea.

Organogenesis of the Drosophila tracheal system involves extensive directed cell migrations leading to a stereotypic series of interconnected tubules. Although numerous gene products have been shown to be essential for tracheal morphogenesis, direct functional relationships between participants have not been previously established. Both the breathless gene, encoding a Drosophila fibroblast growth factor receptor tyrosine kinase homologue, and the POU-domain transcription factor gene, drifter, are expressed in all tracheal cells and are essential for directed cell migrations. We demonstrate here that ubiquitously expressed Breathless protein under control of a heterologous heat-shock promoter is able to rescue the severely disrupted tracheal phenotype associated with drifter loss-of-function mutations. In the absence of Drifter function, breathless expression is initiated normally but transcript levels fall drastically to undetectable levels as tracheal differentiation proceeds. In addition, breathless regulatory DNA contains seven high affinity Drifter binding sites similar to previously identified Drifter recognition elements. These results suggest that the Drifter protein, which maintains its own expression through a tracheal-specific autoregulatory enhancer, is not necessary for initiation of breathless expression but functions as a direct transcriptional regulator necessary for maintenance of breathless transcripts at high levels during tracheal cell migration. This example of a mechanism for maintenance of a committed cell fate offers a model for understanding how essential gene activities can be maintained throughout organogenesis.

Animals↗
PubMed1996

Two distinct roles for Ras in a developmentally regulated cell migration.

Receptor tyrosine kinases have been shown to promote cell movement in a variety of systems. The Ras protein, a well-documented downstream effector for receptor tyrosine kinases, may contribute to receptor tyrosine kinase-mediated motility. In the present study, we have examined the role of Ras in the migration of a small subset of follicle cells, known as the border cells, during Drosophila oogenesis. A dominant-negative Ras protein inhibited cell migration when expressed specifically in border cells during the period when these cells normally migrate. When expressed prior to migration, dominant-negative Ras promoted premature initiation of migration. Conversely, expression of constitutively active Ras prior to migration resulted in a significant delay in the initiation step. Furthermore, the defect in initiation of border cell migration found in slbo1, a mutation at the locus that encodes Drosophila C/EBP, was largely rescued by reducing Ras activity in border cells prior to migration. Taken together, these observations indicate that Ras activity plays two distinct roles in the border cells: (1) reduction in Ras activity promotes the initiation of that migration process and (2) Ras activity is required during border cell migration. We further examined the possible involvement of two downstream effectors of Ras in border cell migration. Raf activity was dispensable to border cell migration while reduced Ral activity inhibited initiation. We therefore suggest that Ras plays a critical role in the dynamic regulation of border cell migration via a Raf-independent pathway.

Animals↗
PubMed1996

A PCR-RFLP method for the detection of activated H-ras oncogene with a point mutation at codon 12 and 61.

To investigate the incidence of the H-ras gene activation in bladder tumor and the feasibility of using urinary washout samples for screening, a series of 33 human bladder tumors and their preoperatively collected urinary washout samples were screened using a mutant specific PCR-RFLP (polymerase chain-restriction fragment length polymorphism) to detect a point mutation of the H-ras gene. Five tumors were found to harbor H-ras mutations where two tumors had a glycine to valine (G-->T) change in codon 12 and three tumors had a glutamine to lysine (C-->A) change in codon 61, respectively. Moreover, we could also detect the same point mutations of the H-ras gene in corresponding urine washout samples. The incidence of H-ras mutation in Korean bladder cancer was estimated at approximately 15.2%. In conclusion, a mutant specific PCR-RFLP method for the detection of H-ras gene mutation is useful for screening or postoperative follow-up of bladder tumor due to its simplicity and high specificity even in urinary samples.

Base Sequence↗
PubMed1996

Demographic modelling of the HIV/AIDS epidemic on the Soweto population--results and health policy implications.

In this paper we present the results of a local HIV/AIDS demographic modelling exercise for Soweto, Johannesburg. The Doyle model was used to project the growth of the HIV/AIDS epidemic in Soweto until the year 2010. High, medium and low AIDS scenarios are projected; these depend on reduction in the average number of sexual partners, increased condom use and effective treatment of sexually transmitted diseases. In 1993 the HIV prevalence was estimated to be 3% for all three of the low, medium and high AIDS scenarios, but differences emerge rapidly after this. By 2010 the projected HIV seroprevalences in the high, medium and low AIDS scenarios are 24%, 15% and 8% respectively, corresponding with 343,000, 222,000 and 118,000 HIV-infected people. By the year 2010, AIDS will have caused 135,000-270,000 deaths and during that year will account for 28-52% of all deaths. The total population will continue to increase in size, even in the high AIDS scenario, with the population growth rate ranging from 1.8% (low AIDS scenario) to 1% (high AIDS scenario) by the year 2010. This modelling exercise has demonstrated the enormous potential impact of timeous and effective implementation of currently available prevention strategies. The need to institute prevention programmes in the short term is therefore stressed. Recommendations are also made about the care of people with HIV/AIDS. Other areas are encouraged to attempt similar exercises in order to stimulate local and regional planning of HIV/AIDS prevention and care.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Physical activity, medical history, and risk of testicular cancer (Alberta and British Columbia, Canada).

In order to evaluate risk factors for germ cell cancers, we conducted a case-control study of 510 men with testicular cancer aged 15 to 79 years and 996 randomly selected age-matched controls in the provinces of British Columbia and Alberta, Canada. Subjects completed a mailed questionnaire providing data on education level, ethnic origin, medical history, smoking, occupation, and recreational and sports activity. The response rate among cases was 80.3 percent and among controls was 68.1 percent. After controlling for age and ethnic origin, undescended testis was associated positively with risk of testicular cancer (odds ratio [OR] = 3.5; 95 percent confidence interval [CI] = 2.2-5.7) as was inguinal hernia requiring surgery (OR = 2.0, CI = 1.3-2.9), and hydrocoele (OR = 2.6, CI = 1.4-5.1). Risk of testicular cancer increased with height, with subjects taller than 180 cm having a significantly increased risk compared with those 174 cm or less (OR = 1.5, CI = 1.1-2.1). A moderate to high level of recreational activity level was associated inversely with testicular cancer risk (OR = 0.6, CI = 0.5-0.8).

Adolescent↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Polyglyconate fixation successfully stabilizes zygomatic osteotomies in a nonhuman primate.

Investigators have reported problems with metal plates and screws, including restriction of craniofacial growth necessitating secondary removal; bone resorption secondary to stress shielding; increased incidence of infection, extrusion, and palpability, especially in regions with minimal soft-tissue coverage; and interference with radiological studies and postoperative radiation therapy. Biodegradable rigid fixation can easily eliminate a majority of these problems because the material provides adequate fixation for a finite interval corresponding to bony repair. For this reason, there has been increasing interest in developing satisfactory biodegradable plate and screw systems. We tested a commercially developed polyglyconate plate and screw system to stabilize zygomatic osteotomies in a nonhuman primate model before embarking on clinical trials. In this experimental model, the stabilized segments revealed satisfactory alignment; in the control animals, the bony fragments became significantly displaced. This polyglyconate plate and screw system appears to have a promising role in the surgical correction of craniomaxillofacial deformities in humans, and clinical testing should commence.

Animals↗
PubMed1995

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↗
PubMed1995

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↗