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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 487 records · Page 27Linked to original sources
PubMed1996

Financing the World Health Organisation: global importance of extrabudgetary funds.

From 1948, when WHO was established, the Organisation has relied on the assessed contributions of its member states for its regular budget. However, since the early 1980s the WHO World Health Assembly has had a policy of zero real growth for the regular budget and has had to rely increasingly, therefore, on attracting additional voluntary contributions, called extrabudgetary funds (EBFs). Between 1984-85 and 1992-93 the real value of the EBFs apparently increased by more than 60% and in the 1990-91 biennium expenditure of extrabudgetary funds exceeded the regular budget for the first time. All WHO programmes, except the Assembly and the Executive Board, receive some EBFs. However, three cosponsored and six large regular programmes account for about 70% of these EBFs, mainly for vertically managed programmes in the areas of disease control, health promotion and human reproduction. Eighty percent of all EBFs received by WHO for assisted activities have been contributed by donor governments, with the top 10 countries (in Europe, North America and Japan) contributing about 90% of this total, whereas the UN funds and the World Bank have donated only about 6% of the total to date. By contrast, about 70% of the regular budget expenditure has been for organisational expenses and for the support of programmes in the area of health systems. Despite the fact that the more successful programmes are heavily reliant on EBFs, there are strong indications that donors, particularly donor governments, are reluctant to maintain the current level of funding without major reforms in the leadership and management of the Organisation. This has major implications for WHO's international role as the leading UN specialised agency for health.

Budgets↗
PubMed1996

Identification of a developmentally regulated protein tyrosine phosphatase in embryonic stem cells that is a marker of pluripotential epiblast and early mesoderm.

A sensitive RT-PCR display technique was used to examine the expression of protein tyrosine phosphatases (PTPs) during the differentiation of mouse embryonic stem (ES) cells. The majority of PTPs are expressed constitutively but one is present only in undifferentiated ES cells. This PTP was cloned and named ES cell phosphatase (ESP). ESP mRNA is detectable in oocytes and throughout early mouse embryo development. At early egg cylinder stages, transcripts are localised in the pluripotential epiblast. As gastrulation commences, however, epiblast expression is lost. Transcripts are present transiently in newly formed embryonic mesoderm. These data suggest that this transmembrane signaling molecule is associated with developmental lability in early embryogenesis.

Amino Acid Sequence↗
PubMed1996

The control and biological importance of intratumoural aromatase in breast cancer.

The existence of aromatase activity in human breast carcinomas has been established for about 20 years but the clinical and biological importance of this remains unclear. A number of studies in clinical material suggest that aromatase activity may be a prerequisite of response to aromatase inhibitors and that aromatase activity may be enhanced in those tumours relapsing during treatment with one such inhibitor, aminoglutethimide. These results would carry more significance, however, if it was demonstrable that the growth of breast carcinomas is affected by the conversion of androgens to oestrogens by intratumoural aromatase. We have tried to address this by establishing model systems with aromatase-transfected MCF7 breast cancer cells. We have demonstrated that these cells can be stimulated mitogenically with androgen and that this proliferation is suppressible with aromatase inhibitors. Similarly the growth of aromatase transfected cells but not wild type cells as xenografts is supported by androstenedione and inhibitable by both the steroidal aromatase inhibitor, 4-hydroxyandrostenedione and non-steroidal inhibitor, CGS 20267. Work with the former of these, which is a suicide inhibitor allowed us to demonstrate that growth can proceed with aromatase activity approximating to the highest level seen in breast carcinomas indicating that at least at this extreme level the intratumoural conversion of androgens to oestrogens may indeed be able to support tumour growth. Further work with this mode system should allow us to define the minimal amount of intratumoural activity which can support tumour growth.

Adenocarcinoma↗
PubMed1996

Pyruvate prevents ischemia-reperfusion mucosal injury of rat small intestine.

BACKGROUND: Since reactive oxygen intermediates (ROI, or free radicals) have been implicated in the pathogenesis of ischemia-reperfusion injury of the small bowel, we evaluated the pretreatment effect of pyruvate, a 3-carbon compound recently shown to inhibit superoxide production, on reperfusion mucosal injury in the rat. METHODS: The small bowel of the ACI rat (n = 6) was divided into 2 5-cm segments, and 10 mL of a liquid diet containing pyruvate (0.32 g) or placebo (0.26 g) was instilled into the lumen of one of the segments for 10 minutes. The bowel was then made completely ischemic for 45 minutes by clamping the superior mesenteric artery, which was followed by 60 minutes of reperfusion. RESULTS: The production of ROI in bowel biopsy samples, estimated by luminol-enhanced chemiluminescence, was at least 80% decreased in the segment containing pyruvate compared with placebo immediately after ischemia (time 0), and compared with 30 and 60 minutes of reperfusion (P < 0.05 for each time point). After 60 minutes of reperfusion, the bowel segment containing the placebo diet showed villus sloughing with destruction of lamina propria and crypts, and mucosal neutrophil infiltration had increased by 80%. Electron microscope evaluation revealed a reduction in number and size of microvilli, dilatation of intercellular spaces, and intracellular vacuoles. The bowel segment containing pyruvate showed the villi and crypts to be intact, without enhanced neutrophil infiltration. CONCLUSION: Pyruvate pretreatment of the rat small bowel inhibits postischemic reperfusion mucosal histologic injury, neutrophil infiltration, and ROI production.

Animals↗
PubMed1996

Preventive treatment of priapism in sickle cell disease with oral and self-administered intracavernous injection of etilefrine.

OBJECTIVES: Priapism is a common and currently unsatisfactorily managed complication of sickle cell disease (SCD). In June 1994, 6 SCD patients received a new therapeutic regimen to prevent the occurrence and recurrence of priapism. METHODS: The patients (5 with SS and 1 with SC) were adults and had frequent episodes of stuttering priapism (SP), and two of them had had acute episodes (AP) lasting more than 3 hours. The treatment consists of preventive oral administration of the alpha-adrenergic agent etilefrine, and self-administered intracavernous injection (SICI) of the same agent to reverse episodes lasting more than 1 hour. RESULTS: Since the beginning of treatment, all patients were protected against AP, 4 patients had no recurrence with the oral treatment alone, 2 had to use SICI, 1 occasionally and 1 constantly. There was no modification of sexual activity and no complications. Blood pressure was unaffected. CONCLUSIONS: This treatment is simple, cheap, and self-administered. It should be proposed to all patients with SCD in all geographic areas as part of an educational program for active prevention of this severe complication.

Administration, Oral↗
PubMed1996

Management of asymptomatic impacted wisdom teeth: a multicentre comparison.

This study was carried out to assess the opinions of clinicians (general practitioners and oral and maxillofacial surgeons) regarding the management of unerupted Mandibular Asymptomatic Impacted Wisdom Teeth (MAIWT) at two centres: Glasgow Dental Hospital and School and its affiliated institutions and Prince Philip Dental Hospital and its affiliated institutions in Hong Kong. Twenty four clinicians, twelve from each centre, of whom six were oral and maxillofacial surgeons (OMS) and six general dental practitioners (GDP) participated in this investigation. The orthopantomographs of 21 cases were used in the study and were examined by each clinician to investigate the management of unerupted MAIWT was recorded using a custom written questionnaire. Hong Kong clinicians showed a greater tendency towards extraction of MAIWT in comparison to Glasgow clinicians. The difference was statistically significant. The data indicates a significant difference between Hong Kong OMS and Glasgow OMS and between Hong Kong OMS and Hong Kong GDP, with Hong Kong OMS showing a greater tendency towards extraction. This study proved the diversity of opinions in one of the most common dento-alveolar procedures. The dilemma to extract or retain MAIWT still exists and controversy is likely to remain. The difference in the rationale of management regimes between the centres are discussed. The medico-legal and financial issues are investigated.

General Practice, Dental↗
PubMed1996

The high-affinity sulphonylurea receptor regulates KATP channels in nerve terminals of the rat motor cortex.

The coexpression of sulphonylurea binding sites and ATP-sensitive K+(KATP) channels was examined in the rat motor cortex, an area of the CNS exhibiting a high density of sulphonylurea binding. These channels were not detected on neuronal cell bodies, but sulphonylurea-sensitive KATP channels and charybdotoxin-sensitive, large-conductance calcium-activated K+ BKCa channels were detected by patch clamping of fused nerve terminals from the motor cortex. Subcellular fractionation revealed that high-affinity sulphonylurea binding sites were enriched in the nerve terminal fraction, whereas glibenclamide increased calcium-independent glutamate efflux from isolated nerve terminals. It is concluded that neuronal sulphonylurea receptors and KATP channels are functionally linked in the motor cortex and that they are both selectively expressed in nerve terminals, where the KATP channel may serve to limit glutamate release under conditions of metabolic stress.

ATP-Binding Cassette Transporters↗
PubMed1996

The development of metacognitive knowledge of basic motor skill: walking.

The development of children's metacognitive knowledge of walking was investigated. Sixty elementary school children (30 boys and 30 girls), 9, 11, and 13 years of age, viewed a video presentation of an adult performing normal walking and six different forms of partial walking (varying in terms of the presence or absence of four essential features of normal walking: arm swing, leg swing, arm-leg coordination, and distance traveled). Then the children were asked to rate the partial walking. A repeated measures ANOVA revealed that children of all these ages appreciated the differences between normal walking and partial walking. As age increased, the degree of importance of the four features became more differentiated. By 13 years of age, the children considered leg swing to be the most important feature of walking, arm swing the second, arm-leg coordination the third, and distance traveled the least important feature.

Adolescent↗
PubMed1996

Emerging resistance of anaerobic bacteria to antimicrobial agents in South Korea.

In previous studies, Bacteroides fragilis group organisms isolated from Korean patients were more frequently resistant to various antimicrobial agents, including clindamycin, than were isolates in other countries. A recent report of increased resistance of Peptostreptococcus species prompted us to include such isolates in a study of antimicrobial susceptibility. anaerobes isolated in 1994 at a tertiary care hospital in Seoul were tested by agar dilution method. None of the B. fragilis group organisms were resistant to imipenem, cefoxitin, chloramphenicol, or metronidazole. However, 6.7% were resistant to ampicillin/sulbactam, 20.2% to cefotetan, 30.3% to piperacillin, 48.3% to cefotaxime, and 42.7% to clindamycin. Almost all of the Clostridium perfringens isolates were susceptible to all of the agents tested, except tetracycline. Peptostreptococcus isolates were susceptible to piperacillin, cefotaxime, and imipenem, while 7.4% were resistant to penicillin G, cefotetan, and metronidazole, and 25.9% were resistant to clindamycin. The isolates resistant to penicillin G, cefotetan, and metronidazole were identified as Peptostreptococcus anaerobius. In conclusion, besides the well-known high rate of resistance of B. fragilis group organisms to clindamycin, the emergence of resistance of Peptostreptococcus species isolates to beta-lactam drugs has become obvious in Korea.

Anti-Bacterial Agents↗
PubMed1996

Exogenous nucleotides alter the proliferation, differentiation and apoptosis of human small intestinal epithelium.

The turnover of intestinal epithelial cells is a finely regulated process extending from undifferentiated crypt stem cells to terminally differentiated villus cells. The final phase of this maturation process is apoptosis and extrusion. Recent studies have shown that programmed cell death (PCD) occurs not only in senescent cells and in rapidly developing tissues but also in response to cellular stress preventing damaged cells from entering uncontrolled proliferation without repair. This study examined the role of exogenous nucleotides on cell proliferation, differentiation and apoptosis in organ cultures of human fetal small intestine. The addition of adenosine monophosphate (AMP), a putative stress reactant, to the culture media resulted in the suppression of crypt cell proliferation followed by the restoration of differentiation and the induction of apoptosis across a broad range of villus epithelium when compared with controls without added nucleotide. In contrast, the addition to cytidine monophosphate (CMP) to the culture media did not increase apoptosis, despite the nucleotide being taken up by the fetal small intestine in a similar dose- and time-dependent manner to AMP. Furthermore, Bax mRNA, an apoptosis-inducer gene, was increased with addition of AMP, suggesting that the induction of apoptosis may be channeled through the p53 pathway. These results suggest that a specific exogenous nucleotide, AMP, may have an important role in controlling the dynamic balance of cellular turnover in the developing human small intestine.

Adenosine Monophosphate↗
PubMed1996

Current progress in the gene therapy of cancer.

Gene transfer for the treatment of cancer is a rapidly expanding field. Recent studies can be divided into four main areas: 1) transfer of suicide genes that convert inactive prodrugs into cytotoxic compounds, 2) transfer of genes encoding cytokines and stimulatory markers to enhance immunogenicity against tumors, 3) transfer of tumor-suppressor genes to block tumor cell proliferation, and 4) transfer of drug resistance genes into hematopoietic stem cells to increase their resistance to myelo-suppressive chemotherapeutic agents. This review discusses recent advances in technique and knowledge and their application to the gene therapy of cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Didanosine reduces atevirdine absorption in subjects with human immunodeficiency virus infections.

Atevirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type 1 and is currently in phase II clinical trials. Atevirdine is most soluble at a pH of < 2, and therefore, normal gastric acidity is most likely necessary for optimal bioavailability. Because of the rapid development of resistance in vitro, atevirdine is being evaluated in combination with didanosine and/or zidovudine in both two- and three-drug combination regimens. To examine the influence of concurrent didanosine (buffered tablet formulation) on the disposition of atevirdine, 12 human immunodeficiency virus type 1-infected subjects (mean CD4+ cell count, 199 cells per mm3; range, 13 to 447 cells/mm3) participated in a three-way, partially randomized, crossover, single-dose study to evaluate the pharmacokinetics of didanosine and atevirdine when each drug was given alone (treatments A and B, respectively) versus concurrently (treatment C). Concurrent administration of didanosine and atevirdine significantly reduced the maximum concentration of atevirdine in serum from 3.45 +/- 2.8 to 0.854 +/- 0.33 microM (P = 0.004). Likewise, the mean atevirdine area under the concentration-time curve from 0 to 24 h after administration of the combination was reduced to 6.47 +/- 2.2 microM.h (P = 0.004) relative to a value of 11.3 +/- 4.8 microM.h for atevirdine alone. Atevirdine had no statistically significant effect on the pharmacokinetic parameters of didanosine. Concurrent administration of single doses of atevirdine and didanosine resulted in a markedly lower maximum concentration of atevirdine in serum and area under the concentration-time curve, with a minimal effect on the disposition of didanosine. It is unknown whether an interaction of similar magnitude would occur under steady-state conditions; thus, combination regimens which include both atevirdine and didanosine should be designed so that their administration times are separated. Since the duration of the buffering effect of didanosine formulations is unknown, atevirdine should be given prior to didanosine.

Adolescent↗