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Biomedical subjects

L Hui

Publications and source records attributed to L Hui.

18 recordsLinked to original sources

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals

Patterns and determinants of use of antibiotics for acute respiratory tract infection in children in China.

BACKGROUND: Use of antibiotics for acute respiratory infection (ARI) of presumed viral etiology is a worldwide problem. The World Health Organization (WHO) has provided guidelines for diagnosis and treatment of ARI for developing countries. METHODS: Specially trained observers applied the WHO criteria to study the diagnosis and treatment of ARI given by 100 randomly selected health care workers (HCWs) in a rural county in China. A total of 750 cases of ARI were evaluated. RESULTS: Before the parents sought medical care, 47% of children in the county hospitals, 25% of those in the townships and 18% of those in the villages had already received antibiotics, available without prescription. Among the HCWs antibiotic abuse (antibiotics for presumably viral disease) was detected in the treatment of 97% of cases, and severe abuse (such as prescription of two incompatible antibiotics) was detected in 37%. Most (197 of 200) patients with bacterial disease received antibiotics, but inappropriate antibiotic treatment (dose or type) was observed in 63% of these cases. HCWs with university training and those with higher test scores on knowledge and attitude prescribed antibiotics more judiciously than those lacking those attributes. CONCLUSIONS: Abuse of antibiotics for ARI is a serious and costly problem in rural China, potentially leading to widespread antibiotic resistance. Educating HCWs in the management of ARI and proper use of antibiotics has high priority in China.

Acute Disease

Characterization of short tandem repeats from thirty-one human telomeres.

Completion of genetic and physical maps requires markers from the ends (telomeres) of every human chromosome. We have searched for short tandem repeats (microsatellites) in cosmid and P1 clones and generated 661 sequence-tagged sites (STS) from the terminal 300 kb of 31 human chromosome ends. PCR assays were successfully designed for 58 microsatellites and mapped both genetically and on radiation hybrids (RHs) to confirm their telomeric location. Sequence analysis revealed marked variation in sequence composition, consistent with the hypothesis that even very highly GC-rich chromosome bands (the T bands) are not homogenous. The STSs that we have generated will be a necessary resource for the construction of physical maps of these complex regions of the genome.

Base Sequence

Low stress response enhances vulnerability of islet cells in diabetes-prone BB rats.

In islet cells isolated from normal outbred Wistar rats, the known high vulnerability of islet cells toward oxygen radicals or nitric oxide can be abolished by inducing a stress response, such as by heat shock. We show here that islet cells from diabetes-prone BB rats are unable to mount such a protective response. Islet cells from diabetes-prone BB rats without recognizable insulitis were heat stressed. Subsequently, cells were exposed to nitric oxide, to oxygen radicals, or to the beta-cell toxin streptozotocin. While prior heat shock substantially increased the survival of toxin-treated Wistar rat islet cells, no protective stress response was noted for islet cells from diabetes-prone BB rats. Islet cells from diabetes-resistant BB rats were protected by heat stress to the same extent as Wistar rats. A survey of four additional major histocompatibility complex (MHC)-disparate rat strains confirmed the existence of a low and high responder type to stress. Parallel analysis of heat shock protein (hsp)70 induction by Western blot showed a low and high hsp70 response phenotype. A high hsp70 response coincided with a protective stress response. The presence (or absence) of a protective stress response correlated with the preservation (or loss) of intracellular NAD+ in toxin-treated islet cells. The lack of a protective stress response in islet cells from diabetes-prone BB rats, but not in diabetes-resistant BB rats, may promote beta-cell lysis and autoantigen release, and hence could be important for initiation or propagation of the disease process.

Animals

Adaptation to optokinetic rotation-induced motion sickness without experiencing nausea.

17 subjects highly susceptible to motion sickness were divided into Nausea and No-nausea groups depending upon whether the subjects experienced nausea during adaptation to nauseagenic rotation. Eight subjects in the Nausea group viewed an optokinetic rotation drum for repeated sessions of 16 min., with an interval of two days between every two sessions. During each session the subjects continuously viewed the rotating drum 16 min. even if they experienced nausea. nine subjects in the No-nausea group likewise viewed an optokinetic rotation drum for at most 16 min. but immediately stopped viewing the rotating drum whenever they experienced nausea during the session. The criteria for full adaptation were that the subject reported no feelings of stomach discomfort and nausea during a 16-min session. The mean number of sessions to reach full adaptation was 3.9 (SD = 0.6) with a range 3 to 5 sessions for the subjects in the Nausea group and 3.2 (SD = 0.8) with a range 2 to 4 for the subjects in the No-nausea group. It was concluded that subjects can adapt to a nauseagenic optokinetic rotation by repeated exposure without experiencing nausea and vomiting during adaptation.

Adaptation, Physiological

Dose-escalation study of weekly 1-hour paclitaxel administration in patients with refractory cancer.

To evaluate the safety and efficacy of weekly low-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with refractory cancer, participating subjects received standard prophylactic medication followed by intravenous paclitaxel once a week for 3 weeks every 4 weeks. The 50-mg/m2 starting dose was increased by 10 mg/m2 for every five patients, as long as no dose-limiting toxicity had occurred in more than two of five patients treated at the preceding level. Eligibility criteria included metastatic and refractory malignant disease; an Eastern Cooperative Oncology Group performance status of 0, 1, or 2; and adequate hematologic, hepatic, and renal functions. Of 30 patients treated and evaluable for toxicity, 25 were evaluable for response. The majority of patients tolerated the treatment very well. In a total of 114 cycles, the worst toxicities observed were leukopenia (one grade 4, two grade 3), granulocytopenia (one grade 3, one grade 4), anemia (one grade 3, two grade 2), and infection (one grade 5, one grade 3). Three patients had grade 2 gastrointestinal toxicity and three had grade 1 peripheral neuropathy. Only one dose-limiting toxicity, at 100 mg/m2, has occurred. This patient died of bilateral pneumonia with neutropenia. We have observed partial responses in seven of 12 patients with breast cancer and three of eight with non-small cell lung cancer. The study remains open at the current dose level of 100 mg/m2/wk. Weekly low-dose paclitaxel is well tolerated and efficacious. Further phase II studies are warranted, to continue evaluation of this schedule of paclitaxel either alone or in combination with other drugs active in paclitaxel-responsive diseases.

Adult

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence

Avascular necrosis of bone after adult acute lymphocytic leukemia treatment with methotrexate, vincristine, L-asparaginase, and dexamethasone (MOAD).

Four of 55 (7%) adult acute lymphocytic leukemia patients, age 27-58 years, who were treated with methotrexate, vincristine, L-asparaginase, and dexamethasone (MOAD) developed avascular necrosis (AVN) of one or both femoral heads 16-39 months after beginning treatment. All patients were treated with total joint replacement without compromise of quality of life during more than 3-9 years of follow-up, and they have remained in complete remission for a total of 6.5 + to 10.5 + years. A review of the literature revealed 11 previously reported cases of AVN of bone in patients with acute lymphocytic leukemia, 10 of whom received dexamethasone. The patients in the present report received a total dexamethasone dose equivalent to that of prednisone, 3.4-5.0 g/M2. Although AVN of bone has been reported in patients receiving chemotherapy without corticosteroids, corticosteroids appear to be the most common class of agents associated with its development, and dexamethasone treatment may be more likely to result in AVN of bone than other corticosteroids, for unknown reasons.

Adult

Ifosfamide, carboplatin, etoposide, and paclitaxel chemotherapy: a dose-escalation study.

Ifosfamide, carboplatin, cisplatin, etoposide, and paclitaxel are chemotherapeutic agents active in treating many malignant diseases. The ICE combination (ifosfamide/carboplatin [or cisplatin]/etoposide) has been studied in breast cancer, small cell and non-small cell lung cancer, testicular cancer, lymphoma, and other malignancies with promising results. We conducted a dose-escalation study of paclitaxel in combination with ICE (ICE-T) to evaluate the toxicity and define the maximum tolerated dose of paclitaxel. To date, 24 patients have been treated with ICE-T. Patients had to have no or minimal prior chemotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate bone marrow, liver, and kidney function. The doses of ICE were as follows: ifosfamide 1.25 g/m2/d days 1 to 3, carboplatin 300 mg/m2 day 1, and etoposide 80 mg/m2/d days 1 to 3. Paclitaxel was given at a dose of 120 mg/m2 to five patients, 135 mg/m2 to five patients, 150 mg/m2 to three patients, and 175 mg/m2 to 11 patients. All patients received granulocyte colony-stimulating factor support. The most common side effect was neutropenia. Grade 4 neutropenia and thrombocytopenia occurred during 34% and 20% of 94 cycles, respectively, with leukopenic fever occurring during 14% of cycles. No treatment-related death or sepsis occurred due to brief nadir durations of 3.5 days for neutropenia and thrombocytopenia. Other toxicities were mostly mild to moderate and did not require dose modification, although alopecia was universal. Nine patients (100%) with metastatic breast cancer and four (67%) with soft tissue sarcoma have attained documented objective responses with four complete remissions (one breast cancer and three sarcoma patients). The maximum tolerated dose of paclitaxel has not yet been defined, and the study is ongoing. In conclusion, this pilot study showed that ICE-T is safe and tolerable. The response to ICE-T is encouraging and warrants further study with this regimen.

Adult

An STS-based map of the human genome.

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

Animals

Immuno-endocrine interactions in early pregnancy.

First we recall briefly the status of inflammatory cytokines in the early implantation period. We then describe the status of leukaemia inhibiting factor (LIF) production in an in-vitro, relatively short-term, human decidual explant culture system. We show that in most infertile women with recurrent implantation failure following successful in-vitro fertilization, LIF production is statistically much lower than normal. Other parameters of LIF production in vitro are summarized briefly, and the effects of RU486 are shown. The TH2 status of normal pregnancy is described, together with the production of TH2 cytokines by decidua and placenta. These cytokines are deficient in the CBAXDBA/2 model of murine spontaneous early pregnancy loss. The defect can be corrected by alloimmunization, and more importantly by the injection of tau interferon. The significance of these data for early pregnancy signalling is discussed.

Animals

Enhancement of the cytolytic effect of anti-bacterial cecropin by the microvilli of cancer cells.

A comparison between IC50s of cecropin B on tumor cells such as KG-1 leukemia and Ags stomach carcinoma and non-tumor cells like fibroblasts and red blood cells was conducted. The IC50s of cecropin B for KG-1 leukemia and Ags carcinoma cells were 20.8 +/- 2.3 microM (MTT) and 18.9 +/- 3.3 microM (trypan blue) and 16.0 +/- 3.5 microM (MTT) & 15.3 +/- 3.7 microM (trypan blue), respectively. The IC50 of cecropin B for 3T6 fibroblast cells was 92.0 +/- 9.1 microM by MTT assay and the HE50 of cecropin B for human red blood cells was 180.0 +/- 20.1 microM at OD414nm. The cytolysis induced by cecropin peptides was more effective for the cancer cells than for the normal cells. Based on the observations from scanning electron microscopy, this may mainly due to the cancer cells having a high population of the irregular microvilli on the cell surface. Since peptides bound to the cell membrane are non-specific, the attraction of peptides by microvilli may be one of the main driving forces before the lysis in membrane bilayers can be efficiently initiated.

Animals