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Biomedical subjects

R Tan

Publications and source records attributed to R Tan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Antineoplastic agents. Part 409: Isolation and structure of montanastatin from a terrestrial actinomycete.

A Montana soil actinomycete, Streptomyces anulatus, produced (1 x 10(-2)% yield) a new cancer cell growth inhibitory cyclooctadepsipeptide named montanastatin (1) accompanied by the potent anticancer antibiotic valinomycin (2) in very high (5.1%) yields. Valinomycin but not montanastatin inhibited growth of a number of pathogenic bacteria and fungi. Interpretation of high-field (500 MHz) NMR and high-resolution FAB mass spectral data allowed assignment of the structure cyclo-(D-Val-L-Lac-L-Val-D-Hiv) to montanastatin. Valinomycin (2) was also isolated from actinomycetes cultured from a tree branch and animal feces collected in Malaysia. Streptomyces exfoliatus, isolated from the tree branch, was found to contain valinomycin in 1.6% yield, while the fecal isolate, S. anulatus, gave valinomycin in 0.9% yield.

Actinomycetales↗
PubMed1999

Antineoplastic agents. 400. Synthesis of the Indian Ocean marine sponge cyclic heptapeptide phakellistatin 2.

Solution-phase synthesis of the marine sponge constituent phakellistatin 2 (1), cyclo(Tyr-Pro-Phe-Pro-Ile-Ile-Pro), was completed using a combination of stepwise coupling and (4 + 3) segment condensation. Use of diethyl phosphorocyanidate for the peptide bond formations gave the linear heptapeptide in 54% yield. Cyclization was achieved in high yields utilizing TBTU (2), BOP-C1 (3), PyBroP (4), and HOAt (5), resulting in 50-65% yields of phakellistatin 2 (1) depending on the method employed. The synthetic cyclic peptide was chemically but not biologically identical with the natural product.

Animals↗
PubMed1999

Isotretinoin therapy for antibiotic-refractory acne in Apert's syndrome.

Apert's syndrome is a congenital disorder characterized by the premature fusion of the cranial sutures and early epiphyseal closure. Severe pustular acne is a common feature. We report a case that failed to respond to conventional antibiotic treatment but resolved following isotretinoin therapy. The patient's permanent tracheostomy proved a management challenge during isotretinoin treatment. The role of androgen-sensitivity is discussed in relation to the skin and bones.

Acne Vulgaris↗
PubMed1999

Evaluation of a commercially available immunoglobulin M capture enzyme-linked immunosorbent assay kit for diagnosing acute dengue infections.

Recently, commercially available kits for the detection of anti-dengue virus (anti-DEN) immunoglobulin M (IgM) antibodies have been developed. These standardized assays have greatly enhanced our ability to effectively diagnose DEN infections. We conducted an evaluation of a test kit manufactured by MRL Diagnostics Inc. that is designed to detect anti-DEN IgM antibodies. Eighty paired samples from DEN-infected individuals were tested by the MRL DEN Fever Virus IgM Capture enzyme-linked immunosorbent assay (ELISA), the PanBio Duo ELISA, the PanBio Rapid Immunochromatographic Test (PRIT), and the IgM-IgG antibody capture (MAC/GAC) ELISA. All infections were confirmed by either PCR-assisted detection of DEN transcripts or by DEN isolation in C6/36 cells. Seventeen paired samples from individuals with no evidence of acute DEN infection were used as negative controls. The PRIT had the best sensitivity (100%), whereas the MAC/GAC ELISA and the PanBio Duo assay had the highest levels of specificity. The MRL ELISA and the PanBio Duo assay were the top performers when taking into consideration both sensitivity and specificity. All assays were able to detect DEN-specific antibodies in samples from patients with either primary or secondary infections, regardless of the infecting DEN serotype.

Acute Disease↗
PubMed1999

A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. studies in 1995-1996.

A prospective study on dengue (DEN) viruses was initiated in October 1995 in Gondokusuman kecamatan, Yogyakarta, Indonesia. This report presents data from the first year of the study. The studied cohort included all children 4-9 years of age living in the kecamatan. Blood samples for serology were collected from 1,837 children in October 1995 and again in October 1996. Blood samples for virus isolation and serology were collected from cohort children who were seen in municipal health clinics with febrile syndromes or admitted to hospitals with a provisional diagnosis of dengue hemorrhagic fever. Dengue serotype antibody prevalence and 1995-1996 infection rates were calculated using a single dilution (1:60) 70% plaque reduction endpoint neutralization test. Prevalence of dengue antibody at the beginning of the study was DEN 1 = 12%, DEN 2 = 16%, DEN 3 = 2%, DEN 4 = 4%, and two or more dengue infections = 22%. Total dengue antibody prevalence increased from 38% in 4-year-old children to 69% in 9-year-old children. During the observation period, primary dengue infection rates were DEN 1 = 4.8%, DEN 2 = 7.7%, DEN 3 = 4.2%, and DEN 4 = 3.4%, while two or more dengue infections occurred in 6.7% of the study population. The secondary dengue infection rate was 19.0%. From febrile cases, all four dengue viruses were isolated with DEN 3 predominating. Seven children were hospitalized, including one fatal case with a hospital diagnosis of dengue shock syndrome. Based upon presence of antibody in the initial cohort bleeding and the serologic response both weeks and several months following illness, all had secondary dengue infections. Neutralizing antibody patterns in the initial cohort bleeding and in late convalescent serum samples permitted recognition of dengue infection sequence in five patients: DEN 2-DEN 1 (3), DEN 2-DEN 4 (1), DEN 1-DEN 3 (1), and none in the sequence DEN 1-DEN 2. In the total cohort 6.5% of the observed secondary infections were of the sequence DEN 2-DEN 1, while 4.9% were DEN 1-DEN 2, a highly pathogenic sequence in previous studies. Reduced pathogenic expression of secondary DEN 2 with enhanced pathogenic expression of secondary DEN 1 infections was an unexpected finding. Further studies will be required to understand the respective contributions to pathogenicity of antibody from initial dengue infections versus the biological attributes of the second infecting dengue viruses.

Age Distribution↗
PubMed1998

Antineoplastic agents. 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (the Republic of Maldives).

The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 micrograms/mL) and 5 (1b, DU-145 prostate GI50 1.9 micrograms/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).

Animals↗
PubMed1998

A novel glutamine-RNA interaction identified by screening libraries in mammalian cells.

The arginine-rich motif provides a versatile framework for RNA recognition in which few amino acids other than arginine are needed to mediate specific binding. Using a mammalian screening system based on transcriptional activation by HIV Tat, we identified novel arginine-rich peptides from combinatorial libraries that bind tightly to the Rev response element of HIV. Remarkably, a single glutamine, but not asparagine, within a stretch of polyarginine can mediate high-affinity binding. These results, together with the structure of a Rev peptide-Rev response element complex, suggest that the carboxamide groups of glutamine or asparagine are well-suited to hydrogen bond to G-A base pairs and begin to establish an RNA recognition code for the arginine-rich motif. The screening approach may provide a relatively general method for screening expression libraries in mammalian cells.

Amino Acid Sequence↗
PubMed1998

Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes.

A major advance in understanding human immunodeficiency virus (HIV) biology was the discovery that the beta-chemokines MIP-1 alpha (macrophage inflammatory protein-1 alpha), MIP-1 beta (macrophage inflammatory protein-1 beta) and RANTES (regulated on activation, normal T-cell expressed and secreted) inhibit entry of HIV-1 into CD4+ cells by blocking the critical interaction between the CCR5 coreceptor and the V3 domain of the viral envelope glycoprotein gp120 [1,2]. CD8+ lymphocytes are a major source of beta-chemokines [3], but the stimulus for chemokine release has not been well defined. Here, we have shown that engagement of CD8+ cytotoxic T lymphocytes (CTLs) with HIV-1-encoded human leukocyte antigen (HLA) class I-restricted peptide antigens caused rapid and specific release of these beta-chemokines. This release paralleled cytolytic activity and could be attenuated by naturally occurring amino acid variation within the HLA class I-restricted peptide sequence. Epitope variants that bound to appropriate HLA class I molecules but failed to stimulate cytolytic activity in CTLs also failed to stimulate chemokine release. We conclude that signalling through the T-cell receptor (TCR) following binding of antigen results in beta-chemokine release from CTLs in addition to cytolytic activity, and that both responses can be abolished by epitope mutation. These results suggest that antigenic variation within HIV-1 might not only allow the host cell to escape lysis, but might also contribute to the propagation of infection by failing to activate beta-chemokine-mediated inhibition of HIV-1 entry.

Chemokine CCL4↗
PubMed1998

Ethylmalonic and methylsuccinic aciduria in ethylmalonic encephalopathy arise from abnormal isoleucine metabolism.

Ethylmalonic encephalopathy (EE), an organic aciduria of unknown etiology characterized by developmental delay, hypotonia, and vascular instability associated with lactic acidemia and urinary excretion of ethylmalonic acid (EMA) and methylsuccinic acid (MSA), has been described in 11 patients. To test the possibility that the underlying biochemical defect involves isoleucine catabolism, we determined the response to oral L-isoleucine (IIe) load (150 mg/kg) in a 5-year-old girl with EE and in three healthy, age- and sex-matched controls. Following IIe load in the patient, there was accumulation of 2-methylbutyrylglycine (2-MBG) and a delayed and lower peak urinary excretion of tiglylglycine (TGL), suggesting a partial defect in 2-methyl-branched chain acylcoenzyme A dehydrogenase (2M-BCAD). In vitro measurements 2M-BCAD activity in cultured skin fibroblasts from patients with EE have been reported to be normal. Our results show that isoleucine is a source for the elevated EMA and MSA in patients with EE, and suggest a functional, possibly secondary, deficiency of activity of 2M-BCAD in vivo.

Administration, Oral↗
PubMed1998

Antineoplastic agents. 386. Isolation of sesterstatins 1-3 from the marine sponge Hyrtios erecta.

The Republic of Maldives' black marine sponge Hyrtios erecta has been found to contain three cancer cell-line inhibitory pentacyclic sesterterpenes designated sesterstatins 1-3 (2-4). One of the sesterterpenes, sesterstatin 2, specifically inhibited the Gram-positive opportunist Staphylococcus aureus. All three of the P-388 lymphocytic-leukemia-active (ED50 0.46 to 4.3 micrograms/mL) sesterstatins were obtained in trace quantities (3.0 x 10-7 to 5.4 x 10-7% yields) and represent structural variations on the more usual scalarin-type porifera sesterterpenes. The structures were elucidated by highfield (500 MHz) 2D NMR techniques augmented by HRMS results.

Animals↗
PubMed1998

Antineoplastic agents. 398. Isolation and structure elucidation of cephalostatins 18 and 19.

Continued investigation of murine leukemia (P-388) active fractions from the African marine worm Cephalodiscus gilchristi has resulted in the discovery of cephalostatins 18 (1b) and 19 (1c). The structures were determined by interpretation of their highfield (500 MHz) 1H, 13C, and 2D NMR and HRMS. Both of these new methoxy steroidal alkaloids exhibited strong activity against the murine P-388 lymphocytic leukemia cell line (ED50 ca. 10(-3) microg/mL), a mini panel of human cancer cell lines (GI50 <10(-3) microg/mL), and the U.S. National Cancer Institute's 60 human cancer cell line panel (mean panel GI50 ca. 10(-9) M).

Animals↗
PubMed1998

Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice.

A vaccine against human immunodeficiency virus (HIV) is still awaited. Although the correlates of protection remain elusive, it is likely that CD8+ T cells play an important role in the control of this infection. To firmly establish the importance of these cells in protective immunity, a means of efficient elicitation of CD8+ T cell responses in the absence of antibody is needed and, when available, might represent a crucial step towards a protective vaccine. Here, a novel vaccine candidate was constructed as a multi-cytotoxic T lymphocyte (CTL) epitope gene delivered and expressed using modified vaccinia virus Ankara (MVA). The immunogen consists of 20 human, one murine and three rhesus macaque epitopes. The non-human epitopes were included so that the vaccine can be tested for immunogenicity and optimal vaccination doses, routes and regimes in experimental animals. Mice were immunized intravenously (i.v.) or intramuscularly (i.m.) using a single dose of 10(6) p.f.u. of the recombinant MVA and the induction of CTL was assessed. It was demonstrated that both administration routes induced specific CTL responses and that the i.v. route was moderately more immunogenic than the i.m. route. The frequencies of ex vivo splenocytes producing interferon-y upon MHC class I-restricted peptide stimulation were determined using an ELISPOT assay. Also, the correct processing and presentation of some HLA-restricted epitopes in human cells was confirmed.

AIDS Vaccines↗
PubMed1998

Case-control study of primary human herpesvirus 6 infection in children with febrile seizures.

RATIONALE: Human herpesvirus 6 (HHV-6) has been demonstrated to be the causative agent in roseola infantum. It has been suggested that HHV-6 may have neurotropic properties and be involved in the pathogenesis of febrile seizures in infants. We describe a case-control study to examine the hypothesis that acute HHV-6 infection occurs more commonly in children with febrile seizures than in controls. METHODS: Patients presenting with a first or second febrile seizure between 6 months and 2 years of age were entered in the study. Control patients did not have a seizure but had similar inclusion and exclusion criteria. Specimens were obtained for HHV-6 viral serology and polymerase chain reaction in the acute stage and approximately 2 weeks later. A diagnosis of HHV-6 infection was based on HHV-6-specific IgM and IgG serology and HHV-6 polymerase chain reaction of peripheral blood mononuclear cells and saliva. RESULTS: Eighty-six patients (45 with febrile seizures; 41 controls) were enrolled. The HHV-6 infection status could be determined in only 68 patients (35 with febrile seizures; 33 controls). Acute HHV-6 infection was identified in 15 of 35 febrile seizure patients and in 15 of 33 controls. Evidence of past HHV-6 infection was demonstrated in 13 febrile seizure patients and in 8 controls. CONCLUSIONS: The incidence of primary HHV-6 infection is similar in patients with febrile seizures and age-matched controls. HHV-6 does not seem to be a major factor in the pathogenesis of first and second febrile seizures.

Acute Disease↗
PubMed1998

Extravisceral masses in the peritoneal cavity: sonographically guided biopsies in 52 patients.

OBJECTIVE: Our objective was to determine the effectiveness of sonographically guided biopsies of extravisceral masses (masses outside the solid organs) in the peritoneal cavity. MATERIALS AND METHODS: We retrospectively reviewed the results of sonographically guided biopsies of extravisceral masses found in the peritoneal cavity of 52 patients (age range, 25-90 years old; mean age, 52 years) from June 1990 to December 1996. Fifty-one patients underwent biopsy through the abdominal wall, and one patient underwent transvaginal biopsy. Sonographic guidance was obtained using 3.5- to 7.0-MHz vector probes. The size, depth, and sonographic characteristics of the mass and the type of biopsy (aspirate versus core) were determined for all lesions. Pathology reports and clinical courses were reviewed. RESULTS: Placement of the biopsy needle within the lesion was successful in all patients. The mean depth from skin surface to lesion was significantly less (p < .0001) when shown by sonography (2.4 cm) than when shown by CT (3.8 cm). Biopsy results were true-positive for malignancy in 37 patients (no false-positives), true-negative for benign masses in 10 patients, and false-negative for malignancy in three patients (sensitivity, 93%; specificity, 100%; accuracy, 94%). Nondiagnostic samples were obtained in two patients (4%). Treatment was based on diagnostic biopsy results in 43 patients (86%). CONCLUSION: Sonography is an effective alternative to CT in guiding biopsy of extravisceral masses in the peritoneal cavity.

Biopsy, Needle↗
PubMed1998

A high resolution ultrastructural comparison of isolated and in situ murine AA amyloid fibrils.

There is an inconsistency between the ultrastructural organization of AA amyloid fibrils that have been isolated, which are composed of a slowly twisting set of two or more protofibrils, and those seen in situ, which are tubular entities with a tight helical substructure. In this study, the ultrastructure of fibrils isolated from experimental murine AA amyloid were observed at high resolution and compared with those seen in situ in the hope of clarifying the reason for this inconsistency. The fibrils in situ were composed of a microfibril-like 8-9 nm wide core covered by a layer of heparan sulfate proteoglycan (HSPG) to which 1 nm wide filaments, immunohistochemically identified as AA protein, were externally associated. Following isolation with the standard distilled water washing procedure, the HSPG layer and AA protein filaments detached from their core and dispersed into the water. The remaining denuded, variously loosened cores lost their typical appearance. In distilled water the detached 1 nm wide AA protein filaments became quite conspicuous and coiled themselves into 3 nm wide tight helices which in turn assembled into the characteristic slowly twisting sets of two parallel protofibrils similar to that previously reported as "isolated amyloid fibrils". The results emphasize that great caution must be taken in extrapolating amyloid fibril structure from isolated preparations to in situ tissue conditions.

Animals↗
PubMed1998

[Effects of matrine on telomerase activity and cell cycle in K562 cell].

OBJECTIVE: In order to search for new tumor differentiation inducer, the effects of matrine of Chinese herbal origin on differentiation of K562 cells and its mechanism were studied. METHODS: Telomerase activity was determined by PCR-ELISA in untreated or treated K562 cells, cell cycle phases were analyzed by fluorescence-activated cell sorter analysis. RESULTS: Telomerase activity of K562 cells was significantly inhibited when treated with matrine, and cell cycle of the treated K562 cells was changed with marked decrease in S phase. CONCLUSION: Matrine can induce differentiation of K562 cells, the mechanism of which might be related to the inhibition of telomerase activity and cell cycle arrest.

Alkaloids↗
PubMed1998

[Seasonal and sexual variety of Ginkgo flavonol glycosides in the leaves of Ginkgo biloba L].

HPLC methods have been developed for the determination of Ginkgo flavonol glycosides in the Ginkgo biloba leaves obtained from May to November in the fallen leaves and in the leaves obtained from female and male trees. The method includes hydrolysis of the leaves and subsequent quantitative chromatographic assay of the aglycones, followed by calculation of Ginkgo flavonol glycosides content. The result shows that the leaves obtained in May have the highest content of 0.96%, and then the content decreases from May to August, and from August to November remains almost the same, that is 0.5% also. Fallen leaves have the lowest content of 0.44%. The content range is 0.96% to 0.44%. Male trees have higher content of glycosides than female trees.

Chromatography, High Pressure Liquid↗