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Biomedical subjects

F Yang

Publications and source records attributed to F Yang.

At least 145 records · Page 8Linked to original sources
PubMed2000

The cytotoxicity and apoptosis induced by 4-tertiary butylphenol in human melanocytes are independent of tyrosinase activity.

It has been known for several decades that cutaneous depigmentation, i.e., contact/occupational vitiligo, can be caused by some phenolic derivatives that have a similar structure to tyrosine. Among these phenolic depigmenting agents, 4-tertiary butylphenol is the most potent. The cutaneous depigmentation induced by phenolic derivatives results from the loss of functional melanocytes. Tyrosinase is a melanocyte specific copper-containing enzyme that catalyzes the conversion of the amino acid tyrosine, through a complex series of intermediates, to melanin. In this study we tested the hypothesis that the cytotoxicity induced by 4-tertiary butylphenol is mediated by tyrosinase and occurs via an apoptotic process. Melanocyte cultures derived from African-American and Caucasian donors exhibiting a 3-fold difference in tyrosinase activity and 14-fold difference in melanin content demonstrate comparable concentration-dependent sensitivity to 4-tertiary butylphenol. In addition, cultures of dermal fibroblasts and epidermal keratinocytes exhibited similar and reduced sensitivity, respectively, to 4-tertiary butylphenol compared with autologous melanocytes. Two melanoma cell lines, one melanotic and one amelanotic lacking the expression of both tyrosinase protein and activity, when transfected with the tyrosinase cDNA, exhibited no alteration in its sensitivity to 4-tertiary butylphenol. These data suggest that 4-tertiary butylphenol cytotoxicity is not mediated via tyrosinase. Melanocytes treated with 4-tertiary butylphenol, however, did exhibit plasma membrane blebbing, DNA fragmentation, and phosphatidylserine relocalization indicating that 4-tertiary butylphenol induced melanocyte destruction occurs by an apoptotic process.

Apoptosis↗
PubMed2000

Loss of heterozygosity on chromosome 19 in secondary glioblastomas.

Glioblastomas develop rapidly de novo (primary glioblastomas) or slowly through progression from low-grade or anaplastic astrocytoma (secondary glioblastomas). Recent studies have shown that these glioblastoma subtypes develop through different genetic pathways. Primary glioblastomas are characterized by EGFR amplification/overexpression, PTEN mutation, homozygous p16 deletion, and loss of heterozygosity (LOH) on entire chromosome 10, whereas secondary glioblastomas frequently contain p53 mutations and show LOH on chromosome 10q. In this study, we analyzed LOH on chromosomes 19q, 1p, and 13q, using polymorphic microsatellite markers in 17 primary glioblastomas and in 13 secondary glioblastomas that progressed from low-grade astrocytomas. LOH on chromosome 19q was frequently found in secondary glioblastomas (7 of 13, 54%) but rarely detected in primary glioblastomas (1 of 17, 6%, p = 0.0094). The common deletion was 19q13.3 (between D19S219 and D19S902). These results suggest that tumor suppressor gene(s) located on chromosome 19q are frequently involved in the progression from low-grade astrocytoma to secondary glioblastoma, but do not play a major role in the evolution of primary glioblastomas. LOH on chromosome 1p was detected in 12% of primary and 15% of secondary glioblastomas. LOH on 13q was detected in 12% of primary and in 38% of secondary glioblastomas and typically included the RB locus. Except for 1 case, LOH 13q and 19q were mutually exclusive.

Astrocytoma↗
PubMed2000

Paraffin section immunophenotype of cutaneous and extracutaneous mast cell disease: comparison to other hematopoietic neoplasms.

Mast cell disease (MCD) is a rare proliferation that may be easily confused with other hematopoietic tumors. Several paraffin section antibodies immunoreact with mast cells but most are not specific. Tryptase, a specific marker of mast cells, may not be cost-effective to maintain in a laboratory because of the rarity of these lesions. This study was undertaken to assess the immunoreactivity of MCD and attempt to select a limited antibody panel for diagnosing MCD among hematopoietic tumors that morphologically mimic MCD. Immunophenotyping of cutaneous ( 10 cases) and extracutaneous (18 cases) MCD, as well as 94 other hematopoietic neoplasms, was performed on paraffin sections. All cases of MCD showed strong and diffuse positivity for CD68 and tryptase. In the vast majority of the cases, the mast cells were also positive for CD117 (27 of 28) and CD43 (25 of 27). Four cases (40%) of cutaneous MCD demonstrated a subpopulation of mast cells expressing myeloperoxidase (MPX), whereas all extracutaneous MCD were negative for MPX. Two (40%) extramedullary myeloid tumors (EMT) expressed CD43, CD68, CD 117, and MPX, but none expressed tryptase. CD43, CD68, CD117, and tryptase were expressed by 25%, 1%, 15%, and 1%, respectively, of all B-cell lymphoid neoplasms, and none expressed more than one of these four antigens. We conclude that (1) cutaneous MCDs may demonstrate a subpopulation of MPX antigen expressing tumor cells and may be confused with cutaneous involvement by myeloid leukemia if other antibodies are not used; (2) tryptase is the most specific mast cell marker among the antibodies studied; and, (3) the detection of tryptase, together with CD68, CD117, and usually CD43, is unique to MCD among hematopoietic tumors.

Adult↗
PubMed2000

Effects of crystal twinning on the ability to solve a macromolecular structure using multiwavelength anomalous diffraction.

The crystal structure of gpD, the capsid-stabilizing protein of bacteriophage lambda, was solved by multiwavelength anomalous diffraction (MAD) for a selenomethionine (SeMet) derivative of the protein at 1.8 A resolution, using crystals in space group P2(1) [Yang et al. (2000), Nature Struct. Biol. 7, 230-237]. Subsequent analysis showed that the crystals of both the original protein and the SeMet derivative were pseudo-merohedrally twinned with a twinning fraction approximately 0.36, owing to the near-identity of the a and c axes. An analysis of the crystal structure solution is presented and the utility of twinned crystals for solving the structure using MAD and of different phasing strategies is discussed; the results obtained with several software packages are compared.

Capsid↗
PubMed2000

Reprogrammable recognition codes in bicoid homeodomain-DNA interaction.

We describe experiments to determine how the homeodomain of the Drosophila morphogenetic protein Bicoid recognizes different types of DNA sequences found in natural enhancers. Our chemical footprint analyses reveal that the Bicoid homeodomain makes both shared and distinct contacts with a consensus site A1 (TAATCC) and a nonconsensus site X1 (TAAGCT). In particular, the guanine of X1 at position 4 (TAAGCT) is protected by Bicoid homeodomain. We provide further evidence suggesting that the unique arginine at position 54 (Arg 54) of the Bicoid homeodomain enables the protein to recognize X1 by specifically interacting with this position 4 guanine. We also describe experiments to analyze the contribution of artificially introduced Arg 54 to DNA recognition by other Bicoid-related homeodomains, including that from the human disease protein Pitx2. Our experiments demonstrate that the role of Arg 54 varies depending on the exact homeodomain framework and DNA sequences. Together, our results suggest that Bicoid and its related homeodomains utilize distinct recognition codes to interact with different DNA sequences, underscoring the need to study DNA recognition by Bicoid-class homeodomains in an individualized manner.

Amino Acid Sequence↗
PubMed2000

Target selectivity of bicoid is dependent on nonconsensus site recognition and protein-protein interaction.

We describe experiments to compare the activities of two Drosophila homeodomain proteins, Bicoid (Bcd) and an altered-specificity mutant of Fushi tarazu, Ftz(Q50K). Although the homeodomains of these proteins share a virtually indistinguishable ability to recognize a consensus Bcd site, only Bcd can activate transcription from natural enhancer elements when assayed in both yeast and Drosophila Schneider S2 cells. Our analysis of chimeric proteins suggests that both the homeodomain of Bcd and sequences outside the homeodomain contribute to its ability to recognize natural enhancer elements. We further show that, unlike the Bcd homeodomain, the Ftz(Q50K) homeodomain fails to recognize nonconsensus sites found in natural enhancer elements. The defect of a chimeric protein containing the homeodomain of Ftz(Q50K) in place of that of Bcd can be preferentially restored by converting the nonconsensus sites in natural enhancer elements to consensus sites. Our experiments suggest that the biological specificity of Bcd is determined by combinatorial contributions of two important mechanisms: the nonconsensus site recognition function conferred by the homeodomain and the cooperativity function conferred primarily by sequences outside the homeodomain. A systematic comparison of different assay methods and enhancer elements further suggests a fluid nature of the requirements for these two Bcd functions in target selection.

Animals↗
PubMed2000

Unusual muscle pathology in McLeod syndrome.

Muscle pathology in McLeod syndrome is usually mild; patchy necrotic or regenerating fibres, occasional internal nuclei, and the absence of an inflammatory cell infiltrate are the usual findings. We report on a 29 year old man presenting with chronic fatiguability and excessive sweating in whom an open quadriceps muscle biopsy demonstrated grouped necrotic fibres accompanied by striking patchy mononuclear cell infiltrates. The diagnosis of McLeod syndrome was made on the basis of red blood cell acanthocytosis, raised serum creatine kinase, and weak expression of Kell blood group antigens. The quadriceps muscle infiltrate consisted principally of histologically typical macrophages. These cells had prominent nucleoli, displayed numerous mitoses, and were strongly CD68+. A small population of typical CD3+, CD43+ lymphocytes was also present. In addition, a small population of large atypical CD3+ cells was noted. Immunoperoxidase stains for CD20, CD30, CD79a, and CD56 were negative. Immunocytochemical studies for the common muscular dystrophies were normal. The muscle biopsy findings highlight a potential for confusion of this condition with idiopathic polymyositis. The expanding range of muscle pathology reported in McLeod syndrome, to which this case adds, may reflect variable involvement of the XK gene on chromosome Xp21, or of the adjacent loci of Duchenne muscular dystrophy and chronic granulomatous disease.

Adult↗
PubMed2000

Unnatural ligands for engineered proteins: new tools for chemical genetics.

Small molecules that modulate the activity of biological signaling molecules can be powerful probes of signal transduction pathways. Highly specific molecules with high affinity are difficult to identify because of the conserved nature of many protein active sites. A newly developed approach to discovery of such small molecules that relies on protein engineering and chemical synthesis has yielded powerful tools for the study of a wide variety of proteins involved in signal transduction (G-proteins, protein kinases, 7-transmembrane receptors, nuclear hormone receptors, and others). Such chemical genetic tools combine the advantages of traditional genetics and the unparalleled temporal control over protein function afforded by small molecule inhibitors/activators that act at diffusion controlled rates with targets.

Alleles↗
PubMed2000

Diminished injury in hypotransferrinemic mice after exposure to a metal-rich particle.

Using the hypotransferrinemic (Hp) mouse model, we studied the effect of altered iron homeostasis on the defense of the lung against a catalytically active metal. The homozygotic (hpx/hpx) Hp mice had greatly diminished concentrations of both serum and lavage fluid transferrin relative to wild-type mice and heterozygotes. Fifty micrograms of a particle containing abundant concentrations of metals (a residual oil fly ash) was instilled into wild-type mice and heterozygotic and homozygotic Hp animals. There was an oxidative stress associated with particle exposure as manifested by decreased lavage fluid concentrations of ascorbate. However, rather than an increase in lung injury, diminished transferrin concentrations in homozygotic Hp mice were associated with decreased indexes of damage, including concentrations of relevant cytokines, inflammatory cell influx, lavage fluid protein, and lavage fluid lactate dehydrogenase. Comparable to other organs in the homozygotic Hp mouse, siderosis of the lung was evident, with elevated concentrations of lavage fluid and tissue iron. Consequent to these increased concentrations of iron, proteins to store and transport iron, ferritin, and lactoferrin, respectively, were increased when assayed by immunoprecipitation and immunohistochemistry. We conclude that the lack of transferrin in Hp mice did not predispose the animals to lung injury after exposure to a particle abundant in metals. Rather, these mice demonstrated a diminished injury that was associated with an increase in the metal storage and transport proteins.

Air Pollution↗
PubMed2000

Dog chromosome-specific paints reveal evolutionary inter- and intrachromosomal rearrangements in the American mink and human.

Forty chromosome-specific paint probes of the domestic dog (Canis familiaris, 2n = 78) were used to delineate conserved segments on metaphase chromosomes of the American mink (Mustela vison, 2n = 30) by fluorescence in situ hybridisation. Half of the 38 canine autosomal probes each painted one pair of homologous segments in a diploid mink metaphase, whereas the other 19 dog probes each painted from two to five pairs of discrete segments. In total, 38 canine autosomal paints highlighted 71 pairs of conserved segments in the mink. These painting results allow us to establish a complete comparative chromosome map between the American mink and domestic dog. This map demonstrates that extensive chromosome rearrangements differentiate the karyotypes of the dog and American mink. The 38 dog autosomes could be reconstructed from the 14 autosomes of the American mink through at least 47 fissions, 25 chromosome fusions, and six inversions. Furthermore, comparison of the current dog/mink map with the published human/dog map discloses 23 cryptic intrachromosomal rearrangements in 10 regions of conserved synteny in the human and American mink genomes and thus further refined the human/mink comparative genome map.

Animals↗
PubMed2000

Pulmonary expression of the human haptoglobin gene.

Haptoglobin (Hp), a member of the acute-phase reactants, has long been known as a major hemoglobin-binding protein associated with hemoglobin catabolism. Recent studies indicate that another important biologic function of Hp is the modulation of the immune response. We found that Hp is expressed at high levels in specific cells, including alveolar macrophages and eosinophils in diseased or inflamed human lung tissues, but not in the normal lung. Expression of the human Hp gene was studied in two transgenic mouse lines carrying a 9-kb human Hp 2 gene. In both lines, the human Hp transgene was expressed constitutively in alveolar macrophages at a high level, whereas the endogenous mouse Hp was synthesized in airway epithelial cells. Expression of the human Hp transgene in lung cells was upregulated when the transgenic mice were treated with endotoxin. In humans and in Hp transgenic mice, human Hp messenger RNA was also detected in circulating eosinophils, but not in other blood cells. Our findings suggest that Hp is involved in a variety of lung inflammatory diseases, including respiratory allergy and asthma. The transgenic mouse line that overexpresses the human Hp gene in alveolar macrophages and eosinophils is a promising system for investigating the function of Hp in vivo during lung inflammation.

Acute-Phase Reaction↗
PubMed2000

Genomic organization of the human metabotropic glutamate receptor subtype 3.

In this study, the genomic organization of the human metabotropic glutamate receptor subtype 3 (mGluR3) gene has been determined. We have identified two transcription initiation sites and the polyadenylation signal by using 5'-rapid amplification of cDNA ends (RACE) and 3'-RACE, respectively. The exon/intron organization of the human mGluR3 gene revealed the presence of 6 exons separated by 5 introns. The size of introns varied from 10.4 to 120 kbp that contained consensus sequences for repetitive elements such as Alu and long interspersed elements. A putative promoter region flanking the 5' sequence of exon 1 was identified by computer-aided analysis. The putative promoter region was characterized by the presence of a CAAT and GC box, and the absence of a TATA box or CpG islands. Several putative binding sites for transcription factors were also identified. In addition, we have isolated, from a mouse genomic library, part of the mouse mGluR3 gene and found it to correspond to exon 2 in the human mGluR3 gene. The mouse mGluR3 gene was then mapped by fluorescent in situ hybridization analysis to chromosome 5qA2.

Animals↗
PubMed2000

Modulation of nitric oxide-evoked apoptosis by the p53-downstream target p21(WAF1/CIP1).

When produced in excess, the inflammatory mediator nitric oxide (NO) attenuates cell-cycle progression at the G1 phase in tight correlation with p21(WAF1/CIP1) expression, provokes accumulation of the tumor suppressor p53, and initiates apoptosis/necrosis as judged on cell accumulation in the sub-G1 phase. To verify the role of p21(WAF1/CIP1) in modulating cell-cycle arrest vs. apoptosis, we transfected stably antisense p21(WAF1/CIP1)-encoding plasmids. Following NO exposure, accumulation of p21(WAF1/CIP1), but not p53, was largely attenuated in antisense p21(WAF1/CIP1) transfectants. Moreover, the G1 cell-cycle arrest was abrogated, and cells were sensitized toward apoptosis compared with parent macrophages. In contrast, antisense elimination of p53 attenuated p53 as well as p21(WAF1/CIP1) expression, abolished the G1 cell-cycle arrest, and prevented apoptosis. We conclude that p21(WAF1/CIP1) is a downstream target of p53 in macrophages that modulate the sensitivity toward the immune-modulator NO.

Animals↗
PubMed2000

[History of surgical treatment for emphysema].

Great efforts have been paid to the effective surgical managements of diffused emphysema in the past century, which can be grossly divided into three stages, namely, the early exploration, lung transplantation and lung volume reduction surgery. Lung transplantation, developed in the 80's, and especially lung volume reduction surgery, which was developed in the 90's, was recognized as the most effective therapy for terminal stage of emphysema, which offers a new approach for the victims of emphysema.

Emphysema↗
PubMed2000

[Washing liquid cytology examination of operative wound in patients with breast tumor].

OBJECTIVES: To study the relation between exfoliated tumor cells in operative wound and clinical pathologic classification and to provide theory for killing exfoliated tumor cells in operation. METHOD: Washing liquid cytology examination of the operative wound was done in 262 patients with breast tumor. The relation between cytology examination and pathological classification was analyzed. RESULTS: In the 262 patients, exfoliated tumor cells were found in 63 patients, (24%). The detection rate in patients with I, II, III and IV stage was 5.3%, 27.1%, 79.3% and 100% respectively; The rate for T(1), T(2), T(3) stage was 6.1%, 18.9% and 51.3% respectively. The detection rate was 58.6% when the number of metastasis lymph node beyond 3; the rate was 14.3% and 14.1% respectively when the number below 3 or no lymphatic metastasis. CONCLUSION: The detection rate of exfoliated tumor cells is related to tumor advance, and it is necessary to kill exfoliated tumor cells in operation.

Breast Neoplasms↗
PubMed2000

[Human physiological regulation in the closed suit with no ventilation].

Objective. To study the effects of the Experimental Closed Suit (ECS) with no active ventilation on human physiological functions and its anti-asphyxic role. Method. Five young healthy male subjects, aged 18-21 years, were tested in the ECS with no active ventilation and no oxygen supply (NAVANOS) when the gas regulatory valve switch was placed on A or B position respectively. Result. (1) Under 1 atm air pressure, each subject could endure at least 15 min while they were aware and resting in the ECS with NAVANOS; (2) There was a balancing period or plateau of the oxygen and the carbon dioxide pressure in the vicinity of the mouth in 5 to 7 min after the sealed helmet was closed, and this period lasted to the end of each test; (3) During the 8-10 min balancing period, the oxygen partial pressure in the vicinity of the mouth ranged from 15.0 to 16.4 kpa, which was slightly hypoxic, and the range of the carbon dioxide partial pressure was 5.21 to 6.49 kPa, which was within the CO2 concentration-time curve of human physiological endurance; (4) No significant difference in human physiological parameters was found when the regulatory valve was placed on A or B position. Conclusion. The anti-asphyxic time of ECS with NAVANOS could at least last 15 min under 1 atm air pressure while the subjects were aware and resting.

Adolescent↗
PubMed2000

[The correlation of serum levels of insulin-like growth factors and intrauterine growth: report of a study in rats].

This animal experiment was designed to investigate the relationship of the serum insulin-like growth factors (IGFs) with fetal intrauterine growth. The serum concentrations of IGF-I, -II in 21 fetal rats were measuerd and their relationships with fetal birth weight, length and tissue weights of brain, lung, liver were analysed respecively. The results showed that both of the serum concentrations of IGF-I, -II were positively correlated (P < 0.01) with fetal birth weight, length and tissue weights of brain, lung, liver respectively. These data suggest that both IGF-I and IGF-II may play an important role in fetal intrauterin growth and their decreased concentrations in serum may be factors contributing to fetal intrauterine growth retardation.

Animals↗