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Biomedical subjects

C M Fan

Publications and source records attributed to C M Fan.

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

Custom bifurcated stent-graft for abdominal aortic aneurysms: initial experience.

PURPOSE: To describe a custom bifurcated stent-graft for possible treatment of abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: Five male patients (mean age, 76 +/- 6 years), who had AAA (mean diameter, 4.7 +/- 0.4 cm) and who were considered to be at high risk for conventional surgery, were treated with a custom modular bifurcated stent-graft constructed with bifurcated 24-mm x 12-mm (upper body diameter x iliac limb diameter) Cooley Veri-Soft Woven polyester grafts and Gianturco-Rösch Z stents. The stent-graft body was delivered through 20-22-F sheaths, and the contralateral iliac limb was delivered through a 16-F sheath by means of surgical exposure of the common femoral arteries. A flared distal limb extender (12 mm to 14 mm) was created for one patient to accommodate a large common iliac artery. RESULTS: Stent-grafts were successfully deployed without complications in all five patients. There were no proximal or distal leaks. A lumbar-to-inferior mesenteric artery leak was seen in one patient at 24 hours. At 6-month follow-up, all devices were intact, with complete exclusion and shrinkage of the aneurysm in four of five patients. Aneurysm size remained stable in the one patient with a lumbar-to-inferior mesenteric artery leak. CONCLUSION: A custom, bifurcated stent-graft was utilized for endovascular treatment of AAA. Long-term follow-up is necessary for the device.

Aged↗
PubMed1998

Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1.

The bHLH-PAS transcription factor SIM1 is expressed during the development of the hypothalamic-pituitary axis in three hypothalamic nuclei: the paraventricular nucleus (PVN), the anterior periventricular nucleus (aPV), and the supraoptic nucleus (SON). To investigate Sim1 function in the hypothalamus, we produced mice carrying a null allele of Sim1 by gene targeting. Homozygous mutant mice die shortly after birth. Histological analysis shows that the PVN and the SON of these mice are hypocellular. At least five distinct types of secretory neurons, identified by the expression of oxytocin, vasopressin, thyrotropin-releasing hormone, corticotropin-releasing hormone, and somatostatin, are absent in the mutant PVN, aPV, and SON. Moreover, we show that SIM1 controls the development of these secretory neurons at the final stages of their differentiation. A subset of these neuronal lineages in the PVN/SON are also missing in mice bearing a mutation in the POU transcription factor BRN2. We provide evidence that, during development of the Sim1 mutant hypothalamus, the prospective PVN/SON region fails to express Brn2. Our results strongly indicate that SIM1 functions upstream to maintain Brn2 expression, which in turn directs the terminal differentiation of specific neuroendocrine lineages within the PVN/SON.

Amino Acid Sequence↗
PubMed1998

Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite.

Embryonic patterning in vertebrates is dependent upon the balance of inductive signals and their specific antagonists. We show that Noggin, which encodes a bone morphogenetic protein (BMP) antagonist expressed in the node, notochord, and dorsal somite, is required for normal mouse development. Although Noggin has been implicated in neural induction, examination of null mutants in the mouse indicates that Noggin is not essential for this process. However, Noggin is required for subsequent growth and patterning of the neural tube. Early BMP-dependent dorsal cell fates, the roof plate and neural crest, form in the absence of Noggin. However, there is a progressive loss of early, Sonic hedgehog (Shh)-dependent ventral cell fates despite the normal expression of Shh in the notochord. Further, somite differentiation is deficient in both muscle and sclerotomal precursors. Addition of BMP2 or BMP4 to paraxial mesoderm explants blocks Shh-mediated induction of Pax-1, a sclerotomal marker, whereas addition of Noggin is sufficient to induce Pax-1. Noggin and Shh induce Pax-1 synergistically. Use of protein kinase A stimulators blocks Shh-mediated induction of Pax-1, but not induction by Noggin, suggesting that induction is mediated by different pathways. Together these data demonstrate that inhibition of BMP signaling by axially secreted Noggin is an important requirement for normal patterning of the vertebrate neural tube and somite.

1-Methyl-3-isobutylxanthine↗
PubMed1997

A role for WNT proteins in induction of dermomyotome.

Dorsoventral patterning of somites into sclerotome and dermomyotome involves antagonistic actions of ventralizing and dorsalizing signals originating from tissues surrounding the somites. The notochord and the floor plate of the neural tube provide a ventralizing signal(s) directing sclerotome development, whereas the surface ectoderm and dorsal neural tube provide a dorsalizing signal(s) directing dermomyotome development. Evidence has been provided that Sonic Hedgehog mediates the ventralizing effects of notochord and floor plate, but the dorsalizing signal(s) that patterns the dermomyotome has not been identified. The documented expression of Wnt1 and Wnt3a in the dorsal neural tube and of Wnt4 and Wnt6 in the surface ectoderm at the time of dermomyotome specification prompted us to investigate the involvement of WNT proteins in patterning the dermomyotome. Here we show that tissue culture cells expressing these WNT family members can maintain and induce dermomyotome marker expression in presomitic mesoderm explants, supporting the hypothesis that WNT proteins mediate the dorsalizing effects of the surface ectoderm and dorsal neural tube on somites.

Animals↗
PubMed1997

Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein.

Drosophila single-minded, which acts as a positive master gene regulator in central nervous system midline formation in Drosophila, its two mouse homologs SIM1 and SIM2, and the mammalian aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) proteins are members of the basic-helix-loop-helix.PAS family of transcription factors. In the yeast two-hybrid system, we demonstrate strong constitutive interaction of ARNT with SIM1 and SIM2 and fully ligand-dependent interaction of ARNT with AHR. Both the helix-loop-helix and the PAS regions of SIM1 and of ARNT are required for efficient heterodimerization. SIM1 and SIM2 do not form homodimers, and they do not interact with AHR. We also failed to detect homodimerization of ARNT. The interaction of ARNT with SIM1 was confirmed with in vitro synthesized proteins. Like AHR, in vitro synthesized SIM1 associates with the 90-kDa heat shock protein. SIM1 inhibits binding of the AHR.ARNT dimer to the xenobiotic response element in vitro. Introduction of SIM1 into hepatoma cells inhibits transcriptional transactivation by the endogenous AHR.ARNT dimer. The mouse SIM1. ARNT dimer binds only weakly to a proposed DNA target for the Drosophila SIM.ARNT dimer. In adult mice mRNA for SIM1 was expressed in lung, skeletal muscle, and kidney, whereas the mRNA for SIM2 was found in the latter two. ARNT is also expressed in these organs. Thus mouse SIM1 and SIM2 are novel heterodimerization partners for ARNT in vitro, and they may function both as positive and negative transcriptional regulators in vivo, during embryogenesis and in the adult organism.

Animals↗
PubMed1997

Routine addition of an automated biopsy device to fine-needle aspiration of the lung: a prospective assessment.

OBJECTIVE: The purpose of this study was to prospectively assess the usefulness of the routine addition of an automated biopsy device (ABD) to fine-needle aspiration (FNA) of the lung and to examine the complication rate of this procedure. SUBJECTS AND METHODS: Fifty biopsies were performed under CT guidance using a coaxial technique with a 19-gauge introducer needle and a 22-gauge aspirating needle followed by a 20-gauge ABD. An average of 3.5 FNA specimens and 2.5 core specimens were obtained. Cytology and histology specimens were interpreted separately by two experienced pathologists who were unaware of the other's interpretation. Final diagnoses were based on surgery, microbiology, definitive biopsy diagnosis, and clinical follow-up. All complications were recorded. RESULTS: Of 34 malignant lesions, we achieved a diagnostic accuracy of 94% for FNA and 59% for core biopsy (p < .01). Combined accuracy was 94%. Of 16 benign lesions, an accurate definitive diagnosis was made in 31% of cases using FNA and in 69% of cases using core biopsy (p = .08). Combined accuracy was 69%. In the subset of benign lesions that were not acute infections (n = 8), an accurate definitive benign diagnosis was made in 12% of cases using FNA and in 75% of cases using core biopsy (p < .05). No false-positive diagnoses of malignancy occurred. Complications included pneumothorax, nine (18%) of 50 cases; chest tube, one (2%) of 50 cases minor pulmonary hemorrhage, seven (14%) of 50 cases; and minor hemoptysis, two (4%) of 50 cases. CONCLUSION: The complication rates of FNA with the addition of an ABD are similar to those reported in the literature for FNA alone. The addition of an ABD significantly increases the diagnostic accuracy only for the subset of benign lesions that are not acute infections.

Adolescent↗
PubMed1996

Early deletion of neuromeres in Wnt-1-/- mutant mice: evaluation by morphological and molecular markers.

The Wnt-1 gene is required for the development of midbrain and cerebellum; previous work showed that knockout of Wnt-1 causes the loss of most molecular markers of these structures in early embryos and deletion of these structures by birth. However, neither the extent of early neuronal defects nor any possible alterations in structures adjacent to presumptive midbrain and cerebellum were examined. By using a neuron-specific antibody and fluorescent axon tracers, we show that central and peripheral neuronal development are altered in mutants during initial axonogenesis on embryonic day 9.5. The absence of neuronal landmarks, including oculomotor and trochlear nerves and cerebellar plate, suggests that both mesencephalon and rhombomere 1 (r1) are delected, with the remaining neural tube fused to form a new border between the caudalmost portion of the prosencephalon (prosomere 1, or p1) and r2. Central axons accurately traverse this novel border by forming normal longitudinal tracts into the rhombencephalon, implying that the cues that direct these axons are aligned across neuromeres and are not affected by the delection. The presence of intact p1 and r2 is further supported by the retention of markers for these two neuromers, including a marker of p1, the Sim-2 gene, and an r2-specific lacZ transgene in mutant embryos. In addition, alterations in the Sim-2 expression domain in ventral prosencephalon, rostral to p1, provide novel evidence for Wnt-1 function in this region.

Animals↗
PubMed1996

Lateral and axial signals involved in avian somite patterning: a role for BMP4.

In vertebrates, muscles of the limbs and body wall derive from the lateral compartment of the embryonic somites, and axial muscles derive from the medial compartment. Whereas the mechanisms that direct patterning of somites along the dorsoventral axis are beginning to be understood, little is known about the tissue interactions and signaling molecules that direct somite patterning along the mediolateral axis. We report the identification of a specific marker for the lateral somitic compartment and its early derivatives, cSim1, an avian homolog of the Drosophila single minded gene. Using this marker, we provide evidence that specification of the lateral somitic lineage results from the antagonistic actions of a diffusible medializing signal from the neural tube and a diffusible lateralizing signal from the lateral plate mesoderm, and we implicate bone morphogenetic protein 4(BMP4) in directing this lateralization.

Amino Acid Sequence↗
PubMed1996

Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome.

The single-minded (sim) gene encodes a transcriptional regulator that functions as a key determinant of central nervous system (CNS) midline development in Drosophila. We report here the identification of two murine homologs of sim, Sim1 and Sim2, whose products show a high degree of sequence conservation with Drosophila SIM in their amino-terminal halves, with each containing a basic helix-loop-helix domain as well as a PAS domain. Sim1 maps to the proximal region of mouse chromosome 10, whereas Sim2 maps to a portion of the distal end of chromosome 16 that is syntenic to the Down syndrome critical region of human chromosome 21. Recent exon-trapping studies have identified in the critical region several exons of a human sim homolog which appears to be the homolog of murine Sim2; this has led to the hypothesis that increased dosage of this sim homolog in cases of trisomy 21 might be a causal factor in the pathogenesis of Down syndrome. We have examined the expression patterns of the Sim genes during embryogenesis. Both genes are expressed in dynamic and selective fashion in specific neuromeric compartments of the developing forebrain, and the expression pattern of Sim2 provides evidence for early regionalization of the diencephalon prior to any overt morphological differentiation in this region. Outside the CNS, Sim1 is expressed in mesodermal and endodermal tissues, including developing somites, mesonephric duct, and foregut. Sim2 is expressed in facial and trunk cartilage, as well as trunk muscles. Both murine Sim genes are also expressed in the developing kidney. Our data suggest that the Sim genes play roles in directing the regionalization of tissues where they are expressed. Moreover, the expression pattern documented for Sim2 may provide insights into its potential roles in Down syndrome.

Amino Acid Sequence↗
PubMed1995

Long-range sclerotome induction by sonic hedgehog: direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway.

A long-range signal encoded by the Sonic hedgehog (Shh) gene has been implicated as the ventral patterning influence from the notochord that induces sclerotome and represses dermomyotome in somite differentiation. Long-range effects of hedgehog (hh) signaling have been suggested to result either from local induction of a secondary diffusible signal or from the direct action of the highly diffusible carboxy-terminal product of HH autoproteolytic cleavage. Here we provide evidence that the long-range somite patterning effects of SHH are instead mediated by a direct action of the amino-terminal cleavage product. We also show that pharmacological manipulations to increase the activity of cyclic AMP-dependent protein kinase A can selectively antagonize the effects of the amino-terminal cleavage product. Our results support the operation of a single evolutionarily conserved signaling pathway for both local and direct long-range inductive actions of HH family members.

Animals↗
PubMed1995

Physical mapping of the holoprosencephaly critical region in 21q22.3, exclusion of SIM2 as a candidate gene for holoprosencephaly, and mapping of SIM2 to a region of chromosome 21 important for Down syndrome.

We set out to define the holoprosencephaly (HPE) critical region on chromosome 21 and also to determine whether there were human homologues of the Drosophila single-minded (sim) gene that might be involved in HPE. Analysis of somatic cell hybrid clones that contained rearranged chromosomes 21 from HPE patients defined the HPE minimal critical region in 21q22.3 as D21S113 to qter. We used established somatic cell hybrid mapping panels to map SIM2 to chromosome 21 within subbands q22.2-q22.3. Analysis of the HPE patient-derived somatic cell hybrids showed that SIM2 is not deleted in two of three patients and thus is not a likely candidate for HPE1, the HPE gene on chromosome 21. However, SIM2 does map within the Down syndrome critical region and thus is a candidate gene that might contribute to the Down syndrome phenotype.

Child, Preschool↗
PubMed1995

[Pharmacokinetics of contragestazol (DL-111-IT), a new non-steroid antifertility agent in monkeys].

The pharmacokinetics of contragestazol, an early pregnancy temperating agent [3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole, DL-111-IT] was studied in Rhesus monkey. The blood concentration of DL-111-IT was determined by coupled column system HPLC method. Using an aqueous vehicle (20% cremophor EL in saline) DL-111-IT was injected intravenously to monkeys at doses of 25, 12.5 and 6.3 mg.kg-1. Blood drug concentration were measured. Using a programmable calculator the calculated pharmacokinetic parameters were as follows: alpha 1.83 h-1, 4.71 h-1 and 3.61 h-1, beta 0.15 h-1, 0.08 h-1 and 0.09 h-1; T1/2 beta 6.63 h, 10.2 h and 10.1 h; AUC 9.54 micrograms.h-1.ml-1, 3.94 micrograms.h-1.ml-1 and 3.75 micrograms.h-1.ml-1. An oil solution of DL-111-IT was injected intramuscularly in monkeys at doses of 50, 25 and 12.5 mg.kg-1. Its blood concentrations were determined at 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 and 24 h after administration. From the time vs concentration curve, the pharmacokinetic parameters obtained were as follows: Ka 0.98 h-1, 1.03 h-1 and 1.45 h-1; Ke 0.42 h-1, 0.37 h-1 and 0.60 h-1; T1/2Ke 1.66 h, 1.90 h and 1.16 h; T (peak) 1.52 h, 1.57 h and 1.09 h; AUC 4.86 micrograms.h-1.ml-1, 5.61 micrograms.h-1.ml-1 and 1.74 micrograms.h-1.ml-1.

Abortifacient Agents, Nonsteroidal↗