Cotransplantation of microencapsulated hepatocytes and islets for acute hepatic failure in rats.
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Biomedical subjects
Publications and source records attributed to C H Chang.
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From January 1986 to December 1991, 100 modified Blalock-Taussig Shunts (MBTS) using PTFE (polytetrafluoroethylene) grafts were performed on 86 patients with complex cyanotic congenital cardiac malformations at this hospital. The ages of patients ranged from 15 days to 22 years. Thirty-seven were operated upon in infancy and one in the neonatal period. Varying sizes of grafts were used: 3 mm in 3 cases, 4 mm in 18, 5 mm in 44, 6 mm in 34 and 8 mm in one. The mean follow-up period was 13.5 months (ranged from one to 50 months). There were one hospital mortality and one morbidity. One year shunt patency rate was 90%. Univariate analysis showed the age of the patient operated upon and graft size were risk factors for shunt patency. With an encouraging 90% early shunt patency rate, we can now adopt MBTS as an alternative without hesitancy. Yet, the surgical technique and perioperative care of those cyanotic neonates receiving this palliation still remain a challenge.
Hormone replacement should provide a serum hormone profile similar to that found in normal physiology. This is generally impractical because hormones are usually released episodically and therefore require frequent administration. However, rather than replacing the hormone directly, in theory, one could administer a mimic or amplifier of the pulse generator that controls pulsatile release of the particular hormone. Using growth hormone (GH) as a paradigm we sought such a mimetic that would provide episodic GH release when administered by the oral route. A GH secretagogue MK0677, is described that has these ideal properties; following oral administration MK0677 amplifies episodic GH release. Mechanistically, it synergizes with growth hormone releasing hormone (GHRH) through a receptor and signal transduction pathway distinct from that of GHRH and is a functional antagonist of somatostatin (SRIF). MK0677 also acts on the arcuate nucleus and appears to stimulate GHRH release. By using 35S-MK0677, a new G-protein coupled receptor for MK0677 was characterized in the plasma membrane fraction of pituitary and hypothalamic tissue. The receptor is present in very low abundance and couples to phospholipase C. Other ligands selective for this receptor also cause synchronization of well-defined pathways leading to GH release. Repeated oral treatment of dogs once daily with MK0677 initiates amplified pulsatile GH release accompanied by increases in IGF-1 that are sustained. The unique biological properties of MK0677 and other synthetic ligands that bind to the same receptor force us to predict that these ligands mimic a naturally occurring hormone that regulates pulsatile GH release. Understanding the regulatory mechanisms involved in this paradigm has broad implications for the control of pulsatile rhythms in the endocrine system.
Class A amphipathic helical peptides have been shown to mimic many properties of exchangeable apolipoproteins. The three analogs of the class A amphipathic peptides were used to probe the structure and function of human very low density lipoproteins (VLDL): 1) 18 residue peptide possessing a single helical domain (18A) with the sequence Asp-Trp-Leu-Lys-Ala-Phe-Tyr-Asp-Lys-Val-Ala-Glu-Lys-Leu-Lys-Glu-Ala-Phe; 2) two domains of 18A separated by a Pro (37pA); and 3) and 18A analog with the end groups protected to increase helicity (Ac-18A-NH2). Upon incubation of the peptides with VLDL at a peptide to VLDL, (protein) ratio of 1:1, the 37pA and Ac-18A-NH2 were able to displace most of apolipoprotein (apo) Cs and E from VLDL without alteration in its lipid composition and morphology while 18A had minimal effect. The extent of displacement was a function of the peptide to VLDL ratio. The rank order of displaceability of apolipoproteins on VLDL was apoE > C-III > C-II. The displacement of apoE and/or Cs from VLDL by peptides variably affected the ability of VLDL to interact with purified bovine milk lipoprotein lipase (LpL) and cultured macrophages. Treatment of VLDL with Ac-18A-NH2 markedly lowered its reactivity to LpL and its ability to induce lipid accumulation in cultured macrophages: however, treatment of VLDL with 37pA or 18A only minimally lowered their abilities. Ac-18A-NH2 treatment of VLDL resulted in the increase of apparent K(m) and a decrease of Vmax for lipoprotein lipase (LpL)-catalyzed hydrolysis of VLDL triglycerides. When an artificial triglyceride emulsion was used as a substrate of LpL, 37pA, but not Ac-18A-NH2, activated LpL. The above data indicate that 1) amphipathic helical peptides can alter the metabolic and functional properties of VLDL by dissociating the functionally important exchangeable apolipoproteins from VLDL as well as by acting as a functional element of VLDL after their incorporation; and 2) the class A amphipathic peptides having different lipid-associating properties exert significantly different effect on VLDL function.
Glass fibers are the most widely distributed mineral fibers because of their multiple applications, chiefly as insulation materials, and have become important in replacing asbestos fibers. Fiberglass dermatitis is one of the most common forms of occupational dermatitis resulting from mechanical irritation. Here we report a typical case. A 30-year-old male worker handled the cutting and grinding of fiberglass mats and then mixed them with resin as reinforcing materials. He complained of intense itching after the first two weeks of employment. Erythematous macules, papules and folliculitis with excoriation developed over his arms, neck, face and upper chest. There were many transparent glass fiber spicules with the diameter around 7-10 microns detected by applying the adhesive tape against the skin lesion, followed by microscopic observation. He was much improved during hospitalization with oral antihistamine and topical steroid ointment. To prevent this occupational disease, we suggest proper procedures of production, storage, transportation and cleaning in the industrial setting and proper protective clothing in personnel to minimize the release of and exposure to glass fibers.
CD7-positive acute myeloid leukaemias (CD7+AML) represent a distinct biological and clinical subtype of AML. The results of previous studies suggested that CD7 expression on myeloid leukaemic blasts might result from leukaemic transformation and maturation arrest of haemopoietic precursors at the stage of early myeloid differentiation when CD7 was transiently expressed. However, CD7+ myeloid progenitors have not yet been directly documented in normal human haemopoietic tissues. In this study, haemopoietic cells from 16 human fetal livers with a gestational age of 16-28 weeks were studied. Double myeloperoxidase (MPO) and CD7-positive cells could be demonstrated on 0-4% (mean 1.8%) of total fetal liver mononuclear cells (FLMC) by double cytochemical reaction of MPO and immunocytochemical staining of CD7. Simultaneous expression of CD7 and myeloid antigens (CD13 and/or CD33) could also be detected on 2.2-15.6% (mean 9.3%) of FLMC by dual-colour immunofluorescence flow cytometry analyses. CD13 and/or CD33 positive (CD13/33+) myeloid cells were positively selected by immunomagnetic bead separation system to a purity of 86.5-99.1% (mean 96.0%) of which < or = 3.3% were CD3+ cells and < or = 1.2% were CD19+ cells. Coexpression of CD7 was detected on 8.7-34.5% (mean 17.3%) of this CD 13/33+ cell population, but it was induced to decrease significantly after short-term in vitro culture with the differentiation-inducing agent phorbol ester (TPA). Coexpression of CD7 and CD13/33 could also be shown on a minor population of adult bone marrow and cord blood mononuclear cells (mean 3.9% and 1% respectively). In conclusion, the normal putative counterparts of blasts from CD7+ AML could be demonstrated in human haemopoietic tissues. The fact that CD7 expression tended to be lost after TPA stimulation suggested that CD7 was transiently expressed in early myeloid differentiation.
Epidermal Langerhans cells (LC) express several co-stimulatory molecules such as B7/BB1, which has been implicated as one of the important determinants for potent antigen-presenting function of LC. Recent studies have shown that B7/BB1 antigens comprise three distinct molecules termed B7-1, B7-2 and B7-3. Previous studies have revealed that the phenotypic and functional properties of murine LC are enormously affected by various cytokines including granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-1 (IL-1), and tumour necrosis factor alpha (TNF-alpha) derived from surrounding keratinocytes. We have already demonstrated that the expression of B7-1 of murine LC is significantly enhanced by GM-CSF, IL-1 or TNF-alpha. In this paper, we present that IL-1, but not TNF-alpha, synergistically up-regulates the GM-CSF-induced B7-1 expression of murine LC.
To elucidate the role of autoantibodies and ultraviolet (UV) exposure in the pathogenesis of the skin lesions in neonatal lupus erythematosus (NLE), keratinocytes were cultured, as the target cells, from a patient with NLE and from a normal neonate. We demonstrated that the expression of nuclear/cytoplasmic Ro/SSA and La/SSB molecules on to the surface of NLE keratinocytes occurred to a much greater extent than that on normal keratinocytes. A dose of 200 mJ/cm2 UVB irradiation on NLE keratinocytes induced a 2.5-3-fold increase in Ro/SSA and La/SSB expression compared to non-irradiated cells. Sera derived from both the NLE patient and from his mother exhibited a cytotoxic effect on NLE keratinocytes, but not on control cells, in the presence of complement. Furthermore, the cytotoxicity of the sera was enhanced on UVB-irradiated NLE keratinocytes, whereas it had no cytotoxic effects on UVB-irradiated control cells. This suggests that the abnormal expression of both Ro/SSA and La/SSB on the surface membrane of NLE keratinocytes induces the autoantibodies and complements to injure the cells. This complement-mediated cytotoxic effect can be augmented by UV irradiation, a concept not incompatible with the exacerbation of the skin eruption in sun-exposed skin sites.
The morphologic and functional characteristics of cultured hair follicle dermal papilla (DP) cells, dermal sheath (DS) cells and interstitial dermal fibroblasts (DF cells) derived from human scalp tissue are compared. DP and DS cells, but not DF cells, showed aggregative behavior at a preconfluent density. All three types of cells stained positive for type I collagen, type IV collagen, laminin and heparan sulfate proteoglycan. Only DP and DS cells expressed smooth muscle alpha-actin. DP and DS cells also synthesized more glycosaminoglycans (GAG) than DF cells, while there was no significant difference between DP and DS cells in GAG synthesis. Ultrastructurally, 7 out of 10 strains of DP and 2 out of 10 strains of DS cells were found to form intranuclear rodlets, while none of the 10 strains of DF cells examined formed intranuclear rodlets. The conditioned medium of the three types of cells was collected and tested for the presence of interleukin (IL)-1 beta, tumor necrosis factor (TGF)-beta 2, IL-6, platelet-derived growth factor-AB, epidermal growth factor, b-FGF, GM-CSF, insulin-like growth factor (IGF)-1 and HGF (hepatocyte growth factor) by ELISA or RIA. Among the tested cytokines and growth factors, TGF-beta 2, IL-6 and IGF-I were detectable in at least some conditioned media. The others were undetectable. There was no significant difference in the production of IL-6 and IGF-I among the three types of cells. In contrast, DP cells produced the highest levels of TGF-beta 2, DS cells produced intermediate levels of TGF-beta 2, and DF cells produced the lowest levels of TGF-beta 2. DP and DS cells are morphologically and functionally different from the nonfollicular, interstitial DF cells. Moreover, the presence of some minor biologic differences between DP and DS cells suggests that they represent follicular mesenchymal cells in different functional or differentiation states.
Paraquat manufacturers in Taiwan have been found to develop solar lentigo, actinic keratosis, as well as skin cancer in sun-exposed areas. Bipyridine has been found to be the responsible agent. At present, the mechanism for the pathogenesis of bipyridine-induced skin cancer is not known and it may be multifactorial. We investigated possible alterations in tumor necrosis factor (TNF)-alpha secretion in keratinocytes treated with 4,4'-bipyridyl dihydrochloride in vitro. Normal human keratinocytes were cultured and treated with bipyridine (10 micrograms/mL) or ultraviolet B (UVB) light (10 mJ/cm2), or with a combination of both. Bipyridine treatment alone resulted in a significant reduction in constitutive TNF-alpha secretion. Furthermore, in contrast to the finding in normal keratinocytes, UVB irradiation failed to promote TNF-alpha secretion in bipyridine-primed keratinocytes.
The best surgical technique in bronchial reconstruction is resection and end to end anastomosis, but in some cases either pathology length, reduction in tissue elasticity, or such circumstances, patch bronchoplasty may be necessary to reestablish air-passage continuity. The purpose of this experiment would thus try to investigate the possibility of using ringed polytetrafluoroethylene (PTFE) graft to repair the diseased bronchus. A 2 x 1 cm patch segment of bronchus resected in 10 dogs were followed up with monthly bronchoscopy and endoscopic photography. Euthanasia was performed at 3, 6 and 9 months or when signs of respiratory distress developed. At postmortem examination, the anastomoses were examined grossly and with light microscopy. In 5 of the 10 dogs that underwent bronchial repair with PTFE, granulation tissue developed at the anastomoses resulting in airway obstruction after 6 to 9 months. No epithelial growth occurred over the graft between the suture lines. We conclude that the granulation tissue formation at the anastomosis and the lack of respiratory epithelial ingrowth across the graft makes PTFE unsuitable for patch repair of the bronchial defect.
BACKGROUND: Failure of vascular access leading to inefficient hemodialysis is the most common cause of morbidity in uremic patients. Careful observation of clinical signs and hemodynamic monitoring are vitally important to prevent complete fistula thrombosis. This study was undertaken to evaluate approaches for early detection and the application of percutaneous transluminal angioplasty in the treatment of failing vascular access. METHODS: From August 1994 to August 1995, 32 uremic patients with failing vascular access (26 native arteriovenous fistulas, 6 polytetrafluroethlene (PTFE) grafts), presented signs of poor arterial flow, high venous pressure, significant recirculation, acute fistula thrombosis and persistent swelling of the access arm. These patients underwent fistulography and subsequent angioplasty in the confirmed obstructed sites. RESULTS: Thirty-seven angioplasty procedures were performed including 32 de novo lesions and 5 restenotic lesions; of the total, 32 (86.5%) were successful. In native arteriovenous (AV) fistulas, the most common problem was inadequate flow with the lesion located within 5 cm from the AV junction (63.6%). In PTFE grafts, the most common presentation was high venous pressure with the lesion located at the PTFE-venous junction (57.1%). CONCLUSIONS: Through clinical surveillance and hemodynamic monitoring during hemodialysis, failing vascular access can be detected early and treated effectively with percutaneous transluminal angioplasty.
Chondrosarcoma involving the heart has been previously reported but is extremely rare. Most chondrosarcoma described in the literature are secondary, and the primary site can be identified. We present an unusual case of primary cardiac chondrosarcoma which originated in the left atrium. Severe pulmonary edema was the first presentation. The sarcoma subsequently metastasized to the mandible and finally recurred in the right heart causing severe pulmonary emboli and myocardial failure.
Neuropeptides such as gastrin releasing peptide and pituitary adenylate cyclase activating polypeptide (PACAP) stimulate CCK secretion from CCK producing cells. We hypothesized that in addition to somatostatin, galanin may also play an inhibitory role on CCK secretion. The effect of galanin on CCK secretion was studied in a CCK-producing murine neuroendocrine tumor cell line, STC-1. Galanin below 10 nM did not affect basal CCK secretion but dose- and time-dependently inhibited KCl-stimulated CCK secretion. Galanin also inhibited forskolin-, bombesin- and PACAP- but not dibutyryl cAMP- or beta-TPA-stimulated CCK secretion. The inhibitory effect of galanin was reduced partially by a blocker of ATP-sensitive K+ channel (K+ ATP), glibenclamide, and prevented by pretreatment of the cells with PTX. The results indicated galanin regulates CCK secretion by modulation of K+ ATP and cAMP production through receptors coupled to a PTX-sensitive G protein.
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CIITA (a major histocompatibility complex [MHC] class II transactivator) has been shown to be required for the expression of MHC class II genes in both B cells and interferon gamma-inducible cells. Here we demonstrate that CIITA not only activates MHC class II genes but also genes required for antigen presentation. Mutant HeLa cells, defective in the expression of classic MHC class II genes, invariant chain, and the newly described human histocompatibility leukocyte antigen-DM genes, were used to study the role of CIITA in the regulation of these genes. Upon transfection with CIITA cDNA, the mutant cells expressed all three genes, suggesting that CIITA is a global regulator for the expression of genes involved in antigen presentation.