[Hamartoma of the head and neck: Clinicopathological analysis of 12cases]
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Biomedical subjects
Publications and source records attributed to W C Wang.
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CD6, a type I cell surface glycoprotein expressed predominantly by thymocytes and mature T lymphocytes, becomes phosphorylated on tyrosine residues following T cell activation and has been implicated as an accessory molecule in T cell activation. The purpose of this study was to identify cell lines and tissues which express CD6 ligand(s), determine the requirements for CD6 binding, and biochemically characterize the putative CD6 ligand(s). Binding studies with a CD6 immunoglobulin fusion protein, CD6-Rg, allowed the identification of a number of human cell lines which express a CD6 ligand(s). The binding to these cell lines was trypsin sensitive, in part required divalent cations, was blocked by an anti-CD6 mAb, and could be downregulated by tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Among the cell lines tested, the human breast carcinoma-derived cell line HBL-100 expressed the highest levels of CD6 ligand(s) and was used for immunoprecipitation studies. Following metabolic labeling, CD6-Rg immunoprecipitated glycoproteins of approximately 100, approximately 90, and approximately 45 kDa from HBL-100 cells. Using CD6-Rg we were able to show that murine thymus, lymph nodes, and skin express high levels of CD6 ligand(s) and that CD6-Rg bound to a murine thymic epithelial cell line and to cultured human epidermal keratinocytes.
We evaluated a 13-month-old boy with cytoplasmic inclusions in hematopoietic cells, transfusion-dependent anemia, splenomegaly, and striking grey skin discoloration. Bright blue inclusions, 1 to 5 microns in diameter, were observed, primarily in the cytoplasm, of 30% to 40% of myeloid cells and in occasional monocytes, megakaryocytes, and lymphocytes on Wright Giemsa-stained bone marrow and blood smears. They occasionally involved the nucleus. The inclusions lacked lysosomes, polysaccharides, or lipids. Ultrastructurally, they lacked limiting membranes and consisted of tightly packed microfilaments averaging 7 nm in diameter, consistent with the size of actin monofilaments. On light microscopy, the inclusions stained with a monoclonal antibody to muscle-specific actin. Inclusion-positive cells contained increased F-actin content and were defective in chemotactic factor-activated actin polymerization; inclusion-negative cells polymerized actin normally. Neutrophil and platelet numbers and functional studies were mildly abnormal. Anemia and skin discoloration resolved spontaneously after 18 months, but the giant inclusions have persisted to the present. We conclude that this child has a previously unreported constellation of clinical and laboratory findings comprising severe anemia, intermittent neutropenia and thrombocytopenia, abnormal neutrophil migration and platelet aggregation, giant inclusions of actin in hematopoietic cells, and grey skin discoloration.
A murine monoclonal antibody, ME20, with high selectivity for melanomas, has been utilized to isolate a unique membrane-bound (designated ME20-M) and secreted (designated ME20-S) antigen from H3606 human melanoma cells. ME20-M was purified from the cell lysate and ME20-S from the conditioned medium of H3606 cells by immunoaffinity chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The apparent molecular weights were 105,000 and 76,000, respectively. Analyses of ME20-M and ME20-S by amino acid sequencing identified the processing sites. Signal peptide cleavage occurs at Thr-24 of pro-ME20 antigen, yielding ME20-M (25 to 661). In addition, proteolytic processing of the precursor at Val-467 yields ME20-S (25 to 467). We report the characterization of Asn-linked glycosylation sites in ME20-M and ME20-S to determine the involvement of oligosaccharides in the proteolytic processing of pro-ME20 antigen. Tryptic peptide maps of ME20-M and ME20-S were prepared and the glycosylation sites identified by sequence analyses. Oligosaccharides were enzymatically released and characterized by high-performance anion-exchange chromatography. We found high-mannose-type structures at Asn-57, Asn-82, and Asn-87 of ME20-M, whereas ME20-S contained 73% complex-type and 27% high-mannose-type oligosaccharides at the same sites. To assess the role of oligosaccharides in the processing of the ME20 antigen, we tested the effect of the oligosaccharide processing modifier deoxymannojirimycin, a compound that inhibits synthesis of hybrid- and complex-type oligosaccharides. Deoxymannojirimycin had no effect on the synthesis and relative rate of synthesis of ME20-M, but markedly reduced the synthesis of ME20-S without affecting the rate of secretion. The reported results suggest that carbohydrate maturation of the ME20 antigen may be important for processing and secretion.
We retrospectively examined the medical and autopsy records of seven previously unpublished cases of fatal pneumococcal septicemia in children with hemoglobin SC disease. The earliest death occurred in a 1-year-old child who had congenital heart disease with cyanosis; the other children were aged 3 1/2 to 15 years. Only one child had received pneumococcal vaccine or prophylactic penicillin therapy. All seven children had an acute febrile illness and rapid clinical deterioration despite parenterally administered antibiotic therapy and intensive medical support. Erythrocyte pit counts in two patients were 40.3% and 41.7%, respectively (normal, < or = 3.6%). Autopsy data from five cases showed marked splenic congestion without infarction in five, splenomegaly in four, and bilateral adrenal hemorrhage in three. These cases illustrate that functional asplenia predisposes some children with hemoglobin SC disease to the development of fatal septicemia after the age of 3 years. We conclude that pneumococcal vaccine should be administered to all children with hemoglobin SC disease and that acute febrile illnesses should be investigated promptly for the possibility of septicemia. The routine use of prophylactic penicillin therapy in infants and children with hemoglobin SC disease remains controversial.
This communication proposes an optical method using forward light scattering to measure the deflection of a micropipette from a normal contact force with a small elastic solid, and the damping coefficient of a small fluid sample through a dynamic interaction with the pipette. An analytical and experimental study of this sensor is performed and described for each property. Topics covered include: 1) forward light scattering technique for determining the diameter of a micropipette (using exact and simplified geometric interference theories); 2) deflection measurement and analysis on the pipette-sample system using the finite element method; and 3) equivalent damping coefficient and resonant frequency measurement of the pipette-fluid system and its numerical solution derived from the finite element model. A comparison of the experimental results and the analytical results is included to provide the means for analyzing the potential of this new method.
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3DCT reconstruction,as a new roentnogenographic technique,has not been yet used so much in Oral Maxillofacial Surgery in our country.Scine early 1993,22 cases of 3DCT reconstruction have been performed on a Siemens Plus-s CT scanner for the diagnosis and surgical planning of jaw bone disease and injuries.It demonstrated that 3DCT reconstruction is a useful technique for the diagnosis and surgical planning of jaw bone disease.
PATIENT: A young boy with hyper-immunoglobulin M (IgM) syndrome had recurrent severe infections, failure to thrive, and chronic neutropenia for 2 years despite treatment with i.v. gammaglobulin (IVIG). METHODS AND RESULTS: With the addition of granulocyte colony-stimulating factor (G-CSF; Filgrastim, Amgen, Inc., Thousand Oaks, CA), increased doses of IVIG, and prophylactic trimethoprim-sulfamethoxazole, his absolute neutrophil count increased from 0.64 x 10(9)/L to 3.36 x 10(9)/L, and he has been free of significant infection for the past 22 months. CONCLUSIONS: The use of G-CSF merits consideration in patients with hyper-IgM syndrome and severe neutropenia.
The role of hemostatic factors in the pathogenesis of cardiovascular disease has gained much attention recently. Information about hemostatic factors, and their age patterns is sparse for orientals. With the data collected in the Cardiovascular Disease Risk Factor Two-township Study in Taiwan, this study shows that, in general, the older the age, the stronger the tendency toward thrombosis. With advancing age, prothrombin time, activated partial thromboplastin time, and antithrombin-III level decreased steadily; but mean values of fibrinogen, factor VIIc, and factor VIIIc increased. Gender differences in the age patterns of the above factors are carefully described. Curvilinear relations between hemostatic factors and age were demonstrated for adults aged 18 and above for all hemostatic factors studied. This curvilinearity should be taken into consideration when adjusting for the effect of age in data analysis to avoid residual confounding, particularly when the age range of the study subjects is wide.
BACKGROUND: Because of their susceptibility to pneumococcal sepsis, children with sickle cell disease and fever are usually hospitalized for antibiotic therapy. Outpatient treatment may be a safe and less expensive alternative for selected patients. METHODS: After evaluation in the emergency room, children ranging from 6 months to 12 years of age who had sickle hemoglobinopathies and temperatures exceeding 38.5 degrees C were randomly assigned to treatment as either inpatients or outpatients. We excluded from randomization children at higher risk of sepsis (as defined by specific criteria, including temperature above 40 degrees C, white-cell count below 5000 per cubic millimeter or above 30,000 per cubic millimeter, and the presence of pulmonary infiltrates) or with complications of sickle cell disease (such as a hemoglobin level below 5 g per deciliter, dehydration, or severe pain); these children were treated as inpatients. All patients received an initial intravenous dose of ceftriaxone (50 mg per kilogram of body weight). Those treated as outpatients returned 24 hours later for a second dose of ceftriaxone, whereas the in patients were treated as directed by their physicians. RESULTS: None of the 86 patients (with a total of 98 febrile episodes) in the randomized groups had sepsis, as compared with 6 of the 70 patients (7 of 86 episodes) excluded because of higher risk (P = 0.004). Among the 44 children (50 episodes) assigned to outpatient treatment, there were 11 hospitalizations (22 percent of episodes) within two weeks after treatment (95 percent confidence interval, 12 to 36 percent), whereas after inpatient care only a single patient (2 percent of episodes) was rehospitalized. When the randomized groups were compared, outpatient treatment saved a mean of $1,195 per febrile episode. The median hospital stay was 3 days (range, 1 to 6) for the children randomly assigned to inpatient care and 4 days (range, 1 to 18) for the higher-risk children treated as inpatients (P < 0.001). CONCLUSIONS: With the use of conservative eligibility criteria, at least half the febrile episodes in children with sickle cell disease can be treated safely on an outpatient basis, with substantial reductions in cost.
Interferon-alpha (IFN-alpha) regulates the growth, differentiation, and recirculation of normal and malignant B lymphocytes. In this report we examine the effects of IFN-alpha on the distribution of the cytoskeletal protein spectrin in peripheral blood B lymphocytes from normal donors and patients diagnosed with chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Exposure of normal and leukemic B cells to IFN-alpha in vitro was shown by immunofluorescence microscopy to cause a dose-dependent increase in the percentage of cells containing discrete focal accumulations of spectrin, ie, a single large aggregate or cap-like structure near the plasma membrane. Although the magnitude of this effect was variable among individual patient samples, in some experiments IFN-alpha induced a fourfold increase in the percentage of leukemic B cells exhibiting focal accumulations of spectrin. Spectrin reorganization induced by IFN-alpha was abrogated by the protein synthesis inhibitor cycloheximide. In addition, IFN-alpha increased the total cellular content of spectrin in B-CLL cells by approximately twofold to fourfold. Finally, a role for protein kinase C in mediating the effects of IFN-alpha on spectrin's organization is implicated by studies in which calphostin C inhibited the IFN-induced focal accumulation of spectrin. Taken together, these studies suggest that the immunomodulatory activities of IFN-alpha in normal and malignant B cells involve a change in the organization of the spectrin-based cytoskeleton.
Fasciclin I is a lipid-linked cell-surface glycoprotein that can act as a homophilic adhesion molecule in tissue culture cells. It is thought to be involved in growth cone guidance in the embryonic insect nervous system. To facilitate structure-function studies, we have generated Chinese hamster ovary (CHO) cell lines expressing high levels of cell surface grasshopper and Drosophila fasciclin I. Grasshopper fasciclin I released by phospholipase C cleavage was purified on an immunoaffinity column and single crystals were obtained that diffracted to approximately 5-A resolution. We also generated CHO and Drosophila S2 cell lines that produce a secreted form of fasciclin I. Fasciclin I expressed in S2 cells contains significantly less carbohydrate than the protein expressed in CHO cells, and may therefore be more suitable for crystallization. Biochemical characterization of purified fasciclin I indicates that the extracellular portion exists as a monomer in solution. Circular dichroism studies suggest that fasciclin I is primarily alpha-helical. Its structure is therefore different from other known cell adhesion molecules, which are predicted to be elongated beta-sheet structures. This suggests that fasciclin I may define a new structural motif used to mediate adhesive interactions between cell surfaces.
The effectiveness of oral RU 486 and anordrin given alone and in combination for terminating early pregnancy was tested in the rat, rabbit, and hamster. In the rat and rabbit, the combination of RU 486 and anordrin is more effective in terminating pregnancy than either of the two compounds used alone. A non-effective dose of RU 486 combined with a non-effective or a sub-effective dose of anordrin, or a low effective dose of RU 486 in combination with a non-effective dose of anordrin, exerted additive or synergistic effects resulting in resorption of embryos and termination of pregnancy in rats and rabbits. The serum progesterone as well as estradiol concentrations were significantly suppressed by these combinations when pregnancy was terminated. In the hamster, however, RU 486 was not effective in interrupting early pregnancy, even at a 4-fold higher dose than was effective in the rat, due to the fact that RU 486 does not bind to the progestin receptor in this species. Unexpectedly, there were also no effects of anordrin on pregnancy termination in the hamster even at high doses. It is concluded that in rat and rabbit, the synergistic action between RU 486 and anordrin not only greatly enhances efficacy in terminating pregnancy but also reduces substantially the doses required to produce this effect.
In view of the unexpected ability of anordrin to synergize with RU 486 in terminating pregnancy, it was pertinent to examine the actions of the dihydroxylated metabolite of anordrin, anordiol, alone and in combination with RU 486. Does of RU 486 (1 mg/kg/day) and anordiol (0.6 mg/kg/day) that were ineffective when given alone terminated pregnancy with complete resorption of embryos when administered together. A smaller dose of anordiol than anordrin is required to achieve this synergistic effect with RU 486. This anordrin metabolite increased uterine weight in the ovariectomized rat similar to estradiol. The estrogenicity of anordiol in the uterine weight assay was about 1/120 of that of estradiol. Anordiol does not exert antiestrogenic activity in the uterine weight assay when administered at doses that terminate pregnancy. Administration of anordiol at doses that do not terminate pregnancy resulted in a significant suppression of serum progesterone concentrations during the period of medication; these observations suggest that anordiol has an inhibitory effect on progesterone biosynthesis. When the same dose of anordiol was given concomitantly with sufficient RU 486 (e.g., 1 mg/kg/day) to terminate pregnancy, the progesterone levels were reduced to low levels throughout the experiment. These observations support the postulate that the actions of anordrin are mediated by its metabolite, anordiol. The administration of anordiol plus RU 486 results in a more dramatic change in the functional progesterone:estradiol ratio than when either agent is administered alone.