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Biomedical subjects

H Choi

Publications and source records attributed to H Choi.

At least 181 records · Page 10Linked to original sources

Proteoglycans and glycosaminoglycans induce gap junction synthesis and function in primary liver cultures.

Intercellular communication via gap junctions, as measured by dye and electrical coupling, disappears within 12 h in primary rat hepatocytes cultured in serum-supplemented media or within 24 h in cells in a serum-free, hormonally defined medium (HDM) designed for hepatocytes. Glucagon and linoleic acid/BSA were the primary factors in the HDM responsible for the extended life span of the electrical coupling. After 24 h of culture, no hormone or growth factor tested could restore the expression of gap junctions. After 4-5 d of culture, the incidence of coupling was undetectable in a serum-supplemented medium and was only 4-5% in HDM alone. However, treatment with glycosaminoglycans or proteoglycans of 24-h cultures, having no detectable gap junction protein, resulted in synthesis of gap junction protein and of reexpression of electrical and dye coupling within 48 h. Most glycosaminoglycans were inactive (heparan sulfates, chondroitin-6 sulfates) or only weakly active (dermatan sulfates, chondroitin 4-sulfates, hyaluronates), the weakly active group increasing the incidence of coupling to 10-30% with the addition of 50-100 micrograms/ml of the factor. Treatment of the cells with 50-100 micrograms/ml of heparins derived from lung or intestine resulted in cells with intermediate levels of coupling (30-50%). By contrast, 10-20 micrograms/ml of chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, or liver-derived heparin resulted in dye coupling in 80-100% of the cells, with numerous cells showing dye spread from a single injected cell. Sulfated polysaccharides of glucose (dextran sulfates) or of galactose (carrageenans) were inactive or only weakly active except for lambda-carrageenan, which induced up to 70% coupling (albeit no multiple coupling in the cultures). The abundance of mRNA (Northern blots) encoding gap junction protein and the amounts of the 27-kD gap junction polypeptide (Western blots) correlated with the degree of electrical and dye coupling indicating that the active glycosaminoglycans and proteoglycans are inducing synthesis and expression of gap junctions. Thus, proteoglycans and glycosaminoglycans, especially those found in abundance in the extracellular matrix of liver cells, are important in the regulation of expression of gap junctions and, thereby, in the regulation of intercellular communication in the liver. The relative potencies of heparins from different tissue sources at inducing gap junction expression are suggestive of functional tissue specificity for these glycosaminoglycans.

Animals↗

Localization of a dermatan sulfate proteoglycan (DS-PGII) in cartilage and the presence of an immunologically related species in other tissues.

A monoclonal antibody to a core-protein-related epitope of a small dermatan sulfate-rich proteoglycan (DS-PGII) isolated from adult bovine articular cartilage (22) was used to localize this molecule, or molecules containing this epitope, in bovine articular cartilages, in cartilage growth plate, and in other connective tissues. Using an indirect method employing peroxidase-labeled pig anti-mouse immunoglobulin G, DS-PGII was shown to be present mainly in the superficial zone of adult articular condylar cartilage of the metacarpal-phalangeal joint. In fetal articular and epiphyseal cartilages, the molecule was uniformly distributed throughout the matrix. By approximately 10 months of age it was confined mainly to the superficial and middle zones of articular cartilage and the inter-territorial and pericellular matrix of the deep zone. DS-PGII was not detected in the primary growth plate of the fetus except in the proliferative zone, where it was sometimes present in trace amounts. In contrast, it was present throughout the adjacent matrix of developing epiphyseal cartilage. In the trabeculae of the metaphysis, strong staining for DS-PGII was seen in decalcified osteoid and bone immediately adjacent to osteoblasts. Staining was also observed on collagen fibrils in skin, tendon, and ligament and in the adventitia of the aorta and of smaller arterial vessels in the skin. These observations indicate that DS-PGII and/or molecules containing this epitope are widely distributed in collagenous tissues, where the molecule is intimately associated with collagen fibrils; in adult cartilage this association is limited mainly to the narrow parallel arrays of fibrils which are found in the superficial zone at the articular surface. From its intimate association and other studies, this molecule may play an important role in determining the sizes and tensile properties of collagen fibrils; it may also be involved in the calcification of osteoid but not of cartilage.

Animals↗

Extracellular matrix regulation of cell-cell communication and tissue-specific gene expression in primary liver cultures.

Epithelial-mesenchymal interactions are effected, in part, by extracellular matrix components. We have spent many years analyzing the influence of extracellular matrix, both as extracts of matrix and as purified matrix components, on the growth and differentiation of normal and neoplastic liver cells. Currently we are focused on analyzing the influence of the extracellular matrix components, glycosaminoglycans and proteoglycans. We have found that these factors induce dramatic morphological changes, are potent inducers of gap junction synthesis and can regulate tissue-specific gene expression. With respect to gap junctions: intercellular communication via gap junctions, as measured by dye and electrical coupling, disappears within 12 hrs in primary rat hepatocytes cultured in serum supplemented media or within 24 hrs in cells in a serum free, hormonally defined medium designed for hepatocytes. Glucagon and linoleic acid/BSA were the primary factors in the HDM responsible for the extended life span of the electrical coupling. Addition of proteoglycans or glycosaminoglycans to hormonally defined medium after 24 hrs resulted in reexpression of electrical and dye coupling when assayed at 96 hrs of culture. The incidence of coupling was less than 5% in hormonally defined medium alone. Coupling incidence increased to 10-30% with the addition of 10 micrograms/ml of glycosaminoglycans (i.e., hyaluronic acid, dermatan sulfate, chondroitin 4- or 6-sulfate, and iota- or kappa-carrageenan) to hormonally defined medium. By contrast, the same concentrations of chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, or lambda-carrageenan resulted in dye coupling in more than 70% of the cells, with numerous cells showing dye spread from a single injected cell (in the case of the proteoglycans). The greatest effect of those tested was elicited by the dermatan sulfate proteoglycans, which induced cell-cell communication in 90-100% of the cells. Heparins gave intermediate responses (30-50%). Western blots demonstrated that the amounts of the main intrinsic gap junction polypeptide (27 KDa) extractable from cells correlated with the degree of electrical and dye coupling. Thus, proteoglycans and glycosaminoglycans appear to elicit the formation and function of gap junctions and may thus play a role in the regulation of intercellular communication under normal and pathological conditions. With respect to gene expression: normal rat hepatocytes maintained in culture on tissue culture plastic and in serum supplemented medium lose their tissue-specific functions within hours to a few days due to loss of synthesis and to rapid degradation of tissue-specific mRNAs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Prolonged survival in Richter syndrome with subsequent reemergence of CLL: a case report including serial cell-surface phenotypic analysis.

The development of a large cell lymphoma in a patient with chronic lymphocytic leukemia (Richter syndrome) is associated with a poor prognosis. There is dispute regarding the clonal origin of the large cell component. We described a patient in whom prolonged remission of the large cell component was achieved with combination chemotherapy, followed by subsequent reemergence of the less aggressive CLL clone. Serial cell surface phenotypic data are presented suggesting origin of both histologies from a common B-cell clone.

B-Lymphocytes↗

Effect of prostaglandin E2 on the electrical activity of cat isolated stomach muscle.

Prostaglandins (PGs) are believed to be present in the gastrointestinal tract and to increase the tone of longitudinal muscle layer. However the influence of PGs on the gastric slow wave (SW) is not clarified yet. We therefore investigated the effect of prostaglandin E2 (PGE2) on the electrical and the mechanical activities of feline isolated stomach muscle strips (7 X 1.5 cm), using five capillary electrodes (Ag-AgCl) and an isometric force transducer connected to the antral edge. One hundred and ninety-six strips, obtained from the corpus and antrum of 196 anaesthetized cats, were studied in a muscle chamber filled with Krebs solution (pH 7.4, temperature 36 degrees C) bubbled with 5% CO2 in O2. Exogenous PGE2 concentration-dependently increased the gastric SW frequency without affecting the spike and mechanical activities. Indomethacin decreased the SW frequency. These responses to PGE2 or indomethacin were not blocked by phentolamine, propranolol, hexamethonium, atropine or tetrodotoxin. It is therefore suggested that PGE2 facilitates the development of the gastric SW by an action on the muscle that does not involve cholinergic or adrenergic mechanism.

Action Potentials↗

Characteristics of long-term survivors after treatment for inoperable carcinoma of the lung.

Between January, 1971 and August, 1978, 410 patients with histologically or cytologically confirmed inoperable or unresectable carcinoma of the lung of all cell types were treated with curative intent. Forty-five patients lived a minimum of 3 years and 32 patients lived 5 or more years. The 3-year survival rate increased from 7.6% (15/197) between January, 1971 and June, 1975 to 14.1% (30/213) for the interval from July, 1975 to August, 1978 (p less than 0.01). Factors associated with long-term survival were performance status (p less than 0.01), early stage (p less than 0.001), high total dose of radiation (p less than 0.02), large cell carcinoma (p less than 0.01), inoperable for medical reasons (p less than 0.001), and thoracotomy to determine unresectability (p less than 0.04). The difference in survival rates between the two time periods was not related to different patient factors. Survival rates were most improved in the second time period for patients with Stage II or Stage III carcinoma of the lung. Eight patients died from cancer between 36 and 54 months of initial treatment. Five patients died of intercurrent disease without evidence of cancer of the lung after 3 years. An increasing proportion of long-term survivors of inoperable carcinoma of the lung can be expected to result from a better understanding of these diseases, more technically sophisticated external irradiation, and the use of combination chemotherapy for small cell carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Hemangioma in a lymph node.

Hemangiomas occurring in lymph nodes are extremely rare and, to our knowledge, have been documented in the literature only once previously. We report an additional case that was found incidentally in a patient who had undergone a right hemicolectomy and small-bowel resection for widespread angiodysplasia. In addition, the patient also had a third type of vascular lesion, namely, a hemangiopericytoma of the oral mucosa. We also reviewed the literature regarding vasoformative lesions occurring in lymph nodes.

Colonic Neoplasms↗

Adenocarcinoma of prostate presenting as brain metastasis.

The diagnosis of brain metastasis from prostate carcinoma is rarely made antemortem, and has previously been reported only in patients with known extensive metastatic disease of long duration. A case of adenocarcinoma of the prostate presenting as a brain metastasis is described. Current concepts of metastatic spread of prostate carcinoma are reviewed.

Adenocarcinoma↗

Primary signet-ring cell carcinoma of the urinary bladder.

Sixty-one cases of adenocarcinoma of the urinary bladder presenting between 1966 and 1981 were reviewed. Among the only seven cases of primary adenocarcinoma of the urinary bladder, three were classified as primary signet-ring cell carcinoma. These 3 cases were reviewed with the 11 previously reported cases in the literature. Primary signet-ring cell carcinoma of the urinary bladder occurs predominantly in men (12 men, 2 women) with age ranging from 38 to 83 years. It usually runs a rapidly fatal course despite therapy. The characteristic clinical, gross, and histomorphologic findings and pathogenesis of this rare bladder malignancy are discussed.

Adenocarcinoma↗

Association of an extracellular protein (chondrocalcin) with the calcification of cartilage in endochondral bone formation.

We examined bovine fetal epiphyseal and growth plate cartilages by immunofluorescence microscopy and immunoelectron microscopy using monospecific antibodies to a newly discovered cartilage-matrix calcium-binding protein that we now call chondrocalcin. Chondrocalcin was evenly distributed at relatively low concentration in resting fetal epiphyseal cartilage. In growth plate cartilage, it was absent from the extracellular matrix in the zone of proliferating chondrocytes but was present in intracellular vacuoles in proliferating, maturing and upper hypertrophic chondrocytes. The protein then disappeared from the lower hypertrophic chondrocytes and appeared in the adjoining extracellular matrix, where it was selectively concentrated in the longitudinal septa in precisely the same location where amorphous mineral was deposited in large amounts as demonstrated by von Kossa staining and electron microscopy. Mineral then spread out from these "nucleation sites" to occupy much of the surrounding matrix. Matrix vesicles were identified in this calcifying matrix but they bore no observable morphological relationship to these major sites of calcification where chondrocalcin was concentrated. Since chondrocalcin is a calcium-binding protein and has a strong affinity for hydroxyapatite, these observations suggest that chondrocalcin may play a fundamental role in the creation of nucleation sites for the calcification of cartilage matrix in endochondral bone formation.

Animals↗

The prognostic significance of histologic subtyping in small cell carcinoma of the lung.

Previously untreated patients with small cell carcinoma of the lung (SCCL), who were treated at the Medical College of Wisconsin with combined chemotherapy and radiation therapy, were retrospectively subtyped according to the 1981 World Health Organization Lung Cancer Classification. Of 54 evaluated patients, 27 (50%) had "oat cell" subtype, 22 (41%) "intermediate cell" variety, and five (9%) were classified as "combined" type. There was no significant difference in response to therapy or median survival between the subtypes. In addition to the absence of prognostic significance among the subtypes, there were many technical factors affecting accuracy of subtyping, including tissue-crushing artifacts, size of biopsy materials, fixation of tissue samples, and variation of subtypes within the same biopsy. We conclude that subtyping of SCCL should not be construed as a prognostic tool or guideline to therapy. However, the recognition that SCCL may manifest in a variety of histologic patterns, some of which may be misinterpreted as a histology other than SCCL, is probably more important for choice of therapy and prognosis than the individual subtypes.

Carcinoma, Small Cell↗

Basophilic staining in pulmonary alveolar proteinosis. Report of three cases.

Material filling the alveoli in pulmonary alveolar proteinosis has been shown to be eosinophilic by hematoxylin-eosin (HE) staining of lung tissue. No previous evidence has suggested a different result from a frozen section. We noted three cases, in 1972, 1973, and 1982, of basophilic staining of this characteristic alveolar material on unfixed, frozen sections; these cases later showed the usual eosinophilic properties when HE staining was performed at room temperature on formaldehyde solution-fixed, paraffin-embedded sections. These observations are important in that failure to recognize this possibility may initially lead the surgical pathologist away from the correct diagnosis or falsely suggest a problem in stains or staining techniques.

Adult↗

The association of a newly discovered protein, called chondrocalcin, with cartilage calcification.

A newly identified calcium binding protein called chondrocalcin with two subunits of molecular weight approximately 35 000 has been studied in bovine, rat and human cartilage matrix using a monospecific polyclonal antibody. Although it is present in small amounts in non-calcifying cartilage, it occurs in local high concentrations wherever cartilage calcification is observed, namely in the calcifying part of the growth plate and in calcified articular cartilage. Immunoelectron microscopy revealed that it is present in exactly the same discrete sites where mineral is first detected. Thus it may act as a nucleating agent for apatite formation. It is deposited in the same sites where unusual local high concentrations of proteoglycan and link protein are detected by immunoelectron microscopy. Chondrocalcin may bind either directly or indirectly to these molecules. Its occurrence within hypertrophic chondrocytes immediately prior to its extracellular appearance suggests that it is synthesised and released by these cells. Its absence from osteoid during intramembranous calcification indicates a selective involvement in endochondral calcification.

Animals↗

Renal oncocytoma. A clinicopathologic study.

Seven cases of renal oncocytomas are described. Two cases were from recent surgical and autopsy material seen within a period of ten months. Four cases were reclassified as renal oncocytomas from a 20 year review of 63 renal cell carcinomas removed operatively. One case was identified from a nine year review of 31 renal cell carcinomas coded in our autopsy files. All patients were males; mean age was 69 years. The smallest tumor measuring 0.3 X 0.3 X 0.3 cm represents the smallest renal oncocytoma reported. The largest tumor weighed 2350 g. It is the largest renal oncocytoma so far reported in the literature. Two of the cases were found in polycystic kidneys. None of the seven patients presented with symptoms related to the tumors and the subsequent clinical course was benign in all cases. Differential diagnosis from renal cell carcinoma is discussed in terms of light and electron microscopic and radiologic aspects. The previously reported cases in the literature are reviewed.

Adenocarcinoma↗