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Biomedical subjects

S S Leong

Publications and source records attributed to S S Leong.

At least 19 recordsLinked to original sources
PubMed1992

Abdominal visceral peliosis associated with bacillary angiomatosis. Ultrastructural evidence of endothelial destruction by bacilli.

Peliosis involving solid internal organs is a rare entity, and it has been reported in association with chronic debilitating diseases. Bacillary angiomatosis (BA), on the other hand, is a recently identified lesion found virtually only in individuals infected by the human immunodeficiency virus. We describe herein two cases of visceral BA and peliosis in human immunodeficiency virus-infected patients. Based on light and electron microscopic findings, we conclude that (1) BA bacilli present in the hepatic sinusoidal endothelial cells, in a suitable host milieu, may be the causative agents of peliosis hepatis; (2) BA bacilli can be found both intracellularly and extracellularly; and (3) peliosis is also identified in association with BA in abdominal lymph nodes.

Abdomen↗
PubMed1988

Demonstration of Chromogranin A in human neuroendocrine cell lines by immunohistology and immunoassay.

We have used immunohistology and radioimmunoassay procedures to study Chromogranin A (CgA) in human neuroendocrine tumor cell lines, especially small cell lung cancers (SCLC). By immunohistology, CgA could be detected in 11 of 18 classical SCLC cell lines, in a medullary thyroid carcinoma (MTC) cell line, and in only one of 13 variant- or non-SCLC cell lines. By radioimmunoassay, CgA could be detected in the cells and culture media of all of the classical SCLC cell lines tested. Many of the classical SCLC cell lines also produced calcitonin (CT). These studies demonstrate that CgA production is a common feature of SCLC cell lines, especially those with neuroendocrine characteristics.

Calcitonin↗
PubMed1988

Atypical stromal smooth muscle hyperplasia of prostate.

A prostatic lesion was resected but recurred six years later with the same atypical smooth muscle hyperplasia in the stroma and without glandular atypia. Ultrastructural study confirms the smooth muscle origin and its atypicality. Review of previous reports of leiomyosarcoma of the prostate show that the minimum criteria for malignancy are gross evidence of capsular invasion and one to two mitotic figures per ten high-power field. Cellular pleomorphism and cellularity by themselves are insufficient to diagnose sarcoma.

Aged↗
PubMed1987

Preferential inhibition by cytarabine of CFU-GM from patients with chronic granulocytic leukemia.

Granulocyte-macrophage colony-forming (CFU-GM) cells from peripheral blood of normal subjects and patients with chronic granulocytic leukemia (CGL) were cultured in soft agar. Drugs under study were added in a liquid overlay 2 days after initiation of cultures, providing prolonged exposure to these agents thereafter. Dose-dependent inhibition of colony growth was recorded with each of eleven agents examined, and at the higher concentrations tested, colony formation was often completely suppressed. Cytarabine showed selectivity against CFU-GM from patients in the chronic stage of CGL (P = 0.006); the median 50% inhibitory concentration for 12 such patients was 3.4 ng/ml versus 11.8 ng/ml for 15 healthy subjects. Such selectivity was not found with busulfan, hydroxyurea, mercaptopurine, thioguanine, daunorubicin, vincristine, vinblastine, methotrexate, desacetylmethylcolchicine, and trimethylcolchicinic acid. One other group has also reported a preferential effect of cytarabine against colony-forming cells from patients with CGL, and this appears to be the only drug for which such selective activity has been recorded to date.

Cell Division↗
PubMed1987

Acetylcholine and affective disorder.

We reviewed the evidence for involvement of central cholinergic neurons in affective disorder. Cholinomimetics inhibit speech, thought, and activity in most subjects, decrease manic symptoms and, in some affective disorder patients, produce depressive symptoms. Cholinomimetics also cause ACTH and cortisol secretion and decrease latency to REM sleep. It is unclear whether cholinomimetics are specifically "antimanic" or "depressogenic" or whether their fundamental effect is nonspecific behavioral inhibition; whether the observed effects of cholinomimetics are mediated largely through cholinergic pathways, are secondary to changes in other neurotransmitters or are part of a nonspecific stress response. The suggestion that anticholinergic agents have mood elevating properties has not yet been subjected to controlled investigation. Although the proposal that affective disorders involve cholinergic neurons has received some support from clinical investigation further research is required to substantiate the intriguing observations to date and to clarify the physiologic and psychologic processes mediating them.

Acetylcholine↗
PubMed1987

Potential therapeutic effect of adriamycin-monoclonal anti-prostatic acid phosphatase antibody conjugate on human prostate tumor.

Adriamycin was conjugated to an IgG1 monoclonal antibody specific for human prostatic acid phosphatase via a dextran bridge. The adriamycin-monoclonal antibody conjugate retained substantially the original immunological activity of the antibody. Antitumor effect of the conjugate in vitro was studied by its inhibition on RNA synthesis in human prostate tumor cells (LNCaP), which exhibited a higher inhibition than that by an identically prepared adriamycin-normal mouse IgG conjugate but was less than that by free adriamycin. The loss in pharmacological activity of the conjugate in vitro was proportional to the extent of dextran oxidation. Antitumor effect in vivo demonstrated that adriamycin-monoclonal antibody conjugate greatly inhibited the growth of xenografted prostate tumor, as compared with control groups, only in the early phase of experiment. These results suggested that although adriamycin conjugated to monoclonal anti-PAP antibody via a dextran bridge may be a potential reagent for experimental immunochemotherapy of prostate tumor, caution must be exercised at this stage of development.

Acid Phosphatase↗
PubMed1986

The regulation of somatostatin production in human medullary thyroid carcinoma cells by dexamethasone.

There have been few studies of physiological importance on the regulation of somatostatin by hormones. We have studied the effect of the synthetic glucocorticoid dexamethasone on somatostatin production in the human medullary thyroid carcinoma TT cell line, a model for somatostatin production by the parafollicular cell. Dexamethasone inhibited somatostatin production in a dose-related manner with a maximal effect at a concentration of 10(-6) M. TT cells treated with dexamethasone (10(-6) M) showed an almost complete inhibition of somatostatin peptide production by 48 h of treatment. Molecular sizing chromatography demonstrated a decrease in both the probable somatostatin precursor (13,000 dalton) and the fully processed peptide. Analysis of mRNA content by hybridization revealed that dexamethasone also caused a decrease in detectable somatostatin mRNA. The hybridizable somatostatin mRNA decreased to approximately 50% of basal levels within 12 h of treatment. Northern blot hybridization showed a decrease in a single RNA species representing mature somatostatin mRNA. Dose-response experiments revealed inhibition of both peptide and mRNA at concentrations from 1 X 10(-8) to 1 X 10(-5) M dexamethasone. Four days after withdrawal from dexamethasone treatment, peptide and mRNA levels were higher than dexamethasone-treated controls. The sex steroid estradiol had no inhibitory effect on somatostatin production. These results suggest a potential regulator of somatostatin production and provide a system for the study of somatostatin gene regulation.

Cell Line↗
PubMed1986

Somatostatin production by a human medullary thyroid carcinoma cell line.

Somatostatin (SRIF, SRIF-14) is a known product of the normal and malignant parafollicular cell of the thyroid. In this report we characterize SRIF production by the TT cells, a line of transformed calcitonin-producing cells derived from a human medullary thyroid carcinoma. The cells were found to contain (5-12 ng/10(6) cells) and secrete (3-10 ng/10(6) cells X 48 h) immunoreactive SRIF. Molecular sieve chromatography of cell extracts under denaturing conditions showed a major peak with a mol wt slightly larger than 12,700, probably representing pro-SRIF and a second peak which coeluted with SRIF; in one gel chromatogram a very small peak was also noted which coeluted with SRIF-28, but represented less than 0.4% of the total immunoreactive SRIF. Short term secretion of calcitonin and SRIF was stimulated by calcium in vitro (0.5-4 mM) in a dose-related manner. mRNA isolated from the TT cells hybridized to a specific bovine fetal pancreatic SRIF DNA (BFPS-2); there was no hybridization to identical amounts of mRNA from the atT-20/D16, 3T3, or RINC5F cell lines. In vitro translation of the TT cell mRNA followed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the product revealed a single protein band of approximately 13,000 daltons. It was completely abolished when the immunoprecipitation was performed in the presence of excess unlabeled SRIF. Northern transfer of TT cell cytoplasmic RNA and hybridization with FBPS-2 cDNA showed a single hybridizing band with an apparent size of approximately 750 nucleotides. Our observations demonstrate the production of SRIF by a continuous line of human medullary thyroid carcinoma cells and provide a model for studying the biosynthesis and secretion of SRIF in the parafollicular cell.

Animals↗
PubMed1986

Effect of methotrexate-monoclonal anti-prostatic acid phosphatase antibody conjugate on human prostate tumor.

Methotrexate (MTX) was conjugated to an immunoglobulin G1 (IgG1) monoclonal antibody specific for human prostatic acid phosphatase (PAP) by the active ester method. The molar ratio of MTX to IgG was 14. MTX-monoclonal antibody conjugate retained substantially the original PAP-binding inhibition activity of the monoclonal antibody. Both MTX-monoclonal antibody conjugate and an identically prepared MTX-normal mouse IgG conjugate preserved 90% of the original dihydrofolate reductase inhibitory activity of MTX. [3H]MTX conjugated to monoclonal anti-PAP antibody was significantly accumulated more in PAP-producing human prostate tumor LNCaP cells than its normal mouse IgG counterpart. No statistical difference was found between the uptake of [3H]MTX conjugated to monoclonal antibody and that of [3H]MTX conjugated to normal mouse IgG by control PAP nonproducing thyroid tumor cells (TT). The antitumor effect of the conjugate was evaluated in vitro by its inhibition on deoxy[6-3H]uridine incorporation into LNCaP cells. The inhibition by MTX-monoclonal antibody conjugate was significantly higher than that by MTX-normal mouse IgG conjugate at 8 micrograms of drug per ml, although it was significantly less than that by free MTX. However, an in vivo tumor and tissue distribution study of [3H]MTX and its conjugates revealed that, 5 days after i.v. administration, [3H]MTX conjugated to monoclonal antibody was preferentially accumulated in LNCaP prostate tumor. Tumor:blood ratios for [3H]MTX, [3H]MTX-monoclonal antibody conjugate, and [3H]MTX-normal mouse IgG conjugate were 1.47, 5.06, and 1.26, respectively. Preliminary results obtained from a pilot study with a small number of animals demonstrated that multiply injected MTX-monoclonal antibody conjugate retarded the growth of xenografted prostate tumor (LNCaP) as compared with the control groups, including free MTX which showed a shorter period of therapeutic effectiveness. This study suggests that MTX conjugated to monoclonal anti-PAP antibody could be a potential reagent for experimental immunochemotherapy of prostate tumor, should the initial in vivo data be extended and confirmed.

Acid Phosphatase↗
PubMed1985

Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma.

Medullary thyroid carcinoma is a tumor of the calcitonin-secreting thyroid C-cell, with a variable malignant potential. Virulent tumors are characterized by decreased calcitonin production, suggesting the emergence of a less differentiated medullary thyroid carcinoma cell. In order to further delineate relationships between tumor progression and status of differentiation of medullary thyroid carcinoma cells, we have sought to chemically manipulate the TT cell line, an established culture of human medullary thyroid carcinoma, derived from a patient with aggressive disease. We found that the phorbol esters, 12-O-tetradecanoyl phorbol 13-acetate and phorbol 12,13-dibutyrate 1) altered the morphology of the TT cells towards that of high-calcitonin-containing cells; 2) enhanced calcitonin secretion 7-fold; 3) increased calcitonin production at the transcriptional level by 2-fold; 4) inhibited cellular proliferation; and 5) decreased, by 80%, the levels of the c-myc gene mRNA. These data suggest that phorbol esters induce, in human medullary thyroid carcinoma cells in culture, a programmed pattern of events resulting in differentiation of these cells.

Calcitonin↗
PubMed1984

Structure and expression of a gene encoding human calcitonin and calcitonin gene related peptide.

Messenger RNAs for calcitonin (CT) and calcitonin gene related peptide (CGRP) have been detected in a human medullary thyroid carcinoma cell line. DNA sequences of their cloned cDNAs, and genomic restriction mapping, indicate that both mRNAs probably originate from a single gene; the separate mRNAs are derived by alternative processing. The calcitonin gene is expressed in 10 of 10 examined culture lines of human lung cancer; most of these lines express a higher ratio of CGRP to CT specific mRNA than does the medullary thyroid carcinoma cell line.

Base Sequence↗
PubMed1984

Human medullary thyroid carcinoma in culture provides a model relating growth dynamics, endocrine cell differentiation, and tumor progression.

We used an unique model, human medullary thyroid carcinoma (MTC) in culture (the TT line), to study features of neuroendocrine-related biochemistry in relationship to growth, differentiation, and tumor progression. Tumor tissues from patients with virulent MTC contain a very heterogeneous distribution of cells staining for calcitonin (CT) and have a high ratio of intracellular L-dopa decarboxylase activity (DDC) to CT. We found, in a culture line of MTC derived from a patient with virulent disease, that the degree of the inverse relationship between DDC and CT and the heterogeneous cellular distribution of CT probably relate to the rate of cellular growth and the biochemical set of individual cell clones. During exponential growth of the parent TT cell line, intracellular DDC and CT varied. DDC increased by 70% and CT decreased by 40%. Single time-point measurements in 54 cell clones or highly enriched cell populations revealed a more dramatic variability for CT (15-fold) than for DDC (5-fold). During growth of the clones having the highest and lowest CT measurements, respectively, inverse dynamics between DDC and CT were again found. However, each clone maintained a distinct range of CT during the entire growth curve, with a 2- to 4-fold difference in CT between the two clones throughout. In the low producing CT clone, ratios between DDC and CT rose to greater than 1.0 during growth, a very high value found before this study only in MTC tissues from patients with virulent disease. Immunohistochemical staining for CT of parent cells and clones grown on embryonic chick skin revealed increased cellular heterogeneity for CT distribution during growth. The TT line provides a powerful tool to study neuroendocrine related biochemical events in relationship to growth, differentiation, and tumor progression in MTC. Our in vitro findings in the TT line well explain observations made previously in patients. We conclude that: (1) DDC, a neural property of MTC, is an early differentiation marker as compared to CT and that the differentiation status of MTC cells varies inversely with cell growth rate; and (2) in patients with MTC, the virulence of the tumor probably varies inversely with differentiation status. The inverse ratio of DDC to CT is probably determined in MTC by the proportion of rapidly growing cells and numbers of cell clones which have a poor ability for maturation.

Calcitonin↗
PubMed1984

Potentiation of the cell growth inhibitory effect of beta interferon by mopidamole.

It was suggested that the antitumor effect of the interferons is based in part on their ability to stimulate increased cAMP production. We have explored the interaction of human fibroblastic beta interferon (HFIF) with a cAMP decomposition inhibitory pyrimido-pyrimidine derivative, Mopidamole (RA-233) in cultures of neoplastic and normal cell lines. Mopidamole potentiated the growth inhibitory effect of HFIF in cultures of ES-1 malignant melanoma cells, LNCaP prostatic carcinoma cells, RT-4 transitional carcinoma cells, HT-29 colon adenocarcinoma cells and in diploid fibroblast cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Antineoplastic effect of the pyrimido-pyrimidine derivative: RA 233.

A number of normal and neoplastic human cell lines in culture were studied by cell count and 3H thymidine incorporation for growth inhibitory effect by the pyrimido-pyrimidine derivative RA-233 (mopidamole). There was more inhibition when the drug was added to the culture in the lag phase than in the logarithmic growth phase. There was more inhibition (particularly at low doses) of the neoplastic cell lines than of the non-neoplastic cell lines.

Antineoplastic Agents↗
PubMed1983

LNCaP model of human prostatic carcinoma.

The LNCaP cell line was established from a metastatic lesion of human prostatic adenocarcinoma. The LNCaP cells grow readily in vitro (up to 8 x 10(5) cells/sq cm; doubling time, 60 hr), form clones in semisolid media, are highly resistant to human fibroblast interferon, and show an aneuploid (modal number, 76 to 91) human male karyotype with several marker chromosomes. The malignant properties of LNCaP cells are maintained. Athymic nude mice develop tumors at the injection site (volume-doubling time, 86 hr). Functional differentiation is preserved; both cultures and tumor produce acid phosphatase. High-affinity specific androgen receptors are present in the cytosol and nuclear fractions of cells in culture and in tumors. Estrogen receptors are demonstrable in the cytosol. The model is hormonally responsive. In vitro, 5 alpha-dihydrotestosterone modulates cell growth and stimulates acid phosphatase production. In vivo, the frequency of tumor development and the mean time of tumor appearance are significantly different for either sex. Male mice develop tumors earlier and at a greater frequency than do females. Hormonal manipulations show that, regardless of sex, the frequency of tumor development correlates with serum androgen levels. The rate of the tumor growth, however, is independent of the gender of hormonal status of the host.

Adenocarcinoma↗