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Biomedical subjects

C L Lee

Publications and source records attributed to C L Lee.

At least 181 records · Page 10Linked to original sources
PubMed1989

Human prostatic acid phosphatase: cDNA cloning, gene mapping and protein sequence homology with lysosomal acid phosphatase.

The cDNAs encoding human prostatic acid phosphatase were cloned and characterized. The mRNAs contain 3' noncoding regions of heterogeneous sizes 646, 1887 or 1913 nucleotides. A dimer and a monomer of the conserved Alu-repeats are present in the longer 3' noncoding sequences. The complete sequence of 354 amino acids for the mature enzyme was determined by sequencing both cDNA and protein. Human prostatic and lysosomal acid phosphatases exhibit 50% sequence homology, including five Cys residues and two putative N-linked glycosylation sites. The Acp-3 gene coding for human prostatic acid phosphatase was mapped onto chromosome 3 in this investigation. The Acp-2 gene coding for lysosomal acid phosphatase has previously been located on chromosome 11, while the Acp-1 gene coding for red blood cell acid phosphatase is on chromosome 2.

Acid Phosphatase↗
PubMed1989

Operant conditioning of primate triceps surae H-reflex produces reflex asymmetry.

Monkeys are able to increase or decrease triceps surae H-reflex when reward depends on reflex amplitude. Operantly conditioned change occurs over weeks and produces persistent alterations in the lumbosacral spinal cord which should be technically accessible substrates of primate memory. Previous work monitored and conditioned triceps surae H-reflex in one leg. To determine whether H-reflex conditioning in one leg affects the control leg, the present study monitored H-reflexes in both legs while the reflex in one leg underwent HR increases or HR decreases conditioning. Under the HR increases mode, H-reflex increase was much greater in the HR increases leg than in the control leg. Under the HR decreases mode, H-reflex decrease was confined to the HR decreases leg. By showing that conditioning of one leg's H-reflex produces H-reflex asymmetry, the data further define the phenomenon and indicate that the other leg can serve as an internal control for physiologic and anatomic studies exploring the sites and mechanisms of the spinal cord memory substrates.

Animals↗
PubMed1989

Pleural effusion coinciding with acute exacerbations in a patient with chronic hepatitis B.

A 28-yr-old man had pleural effusions coinciding with two separate episodes of acute exacerbation of chronic type B hepatitis. In both episodes, the pleural effusion was exudative with lymphocyte predominance, and there was no ascites. Hypocomplementemia was evident in the second episode when the complement level was determined, but immune complexes were not detected in the serum. The hepatitis itself was thought to be directly responsible for the pleural effusions because of meticulous exclusion of other causes and the fact that, without specific treatment, the effusions resolved completely as the hepatitis subsided.

Adult↗
PubMed1989

Memory traces in primate spinal cord produced by operant conditioning of H-reflex.

1. Study of memory traces in higher animals requires experimental models possessing well-localized and technically accessible memory traces--plasticity responsible for behavioral change, not dependent on control from elsewhere, and open to detailed investigation. Our purpose has been to develop such a model based on the wholly spinal, largely monosynaptic path of the spinal stretch reflex. Previous studies described operant conditioning of this reflex and of its electrical analog, the H-reflex. In this study, we sought to determine whether conditioning causes changes in the spinal cord that affect the reflex and are not dependent on continued supraspinal influence, and thus qualify as memory traces. 2. Sixteen monkeys underwent chronic conditioning of the triceps surae H-reflex. Eight were rewarded for increasing H-reflex amplitude (HR increases mode), and eight were rewarded for decreasing it (HR decreases mode). In each animal, the other leg was an internal control. Over several months of conditioning, H-reflex amplitude in the conditioned leg rose in HR increases animals and fell in HR decreases animals. H-reflex amplitude in the control leg changed little. 3. After HR increases or HR decreases conditioning, each animal was deeply anesthetized and surgically prepared. The reflex response to supramaximal dorsal root stimulation was measured from the triceps surae nerve as percent of response to supramaximal ventral root stimulation, which was the maximum possible response. Data from both legs were collected before and for up to 3 days after thoracic (T9-10) cord transection. The animal remained deeply anesthetized throughout and was killed by overdose. 4. The reflex asymmetries produced by conditioning were still present several days after transection removed supraspinal influence: reflexes of HR increases animals were significantly larger in HR increases legs than in control legs and reflexes of HR decreases animals were significantly smaller in HR decreases legs than in control legs. 5. Reflex amplitude was much greater in the control legs of anesthetized HR decreases animals than in the control legs of anesthetized HR increases animals. 6. Chronic conditioning had at least two effects on the spinal cord. The first effect, task-appropriate reflex asymmetry, was evident both in the awake behaving animal and in the anesthetized transected animal. The second effect, larger control leg reflexes in HR decreases than in HR increases animals, was evident only in the anesthetized animal. By removing supraspinal control, anesthesia and transection revealed a previously hidden effect of conditioning.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

The emergence and establishment of a clonal subline with partial duplication of chromosome 1q from a tumorigenic human chronic lymphocytic leukemic B-cell line.

Sequential analysis was performed on a tumorigenic human B-cell chronic lymphocytic leukemia cell line in which the initial population consisted of two abnormal clones, one with trisomy 12 (47%), the other with duplication of 1q; that is, 46,XY,dup(1)(q11----q32) (10%), and rest of the population had a normal karyotype. The clone with 1q+ marker expanded steadily and after 11 weeks became the only proliferating cell population in vitro and remained so till the end of an observation period of 75 weeks. All tumors recovered from nude mice that were inoculated with this newly established subline had retained the 1q+ marker. All the secondary clones also carried this aberration.

Animals↗
PubMed1988

Retrograde transport of the lectin Phaseolus vulgaris leucoagglutinin (PHA-L) by rat spinal motoneurons.

The lectin Phaseolus vulgaris leucoagglutinin (PHA-L) has been used primarily as an anterograde transport tracer in the CNS. We present evidence of PHA-L retrograde transport by rat spinal motoneurons after injection into the triceps brachii. Labelled motoneurons were localized in specific and well-defined neuron pools in the ventral horn. Primary afferent labelling was not seen in the spinal gray matter. Dorsal rhizotomy did not eliminate or decrease motoneuron labelling. The retrograde transport rate was about 8 mm/day. PHA-L can clearly undergo retrograde, as well as anterograde, transport.

Animals↗
PubMed1988

Progression of a human B cell chronic lymphocytic leukemia line in nude mice.

Subcutaneous (s.c.) inoculation of the 85-4LN subline, derived from a lymph nodal metastasis of the Epstein-Barr virus (EBV) transformed human chronic lymphocytic leukemia (CLL) B cell line, EBV-CLL (1), produced progressively growing lethal tumors in 31/35 nonirradiated (88.6%) and 22/25 (88%) of whole-body irradiated (440 rad) nude mice. In contrast, EBV-CLL(1) could produce progressive tumors only in irradiated nude mice. All 85-4LN cells had Epstein-Barr virus nuclear antigen and reacted with pan B and anti-la antibodies. The morphology and ultrastructural features was consistent with the lymphoblastoid nature of the cells. In all s.c. tumor bearing mice, there was enlargement of the spleen and draining lymph nodes. Karyological studies revealed human cells in the spleen and draining nodes in all the mice investigated. Metastases in nonlymphoid organs were seen in 1/8 irradiated and 8/12 nonirradiated mice. The subline contained 77% cells with 47,XY, +12 and 23% cells with 45,XY karyotype. The clone with trisomy 12 did not have any growth advantage either in s.c. transplants or in splenic/lymph nodal metastases. Treatment with the maximum permissible doses of methotrexate (MTX) or chlorambucil (CBL) revealed xenografts to be more sensitive to MTX than CBL. A clone with a 1g+ marker, i.e., 46,XY,Dup(1) (q11----q32) appeared to be associated with resistance to CBL. We have not seen any previous report on the growth and dissemination of human CLL B cells in nonirradiated nude mice. The 85-4LN subline, thus, provides a model for studying the progression, dissemination and therapeutic response of human CLL-B cells.

Animals↗
PubMed1988

Organ preference of metastasis. The role of organ-specifically modulated endothelial cells.

Many cancers display characteristic organ colonization patterns that do not fit simple, anatomical-mechanical trapping theories of tumor cell dissemination. Organ preferences of metastatic spread appear to be mediated partly by the selective attachment of tumor cells to organ-specific, microvascular endothelium. To study these tumor cell-endothelial cell interactions in an efficient and reproducible manner, we have designed a novel in vitro assay system wherein endothelial cells isolated from large vessels (e.g., aorta) can be modulated to assume phenotypic traits of organ-specific, microvascular endothelium. Modulation is achieved by growing bovine aortic endothelial cells (BAEC) on organ-specific matrix components, termed tumor attachment modulators (TAMs). Using monolayers of modulated BAEC in a tumor attachment assay, we show here that tumor cells which metastasize to a given organ, have a significantly higher binding affinity for BAEC grown on TAMs of the preferred, metastasized organ, than they have for BAEC grown on TAMs of any other organ not colonized by these tumor cells. Lung-metastatic tumor cells (R3230AC-MET, B16-F10) adhere preferentially to BAEC monolayers grown on lung-specific TAMs, whereas liver-metastatic tumor cells (RAW117-H10, M5076) selectively adhere to BAEC grown on liver-specific TAMs. In contrast, nonmetastatic tumors cells (R3230AC-LR, RBTCC-1, 647V) show no such adhesion preferences. Preferential tumor cell adherence is increased by growing BAEC for prolonged periods on organ-specific TAMs. Metastatic preference and organ distribution are mediated, at least in part, by urea-extractable endothelial cell surface components that are regulated by the extracellular matrix.

Adenocarcinoma↗
PubMed1987

Motoneuron response to dorsal root stimulation in anesthetized monkeys after spinal cord transection.

In preparation for studying the spinal cord alterations produced by operant conditioning of spinal reflexes, we studied peripheral nerve responses to supramaximal dorsal root stimulation in the lumbosacral cord of deeply anesthetized monkeys before and after thoracic cord transection. Except for variable depression in the first few minutes, reflex responses were not reduced or otherwise significantly affected by transection in the hour immediately following the lesion or for at least 50 h. The results suggest that reduction in muscle spindle sensitivity and/or in polysynaptic motoneuron excitation contributes to stretch reflex depression after cord transection.

Anesthesia↗
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↗
PubMed1987

[A simple latex slide text for detection of cholera toxin].

A latex agglutination inhibition test was developed for detection of cholera toxin. Cell-free extract was at first neutralized with anti-cholera toxin, then the latex particles having coupled covalently with cholera toxin were added to detect the presence of cholera toxin. The test was performed on glass slide. Using this method, the concentration of cholera toxin as low as 1.25 micrograms/ml can be detected within 2 minutes at room temperature. Procedure for covalent conjugation of cholera toxin to polystyrene latex particles was simple and the conjugation preparations were stable at 4 degrees C for at least 6 months.

Cholera Toxin↗
PubMed1986

Central projections of identified, unmyelinated (C) afferent fibers innervating mammalian skin.

Unmyelinated (C) fibers are the most numerous sensory elements of mammalian peripheral nerve and comprise many of those responsible for initiating pain and temperature reactions; however, direct evidence has been lacking as to where and how these fibers terminate in the central nervous system. A plant lectin (Phaseolus vulgaris leukoagglutinin) was applied intracellularly by iontophoresis as an immunocytochemical marker. This permitted visualization of the central terminations of cutaneous C sensory fibers that had been identified by the nature of stimuli that excited them. The central branch of C-fiber units arborized and terminated mainly in the superficial layers of the spinal dorsal horn in defined patterns that related to their functional attributes. Thus, the superficial dorsal horn seems to act as a processing station for signals from fine sensory fibers.

Animals↗
PubMed1986

Balloon dilatation pulmonary valvuloplasty in pulmonary stenosis.

Balloon valvuloplasty was used to treat congenital pulmonary valve stenosis in 13 patients, 11 with isolated pulmonary stenosis, one associated with complex univentricular heart and tricuspid atresia, and one associated with tetralogy of Fallot. A balloon catheter was introduced through the pulmonary valve over a guidewire positioned in the distal pulmonary artery and inflated for 15 seconds on two or three occasions to 3 to 5 atmospheres and rapidly deflated. Marked improvement in pressure gradients was achieved in eight of the 11 patients with isolated pulmonary valve stenosis and symptoms disappeared in the only patient in this group who was symptomatic. The two patients with complex congenital malformations improved clinically. The procedure was without complication and satisfactory results have been maintained from two to twelve months later. The procedure offers effective treatment. We believe that pulmonary balloon valvuloplasty should be the initial treatment for isolated severe and moderate pulmonary valve stenosis.

Catheterization↗
PubMed1986

Tyrosyl kinase activity is inversely related to prostatic acid phosphatase activity in two human prostate carcinoma cell lines.

Alterations in prostatic acid phosphatase (PAcP), a phosphotyrosyl phosphatase, corresponded to changes in overall tyrosyl kinase activity. PAcP added to extracts of prostate carcinoma cells with a low endogenous level of PAcP activity and elevated tyrosyl kinase activity decreased the tyrosyl kinase activity. On the other hand, when PAcP activity was decreased by the addition of androgens to cells, there was a corresponding increase in tyrosyl kinase activity.

Acid Phosphatase↗
PubMed1986

Growth and spread in nude mice of Epstein-Barr virus transformed B-cells from a chronic lymphocytic leukemia patient.

Subcutaneous inoculation of Epstein-Barr virus (EBV) transformed peripheral blood B-lymphocytes (PBL) from an untreated chronic lymphocytic leukemia (CLL) patient produced progressively growing lethal tumors in 4 of 11 whole body irradiated (440 rads) nude mice. In one tumor bearing mouse there was splenomegaly and generalized enlargement of lymph nodes. Chromosomal analysis and membrane immunofluorescence revealed that cells in all the 4 s.c. tumors and a proportion of cells in the enlarged spleen and lymph nodes had human chromosomes and contained human kappa or lambda chains demonstrating that these were polyclonal human B-cells. Epstein-Barr virus associated nuclear antigen could be detected in 100% of cells in all the 4 EBV transformed B-cell lines in vitro and aliquots of cells from several s.c. tumors and metastatic lesions examined. Successful serial transplantation into irradiated nude mice was possible for at least 3 generations with one of the 4 s.c. tumors. During serial transplantation, spread of tumor cells to the spleen and lymph nodes could be detected in all the 3 passage mice investigated; however, there was no evidence in any mouse of dissemination of tumor cells into the bloodstream or into any organ other than lymph nodes and spleen. s.c. tumors also developed in a proportion of irradiated nude mice after inoculation of cells from two other s.c. tumors and the metastatic spleen and lymph nodes, but all these tumors regressed during the first or second transplant passage. Two % of PBL from the untreated patient and 4% of EBV transformed PBL maintained in vitro were found to have trisomy of chromosome 12 which is the most frequently reported anomaly associated with human CLL B-cells. It is highly probable that the cells with trisomy were derived from the leukemic clone of this patient. Cells with this trisomy predominated in most metastatic sites compared to the parent s.c. tumors. Inoculation of irradiated nude mice with EBV transformed PBL from this patient after chlorambucil therapy (100% metaphase plates with 46,XY,11q+ karyotype) or with EBV transformed PBL from 2 normal adults failed to produce any progressively growing tumor in a total of 12 irradiated animals observed greater than 300 days. Although there are several reports of EBV induced immortalization of CLL B-cells in vitro, we have not seen any previous report on the successful serial transplantation and dissemination of EBV transformed CLL B-cells in nude mice.

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↗