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Biomedical subjects

A Louie

Publications and source records attributed to A Louie.

At least 55 records · Page 3Linked to original sources
PubMed1991

Differential effects of insulin-like growth factor (IGF)-I and IGF-II on the expression of IGF binding proteins (IGFBPs) in a rat neuroblastoma cell line: isolation and characterization of two forms of IGFBP-4.

The isolation and hormonal regulation of two low molecular weight insulin-like growth factor binding proteins (IGFBPs) present in the conditioned medium (CM) of the rat neuroblastoma cell line B104 cells has been performed. IGFBPs were purified by ZnSO4 precipitation, insulin-like growth factor-I 1IGF-I) affinity chromatography, and reverse phase HPLC. Final isolation and N-terminal analysis was accomplished by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroblotting to polyvinylidene difluoride membranes, and sequencing of the bound proteins. Two IGFBPs, with apparent Mr of 28K and 24K were coisolated and sequenced. Both proteins had identical N-terminal sequences and appear to be two forms of IGFBP-4. Treatment of the IGFBPs with endoglycosidase-F caused a shift in the apparent Mr of the 28K IGFBP to 24K. However, there was no change in the apparent Mr of the 24K IGFBP. The data from this study suggest that the IGFBP-4 exists as both a glycosylated and nonglycosylated protein. Treatment of B104 cells with IGF-I increased the expression of both the 24K and 28K IGFBPs and also resulted in the appearance of IGFBP-3 and an unknown IGFBP at 29K. When added to subconfluent cells, IGF-I was also mitogenic in B104 cells. Similar to IGF-I, IGF-II treatment increased cell number and resulted in the appearance of IGFBP-3 and the 29K IGFBP. However, IGF-II treatment resulted in a significant decrease (approximately 50%) in the 24K IGFBP and also decreased the 28K IGFBP. This decrease in the expression of the 24K and 28K IGFBPs was dose-dependent and was blocked by addition of IGF-I to the cells. When an IGF-II receptor antibody was added to the cells it mimicked the effects of IGF-II on B104 cells, suggesting that the inhibitory effects of IGF-II are mediated through the type II IGF receptor. Although both IGF-I and IGF-II affected the amount of the 24K IGFBP in the CM, neither peptide affected the expression of the messenger RNA for the 24K IGFBP. In conclusion, we have isolated two IGFBPs from the CM of B104 cells. Both the 24K and 28K IGFBPs appear to be isoforms of the same protein, and sequence data suggest these proteins are two forms of IGFBP-4. IGF-I increases the expression of both of these IGFBPs, whereas IGF-II decreases their expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1990

Photolabeling of the alpha-neuraminidase/beta-galactosidase complex from human placenta with a photoreactive neuraminidase inhibitor.

Photolabeling of the alpha-neuraminidase/beta-galactosidase complex in human placenta (Verheijen, F.W. et al (1987) Eur. J. Biochem. 162, 63-67) was carried out using the radioactive photoprobe, 9-S-(4-azido-3,5-3H-2-nitrophenyl)-5-acetamido-2,6 anhydro-2,3,5,9- tetradeoxy-9- thio-D-glycero-D-galacto-non-2-enonic acid. Two intensely labeled bands at 61 and 46 kD were detected with autoradiography. Labeling of the 46 kD protein was blocked with the inclusion of the surfactant Triton X-100 in the photolysis mixture, indicating a nonspecific, hydrophobic interaction. The 61 kD protein was protected from labeling only when the neuraminidase inhibitor 2,3 dehydro N-acetyl neuraminic acid (1 mM) was present during photolysis. These results suggest that the neuraminidase activity resides among the proteins in the 61 kD molecular weight range comigrating with the lysosomal beta-galactosidase, under denaturing conditions.

Affinity Labels↗
PubMed1990

Phase I trial of tallysomycin S10b, a bleomycin analogue.

Bleomycin is an agent with significant antitumor efficacy whose major dose limiting toxicity is pulmonary fibrosis. Attempts have thus been made to identify congeners with reduced toxicity and with comparable or greater antitumor activity. Tallysomycin S10b is a bleomycin analogue possessing significantly greater potency, equal or reduced lung toxicity, and slightly greater antineoplastic activity when compared to the parent compound in preclinical studies. This report describes our experience with tallysomycin S10b in 30 patients with a variety of non-hematologic neoplasms. Pulmonary toxicity, occurring in 4 patients, was the major toxicity. The recommended cumulative dose of tallysomycin S10b was difficult to establish from the results of this study, as pulmonary toxicity appeared to be more idiosyncratic than dose- or schedule-dependent. The employment of more sensitive methods for detecting pulmonary toxicity in this study suggest that tallysomycin S10b may have reduced pulmonary toxicity compared to the parent compound. Both bleomycin and tallysomycin S10b have similar t1/2 beta half-lives of 2-4 h. Six patients had prolonged terminal elimination half-lives of tallysomycin S10b, but no clear relationship between this phenomenon and efficacy or toxicity was evident. No complete or partial responses occurred. Disease stabilization occurred in 4 of 15 patients with diagnoses of renal cell carcinoma, rectal cancer and lung cancer. Five of eight patients with non-measurable disease had stable disease, including one with mesothelioma, one with carcinoma of the head and neck, two with renal cell cancer and one with colon carcinoma.

Adult↗
PubMed1989

A phase II trial of iproplatin (CHIP) in previously treated advanced breast cancer.

Iproplatin (CHIP) was administered to 35 previously treated women with metastatic adenocarcinoma of the breast. The drug was given at a dose of 45 mg/m2 intravenously for 5 consecutive days and was repeated every 28 days. In this trial, there was one partial response and two patients with stable disease out of 29 evaluable patients. The median duration of response in patients with either a partial response or stable disease was 4.8 months. Myelosuppression was the major toxicity, 11 patients had severe thrombocytopenia and 3 severe neutropenia. Mild renal insufficiency, anemia, and nausea and vomiting were also noted. Iproplatin has limited activity in heavily pretreated women with advanced breast carcinoma; further studies in patients less heavily treated may show an improved response rate.

Adenocarcinoma↗
PubMed1989

Phase II study of iproplatin (CHIP) in previously treated small-cell lung cancer.

Eighteen patients with previously treated extensive small-cell carcinoma of the lung were entered into a Phase II study employing iproplatin (CHIP), a cis-platin analog. Patients had received a mean of two prior chemotherapeutic regimens. Fifty-five percent had received prior cis-platinum and 33% had received prior radiation therapy. CHIP (225 mg/m2) was administered by intermittent intravenous infusion over 30 min for 5 days of a 28-day cycle without prehydration. Sixteen patients with Zubrod performance scores of less than or equal to 3 received 27 courses of therapy (mean 1.7, range 1-6). One partial response of 167 days duration was observed, with complete regression of involved lymph nodes and stabilization of nonevaluable disease in the chest. Six patients had stable disease following one cycle of CHIP, but all progressed following a second cycle of drug. The main toxicity was myelosuppression with prominent thrombocytopenia. Median survival was 75 days from initiation of therapy. In this group of heavily pretreated patients with advanced disease, iproplatin has only minimal activity as a single agent and does not show non-cross-resistance with cis-platinum.

Aged↗
PubMed1989

Organization of genes encoding the L11, L1, L10, and L12 equivalent ribosomal proteins in eubacteria, archaebacteria, and eucaryotes.

Archaebacterial and eucaryotic cytoplasmic ribosomes contain proteins equivalent to the L11, L1, L10, and L12 proteins of the eubacterium Escherichia coli. In E. coli the genes encoding these ribosomal proteins are clustered, cotranscribed, and autogenously regulated at the level of mRNA translation. Genomic restriction fragments encoding the L11e, L1e, L10e, and L12e (equivalent) proteins from two divergent archaebacteria. Halobacterium cutirubrum and Sulfolobus solfataricus, and the L10e and L12e proteins from the eucaryote Saccharomyces cerevisiae have been cloned, sequenced, and analyzed. In the archaebacteria, as in eubacteria, the four genes are clustered and the L11e, L1e, L10e, and L12e order is maintained. The transcription pattern of the H. cutirubrum cluster is different from the E. coli pattern and the flanking genes on either side of the tetragenic clusters in E. coli, H. cutirubrum, and Sulfolobus solfataricus are all unrelated to each other. In the eucaryote Saccharomyces cerevisiae there is a single L10e gene and four separate L12e genes that are designated L12eIA, L12eIB, L12eIIA, and L12eIIB. These five genes are not closely linked and each is transcribed as a monocistronic mRNA; the L10e, L12eIA, L12eIB, and the L12eIIA genes are contiguous and uninterrupted, whereas the L12eIIB gene is interrupted by a 301 nucleotide long intron located between codons 38 and 39.

Amino Acid Sequence↗
PubMed1988

Phase I--preliminary phase II trial of iproplatin, a cisplatin analogue.

Iproplatin was administered intravenously over 30 min daily for 5 consecutive days every 3 weeks to 80 evaluable patients with a variety of refractory solid tumor malignancies. Thrombocytopenia was the dose-limiting toxicity. Reversible drug-induced renal dysfunction was observed in 3 patients. One patient sustained mild ototoxicity but neurotoxicity was not encountered. Transient neutropenia, anemia, nausea, vomiting, diarrhea, elevations of liver enzymes, alopecia, and skin rash also occurred. The spectrum and severity of toxicity of iproplatin were found to differ from those of cisplatin. The maximally tolerated dose (MTD) was 45 mg/m2/day in patients who received prior chemotherapy and 65 mg/m2/day in those who did not. No complete responses occurred. Partial responses were obtained in 2/15 patients with colon cancer, 3/18 with breast cancer, 2/4 with carcinoma of unknown primary site and 1/2 with pancreatic cancer. Thirteen patients with lung (5), breast (4), colon (2), head and neck (1) and cervical (1) cancers had stable disease. Based on the different toxicity profiles between iproplatin and cisplatin and the possible antitumor efficacy of the former, phase II investigation of iproplatin has been initiated.

Adult↗
PubMed1988

Phase II trial of iproplatin (CHIP) in previously untreated patients with colorectal cancer.

Nineteen previously untreated patients with colorectal cancer and measurable disease were treated with iproplatin (CHIP), 75 mg/m2 daily, for 5 days every 4 weeks for at least 2 courses. Toxicities included myelosuppression, mild nausea and vomiting, and rare mild nephrotoxicity. The dose-limiting toxicity was thrombocytopenia, which appeared to be cumulative. Dose reduction was frequently necessary. There were no toxic deaths. One partial response was observed, and four patients had stable disease for a median of 2 months. Iproplatin does not appear to have significant activity against colorectal cancer.

Adenocarcinoma↗
PubMed1988

Immunohistochemical, electron microscopic and in situ hybridization evidence for the involvement of lymphatics in the spread of HIV-1.

To investigate the role of the lymphatic vessels and the sinus systems of the lymph node in the spread of HIV-1, we evaluated 15 lymph nodes from patients with persistent generalized lymphadenopathy (PGL). Fifteen lymph nodes taken from patients with follicular hyperplasia not related to HIV-1 infection served as controls. Immunohistochemical and in situ hybridization techniques revealed infected cells within the sinuses and the efferent lymphatics of the PGL lymph nodes. In contrast, infected cells could not be detected within the walls of the high endothelial venules nor in the areas immediately adjacent. The parenchymal side of the marginal sinus was lined by a discontinuous endothelium. Macrophages and lymphocytes were located within the gaps of this endothelium. More importantly, when the enlarged follicle extended as far as the wall of the marginal sinus, the processes of follicular dendritic cells could be seen extending through the gaps into the lumen of the sinus. This suggests that these cells could transport antigens (including HIV-1) from the sinuses directly to the germinal centers. In addition, HIV-1 particles within cytoplasmic vacuoles were seen in infected macrophages located in the submarginal zone. Positive cells were also found in the extrafollicular lymphoid parenchyma, especially in the area between the marginal sinus and the follicles. The observed distribution of the virus-positive cells within the PGL lymph nodes strongly implicates the lymphatic vessels in the spread of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Kinetic studies of Escherichia coli elongation factor Tu-guanosine 5'-triphosphate-aminoacyl-tRNA complexes.

A new method for measuring the dissociation rate of the Escherichia coli elongation factor Tu-GTP--aminoacyl-tRNA complex has been developed and applied to the determination of the dissociation rates of ternary complexes formed between E. coli EF-Tu-GTP and a set of E. coli aminoacyl-tRNAs. The set of aminoacyl-tRNAs includes at least one tRNA coding for each of the 20 amino acids as well as purified isoacceptor tRNA species for arginine, glycine, leucine, lysine, and tyrosine. The results reveal that the dissociation rates vary for each ternary complex. Tu-GTP-Gln-tRNA dissociates the slowest and Tu-GTP-Val-tRNA the fastest of all noninitiator ternary complexes at 4 degrees C, pH 7.4. The equilibrium dissociation constant for Tu-GTP-Thr-tRNA has been determined to be 1.3 (0.4) X 10(-9) M under identical reaction conditions, and the absolute value of the equilibrium dissociation constant has been calculated for 28 ternary complexes from the relative equilibrium dissociation constant ratios previously measured [Louie, A., Ribeiro, N. S., Reid, B. R., & Jurnak, F. (1984) J. Biol. Chem. 259, 5010-5016]. The association rate of each ternary complex has been estimated from the ratio of the dissociation rate relative to the equilibrium dissociation constant. Tu-GTP-His-tRNA associates the fastest and Tu-GTP-Leu-tRNA1Leu the slowest. By inclusion of Tu-GTP-Met-tRNAfMet in the studies, evidence has been obtained that suggests that the initiator ternary complex does not function in the elongation cycle because the dissociation rate of the complex is very fast.

Amino Acids↗
PubMed1985

Human interferon alpha in malignant lymphoma and Hodgkin's disease. Results of the American Cancer Society trial.

Forty-nine patients with non-Hodgkin's lymphoma or Hodgkin's disease were entered into a multi-institutional phase II trial to evaluate the antitumor activity of human interferon alpha, prepared from buffy coats. Interferon alpha was administered intramuscularly in doses of 1 X 10(6) u, 3 X 10(6) u or 9 X 10(6) u daily for 30 days. Objective partial responses were seen in 3 of 18 patients with nodular lymphoma, all at the 9 X 10(6) u dose. Interferon alpha was not observed to be of therapeutic benefit in the other subtypes of non-Hodgkin's lymphoma or Hodgkin's disease. The major toxicities consisted of fatigue, fever, myalgias and weight loss. Serum interferon levels obtained 3 to 4 hours after injection varied widely, even among patients treated at the same dose level. Despite the relatively low doses of interferon used and the brief period of administration, this study extends the earlier observations of the antitumor effect of interferon in nodular lymphoma. These results are discussed in relation to the cumulative experience in human lymphoma using alpha interferons induced in human leukocytes and those produced in bacteria by recombinant DNA techniques.

Adolescent↗
PubMed1985

Effect of trypsin modification of the Escherichia coli elongation factor Tu on the ternary complex with aminoacyl-tRNA.

The ribonuclease resistance assay has been used to probe the effect of trypsin modification of the Escherichia coli elongation factor Tu X GTP on the interaction with E. coli aminoacyl-tRNAs. First, the equilibrium dissociation constant of the trypsin-modified Tu X GTP X Thr-tRNA complex was determined to be 2.3 (0.1) X 10(-5)M at 4 degrees C, pH 7.4. Second, binding of 17 of 20 noninitiator aminoacyl-tRNAs and four sets of purified isoacceptor tRNAs to the modified protein was measured. At 4 degrees C, the complex stabilities vary 500-fold over the range of aminoacyl-tRNAs, with Gln-tRNA forming the strongest ternary complex and Val-tRNA, the weakest. The results are compared to a similar study of ternary complex formation using intact elongation factor Tu X GTP, and the major differences are discussed. An analysis of both data sets, particularly that for the leucine isoacceptor tRNAs, suggests that the trypsin modification of elongation factor Tu X GTP disrupts a region of protein that is involved with the aminoacyl side chain rather than that of the acceptor stem helix region of the aminoacyl-tRNA.

Amino Acid Sequence↗
PubMed1984

Relative affinities of all Escherichia coli aminoacyl-tRNAs for elongation factor Tu-GTP.

The relative affinities of all Escherichia coli amino-acyl-tRNAs for E. coli elongation factor (EF) Tu-GTP have been measured by two independent applications of the competition form of the ribonuclease resistance assay. The set of aminoacyl-tRNAs includes at least one tRNA for each of the 20 amino acids as well as purified isoacceptor tRNA species for arginine, glycine, leucine, lysine, and tyrosine. In the first competition study, [3H]Phe-tRNA was used as the competing aminoacyl-tRNA against [14C]aminoacyl-tRNA in the set of all tRNAs; in the second study, [3H]Leu-tRNALeu4 was used as the competing aminoacyl-tRNA. The relative order of aminoacyl-tRNA affinities for EF-Tu-GTP was the same in each study. The results indicate that the affinity of EF-Tu-GTP at 4 degrees C, pH 7.4, is strongest for Gln-tRNA and weakest for Val-tRNA. Both Gly-tRNA and Pro-tRNA bind very strongly to EF-Tu-GTP relative to other aminoacyl-tRNAs. Various models of ternary complex interactions are discussed in light of the new data. Although the properties of the amino acid substituent are primarily responsible for the differences in relative affinities among the noninitiator aminoacyl-tRNAs, the results for the four isoacceptor species of Leu-tRNALeu indicate that the secondary structural features of the tRNA are also influential.

Escherichia coli↗
PubMed1984

Affinity purification of aminoacyl-tRNA.

A procedure for separating Escherichia coli aminoacyl-tRNA from unacylated tRNA or components of the aminoacylation reaction, thereby achieving an aminoacyl-tRNA product with a very high specific activity, is described. The method utilizes the specific recognition of aminoacyl-tRNA for E. coli protein synthesis elongation factor Tu which has been immobilized on an affinity matrix. The application of the affinity procedure as a means of purifying a single aminoacyl-tRNA from an unfractionated mixture of tRNAs is also discussed.

Chemical Phenomena↗
PubMed1982

Metastases in malignant melanoma.

A study has been made of 76 cases of metastatic melanoma presenting over a ten year period. Of this group, 64.5 per cent developed clinical metastases within 12 months of presentation with the primary disease while 80 per cent had developed metastases by three years. Fifty per cent of our patients had ulcerated lesions, and most patients had thick lesions on histological examination. The site of the first metastasis occurred in the regional lymph nodes in 65 per cent and in viscera in 22 per cent. Subsequent clinical metastases were widespread and their distribution is recorded. Of those patients with nodal involvement, 75 per cent had only one node involved in histological examination. Only 14 of the 76 patients are alive and of these nine are alive without disease. The surviving patients had regional node, intransit or local metastases present. Disease beyond these areas was fatal. We have recorded the therapeutic modalities used without attempting to study them objectively.

Adolescent↗