Search PubMed⌕ Search

Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 757 records · Page 42Linked to original sources
PubMed1988

Phase I trial of the amsacrine analogue 9-[( 2-methoxy-4-[(methylsulfonyl)amino]-phenyl]amino)-N,5-dimethyl-4- acridinecarboxamide (CI-921).

CI-921, an analogue of amsacrine with superior activity against in vivo and in vitro experimental tumor models, has been studied in 16 patients with solid tumors refractory to chemotherapy or for which conventional therapy does not exist. Thirty-nine cycles were given and doses escalated from 39 to 810 mg/m2. This total dose was divided over 3 consecutive days and administered by 15-min infusion each day, repeated three times weekly. Neutropenia (Eastern Cooperative Oncology Group) Grade greater than or equal to 3 occurred at Day 8 (range, 7-13) in 10/13 courses at 648 mg/m2 and in 2/2 courses at 810 mg/m2 with recovery in 10 (range, 4-20) days. At 810 mg/m2 Grade 2 mucositis and phlebitis were noted. Mild nausea and venous irritation occurred in some patients at doses greater than or equal to 288 mg/m2. No objective response was seen. Pharmacokinetics were evaluated following 65 infusions on Days 1 and 3 with plasma concentrations of CI-921 measured by high performance liquid chromatography. Peak plasma concentrations ranged from 3.36 to 85.6 mumol/liter and were significantly correlated with dose. Mean (range) model-independent pharmacokinetic parameters were: distribution half-life, 0.46 h (0.24-1.08); elimination half-life, 2.63 h (1.08-4.98); mean residence time, 2.0 h (1.05-3.35); plasma clearance, 158 ml/h/kg (95-290); and steady-state volume of distribution, 319 ml/kg (219-614) with no significant difference between Day 1 and 3. Toxicity as defined by absolute granulocyte count nadir was significantly correlated with dose, area under concentration-time curve, and peak plasma concentration. The recommended dose for Phase II studies in this schedule is 648 mg/m2 (216 mg/m2 daily for 3 days) repeated every three weeks.

Adult↗
PubMed1988

The mighty MMR.

Explore the source record for details and available documents.

Child, Preschool↗
PubMed1988

Murine epidermal growth factor: structure and function.

Murine epidermal growth factor (EGF), a 53 amino acid protein, has been modified by enzymic digestion, site-specific chemical reactions, and recombinant DNA technology. After trypsin digestion the EGF derivatives EGF1-48 (called EGF-T) and EGF1-45 (called EGF-T2) were separated from the residual EGF and the C-terminal pentapeptide by reversed-phase high-performance liquid chromatography. EGF-T competes for binding to EGF receptors with the same efficiency as EGF. The EGF-T2 derivative had no detectable receptor binding activity even at 100 nM. The in vitro mitogenic potencies of EGF and EGF-T for Balb/c 3T3 cells were indistinguishable. Treatment of EGF-T with carboxypeptidase Y yielded two derivatives, EGF-T-(des-Arg48) and EGF-T-des(Leu47-Arg48). There was only a 3-7-fold diminution in the binding efficiency and mitogenic potency for EGF-T-(des-Arg48). However, there was more than a 100-fold decrease in the binding efficiency and mitogenic activity of EGF-T-des (Leu47-Arg48). These results indicated that Leu47 is intimately involved in the formation of the ligand-receptor complex. Studies with a number of proteases indicated that the C-terminus of EGF was susceptible to enzymic digestion; however, the N-terminus appears to be folded into a conformation which prevents access to proteolytic digestion. Consequently, the N-terminus was modified by preparing an analogue with recombinant DNA technology. Oligonucleotides corresponding to EGF(3-48). Met3 Lys21 residues were ligated in frame to a beta-galactosidase expression vector. The beta-Gal-EGF fusion protein was cleaved with cyanogen bromide and EGF(4-48).Lys21 purified.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1988

Experimental transmission of bovine leukosis virus by simulated rectal palpation.

Eight six-month-old Holstein male calves were experimentally inoculated by rectal palpation with whole blood from a donor seropositive to bovine leukosis virus. The inoculation consisted of the deposition of 2 ml of whole blood on a disposable obstetrical sleeve followed by a 30 second rectal palpation to simulate the process of pregnancy detection or artificial insemination. This procedure was repeated at weekly intervals for three consecutive weeks. All eight calves developed antibodies to bovine leukosis virus within five weeks after the initial palpation. The presence of the virus was demonstrated in the peripheral blood leucocytes of all eight calves at nine weeks. These results indicated that routine rectal palpation may be an effective mode of spread of bovine leukosis virus in susceptible cattle.

Animals↗
PubMed1988

Molecular cloning and sequencing of a cDNA encoding the thioesterase domain of the rat fatty acid synthetase.

A cloned cDNA containing the entire coding sequence for the long-chain S-acyl fatty acid synthetase thioester hydrolase (thioesterase I) component as well as the 3'-noncoding region of the fatty acid synthetase has been isolated using an expression vector and domain-specific antibodies. The coding region was assigned to the thioesterase I domain by identification of sequences coding for characterized peptide fragments, amino-terminal analysis of the isolated thioesterase I domain and the presence of the serine esterase active-site sequence motif. The thioesterase I domain is 306 amino acids long with a calculated molecular mass of 33,476 daltons; its DNA is flanked at the 5'-end by a region coding for the acyl carrier protein domain and at the 3'-end by a 1,537-base pairs-long noncoding sequence with a poly(A) tail. The thioesterase I domain exhibits a low, albeit discernible, homology with the discrete medium-chain S-acyl fatty acid synthetase thioester hydrolases (thioesterase II) from rat mammary gland and duck uropygial gland, suggesting a distant but common evolutionary ancestry for these proteins.

Amino Acid Sequence↗
PubMed1988

Role of IIb-IIIa-like glycoproteins in cell-substratum adhesion of human melanoma cells.

The platelet fibrinogen receptor, glycoprotein complex IIb-IIIa, was isolated from human platelets by lectin and monoclonal antibody affinity chromatography and a polyclonal antiserum (anti-IIb-IIIa) was generated and used to probe for the presence and function of IIb-IIIa-like molecules in two adherent human cell lines. Both C32 melanoma cells and WI38 fibroblasts expressed a IIb-IIIa-like complex on their surface as indicated by immunoprecipitation of detergent extracts of surface radiolabeled cells. When added to cells plated in medium containing 10% serum, the anti-IIb-IIIa antiserum perturbed the adhesion of C32 melanoma cells, but not of WI38 fibroblasts. In a serum-free system, anti-IIb-IIIa antibodies inhibited attachment and spreading of C32 cells to fibrinogen, vitronectin, and fibronectin adsorbed to glass. Anti-IIb-IIIa had no effect on the attachment and spreading of WI38 cells to the extracellular matrix proteins, however. Thus, the IIb-IIIa-like complex appears to play a predominant role in cell-substratum adhesion of C32 cells, but not WI38 cells, and may result from the fact that, on a protein basis, the C32 melanoma cells express approximately 3 times more complex on their surface than do WI38 fibroblasts. The results suggest that the relative abundance of a particular adhesion receptor on the cell surface may govern its importance to cell-substratum adhesion.

Cell Adhesion↗
PubMed1988

The development and use of a standard symphysial-fundal height growth curve in the prediction of small for gestational age neonates.

The symphysial-fundal height (SF) measurement has been routinely used in obstetrics, although its value in the prediction of small-for-gestational-age (SGA) infants remains controversial. A retrospective study was performed in order to assess the sensitivity and specificity of the SF distance and establish guidelines for its use. Local neonatal birthweight distribution and SF growth curves were developed. Eighty-six percent of 28 SGA infants demonstrated one measurement under--1 S.D. of the mean SF growth curve as did 36% of appropriate for gestational age (AGA) neonates. Seventy-five percent of SGA infants subsequently demonstrated a second measurement below--1 S.D. of the mean curve, 90% prior to 36 weeks. Only 16% of AGA exhibited such a SF growth pattern. A protocol for maximizing the use of this inexpensive and easily obtained parameter is proposed.

Adult↗
PubMed1988

Detection of DNA transcripts of measles genes in multiple sclerosis brain tissue by transfection.

Transfection studies on DNA obtained from 16 multiple sclerosis (MS) and 13 non-MS brain tissues suggested that 3/16 (19%) MS and 3/13 (23%) non-MS samples contained contaminating measles virus double-stranded RNA, and that 6/16 (38%) MS and 0/13 non-MS samples contained DNA transcripts of measles genes. It is argued that the DNA transcripts most probably originated from dual retrovirus and measles infections in the subjects.

Adult↗
PubMed1988

Priming semantic relations in patients with Huntington's disease.

To investigate the hypothesis that Huntington's Disease involves a breakdown in the organization of the lexico-semantic representational system, mildly and moderately demented patients with Huntington's Disease and age-matched normal control subjects were given a brief battery of language tests and a semantic priming free association task. Results of the language tests provided suggestive, but confounded, evidence for a semantic deficit in Huntington's Disease. Less equivocal evidence was yielded by results of the priming task, which showed a decline in the effect of association strength of primed stimulus-target word pairs on target hit rates. This finding was interpreted as a disruption in the system of spreading activation in a lexico-semantic network. This breakdown was contrasted with the more severe language deficits found in dementias which are primarily cortical in origin.

Dementia↗