Biomedical subjects
L Anderson
Publications and source records attributed to L Anderson.
We need access, not excess.
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Walter Bierring and the Flexner Revolution: at the University of Iowa College of Medicine.
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Health-care reform: a 'consciously incremental approach'.
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Premarital HIV-1 testing in New Jersey.
To answer questions related to the usefulness of premarital testing for human immunodeficiency virus type 1 (HIV-1), two "blinded" or "nonlinked" HIV-1 serosurveys were done in New Jersey, a state with a high incidence of AIDS, on blood specimens submitted for a premarital serologic test for syphilis. The first survey involved premarital blood specimens submitted to the New Jersey Department of Health laboratory for the year starting September 1987. The second survey involved premarital specimens submitted to five private or hospital clinical laboratories in the spring of 1989, of which approximately 1,000 consecutive premarital specimens from each laboratory were sent to the Department of Health laboratory for HIV-1 testing. Of 4,247 specimens tested in the 1987-1988 survey, 21 (0.49%) were positive for antibodies to HIV-1, while among 4,696 specimens in the 1989 survey, 29 (0.62%) were positive. When the survey results were weighted by the number of marriages by geographic regions of the state, the weighted premarital HIV-1 seroprevalence was 0.55% for the 1987-1988 survey and 0.62% for the 1989 survey. The male/female ratio of positive tests was 2.7:1 in 1987-1988 and 1.6:1 in 1989. Of the 8,943 specimens in both surveys, 5 (0.06%) gave an indeterminate immunoblot result, compared with 50 positive results. These percentages of premarital HIV-1 infections are much higher than earlier estimates and reports and are of the same magnitude as recently reported blinded premarital HIV-1 testing elsewhere. Results of this magnitude support a recommendation in New Jersey of voluntary HIV-1 counseling and testing for marriage applicants.
Cloning, sequencing and tissue distribution of a candidate G protein-coupled receptor from rat pituitary gland.
A new member of the family of G protein-coupled receptors has been isolated from a rat pituitary cDNA library by the polymerase chain reaction (PCR) using degenerate oligonucleotide primers. The corresponding protein sequence shows seven transmembrane domains and contains conserved regions of homology characteristic of the G protein-coupled class of receptors. The novel receptor mRNA is expressed in the brain, pituitary gland and testis, and has been localized by in situ hybridization in discrete regions of the brain. Expression of the receptor mRNA in Xenopus oocytes and in transfected mammalian cells has not yet permitted identification of the corresponding ligand for this receptor.
An improved synthesis of trehalose 6-mono- and 6,6'-di-corynomycolates and related esters.
A simplified synthesis of 6-mono- and 6,6'-di-corynomycolate esters of alpha,alpha-trehalose, and related compounds, was achieved by coupling the (hydroxyl-protected) acids to the partially trimethylsilylated sugar in the presence of dicyclohexylcarbodiimide and 4-dimethylaminopyridine. As acid reactants, (2-RS,3-RS)-3-hydroxy-2-tetradecyloctadecanoic acid (DL-corynomycolic acid) and its 2RS,3SR diastereomer were prepared from methyl palmitate by sequential Claisen condensation, reduction, chromatographic separation, and saponification. Reaction with tert-butylchlorodimethylsilane (imidazole) gave the disubstituted ether-esters, which were converted into the required 3-tert-butyldimethylsilyl ethers by partial hydrolysis. 6-Linked monocorynomycolate was obtained in excellent yield (78%) from the reaction of the RS,SR acid with the known heptakis-O-(trimethylsilyl)trehalose, and in good yield from equimolar portions of RS,RS acid and hexakis-O-(trimethylsilyl)trehalose. An excess (2.5-molar portions) of the RS,RS acid gave the 6,6'-diester (69%). The mono- and di-palmitate were similarly obtained from (Me3Si)6-trehalose. The mono (RS,RS)-(Me3Si)6-trehalose coupling product was partially resolved on a silica gel column into its RR and SS diastereomers, the former corresponding to the naturally occurring trehalose monocorynomycolate. All coupling products were deprotected to free trehalose esters by treatment first with K2CO3 in methanol, then tetrabutylammonium fluoride-trifluoracetic acid in oxolane.
The role of protein kinase C and the phosphatidylinositol cycle in multidrug resistance in human ovarian cancer cells.
The present study aimed to investigate the role of protein kinase C (PKC), the phosphatidylinositol pathway (PI) and cytosolic calcium in multidrug resistance (MDR) in human ovarian carcinoma cells. Binding of the phorbol ester 13,14-dibutyrate (PDBu) was 3-fold higher in resistant A2780AD versus sensitive A2780 cells indicating increased PKC activity. However, when inositol phosphate production (IP) was measured in quiescent cells similar total IP release was seen in both lines suggesting no difference in the basal turnover of PI. Non-specific stimulation of the PI pathway was achieved with the calcium ionophore A23187 which increased IP production in a time- and dose-dependent fashion in both cell lines but was significantly less effective in A2780AD. The PI pathway was investigated further using the agonists aluminium fluoride, serum and bombesin but these agents failed to elicit a response. The effect of a wide range of Adriamycin concentrations on the PI cycle and cell growth was also studied. Intracellular calcium was measured with the fluorescent dye fura-2-pentaacetoxymethylester (Fura-2). A23187 produced a rise in cytosolic calcium in A2780 and A2780AD but from a level 3-fold lower in the unstimulated resistant cell line. The dose responsiveness of this effect was greater but irreversible in A2780AD cells. Collectively these results imply that alterations in PI turnover appear not to be responsible for the differences in PDBu binding and calcium handling observed between A2780 and A2780AD and suggests only a minor role for the PI cycle in the maintenance of MDR in human ovarian cancer cell lines.
Patterns of gene expression that characterize the colonic mucosa in patients at genetic risk for colonic cancer.
We have used a computer-driven scanning and image-processing system to identify a panel of 30 cDNA clones whose pattern of expression in individual biopsy specimens distinguishes the flat, normal-appearing colonic mucosa of patients in two genetic groups at high risk for development of colorectal cancer from that of normal colonic mucosa in low-risk individuals. The two high-risk groups, familial adenomatous polyposis and hereditary nonpolyposis colon cancer, are indistinguishable based on the pattern of expression of the 30 selected clones. This suggests that the extensive pleiotropic effects of the inherited loci, which may play an important role in the mechanism of increased risk and early onset of the disease, are similar in these populations.
A specific acyl-ACP thioesterase implicated in medium-chain fatty acid production in immature cotyledons of Umbellularia californica.
Umbellularia californica (California Bay) seeds accumulate 10:0 and 12:0 as principal reserve fatty acyl groups. An in vitro fatty acid synthesis system from the developing cotyledons produces chiefly 10:0 and 12:0, in approximately the same proportions as the intact tissue. The kinetics of acyl thioester and free fatty acid formation in this system suggest that a medium-chain specific acyl-acyl-carrier protein (ACP) hydrolysis mechanism is responsible for the preponderance of medium-chain products. A crude extract of the developing cotyledons exhibits hydrolytic activity toward acyl-ACPs, with marked preference for 12:0-ACP and 18:1-ACP in the test series 6:0, 8:0, 10:0, 11:0, 12:0, 14:0, 16:0, and 18:1-ACPs. Partial purification of the 12:0-ACP hydrolytic activity has resulted in its separation from the 18:1-ACP hydrolase(s) and the 12:0-coenzyme A hydrolase(s) that are also present, thereby demonstrating its specificity for the 12-carbon acyl chain length and the ACP derivative. During cotyledon development, as the proportion of medium-chain to other fatty acyl groups increases, the extractable yield of this activity also increases substantially. Collectively these results suggest a role for this 12-ACP thioesterase in medium-chain production in vivo.
Prehospital diagnosis and treatment of acute myocardial infarction: a north-south perspective. The Cincinnati Heart Project and the Nashville Prehospital TPA Trial.
Intravenous thrombolytic therapy improves left ventricular function and reduces mortality in patients with acute myocardial infarction (AMI). In European and Middle Eastern trials, prehospital delivery of thrombolytic agents by physician-directed mobile intensive care units has been successful. This report describes two independently conceived and performed trials that used cellular telephone transmission of 12-lead ECGs to deliver recombinant tissue plasminogen activator (r-tPA) in the field to patients with AMI. In the Nashville Prehospital TPA Trial, 85 patients with chest pain were evaluated in the field for possible administration of r-tPA over a 6-month period. Three of 85 patients (3.5%) were found to be actual candidates for r-tPA treatment in the field. In phase II (dry-run phase) of the Cincinnati Heart Project, 374 patients were evaluated in the field with 14 documented cases of AMI (3.7%) before r-tPA was placed in ambulances for administration by paramedics. In phase III (active with r-TPA in ambulances), over a 1-year period 103 patients were evaluated with six (5.8%) documented cases of AMI. Three of five r-tPA field treatment decisions by emergency physicians using transmitted 12-lead ECGs were accurate (60%). When patients in phases II and III were combined, only 20 of 477 total patients (4.2%) were documented to have AMI. A decline in paramedic skills was noted because of the infrequent administration of the thrombolytic agent. Combining the Nashville and Cincinnati experiences, only 27 of 562 total patients with chest pain (4.8%) were candidates for prehospital thrombolysis. We conclude that few patients evaluated in the prehospital setting are actual candidates for thrombolytic therapy. Substantial allocation of financial and human resources for prehospital delivery of intravenous thrombolytic therapy does not appear warranted.
Developmental induction, purification, and further characterization of 12:0-ACP thioesterase from immature cotyledons of Umbellularia californica.
The fatty acyl content of developing cotyledons of Umbellularia californica (California Bay) changes from a long-chain composition to a predominance of 10:0 and 12:0 in just 4-5 days at the beginning of an approximately 100-day period of medium-chain deposition. This striking change occurs at the earliest appearance of 12:0-acyl-carrier protein (ACP) thioesterase activity. The coincidence of these rapid events is consistent with the hypothesis that the enzyme plays a major role in medium-chain biosynthesis. The 12:0-ACP thioesterase has been substantially purified; enzyme activity consistently comigrates in chromatographic and electrophoretic systems with a protein or pair of proteins having an apparent molecular weight of approximately 34 kDa. A native molecular weight of approximately 42 kDa has been estimated by gel filtration chromatography, suggesting that the enzyme is a monomer. Affinity chromatography on immobilized ACP is a critical step in the purification procedure, and resolves the 12:0-ACP and 18:1-ACP thioesterases sufficiently to confirm that the medium-chain enzyme has negligible action on 18:1-ACP.
The molecular pharmacology of doxorubicin in vivo.
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Characterisation and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon.
Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.
Reviewing graduate medical education programs: a cancer center experience. Members of the Graduate Training Committee.
The Graduate Training Committee at Memorial Sloan-Kettering Cancer Center developed procedures for comprehensively reviewing the 32 graduate training programs at our institution. The methods used to carry out this review, the problems encountered, and the results of this review are presented. As this type of program review is now mandated by the Accreditation Council for Graduate Medical Education (ACGME), our method and experience should prove useful to other institutions planning a similar review process.
"Headlights upon sanitary medicine": public health and medical reform in late nineteenth-century Iowa.
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Fluorescence immunoassay for detecting periodontal bacterial pathogens in plaque.
A particle concentration fluorescence immunoassay has been modified into a bacterial concentration fluorescence immunoassay (BCFIA) to rapidly detect periodontopathic bacteria in human plaque samples. The BCFIA utilizes fluorescently tagged monoclonal antibodies (MAbs) directed against the lipopolysaccharide of selected gram-negative plaque bacteria. Microorganisms closely associated with periodontal disease that can be identified in plaque with the BCFIA include Porphyromonas gingivalis, Bacteroides intermedius, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Eikenella corrodens. Briefly, the procedure involved mixing a patient's plaque sample or other bacterial preparation with a species-specific fluorescein isothiocyanate-labeled MAb in a specialized microtiter plate. This mixture was incubated to allow binding of the MAb to its homologous bacteria. The bound and unbound fluorescent tagged MAbs were separated by filtration in the modified microtiter plate, and the total bacterial bound fluorescence was determined with a fluorimeter. The number of a specific bacterial species in a given plaque sample or other bacterial suspension was estimated by reference to a primary standard carried through the BCFIA. The lower detection limit of the BCFIA was 10(3) to 10(4) bacterial cells from single cultures of bacteria or 10(4) bacterial cells in mixed cultures. The coefficient of variation within and between plates for each of the five bacterium-specific MAbs in screening plaque for the periodontal pathogens was less than 10%. These results demonstrate that microbes in plaque can be used as the solid phase in the BCFIA to detect and quantitate MAbs associated with specific bacteria quickly and reliably.
Staining plant cells with silver. I. The salt-nylon technique.
A technique is described for selectively silver staining nucleoli, active nucleolus organizers, nucleolar material attached to chromosomes, kinetochores, synaptonemal complexes, and chromosome cores in plant cells. The technique, called salt-nylon silver staining, involves spreading cells on glass slides, treating the cells with a solution of saline sodium citrate, and incubating the cells in a silver nitrate solution covered with nylon screen. Selected variables important for achieving reliable silver staining are considered.