Biomedical subjects
C Latham
Publications and source records attributed to C Latham.
Frequent co-amplification of two different regions on 17q in aneuploid breast carcinomas.
Chromosome 17q is highly susceptible to rearrangement mutations in breast cancer. c-erbB-2 at 17q11.2 approximately q21.1 is frequently amplified, as is a region at 17q22 approximately q24. As a step in the search for the target gene(s) of the 17q22-q24 amplification we determined whether the placental lactogen (PL) genes at 17q23 were amplified in 59 breast carcinomas. These genes were selected as their upregulation could theoretically be involved in breast cancer tumorigenesis. Amplification of the PL genes, and also of c-erbB-2, was detected using semi-quantitative PCR. The reliability of this method was confirmed since c-erbB-2 results obtained using PCR, Southern blotting and immunohistochemistry were in good agreement. The PL genes were amplified in 13 (22%) of the tumors. Furthermore, the PL and c-erbB-2 genes were frequently co-amplified although there is a non-amplified region between them. Expression of PL was investigated in 26 tumors and was detected in 16 of these cases including all 10 tumors with amplification of the PL genes. The tumors with PL gene amplification were all aneuploid. A trend was seen towards an increased incidence of lymph node involvement for tumors with amplification of the PL genes and for tumors with co-amplification of PL and c-erbB-2, which suggests a possible association with high malignancy.
Pharmacological profile of SL 59.1227, a novel inhibitor of the sodium/hydrogen exchanger.
1. The NHE1 isoform of the Na(+)/H(+) exchanger plays an important role in the regulation of intracellular pH and in cardiac cell injury caused by ischaemia and reperfusion. SL 59.1227 is a novel imidazolypiperidine Na(+)/H(+) antiport inhibitor which is structurally unrelated to previously described acylguanidine inhibitors such as cariporide. 2. Recovery of pH(i) following an intracellular acid load was measured in CCL39-derived PS120 variant cells, selectively expressing either NHE1 or NHE2 isoforms of the Na(+)/H(+) exchanger. pH(i) recovery was potently and selectively slowed by SL 59.1227 in NHE1-expressing cells (IC(50) 3.3+/-1.3 nM) versus NHE2-expressing cells (2.3+/-1.0 microM). The respective IC(50) values for cariporide were 103+/-28 nM (NHE1) and 73+/-46 microM (NHE2). 3. In anaesthetized rats following left coronary artery occlusion (7 min) and reperfusion (10 min) SL 59.1227 (10 - 100 microg kg(-1) min(-1) i.v.) inhibited ischaemia-mediated ventricular tachycardia (71 - 100%) and reperfusion-induced ventricular fibrillation (75 - 87%) and prevented mortality. Bolus i.v. administration of SL 59.1227 (1 mg kg(-1)) produced anti-arrhythmic effects when administered either before or during ischaemia. 4. Cardiac infarct size was determined in anaesthetized rabbits following left coronary artery occlusion (30 min) and reperfusion (120 min). Infarct size measured as a percentage of the area at risk was 36.2+/-3.4% (control group) versus 15.3+/-3.9% (SL 59.1227 0.6 mg kg(-1) i.v.). 5. SL 59.1227 is the first example of a potent and NHE1-selective non-acylguanidine Na(+)/H(+) exchanger inhibitor. It possesses marked cardioprotective properties.
Inhibition of plasminogen activator inhibitor-1 activity by two diketopiperazines, XR330 and XR334 produced by Streptomyces sp.
Two diketopiperazines, XR334 (1) and the novel compound XR330 (2), were isolated from the lyophilised biomass of an unidentified Streptomyces sp. Their structures were elucidated on the basis of spectroscopic studies and confirmed by chemical synthesis. Both compounds inhibited plasminogen activator inhibitor-1 activity in an amidolytic assay of tissue plasminogen activator mediated plasmin generation. Compound 1 also enhanced fibrinolysis ex vivo and protected against thrombus formation in the rat. These diketopiperazines represent the first low molecular weight inhibitors of plasminogen activator inhibitor-1, a physiological regulator of fibrinolysis.
Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenomas and diploid and aneuploid carcinomas.
Comparative genomic hybridization serves as a screening test for regions of copy number changes in tumor genomes. We have applied the technique to map DNA gains and losses in 33 cases of formalin-fixed, paraffin-embedded primary breast tumors (13 fibroadenomas and 10 diploid and 10 aneuploid carcinomas). No genomic imbalances were found in fibroadenomas. Recurrent findings in adenocarcinomas include copy number increases for chromosomes 1q (14 of 20 samples), 8q (10 of 20), 17q (5 of 20), 6p (3 of 20), 13q (3 of 20), and 16p (3 of 20), and copy number decreases for chromosomes 22 (7 of 20), 17p (6 of 20), and 20 (3 of 20). Regional high level copy number increases were observed on chromosome bands 1q32, 8p11, 8q24, 10p, 11q13, 12p, 12q15, 17q11-12, and 17q22-24. The majority of the samples were studied for gene amplification of c-myc, c-erbB2, cycD1, and int-2 by means of Southern blot analysis. The comparison with DNA ploidy measurements revealed a different distribution and a significantly higher number of chromosomal aberrations in aneuploid tumors than in diploid tumors and in fibroadenomas.
A model for multicultural curriculum development in baccalaureate nursing education.
Valuing multiculturalism is essential to the education of professional nurses in order to incorporate knowledge of and respect for cultural values into nursing care. This article briefly examines the definitions of multicultural concepts in nursing curricula. An innovative model for curricular analysis based on a broad operational definition of multiculturalism is described and applied to a baccalaureate upper-division nursing curriculum. Faculty and student interview data are discussed. Results of the examination of course syllabi, materials, textbooks, instructional videos, and clinical experiences are enumerated. Findings include strengths as well as areas of omission, bias, and insensitivity. Implications for faculty development, recommendations for administrative action, and specific curricular changes are outlined. Heightened sensitivity to the value of multiculturalism and the need for lifelong learning on this topic are emphasized.
Abolition of mevinolin-induced growth inhibition in human fibroblasts following transformation by simian virus 40.
The basal level of the gene expression and the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase was higher in SV40-transformed human fibroblasts (90-VA VI) than in normal ones (HDF). In both these cell types mevinolin (25 microM) caused an 85-90% depression of HMG CoA reductase activity and of the incorporation of [3H]acetate into sterols. In HDF this was coupled to an efficient block of cell growth, whereas the growth of 90-VA VI was only slightly reduced by mevinolin. In HDF, mevinolin (25 microM) also abolished essentially all dilichol synthesis, as measured by incorporation of [3H]acetate. In contrast, dolichol synthesis remained unaltered, or was increased, in mevinolin-treated 90-VA VI. We suggest that these different responses of dolichol synthesis may depend on different substrate affinities of the rate-limiting enzyme in the dolichol pathway. However, if 90-VA VI was treated with 25-hydroxycholesterol (25-OH), an alternative inhibitor of HMG CoA reductase, the cellular growth as well as dolichol synthesis was significantly decreased. Since the inhibitory effect of 25OH on HMG CoA reductase activity did not exceed that of mevinolin, it seems that 25-OH, besides HMG CoA reductase, inhibits steps distal to HMG CoA reductase. This notion was further supported by the finding that addition of mevalonate did not prevent the 25-OH-induced growth inhibition. However, if dolichol was added along with 25-OH, the block was partially prevented, indicating that a critical level of de novo synthesis of dolichol for cellular growth.
Cell cycle regulation of human diploid fibroblasts: possible mechanisms of platelet-derived growth factor.
Cell-cycle regulation of human diploid fibroblasts (HDF) is located in the proximal half of G1, designated G1-pm (G1-postmitosis). In order to traverse this subphase, cells require serum factors or PDGF. However, when cells have traversed into the distal half of G1, designated G1-ps (G1-pre-DNA synthesis), they become independent of serum or PDGF and progress through the remainder of the cell cycle at an invariable rate. From this, it follows that a specific G1-pm block can be induced by serum depletion. A similar G1-pm block could also be induced by a moderate inhibition of overall protein synthesis following treatment with CHM. Even this block could be prevented by the addition of PDGF, suggesting that a high level of protein synthesis in itself is not necessary for sustaining cell-cycle traverse. Nevertheless, a critical accumulation of some specific proteins might be required for the G1-pm/G1-ps-transition. However, the underlying mechanisms of modulation of the accumulation of such proteins by PDGF must involve alternative regulatory events (e.g., gene expression, protein stabilization) rather than protein synthesis. Among the possible cell cycle-regulatory proteins, the present study focused on 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. This enzyme is regulated by various kinds of control mechanisms and regulates the biosynthesis of sterols and nonsterol isoprenes, some of which are proposed to be necessary for mammalian cell growth (Brown and Goldstein, 1980). The present results suggest that regulation of HMG CoA reductase may be involved in the control of the G1-pm/G1-ps-progression in HDF.
A follow-up study of a language intervention programme.
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Fecal alpha 1-antitrypsin and infant feeding.
Stool samples from 232 infants aged 7 days to 18 months were analyzed for alpha 1-antitrypsin and for occult blood by two techniques. Among the 450 stool samples, no correlation between positive tests for occult blood and the concentration of alpha 1-antitrypsin was found. The alpha 1-antitrypsin concentration in the stool decreased after the age of 6 months in both breast-fed (P less than 0.05) and formula-fed (P less than 0.001) groups. In the 7- to 30-day-old infants, breast-feeding was associated with both lower fecal alpha 1-antitrypsin (P less than 0.001) and less frequent positive tests for occult blood (P less than 0.02) than found in the formula-fed infants. Between 6 and 12 months of age, alpha 1-antitrypsin was lower in cow milk-fed infants than in those receiving either breast-feeding supplemented with formula (P less than 0.01) or soy formula (P less than 0.05). Age and feeding differences in the concentration of alpha 1-antitrypsin in the stool may reflect subtle changes in gastrointestinal tract function in infancy.
Optokinetic nystagmus and pursuit eye movements in schizophrenia.
This study of two types of optokinetic nystagmus (OKN) provides evidence that previously reported pursuit impairments in schizophrenics may be due to a cortical dysfunction. Differences in responses to partial-field and full-field OKN stimuli strongly support the hypothesis that there are two functionally distinct but anatomically overlapping mechanisms that can produce nystagmus responses. Partial-field OKN is composed of alternating phases of pursuit and saccadic movements. The slow phases of partial-field OKN, like pursuit eye movements, are of significantly poorer quality in schizophrenics compared with normal controls. Full-field OKN, however, is intact in both groups. Partial-field OKN is an improved test for pursuit abnormalities that reflect disturbances of nonvoluntary attention.
Of interest to smaller hospitals: attracting qualified personnel.
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Iron nutrition in the breast-fed infant.
Breast-fed infants were compared with infants fed a prepared formula not fortified with iron during the first nine months of life. Despite efforts to provide equal iron intakes from cereal and other foods, the breast-fed infants ate less iron-containing foods than the formula-fed infants. The incidence of mild anemia and biochemical iron deficiency was the same in both groups. The breast-fed infants had a significantly lower total iron binding capacity. Breast-fed infants appear to utilize iron more efficiently than formula-fed infants.
Homeless where the heart is.
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