Biomedical subjects

J E Watson

Publications and source records attributed to J E Watson.

At least 19 recordsLinked to original sources

PubMed1999

Ectopic expression of protein kinase CbetaII, -delta, and -epsilon, but not -betaI or -zeta, provide for insulin stimulation of glucose uptake in NIH-3T3 cells.

Insulin regulates a diverse array of signaling pathways involved in the control of growth, differentiation, proliferation, and metabolism. Insulin increases in glucose uptake via a protein kinase C-dependent pathway in target tissues such as fat and muscle are well documented. Insulin-regulated events, however, occur in all cells. The utilization of glucose as a preferred energy source is a ubiquitous event in eukaryotic cells. In NIH-3T3 fibroblasts, insulin treatment increased levels of the cPKC and nPKC activator, diacylglycerol. Insulin-responsive 2-[(3)H]deoxyglucose uptake was stimulated in a dose-dependent manner. The overexpression of protein kinase C (PKC)betaI, -betaII, -delta, -epsilon, and -zeta was used to investigate the specificity of PKC isozymes for insulin-sensitive glucose uptake. The stable overexpression of PKCbetaII, -delta, and -epsilon resulted in increases in insulin-stimulated 2-[(3)H]deoxyglucose uptake compared to vector control cells, while basal 2-deoxyglucose uptake levels were not elevated. Overexpression of PKCbetaI and PKCzeta isozymes had no further effect on basal or insulin-stimulated 2-deoxyglucose uptake. The PKC-specific inhibitor, CGP41251, blocked insulin effects on 2-deoxyglucose uptake but not its effects on tyrosine phosphorylation of cellular substrates. Insulin-stimulated 3-O-methylglucose uptake was also greater in cells overexpressing PKCbetaII, -delta, and -epsilon, compared to control cells. The increased responsiveness was not accompanied by conversion of 3T3 cells to the adipocyte phenotype or the increased expression of insulin receptors or glucose transporters (GLUT1-type). Insulin-stimulated recruitment of GLUT1 to plasma membranes of cells overexpressing PKCbetaII, -delta, and -epsilon, was greater than that in control cells. The data suggest that more than one PKC isozyme is involved in insulin signaling pathways in fibroblasts, resulting in increased GLUT1 transporter recruitment to cell membranes.

3-O-Methylglucose↗

PubMed1999

Identification of a region of frequent loss of heterozygosity at 11q24 in colorectal cancer.

Loss of heterozygosity (LOH) at 11q23-qter occurs frequently in ovarian and other cancers, but for colorectal cancer, the evidence is conflicting. Seven polymorphic loci were analyzed between D11S897 and D11S969 in 50 colorectal tumors. Two distinct LOH regions were detected, suggesting possible sites for tumor-suppressor genes involved in colorectal neoplasia: a large centromeric region between D11S897 and D11S925, and a telomeric 4.9-Mb region between D11S912 and D11S969. There was no correlation with clinicopathological features. This analysis describes a region of LOH in the region 11q23.3-24.3 for the first time in colorectal cancer and provides complementary evidence for the ongoing effort to identify the gene(s) involved.

Aged↗

PubMed1999

Acute hyperglycemia regulates transcription and posttranscriptional stability of PKCbetaII mRNA in vascular smooth muscle cells.

Acute hyperglycemia may contribute to the progression of atherosclerosis by regulating protein kinase C (PKC) isozymes and by accelerating vascular smooth muscle cell (VSMC) proliferation. We investigated acute glucose regulation of PKCbeta gene expression in A10 cells, a rat aortic smooth muscle cell line. Western blot analysis showed that PKCbetaII protein levels decreased with high glucose (25 mM) compared to normal glucose (5.5 mM), whereas PKCbetaI levels were unaltered. PKCbeta mRNA levels were depleted by 60-75% in hyperglycemic conditions. To elucidate whether high glucose regulated PKCbeta expression via the common promoter for PKCbetaI and PKCbetaII, deletion constructs of the PKCbeta promoter ligated to CAT as reporter gene were transfected into A10 cells. Construct D (-411 to +179CAT) showed quenching in high glucose (25 mM) and suggested the involvement of a carbohydrate response element in the 5' promoter region of the PKCbeta gene. In actinomycin D-treated A10 cells, a 60% decrease in PKCbeta mRNA with high glucose treatment indicated that posttranscriptional destabilization by glucose was also occurring. We have demonstrated that glucose-induced posttranscriptional destabilization of PKCbetaII message is mediated via a nuclease activity present in the cytosol. The specificity of glucose to posttranscriptionally destabilize PKCbetaII mRNA, but not the PKCbetaI mRNA, was confirmed in both A10 cells and primary cultures from human aorta.

Animals↗

PubMed1999

Use of 222Rn-resistant techniques in new home construction.

The objective of this project was to assess the status of the use of 222Rn-resistant construction techniques in new home construction in the eight Zone 1 counties of North Carolina. Zone 1 counties have an average predicted indoor 222Rn screening potential greater than 148 Bq m(-3)(4 pCi L(-1)). To facilitate a response from builders, a brief survey form was designed and printed on the back of a self-addressed, postage-paid postcard. This survey form was mailed to 460 home builders in the Zone 1 counties. The response rate was 17%, which can be compared to the 4.9% response rate obtained in a national survey conducted by the National Association of Home Builders Research Center. In our survey, 62% of the responding builders reported that they had built some or many homes in 1996 "using construction techniques to reduce the entry of radon into homes," but only 10% of the builders reported using these techniques for many homes. The National Association of Home Builders survey determined that, nationally, 30% of homes built in Zone 1 counties had 222Rn venting features. There is the potential for bias in the results of our survey (as well as in the results of the National Association of Home Builders survey) since the response rates were low.

Construction Materials↗

PubMed1999

Identification and characterization of a homozygous deletion found in ovarian ascites by representational difference analysis.

We have performed representational difference analysis (RDA) on DNA from tumor cells and normal fibroblasts isolated from the ascites of a patient with ovarian cancer. Five of six products of the RDA were homozygously deleted from the tumor DNA. One of these products has been characterized and identifies a homozygous deletion of approximately 6.9 Mb at chromosome 9p21 in the original ovarian tumor material. This deletion encompasses CDKN2A (p16), CDKN2B (p15), and IFN-alpha. PCR analysis of other tumor cell lines using the novel STS based on the RDA product has shown it to lie between IFN-alpha and p16, and to identify the distal extent of a homozygous deletion in another ovarian cancer cell line. These data provide further evidence for a tumor suppressor locus distinct from, but mapping close to, p16 on 9p21. Cytogenetic analysis using comparative genomic hybridization (CGH) performed on the same primary tumor confirmed a loss of material from chromosome 9p. However, the CGH technique had neither the resolution nor the sensitivity to define a subregion of homozygous loss.

Ascites↗

PubMed1998

The roles of protein kinase C beta I and beta II in vascular smooth muscle cell proliferation.

The role of protein kinase C (PKC) on proliferation of A10 vascular smooth muscle cells (VSMC) was studied by overexpressing specific PKC-beta I and -beta II isozymes. PKC-beta I and -beta II are derived from alternative splicing of the exon encoding the carboxy-terminal (C-terminal) 50 or 52 amino acids, respectively. The differential functions of the two isozymes with regard to cell proliferation, DNA synthesis, and the cell cycle were investigated in A10 cells, a clonal cell line of VSMC from rat aorta, and in A10 cells overexpressing PKC-beta I and PKC-beta II (beta I-A10 and beta II-A10). PKC levels were increased three- to fourfold in heterogeneous cultures of stably transfected cells. Although doubling time of A10 cells was 36 h, the cell doubling time in beta I-A10 cells decreased by 12 h, and, in contrast, the doubling time of beta II-A10 cells increased by 12 h compared to A10 cells. The increase of [3H]thymidine (TdR) incorporation was accelerated and increased in beta I-A10 cells, but slowed and diminished in beta II-A10 cells compared to A10 and control cells transfected with empty vector. Cell cycle analysis of beta I-A10 cells showed an acceleration of S phase entry while beta II-A10 cells slowed S phase entry. These results suggest that PKC-beta I and PKC-beta II regulate cell proliferation bidirectionally and that PKC-beta I and PKC-beta II may have distinct and opposing functions as cell cycle check point mediators during late G1 phase and may regulate S phase entry in A10 VSMC.

Animals↗

PubMed1998

Insulin regulates protein kinase CbetaII expression through enhanced exon inclusion in L6 skeletal muscle cells. A novel mechanism of insulin- and insulin-like growth factor-i-induced 5' splice site selection.

The protein kinase Cbeta (PKCbeta) gene encodes two isoforms, PKCbetaI and PKCbetaII, as a result of alternative splicing. The unique mechanism that underlies insulin-induced alternative splicing of PKCbeta pre-mRNA was examined in L6 myotubes. Mature PKCbetaII mRNA and protein rapidly increased >3-fold following acute insulin treatment, while PKCbetaI mRNA and protein levels remained unchanged. Mature PKCbetaII mRNA resulted from inclusion of the PKCbetaII-specific exon rather than from selection of an alternative polyadenylation site. Increased PKCbetaII expression was also not likely accounted for by transcriptional activation of the gene or increased stabilization of the PKCbetaII mRNA, and suggest that PKCbetaII expression is regulated primarily at the level of alternative splicing. Insulin effects on exon inclusion were observed as early as 15 min after insulin treatment; by 20 min, a new 5'-splice site variant of PKCbetaII was also observed. After 30 min, the longer 5'-splice site variant became the predominate species through activation of a downstream 5' splice site. Similar results were obtained using IGF-I. Although the role of this new PKCbetaII mRNA species is presently unknown, inclusion of either PKCbetaII-specific exon results in the same PKCbetaII protein.

Alternative Splicing↗

PubMed1997

Variation of 222Rn in public drinking water supplies.

The U.S. Environmental Protection Agency has proposed regulating 222Rn in public drinking water. When implemented, the regulation will require periodic sampling to demonstrate compliance. The work reported in this paper was conducted to evaluate how reliably grab samples can be used to characterize the average 222Rn concentration in a groundwater source. Periodic samples were collected from 14 wells over sampling periods ranging from 2 to 26 mo. Samples were collected using a "slow-flow" collection method, and samples were analyzed using liquid scintillation techniques. The results reveal variation in 222Rn concentration over the study period; however, for the 1,468 samples collected from the 14 wells, approximately 97% of the measurement results were within 30% of the mean value for the well.

Geological Phenomena↗

PubMed1997

Quality of lipid and lipoprotein measurements in community laboratories.

OBJECTIVE: To determine the reliability of cholesterol and lipoprotein measurements conducted in local community laboratories. METHODS: Standardized duplicate serum aliquots at three concentrations (low, intermediate, and high) of total cholesterol, triglycerides, and high-density lipoprotein cholesterol were sent to 21 laboratories used by the physicians participating in the Cholesterol-Lowering Intervention Program. Results obtained from the laboratories were compared with values obtained from the Centers for Disease Control and Prevention-standardized Heinz Lipid Laboratory and with the means of the entire sample. RESULTS: The mean coefficient of variation (CV) was 1.3% or less for all three levels of total cholesterol, which demonstrates a high degree of precision. Accuracy was also high; over 80% of all laboratories were within 5% of the Heinz Laboratory low reference value, and all were within the 5% range for the medium and high samples. The CVs for triglycerides (< 2.3%) and high-density lipoprotein cholesterol (< 2.2%) were similar to that for total cholesterol, but up to 56% and 61% of the values fell outside the Heinz reference range for high-density lipoprotein cholesterol (intermediate concentration) and triglycerides (low concentration), respectively. As the Heinz Laboratory has a negative 2.7% bias versus the Centers for Disease Control and Prevention for total cholesterol and high-density lipoprotein cholesterol measurements, a higher percentage of laboratories fell outside the Centers for Disease Control and Prevention range. For medium and high total cholesterol samples, 16% of the laboratories were outside the 5% Centers for Disease Control and Prevention range, and the value was 58% for the low total cholesterol sample. For high-density lipoprotein cholesterol the percentages were 61%, 56%, and 39% for the low, medium, and high samples, respectively. CONCLUSIONS: These data suggest that according to the standards set by the National Cholesterol Education Program Laboratory Standardization Panel, reliability of total cholesterol measurements in local laboratories is high. Lower levels of accuracy were noted for triglycerides and high-density lipoprotein cholesterol measurements.

Blood Chemical Analysis↗

PubMed1996

Cholesterol-lowering intervention program. Effect of the step I diet in community office practices.

BACKGROUND: A randomized study was conducted to test the feasibility of cholesterol lowering in physician office practices using the National Cholesterol Education Program Adult Treatment Panel 1 guidelines. METHODS: Twenty-two physician practices in phase 1 and 23 in phase 2 were recruited from communities in Western Pennsylvania and West Virginia. These physicians treated a total of 450 adults in phase 1 (190 men and 260 women) and 480 adults in phase 2 (184 men and 296 women) with hypercholesterolemia. Three models (Usual Care [phase 1], Office Assisted [phase 2], and Nutrition Center [phase 2]) for implementing the National Cholesterol Education Program Adult Treatment Panel 1 guidelines were tested over an 18-month period. The baseline serum cholesterol levels were as follows: 6.51 mmol/L (252 mg/dL) in the Usual Care Model; 6.80 mmol/L (262 mg/dL) in the Office Assisted Model; and 6.96 mmol/L (269 mg/dL) in the Nutrition Center Model. RESULTS: In the patients who were not taking lipid-lowering medication, the mean cholesterol response was significantly different between the 3 models (P < .01). Serum cholesterol levels declined by 0.14 mmol/L (5.4 mg/dL) in the Usual Care Model; by 0.31 mmol/L (12 mg/dL) in the Office Assisted Model; and by 0.54 mmol/L (20.9 mg/dL) in the Nutrition Center Model. Two factors-length of time to follow-up measurement and change in weight-were independently related to cholesterol response across all models. African Americans demonstrated a significantly smaller response than whites in the Usual Care Model, while men demonstrated greater declines in serum cholesterol levels than women in the Office Assisted Model. Patient satisfaction was very favorable in both enhanced conditions; however, those treated in the the Nutrition Center Model were more satisfied (P < .05) with program components. CONCLUSIONS: The impact of nutrition intervention delivered through physician practices on serum cholesterol levels is less than clinically desirable, and new approaches with more aggressive therapy should be tested and implemented.

Anticholesteremic Agents↗

PubMed1996

Definition and refinement of a region of loss of heterozygosity at 11q23.3-q24.3 in epithelial ovarian cancer associated with poor prognosis.

Previous cytogenetic and loss of heterozygosity (LOH) data suggest that disruption of chromosome 11q23-qter occurs frequently in epithelial ovarian cancer and is associated with an adverse clinicopathological phenotype. Ten polymorphic microsatellite repeat loci were analyzed by PCR from the 11q22-q25 region between D11S35 and D11S968 in 40 ovarian tumors (including 31 epithelial ovarian cancers). Two distinct regions of loss were detected, suggesting possible sites for genes involved in epithelial ovarian neoplasia: a large centromeric region between D11S35 and D11S933 (11q22-q23.3) and a telomeric 8.5-Mb region lying between D11S934 and D11S1320 (11q23.3-24.3) not previously defined. LOH of the latter region but not the former one was significantly associated with poor survival, despite all tumors in this study having LOH somewhere on chromosome 11. This analysis provides a starting point for positional cloning.

Carcinoma↗

PubMed1996

Effects of poverty on home environment: an analysis of three-year outcome data for low birth weight premature infants.

Investigated the relationship between poverty and parenting in a sample of low birth weight (< or = 2,500 grams) premature (LBWPT) infants (gestation < or = 37 weeks) who were control subjects in the Infant Health and Development Program. When classified using federal poverty levels, poor families scored lower on the HOME inventory (used to measure the caregiving environment) than nonpoor families. A regression model including poverty, race, site, and representative environmental, maternal, and child variables accounted for 60% of variance in total HOME scores. Poverty and maternal IQ had significant and independent effects on HOME scores, whereas maternal distress accounted for little of the variance. In a LBWPT sample, our results find a strong relationship between parenting and poverty, suggest a modest role for maternal psychological distress in this relationship, and indicate that the influence of poverty likely extends beyond commonly measured environmental, maternal, and child factors.

Child, Preschool↗

PubMed1996

Tc-99m sestamibi cardiac SPECT imaging during coronary artery occlusion in humans: comparison with dipyridamole stress studies.

PURPOSE: To compare the magnitude of change in regional myocardial perfusion during dipyridamole stress with that during coronary occlusion. MATERIALS AND METHODS: The authors prospectively studied 14 men with more than 50% diameter stenosis in at least one major coronary artery. Same-day rest and dipyridamole technetium-99m sestamibi single photon emission computed tomography (SPECT) was performed 24 hours before coronary angioplasty. During angioplasty, while the vessel was occluded, 15 mCi(555 MBq) of tracer was injected, and SPECT studies were obtained 60 minutes later. Extent of regional perfusion abnormalities was estimated. RESULTS: Regional perfusion defect was greater during stress and occlusion than during rest (20%, P = .001 and 14%, P = .009, respectively). SPECT defect during coronary occlusion was similar to that obtained during pharmacologic stress with dipyridamole (53% vs 47%, P = .02). CONCLUSION: Tc-99m sestamibi SPECT with dipyridamole stress is a good predictor of the extent of perfusion abnormalities that occur during coronary occlusion and may facilitate estimation of the total myocardium in jeopardy from a stenotic lesion.

Adult↗

PubMed1996

A carboxy-terminal deletion mutant of protein kinase C beta II inhibits insulin-stimulated 2-deoxyglucose uptake in L6 rat skeletal muscle cells.

Alternative splicing of pre-mRNA encoding the carboxy-terminal (C-terminal) exons of protein kinase C beta (PKC beta) leads to the expression of two protein isoforms, PKC beta 1 and PKC beta II, with the potential for different functions. PKC beta II expression is regulated by insulin via alternative mRNA splicing. A physiological consequence of its activation was investigated in L6 rat skeletal muscle cells expressing GLUT4 transporters, a cell line in which PKC is involved in glucose transport. We examined the contribution of PKC beta II for insulin-stimulated [3H]2-deoxyglucose uptake by constructing three PKC beta II C-terminal deletion mutants designated M216, M217, and M218. When transiently expressed in COS1 cells, M217, with nine amino acids deleted, demonstrated autophosphorylation activity 10-fold less than full-length PKC beta II. The mutants M218, with 13 amino acids deleted, and M216, with 52 amino acids deleted, demonstrated no autophosphorylation activity and are kinase negative. When transiently expressed in L6 myotubes, M217 inhibited insulin-stimulated 2-deoxyglucose uptake by 45% (with a 45% transfection efficiency) whereas M216 and M218, kinase-negative mutants, had no effect compared with cells transfected with control plasmid. Cotransfection of full-length PKC beta II with M217 was able to rescue the inhibition of insulin-stimulated 2-deoxyglucose uptake as compared with cotransfection of M217 with the control plasmid, suggesting that M217 acts as a dominant-negative. In contrast, cotransfection of full-length PKC beta I, the other alternatively spliced form, did not rescue inhibition of insulin-stimulated 2-deoxyglucose uptake by M217. To further demonstrate the involvement of PKC, specifically PKC beta II, in insulin-stimulated 2-deoxyglucose uptake, we used two inhibitors, CG41251 (a specific PKC inhibitor) and CG53353 (a PKC beta II-specific inhibitor at 1 microM). Both inhibited insulin-stimulated 2-deoxyglucose uptake 50-60% in L6 myotubes. We conclude that M217 may act as a specific PKC beta II dominant-negative and that PKC beta II is more specific for insulin-stimulated 2-deoxyglucose uptake in these cells than PKC beta I.

Amino Acid Sequence↗

PubMed1995

Regulation of alternative splicing of protein kinase C beta by insulin.

Insulin regulates a diverse array of cellular signaling processes involved in the control of growth, differentiation, and cellular metabolism. Insulin increases glucose transport via a protein kinase C (PKC)-dependent pathway in BC3H-1 myocytes, but the function of specific PKC isozymes in insulin action has not been elucidated. Two isoforms of PKC beta result via alternative splicing of precursor mRNA. As now shown, both isoforms are present in BC3H-1 myocytes, and insulin induces alternative splicing of the PKC beta mRNA thereby switching expression from PKC beta I to PKC beta II mRNA. This effect occurs rapidly (15 min after insulin treatment) and is dose-dependent. The switch in mRNA is reflected by increases in the protein levels of PKC beta II. High levels of 12-0-tetradecanoylphorbol-13-acetate, which are commonly used to deplete or down-regulate PKC in cells, also induce the switch to PKC beta II mRNA following overnight treatment, and protein levels of PKC beta II reflected mRNA increases. To investigate the functional importance of the shift in PKC beta isoform expression, stable transfectants of NIH-3T3 fibroblasts overexpressing PKC beta I and PKC beta II were established. The overexpression of PKC beta II but not PKC beta I in NIH-3T3 cells significantly enhanced insulin effects on glucose transport. This suggests that PKC beta II may be more selective than PKC beta I for enhancing the glucose transport effects of insulin in at least certain cells and, furthermore, that insulin can regulate the expression of PKC beta II by alternative mRNA splicing.

3T3 Cells↗

PubMed1995

Evaluating the efficacy of the National Cholesterol Education Program adult treatment guidelines: cholesterol lowering intervention program.

BACKGROUND: A cross-sectional analysis was conducted to test the feasibility of the National Cholesterol Education Program Adult Treatment Panel I Guidelines (ATPI) in physician office practices. METHODS: Twenty-two physician practices in communities from western Pennsylvania and West Virginia were recruited. Using a patient tracking system, 9,171 patients were assessed for cholesterol screening and treatment by their physicians according to the ATPI guidelines. RESULTS: Cholesterol screening was ordered for 1,698 patients or 19% of the population visiting the physician offices. The reasons for not screening included the patient was already under therapy (2,371), screened within the past 5 years (1,714), or acutely ill at the time of the visit (1,691). The frequency of patient refusal for screening was low (444). However, the majority of patient diagnoses were based on a single lipid measurement, and only 817 or 56% of patients evaluated had lipoprotein measures obtained prior to treatment. Follow-up measurement was not performed according to the ATPI schedule, and the magnitude of cholesterol response was inversely related to time to first follow-up measurement. CONCLUSIONS: Many patients in these physician practices had initial cholesterol screening. However, repeat measurements as recommended for initial evaluation were not performed routinely, nor were most patients followed within the recommended 3-month time period. This lack of follow-up is detrimental to effective, long-term patient management since the magnitude of the cholesterol response is related to time of the first follow-up measurement.

Adult↗

PubMed1995

222Rn in water: a study of two sample collection methods, effects of mailing samples, and temporal variation of concentrations in North Carolina groundwater.

The U.S. Environmental Protection Agency has proposed a drinking water standard for 222Rn in public water supplies. When promulgated, operators of public water supplies will be required to determine water 222Rn concentrations. Most likely, water samples will be collected and mailed to laboratories for analyses. Additionally, it is probable that homeowners will test private well water in a similar manner by collecting water samples and mailing them to a laboratory for 222Rn analyses. In anticipation of these actions, this study was conducted to evaluate two methods of water sample collection and to evaluate the potential losses of 222Rn from water samples mailed to a laboratory. Thirdly, temporal variations in 222Rn concentrations in several groundwater supplies in North Carolina were examined. Water supplies at four sites in eastern North Carolina and five sites in western North Carolina were sampled over a 7-mo period beginning in the fall of 1993 and continuing through the spring of 1994. Samples were analyzed using a liquid scintillation method. This study showed that a "slow-flow" method is not only suitable for sample collection, but may be the preferable method for water sample collection since slow-flow collection resulted in less 222Rn loss than was observed during syringe collection, i.e., the water 222Rn concentrations in samples collected by the slow-flow method were generally higher. Further, based on this study, mailing water samples to a laboratory for analysis should not have a substantial effect on the measured 222Rn concentrations. Consequently, water samples can be collected by the slow-flow method by water supply operators, as well as homeowners, and mailed to laboratories for 222Rn analyses with reasonable assurance that the samples have not suffered significant 222Rn loss. Temporal variations in water 222Rn concentrations were observed in this study. One factor complicating the study of temporal variations in 222Rn concentrations was the striking influence that inconstant water usage and inadequate well purging prior to sample collection had on 222Rn loss from the water.

Evaluation Studies as Topic↗

PubMed1995

Human repeat-mediated integration of selectable markers into somatic cell hybrids.

We describe a strategy to introduce preferentially the dominant selectable marker neoR into the human chromosome within a monochromosome hybrid cell line. Integration of a construct containing the marker is mediated by human-specific repeat elements that promote multilocus human-specific integration with a single targeting vector. We tested two classes of repeat elements: the Alu family of SINE repeats and the Line1 repeat family. We show that Alu sequences alone are insufficient to direct human-specific integration but when used in combination with a Line1 element, or when only Line1 elements are included, integration of the vector into the human component of a monochromosome somatic cell hybrid is favored. The vectors also carry sequences that facilitate mapping and selective cloning of the targeted region. This strategy provides a means to generate selectable human subchromosomal fragments that can be used for localization of genes through positional cloning and, more important, for the identification of functional units through DNA transfer.

Anti-Bacterial Agents↗