Biomedical subjects

R Callahan

Publications and source records attributed to R Callahan.

At least 73 records · Page 4Linked to original sources

PubMed1991

Meconium-stained amniotic fluid: a risk factor for microbial invasion of the amniotic cavity.

The purpose of this study was to determine whether meconium-stained amniotic fluid is a marker for microbial invasion of the amniotic cavity. Amniocentesis was performed on 707 patients presenting with preterm labor and intact membranes. Meconium-stained amniotic fluid was present in 4.2% (30/707) of patients with preterm labor. The prevalence of positive amniotic fluid cultures was significantly higher in women with meconium-stained amniotic fluid than in women with clear fluid (33% [10/30] vs 11% [75/677]; p = 0.001; odds ratio = 4.01; 95% confidence interval = 1.6 to 9.4). Patients with meconium-stained amniotic fluid were also more likely to have failed tocolysis and delivered a preterm neonate more frequently than patients with clear fluid (83% [25/30] vs 38% (258/677); p = 0.0001; odds ratio = 8.1; 95% confidence interval = 2.9 to 24.4). We conclude that meconium-stained amniotic fluid is a risk factor for microbial invasion of the amniotic cavity and preterm delivery in women with preterm labor and intact membranes.

Amniotic Fluid↗

PubMed1991

The mouse biliary glycoprotein gene (Bgp): partial nucleotide sequence, expression, and chromosomal assignment.

Transcripts related to the human carcinoembryonic antigen were found in mRNA isolated from both dimethylbenzanthracene-induced and mouse mammary tumor virus-induced mammary tumors. A cDNA library was prepared from a dimethylbenzanthracene-induced tumor, and a clone was isolated by hybridization with a human carcinoembryonic antigen cDNA probe. Its sequence, when compared to those of members of the human carcinoembryonic antigen gene family, was most homologous to the sequence of the human biliary glycoprotein (BGP) gene. Thus, this clone appears to encode a portion of the mouse biliary glycoprotein gene. Southern blot analysis of EcoRI-digested mouse cellular DNA with this probe detected four restriction fragments, all of which appear to be located on mouse chromosome 7, Northern blot analysis using the mouse probe demonstrated that related mRNA species were expressed in some normal adult mouse tissues.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Imaging of Pneumocystis carinii pneumonia with 111In-labelled non-specific polyclonal IgG: an experimental study in rats.

The relative sensitivity of imaging with 67Ga-citrate (67Ga) and non-specific human polyclonal IgG radiolabelled with 111In (111In-IgG) for the detection of Pneumocystis carinii pneumonia (PCP) was determined in rats. Pneumocystis carinii pneumonia was induced by low protein diet and dexamethasone. The course of the disease was monitored by serial imaging with 111In-IgG and 67Ga. Diffuse accumulation of both radiopharmaceuticals was observed in the lungs of infected animals (infection was verified by histological examination of the lungs), however, accumulation of 111In-IgG was consistently higher. In rats with early PCP, 111In-IgG imaging revealed pulmonary accumulation in animals with normal chest radiographs and 67Ga scans. In animals successfully treated for PCP, decreased pulmonary accumulation of 111In-IgG coincided with histological improvements. Several animals developed superinfection with bacteria or fungi. These animals had striking focal accumulation of 111In-IgG, in addition to the pattern of generalized uptake. Gallium concentration in these animals did not show this focal accumulation. These observations suggest that 111In-IgG may be useful for detecting PCP and pulmonary abscesses in the immunocompromised host.

Animals↗

PubMed1991

Differentiation of regional perfusion and fatty acid uptake in zones of myocardial injury.

The relative myocardial distribution of 201Tl and modified fatty acid (123I-labelled 3-methyl-p-[iodo]-phenyl pentadecanoic acid, MFA) was determined in eight patients with unstable angina (UA) and six patients with acute myocardial infarction treated with reperfusion therapy within 4.1 h (MI). The results of radionuclide imaging were correlated with coronary angiography and quantitative left ventriculography performed within 10 days of the radionuclide procedures. Zones of injury were identified as areas with diminished 201Tl uptake distal to sites of coronary narrowing. A nearly parallel reduction in regional fatty acid concentration was observed in these areas. Comparison of the regional distributions of the two agents revealed subtle differences in their distributions in the ischaemic zones. Three patterns were recognized: (a) MFA uptake greater than Tl (MFA greater than Tl), (b) matched decrease of MFA and Tl (MFA = Tl), (c) MFA uptake less than Tl (MFA less than Tl). Seven of eight patients with UA had normokinesis or hypokinesis on quantitative left ventriculography. Five of the seven showed the MFA greater than Tl pattern, while one had the MFA less than Tl pattern and one had the MFA = Tl pattern. The eighth patient with UA had akinesis and the MFA = Tl pattern. All six patients with acute infarction had akinesis on ventriculography. One of these patients had the MFA greater than Tl pattern, two had the MFA = Tl pattern and three had the MFA less than Tl pattern. These results suggest that fatty acid and thallium have grossly similar distributions in areas of acute myocardial ischaemia. On careful inspection, zones of slight relative excess fatty acid concentration are observed more often in areas of acute ischaemia with normal wall motion.

Adult↗

PubMed1991

Long-term in vivo expression of genes introduced by retrovirus-mediated transfer into mammary epithelial cells.

Nonimmortalized mouse mammary epithelial cells expressing Escherichia coli beta-galactosidase from a murine amphotropic packaged retroviral vector were injected into the epithelium-divested mammary fat pads of syngeneic mice. Mammary glands formed from the injected mammary epithelial cells contained ductal and lobular cells, both of which expressed beta-galactosidase when examined in situ more than 12 months later. These results indicate that stable recombinant gene expression can be achieved in vivo in the mammary gland without altering the growth properties of normal mammary epithelium.

3T3 Cells↗

PubMed1991

Host genetic background effect on the frequency of mouse mammary tumor virus-induced rearrangements of the int-1 and int-2 loci in mouse mammary tumors.

The frequency with which int-1 and int-2 are rearranged in mouse mammary tumors by mouse mammary tumor virus (MMTV)-induced insertional mutagenesis is a consequence of the host genetic background. In 75% of C3H mammary tumors, int-1 is rearranged by MMTV insertion, whereas only 30% of BALB/cfC3H tumors contain a virus-induced rearrangement of int-1. This difference is significant (P less than 0.005) and could not be accounted for by the potentially additive effect of the genetically transmitted Mtv-1-encoded virus in C3H mice. Similarly, MMTV-induced rearrangement of the int-2 gene in mammary tumors of the R111 mouse strain (59%) occurred at a significantly (P less than 0.025) higher frequency than in BALB/cfR111 (25%) mammary tumors. Moreover, in BALB/cfR111 mammary tumors, there is evidence that rearrangement of int-1 and int-2 does not occur independently (P less than 0.025). These results suggest that the long history of inbreeding for high tumor incidence of C3H and R111 mouse strains has selected for the fixation of host mutations which either complement the action of the particular int gene or affect the sensitivity of specific subpopulations of mammary epithelium to infection by particular strains of MMTV.

Animals↗

PubMed1991

Detection of loss of heterozygosity in tumor DNA samples by PCR.

We demonstrate that PCR amplification of human genomic DNA can be used for the detection of loss of heterozygosity (LOH) in tumor samples. A 250-bp fragment containing codon 72 of the human p53 gene was amplified, ThaI digested and electrophoresed. Tumor LOH is detectable both by ethidium bromide staining and autoradiography, despite 25% contamination with normal DNA. This technique provides a fast and reproducible alternative to conventional Southern blotting and has minimal sample requirements.

Base Sequence↗

PubMed1990

Loss of heterozygosity of the L-myc oncogene in human breast tumors.

Recent studies suggest that loss of heterozygosity may play an important role in various human neoplasia. Cytogenetic abnormalities detected in primary breast tumors led us to examine breast tumor DNAs for deletions. In the present study, we demonstrate, using restriction fragment length polymorphism (RFLP) analysis at the L-myc proto-oncogene (chromosome 1p32), a frequent loss of heterozygosity in primary breast tumor DNAs (55 out of 152 informative tumor DNAs). Most of these deletions appear to be limited to chromosome 1p. No correlation was observed between this genetic alteration and several parameters of each patient's history or characteristics of the tumor. However, a significantly (P = 0.011) shorter survival period after relapse was observed for patients with loss of heterozygosity at L-myc in primary tumor DNAs compared with patients with tumor DNAs lacking this alteration.

Blotting, Southern↗

PubMed1990

Chimeric B72.3 mouse/human (IgG1) antibody directs the lysis of tumor cells by lymphokine-activated killer cells.

Chimeric mouse/human B72.3 (cB72.3) antibodies having a human IgG1 (gamma 1) or IgG4 (gamma 4) constant region were compared to the native murine IgG1 B72.3 (nB72.3) monoclonal antibody (mAb) for their ability to participate with human effector cells in antibody-dependent cellular cytotoxicity (ADCC). Because the TAG-72 antigen recognized by B72.3 is poorly expressed on tissue-cultured tumor cell lines, the xenografted OVCAR-3 human ovarian carcinoma ascites was used as a cytotoxicity target. The lytic activity of the cB72.3(gamma 1) mAb with peripheral blood lymphocytes was 1.5- to 50-fold greater than that of the nB72.3 mAb and usually the cB72.3(gamma 4) mAb. However, lymphocytes from some donors had similar ADCC activity with either the cB72.3(gamma 1) or cB72.3(gamma 4) mAb. The cB72.3(gamma 1) and the murine anti-colon carcinoma CO17-1A mAb had comparable activity in mediating ADCC against the OVCAR-3 tumor. Exposure of lymphoid cells to interleukin-2 (IL-2) (100-500 U/ml) for 24 h to generate lymphokine-activated killer (LAK) cells augmented ADCC mediated by the cB72.3(gamma 1) mAb 2- to 22-fold. By contrast, LAK cells from most donors expressed weak non-specific cytotoxicity against OVCAR-3 ascites tumor cells. The cB72.3(gamma 1), and to a lesser extent, the cB72.3(gamma 4) chimera also participated with monocytes in mediating ADCC, but the antibody-dependent lytic potency of monocytic effectors was much weaker than that of IL-2-activated lymphoid cells. These studies show that the cB72.3(gamma 1) mAb has appreciable ADCC-mediating properties, suggesting a potential role for its incorporation into treatment strategies utilizing adoptive killer cell and/or lymphokine therapy.

Animals↗

PubMed1990

Infection and labor. VI. Prevalence, microbiology, and clinical significance of intraamniotic infection in twin gestations with preterm labor.

The purpose of this study was to establish the prevalence, microbiology, and outcome of microbial invasion of the amniotic cavity in twin gestation presenting with preterm labor and intact membranes. Amniocenteses were performed on both sacs of 46 women with twin gestations, preterm labor, and intact membranes. Indigo carmine was injected to ensure sampling of both amniotic sacs. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Mycoplasma hominis, and Ureaplasma urealyticum. A positive amniotic fluid culture of at least one sac was noted in 10.8% (5/46) of patients admitted in preterm labor and in 11.9% (5/42) of women delivered of preterm neonates. Of the five patients with microbial invasion of the amniotic cavity, three had microorganisms isolated from both sacs. The presenting sac was involved in all cases, supporting an ascending route for microbial invasion of the amniotic cavity in twin gestation. Polymicrobial infection was found in three of the eight amniotic sacs with positive cultures. In two cases different organisms were isolated from each sac. All patients with positive amniotic fluid cultures were delivered of preterm infants within 48 hours of amniocentesis. Patients with positive amniotic fluid cultures presented with preterm labor at an earlier gestational age and with more advanced cervical dilatation than did women with negative amniotic fluid cultures. Clinical evidence of chorioamnionitis subsequently developed in two of five women with positive amniotic fluid cultures. The interval between amniocentesis and delivery was shorter in women with positive amniotic fluid cultures than in women with negative amniotic fluid cultures (median: 3.5 vs 168 hours, p less than 0.0001). Infants born to women with microbial invasion of the amniotic cavity had a lower median birth weight and a higher incidence of respiratory distress syndrome than those born to women with negative amniotic fluid cultures (birth weight: 1085 vs 1975 gm, p = 0.024; respiratory distress syndrome: 37.5% vs 8.3%, p = 0.04).

Amniotic Fluid↗

PubMed1990

Amniotic fluid glucose concentration: a rapid and simple method for the detection of intraamniotic infection in preterm labor.

The purpose of this study was to determine whether amniotic fluid glucose concentrations is of value in the rapid diagnosis of intraamniotic infection. Amniocenteses were performed in 168 patients with preterm labor and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as Mycoplasma species. The prevalence of positive amniotic fluid cultures was 13.6% (23/168). Patients with positive amniotic fluid cultures for microorganisms had significantly lower median amniotic fluid glucose concentrations than patients with negative amniotic fluid cultures (median 11 mg/dl, range 2 to 30 mg/dl vs median 28 mg/dl, range 3 to 74, respectively; p less than 0.001). Amniotic fluid glucose concentrations below 14 mg/dl had a sensitivity of 86.9% (20/23), a specificity of 91.7% (133/145), a positive predictive value of 62.5% (20/32), and a negative predictive value of 97.8% (133/136) in the detection of a positive amniotic fluid culture. Amniotic fluid glucose determination is a rapid, sensitive, inexpensive, and simple test for the detection of intraamniotic infection in women with preterm labor and intact membranes.

Amniotic Fluid↗

PubMed1990

Transforming growth factor-alpha messenger RNA localization in the developing adult rat and human mammary gland by in situ hybridization.

Transforming growth factor-alpha (TGF alpha) has been implicated in the autocrine growth control of a number of different rodent and human tumor cells, including breast cancer cells. Although TGF alpha has been detected in a limited number of normal tissues, its distribution and physiological function in the mammary gland are relatively unknown. TGF alpha mRNA expression was detected by in situ hybridization with a labeled TGF alpha antisense RNA probe and quantitated by application of computer-assisted digital image processing in both the ductal and alveolar epithelial cells in the virgin rat and nulliparous and parous human mammary glands. During pregnancy and lactation, the level of TGF alpha mRNA expression in the ductal and alveolar epithelial cells increased two- to threefold, while a heterogeneous yet strong expression of TGF alpha mRNA could also be detected in approximately 10-15% of the surrounding stromal cells in the pregnant mammary gland.

Animals↗

PubMed1990

Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified.

The loss of heterozygosity (LOH) at specific regions of the human genome in tumor DNA is recognized as evidence for a tumor-suppressor gene located within the corresponding region of the homologous chromosome. Restriction fragment length polymorphism analysis of a panel of primary human breast tumor DNAs has led to the identification of two additional regions on chromosomes 17q and 18q that frequently are affected by LOH. Deletions of each of these regions have a significant correlation with clinical parameters that are associated with aggressive breast carcinomas. Previous restriction fragment length polymorphism analysis of this panel of tumors has uncovered several other frequently occurring mutations. LOH on chromosome 18q frequently occurs in tumors with concomitant LOH of loci on chromosomes 17p and 11p. Similarly, tumors having LOH on 17q also have LOH on chromosomes 1p and 3p. This suggests that certain combinations of mutations may collaborate in the development and malignant progression of breast carcinomas.

Blotting, Southern↗

PubMed1990

Redistribution of regional and organ blood volume and effect on cardiac function in relation to upright exercise intensity in healthy human subjects.

To determine the effect of relative exercise intensity on organ blood volume and its relation to cardiac function, changes in relative blood volume and cardiac function were monitored with radionuclide techniques in 14 healthy volunteers. After labeling the subject's red cells with technetium 99m, we acquired data at rest, zero-load cycling, and at 50%, 75%, and 100% of maximal oxygen uptake. From rest to zero-load cycling, leg blood volume decreased 32 +/- 2% (mean +/- SEM), whereas relative end-diastolic blood volume increased 9.6 +/- 1.2%, and lung blood volume increased 18 +/- 2%, suggesting that the lungs may act as a blood volume buffer during periods of acutely increased venous return. With relative increasing exercise, leg blood volume stabilized, and then the blood volume in the abdominal organs decreased, further augmenting cardiopulmonary blood volume; leg blood volume and abdominal blood volume decreased by 23 +/- 2% and 19 +/- 2% from baseline, respectively, whereas thoracic blood volume increased 38 +/- 4%. In the abdomen, large decreases in blood volume were observed in the spleen (46 +/- 2%), kidney (24 +/- 4%), and liver (18 +/- 4%). In contrast, lung blood volume increased 50 +/- 4%, with the upper lung fields increasing more than the lower. Blood sampling revealed an increase in the hematocrit level by 4.3 +/- 0.4 units at peak exercise that paralleled the decrease in splenic blood volume (r2 = -0.64, p less than 0.001), suggesting a role for the spleen in augmenting cardiovascular performance by the release of concentrated red blood cells into general circulation. We conclude that upright exercise results in marked blood volume shifts from the legs and abdominal organs to the heart and lungs in a dynamic process correlating closely with oxygen consumption.

Adult↗

PubMed1989

Frequent alteration of the DF3 tumor-associated antigen gene in primary human breast carcinomas.

The gene for the human DF3 breast carcinoma-associated antigen contains a conserved (G + C)-rich 60-base pair tandem repeat and maps to chromosome 1q21-24. In the present study we isolated and characterized 1220 base pairs of nonrepetitive adjacent sequences. Multiple alleles were identified by fragment size. Signal intensity of hybrids with the tandem and unique sequence probes indicated that allelic variation is due to different numbers of repeats. Probes for both the tandem and the unique sequences were used to study the DF3 locus in human breast tumor DNAs. Seventy of 110 breast tumor DNAs were informative at the DF3 locus. Of these, 20 (29%) showed a loss of heterozygosity, while eight (11%) had an increased copy number of one allele. In some cases, the loss of heterozygosity or increased copy number did not extend to other markers on chromosome 1q or 1p. These data indicate that the chromosomal region around the DF3 locus is affected by mutations at high frequency.

Amino Acid Sequence↗

PubMed1989

Mutations in human breast cancer: an overview.

Studies of mammary tumorigenesis in mice infected with the mouse mammary tumor virus and in certain strains of transgenic mice with an activated oncogene have provided strong evidence that multiple mutations contribute to the initiation and progression of malignancies in the breast. The increasing availability of recombinant DNA probes that detect various proto-oncogenes, growth factor genes, and growth factor receptor genes, as well as restriction fragment length polymorphisms in the human population, have made possible a molecular approach for the identification of frequently occurring mutations in primary human breast tumor DNA. The aim of studies using this molecular approach has been to investigate whether specific mutations are highly associated with various clinical parameters, including disease prognosis. Eight mutations have been identified, including amplification of c-myc, c-erbB2, and int-2, as well as loss of heterozygosity on five chromosomes (1q, 3p, 11p, 13q, and 17p). Loss of heterozygosity is thought to unmask recessive mutations of tumor-suppressor genes. In some studies, amplification of either c-myc, c-erbB2, or int-2 has been found to have a significant association with high risk of relapse or poor survival. The current status of these mutations as potentially useful prognostic indicators for the management of the disease is controversial and points to the need for further research in this area.

Animals↗

PubMed1989

Presence of two members of c-erbA receptor gene family (c-erbA beta and c-erbA2) in smallest region of somatic homozygosity on chromosome 3p21-p25 in human breast carcinoma.

The loss of heterozygosity of genes on the short arm of chromosome 3 (3p) in human breast carcinomas occurs in a region involved in other malignancies, including renal cell carcinoma, lung cancers, and von Hippel-Lindau disease. This finding suggests the presence of a gene(s) that plays a crucial role in multiple cancers. In our study of 84 informative (heterozygous) primary breast tumors, 30% showed losses of heterozygosity on chromosome 3. The shortest region of homozygosity in primary human breast tumor is located between the DNF15S2 and RAF1 loci in the 3p21-p25 region on the short arm of chromosome 3. This region includes at least two members of the c-erbA steroid/thyroid hormone receptor family (c-erbA beta and c-erbA2) that may be of special relevance to breast cancer. Furthermore, tumors with a loss of heterozygosity of genes on chromosome 3 were previously reported to have frequent allelic deletions on chromosome 11p and amplification of the c-myc proto-oncogene. These results highlight the occurrence of multiple genetic alterations in breast tumors.

Breast Neoplasms↗

PubMed1989

Amplification of the proto-oncogenes int-2, c-erb B-2 and c-myc in human breast cancer.

int-2 is a proto-oncogene that is partially homologous to angiogenesis-inducing fibroblast growth factor and is believed to play a role in mouse mammary carcinogenesis. Recent evidence has suggested that this proto-oncogene may also play a role in human breast cancer. In the present study, we used Southern hybridization analysis to examine DNA from 79 primary and 11 recurrent human breast cancers for evidence of activation of int-2 through either gene rearrangement or amplification. A similar analysis was performed for two other proto-oncogenes, c-erbB-2 and c-myc, also suspected of playing a role in the development of human breast cancer. Proto-oncogene status was correlated with estrogen (ER) and progesterone (PR) receptor status, patient age, and lymph node (LN) status at the time of surgery. Gene rearrangement was not a frequent occurrence with any of the proto-oncogenes. However, amplification of int-2 occurred at a significantly higher frequency in recurrent breast cancers than in primary cancers and in patients with primary cancers who were less than or equal to 50 years of age versus greater than 50 years of age at surgery. Although amplification of all three proto-oncogenes occurred at a greater frequency in primary tumors from patients with lymph node metastases than from those without lymph node metastases, a significant difference was noted only in the case of c-myc amplification. These findings confirm and extend earlier results of studies of int-2, c-erbB-2 and c-myc amplification in human breast cancers and point to a role for int-2 activation in certain cases of recurrent breast malignant neoplasia.

Breast Neoplasms↗