PubMed Health⌕ Search

Biomedical subjects

H S Smith

Publications and source records attributed to H S Smith.

At least 73 records · Page 4Linked to original sources
PubMed1991

"Superscan" appearance in distal renal tubular acidosis.

Distal renal tubular acidosis (RTA) is known to cause metabolic bone abnormalities. For the first time to our knowledge, a case of distal RTA is reported in association with a superscan on bone scintigraphy. Reported cases of metabolic bone diseases producing a superscan appearance were reviewed, and underlying mechanisms are discussed. We speculate that impaired hydrogen ion secretion in this patient with distal RTA subclinically increased bone turnover, contributing to the superscan appearance on bone scintigraphy.

Acidosis, Renal Tubular↗
PubMed1991

The use of the Penlon Nuffield 200 in a monoplace hyperbaric oxygen chamber. An evaluation of its use and a clinical report in two patients requiring ventilation for carbon monoxide poisoning.

We modified a Penlon Nuffield 200 for use in a monoplace hyperbaric oxygen chamber by feeding back the chamber pressure to the reducing valve of the Nuffield 200. This provides a compensating mechanism, allowing the ventilator to deliver adequate tidal volumes at pressures of up to 3 atmospheres. We report the laboratory testing of the ventilator and our experience of ventilating two patients with carbon monoxide poisoning. Although compensation is not complete the modification is adequate for short-term clinical use in patients in whom the airway is compromised but who need hyperbaric oxygen therapy.

Adult↗
PubMed1991

A comparison between bromodeoxyuridine and 3H thymidine labeling in human breast tumors.

The fraction of tumor cells in the DNA synthesis (S) phase of the cell cycle is a strong prognostic indicator in human breast cancer. Most studies measuring S-phase in primary tumors have used either in vitro labeling with 3H thymidine or DNA flow cytometry. The former involves a cumbersome and time-consuming radioactive assay, while the latter is heavily dependent on the quality of the preparation and the effectiveness of the algorithms used. In this study, in vivo or in vitro labeling with bromodeoxyuridine (BrdUrd) was compared with in vitro labeling using 3H thymidine in a series of 33 human breast tumors. Thymidine labeling showed strong correlation with both in vitro (r = 0.96) and in vivo (r = 0.83) BrdUrd incorporation. The reliability between observers was higher for BrdUrd counting (r = 0.94) than for thymidine counting (r = 0.87). The mean labeling index of 15 tumors labeled in vivo with BrdUrd was 5.9% compared to 4.7% for 18 tumors labeled in vitro (p = 0.34). There was poor correlation between flow cytometric and microscopic analysis of BrdUrd incorporation (r = 0.37). We conclude that microscopic analysis of in vivo or in vitro BrdUrd incorporation is a rapid and reliable method to estimate breast tumor proliferation.

Analysis of Variance↗
PubMed1991

Proliferation of normal breast epithelial cells as shown by in vivo labeling with bromodeoxyuridine.

The proliferative activity of normal acinar and ductal breast epithelial cells was studied by in vivo labeling with 5-bromodeoxyuridine (BrdUrd) in 26 cases with concurrent breast carcinoma. The BrdUrd-labeled cells were recognized in histologic sections of paraffin-embedded tissue, using an anti-BrdUrd antibody and an immunoperoxidase reaction. The percentage of BrdUrd-labeled cells showed great variability for both acinar (0% to 2.66%; mean, 0.70%; standard deviation [SD], 0.80%) and ductal cells (0% to 1.99%; mean, 0.51%; SD, 0.57%). The fraction of proliferating epithelial cells declined with the age of the patients and was significantly higher in premenopausal women (1.16% +/- 0.85% for acinar and 0.94% +/- 0.60% for ductal cells) as compared with the postmenopausal women (0.27% +/- 0.46% for acinar and 0.17% +/- 0.22% for ductal cells), P less than 0.01 for acinar and P less than 0.001 for ductal cells, respectively. In some patients, great variability in distribution of proliferating acinar and ductal cells among different lobules and ducts was observed. No difference was found in the number of proliferating acinar and ductal cells situated near or far from their corresponding tumors. No correlation was seen between cell proliferation of normal acinar or ductal cells and cell proliferation of the respective tumors.

Adult↗
PubMed1990

Preliminary correlations of clinical outcome with in vitro chemosensitivity of second passage human breast cancer cells.

These studies describe the clinical correlations of 63 in vitro chemosensitivity assays on breast cancer cells after short-term monolayer culture. Forty-five of the assays were single agent correlations. Based on cut-off values determined empirically, the test accurately predicted resistance for 36 of 41 patients (88%) who did not respond to the drug. It also predicted sensitivity with a high degree of accuracy: 21 of 22 patients (95%) who responded to the drug tested had a sensitive assay. In five cases, two biopsies were evaluated from the same patient. Whenever assays were performed before and after treatment with a given drug, tumor cells from the second biopsy were more resistant in vitro if the patient failed on therapy. If the patient did not fail, but stopped therapy for other reasons, or if there was no intervening therapy with the tested drug, the two biopsies remained similar in drug sensitivity. These results suggest that in vitro chemosensitivity assays which accurately predict both sensitivity and resistance can be obtained with breast cancer cells after short-term culture and that further prospective trials are warranted.

Antineoplastic Agents↗
PubMed1990

DNA amplification is rare in normal human cells.

Three types of normal human cells were selected in tissue culture with three drugs without observing a single amplification event from a total of 5 x 10(8) cells. No drug-resistant colonies were observed when normal foreskin keratinocytes were selected with N-(phosphonacetyl)-L-aspartate or with hydroxyurea or when normal mammary epithelial cells were selected with methotrexate. Some slightly resistant colonies with limited potential for growth were obtained when normal diploid fibroblast cells derived from fetal lung were selected with methotrexate or hydroxyurea but careful copy-number analysis of the dihydrofolate reductase and ribonucleotide reductase genes revealed no evidence of amplification. The rarity of DNA amplification in normal human cells contrasts strongly with the situation in tumors and in established cell lines, where amplification of oncogenes and of genes mediating drug resistance is frequent. The results suggest that tumors and cell lines have acquired the abnormal ability to amplify DNA with high frequency.

Breast↗
PubMed1990

Morphometric analysis of epidermal differentiation in primary roots of Zea mays.

Epidermal differentiation in primary roots of Zea mays was divided into six cell types based on cellular shape and cytoplasmic appearance. These six cell types are: 1) apical protoderm, located at the tip of the root pole and characterized by periclinally flattened cells; 2) cuboidal protoderm, located approximately 230 microns from the root pole and characterized by cuboidal cells; 3) tabular epidermis, located approximately 450 microns from the root pole and characterized by anticlinally flattened cells; 4) cuboidal epidermis, located approximately 900 microns from the root pole and characterized by cuboidal cells having numerous small vacuoles; 5) vacuolate cuboidal epidermis, located approximately 1,500 microns from the root pole and characterized by cuboidal cells containing several large vacuoles; and 6) columnar epidermis, located approximately 2,200 microns from the root pole (i.e., at the beginning of the zone of elongation) and characterized by elongated cells. We also used stereology to quantify the cellular changes associated with epidermal differentiation. The quiescent center and the apical protoderm have significantly different ultrastructures. The relative volume of dictyosomes increases dramatically during the early stages of epidermal differentiation. This increase correlates inversely with the amount of coverage provided by the root cap and mucilage.

Cell Compartmentation↗
PubMed1990

Molecular, biochemical, and cellular biology of human breast cancer.

The meeting at Tamarron illustrated the multiplicity of molecular changes found in breast cancer and concluded with the disquieting sense that, so far, there is no simple unifying molecular model to explain the etiology of the disease. Perhaps the complex nature of breast cancer precludes formulation of a simple model. The biologic heterogeneity of breast cancers may reflect the fact that, at the molecular level, there is more than one way to accomplish each of the phenotypic changes necessary for malignant growth. At this point in time, it is difficult to evaluate which molecular changes will be important to understanding and subsequently interfering with the disease process. Additional studies correlating molecular and biochemical changes in human breast tumors with clinical disease characteristics and patient outcome should help to clarify these issues.

Breast Neoplasms↗
PubMed1990

Overexpression of matrix Gla protein mRNA in malignant human breast cells: isolation by differential cDNA hybridization.

Genetic alterations are involved in the development of human breast cancer. We sought to isolate genes that are differentially expressed or suppressed in cultured human breast carcinoma cells as compared to cultured normal human breast epithelial cells by employing differential screening of selected cDNA libraries. Analysis of several clones thus isolated revealed that the matrix Gla protein (MGP) gene is overexpressed in the breast cancer cell line 600 PEI, though is transcribed at lower levels in most other mammary derived cultures. MGP requires vitamin K dependent gamma-carboxylation for its known function and thus can be inhibited by vitamin K antagonists. This raises the possibility that MGP may be among those factors that when inhibited by vitamin K antagonists reduce metastases in experimental models. Among the gene whose transcription is consistently suppressed upon mammary transformation were fibronectin and the type I keratin, K14. Differential cDNA screening therefore is an effective method of identifying genes involved in various aspects of mammary cell transformation.

Base Sequence↗
PubMed1989

Expression of c-myc, c-Ha-ras1, and c-erbB-2 proto-oncogenes in normal and malignant human breast epithelial cells.

Short-term cultures of normal human mammary epithelial cells were used to determine the extent to which c-myc, c-Ha-ras1, and c-erbB-2 proto-oncogenes were expressed in proliferating normal cells. This level of expression was compared with that of primary tumor cells, malignant effusion cells, or permanently established breast cancer cell lines. Pure preparations of epithelial organoids from seven different reduction mammoplasty tissue samples yielded proliferating normal epithelial cells upon short-term tissue culture. In every sample, proto-oncogene transcript levels increased upon short-term culture of the epithelial cells. These levels often exceeded by 10-fold the levels measured in uncultured organoids from the same tissue. In four of the seven cultured normal breast samples, at least one of the proto-oncogenes increased its expression to a level equaling or exceeding that found in a proliferating breast cancer cell line, MCF7. One effusion metastasis sample and two primary ductal adenocarcinomas were also examined for proto-oncogene expression. The effusion metastasis sample expressed high levels of c-erbB-2 messenger RNA, in accord with its amplified gene copy number; otherwise, the levels of proto-oncogene transcripts were low in unprocessed tumor and uncultured organoids, but they increased with proliferation of the tumor cells in culture. These results indicate that the variable expression of these proto-oncogenes observed in breast biopsy specimens needs to be controlled for cellular growth rate or proliferation index. Furthermore, these findings suggest that dysregulated proto-oncogene expression, rather than overexpression per se, needs to be evaluated as a possible mechanism contributing to the development of human breast cancer.

Blotting, Northern↗
PubMed1989

Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio.

One hundred one patients with coronary artery disease and pretreatment ratios of total cholesterol to high density lipoprotein (HDL) cholesterol greater than 4.0 were treated with niacin, commencing at low dosages (100 to 250 mg twice daily) and gradually increasing the dosage over 4 to 8 weeks to 1,000 mg twice daily. Dosage adjustments were made to minimize side effects. At a mean follow-up duration of 11 +/- 7 months, and a mean dosage of 1,415 +/- 698 mg/day, the group had a 13% reduction in total cholesterol, 31% increase in HDL and 32% decrease in the cholesterol to HDL ratio. A subgroup of 62 patients taking greater than 1,000 mg/day of niacin had an 18% reduction in total cholesterol, 32% increase in HDL and 36% improvement in the cholesterol to HDL ratio. A subgroup of 39 patients taking less than or equal to 1,000 mg/day of niacin had only a 5% reduction in total cholesterol, although a 29% increase in HDL and a 24% decrease in the cholesterol to HDL ratio were recorded. Side effects of niacin were reported in 38% of the patients, but led to discontinuation of therapy in only 4. Niacin can be administered in a fashion that is well tolerated, inexpensive and very effective in improving the cholesterol to HDL ratio.

Adult↗
PubMed1989

Incidence of activating ras oncogene mutations associated with primary and metastatic human breast cancer.

To test the hypothesis that ras activation is involved in the final stages of breast cancer progression, we analyzed tumor DNA derived from 60 different patients and extracted from 40 invasive primary breast tumors, seven lymph node and skin metastases, nine metastatic effusions, and five established breast cancer cell lines. The polymerase chain reaction technique was used to amplify DNA fragments containing Kirsten-(Ki-), Harvey-(Ha-), and N-ras codons 12, 13, and 61 which were then probed on slot-blots with labeled synthetic oligomers to detect nonconservative single base mutations. Activating mutations were found in one of 40 primary tumors (Ki-ras codon 13), zero of seven lymph node and skin metastases, one of nine metastatic effusions (Ki-ras codon 12), and two of five cell lines (Ki-ras codons 12 and 13). These results indicate that activating ras mutations are rarely involved in either the initiation or metastatic progression of human breast cancer.

Breast Neoplasms↗
PubMed1989

Cell dissociation techniques in human breast cancer--variations in tumor cell viability and DNA ploidy.

Approximately 70% of breast cancers contain cell populations with hyperdiploid (greater than G0/G1) DNA content; however, cells cultured from breast cancers have only diploid DNA contents and karyotypes. Mechanically dissociated cells rarely, if ever, grow in culture, while enzymatically dissociated cells do grow in most cases. To determine if cell dissociation techniques used to prepare cells for culture and other laboratory procedures select for cells with specific features, and if tumor cells are killed in the process, breast cancer cells obtained by mechanical dissociation and by enzymatic dissociation were examined for DNA content and cell viability (measured by dye exclusion). Mechanical dissociation yielded more dead cells and cells with hyperdiploid (greater than G0/G1) DNA than did enzymatic dissociation. Hyperdiploid cells were also found in the dye-excluding population with each dissociation technique, suggesting that the hyperdiploid cells were not always dead. We conclude that, in vivo, tumors contain cellular subpopulations with low viability and hyperdiploid (greater than G0/G1) DNA patterns. The extent to which these subpopulations are present in a sample depends on the dissociation technique employed. That only diploid cells are found in cultures of primary breast cancers may be because enzymatic dissociation, used to prepare cells for culture, yields predominantly diploid cells. These observations also have important implications for interpreting measurements made on dispersed cells, e.g., viability, DNA content, and other cytochemical markers.

Breast Neoplasms↗
PubMed1989

Loss of heterozygosity on chromosome 1q in human breast cancer.

Cytogenetic markers involving the long arm of chromosome 1 are the most frequently observed karyotypic changes seen in breast cancer. Based on cytogenetic data, we have used polymorphic DNA markers to search for allelic losses at this chromosome region among 48 breast carcinomas. For SPTA1, allelic losses were seen in 6 of 26 (23%) informative carcinomas, while 3 of 13 (23%) and 5 of 19 (26%) informative patients showed losses at AT3 and D1S53, respectively. The background frequency of allelic loss was obtained from data using 3 other loci on the 1q arm and 2 on the p arm of chromosome 1. With these markers, only 6 of 62 informative patients (8%) showed an allelic loss, with the range being 0-13%. The allelic losses seen on 1q, which were found in 9 carcinomas, comprised an overlapping set; the common region deleted was approximately 26 centimorgans on the q arm of chromosome 1 (bands q23-32 between AT3 and D1S53). These results suggest that inactivation of a gene(s) located on 1q23-32 might contribute to the genesis of breast cancer.

Alleles↗