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Biomedical subjects

S R Helms

Publications and source records attributed to S R Helms.

10 recordsLinked to original sources
PubMed2000

Systemic Exophiala jeanselmei infection in a cat.

A 14-year-old spayed domestic shorthair cat was referred for ultrasonographic evaluation of abnormally shaped kidneys. Multifocal lesions were detected ultrasonographically in the liver and kidneys; a fine-needle aspirate of the kidneys was performed, and numerous clumps of fungal hyphae were identified. The following day, the cat was recumbent with advanced neurologic signs. The cat was euthanatized, and a necropsy was performed. Multifocal granuloma-like masses were seen on the liver, kidneys, abdominal wall, mesentery, thoracic wall, pericardium, and epicardium. Similar lesions were found on the cervical portion of the spinal cord, the cerebrum, and cerebellum. Exophiala jeanselmei, an organism of the phaeohyphomycotic group, was identified on fungal culture. To our knowledge, systemic infections caused by this organism have not been reported. However, phaeohyphomycotic infections are believed to be an emerging disease in humans.

Abdomen↗
PubMed1991

Etoposide (VP-16-213)-induced gene alterations: potential contribution to cell death.

We have shown previously a good correlation between etoposide-induced sister chromatid exchanges (SCE) and cytotoxicity. A semisynthetic derivative of podophyllotoxin, etoposide is also called Vepesid (Bristol; code designation VP-16-213, abbreviated VP-16). Since SCE represent DNA recombinational events, we hypothesized that VP-16-induced SCE might result in nonhomologous recombination in which segments of DNA were either deleted or added, leading to an alteration of gene sequences responsible for essential cell proteins. Alterations of such essential genes and consequent interference with formation of their products could consequently lead to cell death. To evaluate whether VP-16 treatment caused sufficient levels of DNA sequence alterations to interfere with gene product formation, we isolated hypoxanthine (guanine) phosphoribosyltransferase (HPRT)-deficient mutants from Chinese hamster V79 cells grown in the presence or absence of VP-16. DNA from 3 spontaneous mutants and 10 VP-16-induced mutants was analyzed by Southern blot hybridization to a full-length hamster HPRT cDNA probe. Most of the VP-16-induced mutants showed partial deletions and/or rearrangements of the HPRT gene. In contrast, spontaneous mutants showed negligible deletions or rearrangements. These results provide strong support for our hypothesis that deletion of genetic sequences may constitute an important component of the mechanism of VP-16-induced cell death.

Animals↗
PubMed1990

Characterization of an inducible promoter system to investigate decay of stable mRNA molecules.

We have developed a system in which the decay of stable mRNAs can be studied without the use of inhibitors of transcription. The Drosophila hsp70 heat shock promoter linked to the bovine growth hormone (BGH) gene was used to establish stable cell lines in which the BGH gene is transcribed in a conditional manner. The BGH mRNA is synthesized only after induction at 43 degrees C. Following a brief period of re-equilibration at 37 degrees C during which transcription of the heat shock-driven gene ceases, the stable BGH mRNA decays with typical first-order kinetics. Hence, the decay of the mRNA can be studied without assumptions regarding radioactive labeling of precursor pools or transcriptional inhibitors. The system is applicable to any stable mRNA.

Animals↗
PubMed1987

Identification of an enhancer-like element upstream from a cell cycle dependent human H4 histone gene.

We have identified a segment of DNA in the region 6,500 nucleotides upstream from a cell-cycle-dependent human H4 histone gene (pF0108A) which exhibits properties of an enhancer element. This distal element is not required for cap site initiation from the F0108A H4 histone gene. When the enhancer element is present in the genome as a stable integrated sequence, either in its natural upstream location or in a construct where the element is moved just upstream from the proximal promoter sequences, a 25-fold increase in the level of human H4 histone RNAs is observed. This increased level of mRNA reflects an increase in the rate of transcription. The enhancer effect is also observed when the distal element is inserted in inverse orientation with respect to this gene. In addition, the far upstream element can increase expression of a prokaryotic chloramphenicol acetyl transferase (CAT) gene under control of the simian virus 40 (SV40) early promotor, indicating that the ability to influence transcription is not confined to the gene with which it is normally associated. The ability of the histone gene distal enhancer element to function in both mouse and human cells indicates that transacting regulatory factors encoded by either the human or murine genome are capable of mediating the functional properties of this element, further supporting the cross-species compatibility of regulatory sequences and molecules that influence transcription of human histone genes.

Acetyltransferases↗
PubMed1977

"Prostatic acid phosphatase?" A comparison of acid phosphatase activities in epithelial cells, granulocytes, monocytes, lymphocytes, and platelets purified by velocity sedimentation in isokinetic gradients of Ficoll in tissue culture medium.

Numerous investigators have found several substrates and inhibitors to be particularly suited for the demonstration of acid phosphatase of prostatic origin. There has been much controversy over the specificity or lack of specificity of several substrates and inhibitors. We have investigated acid phosphatase activities obtained from several kinds of purified cells. None of the substrates or inhibitors which we studied permitted us to discriminate "prostatic" acid phosphatase from acid phosphatase activities obtained from other kinds of cells.

Acid Phosphatase↗
PubMed1976

Separation of cells with histochemically demonstrable acid phosphatase activity from suspensions of cells from human prostatic carcinomas in an isokinetic gradient of Ficoll in tissue culture medium.

This report describes the separation of cells exhibiting histochemically demonstrable acid phosphatase from suspensions of cells obtained from human prostatic carcinomas by velocity sedimentation. In the unseparated suspensions of cells, 40.5 +/- 7.7% of nucleated cells contained histochemically evident acid phosphatase. After cells were separated by velocity sedimentation, 86.4 +/- 9.4% of the nucleated cells in the purest fractions exhibited histochemically demonstrable acid phosphatase activity. More than 95% of these cells excluded trypan blue. To our knowledge, this is the first report of a method for the separation of viable epithelial cells from human prostatic carcinomas.

Acid Phosphatase↗
PubMed1975

Separation of cells with histochemically demonstrable acid phosphatase activity from suspensions of human prostatic cells in an isokinetic gradient of Ficoll in tissue culture medium.

Collagenase, trypsin, and pronase were used in separate, parallel experiments to obtain cell suspensions from human prostates obtained from surgical resections and autopsies. All of the examined prostates demonstrated benign hyperplasia. The dissociation using pronase gave both the largest number of nucleated cells and the largest proportion of viable cells from prostates. Surgically resected prostates gave a larger number of cells per gram of tissue than prostates obtained from autopsy. Cells obtained from surgically resected prostates were separated both by isopycnic sedimentation and by velocity sedimentation in a previously described isokinetic gradient. We studied fifteen prostates obtained at surgery; using pronase, we obtained 2.1 plus or minus 3.5 times 10(6) cells/g. Of these cells, 34.0 plus or minus 14.7% contained histochemically demonstrable acid phosphatase. Cells from six prostates were separated by velocity sedimentation in the isokinetic gradients; in the purest fractions from the isokinetic gradients, 81.0 plus or minus 12.2% of nucleated cells had histochemically demonstrable acid phosphatase. The cells in the purest fractions appeared to be epithelial cells. More than 99% of these separated cells excluded trypan blue. Isopycnic sedimentation was not an effective means of purifying epithelial cells from human prostates.

Acid Phosphatase↗
PubMedDate not supplied

Etoposide, carmustine, bleomycin, and methotrexate with leucovorin rescue as re-treatment for unfavorable non-Hodgkin's lymphoma.

Fifteen patients with unfavorable, non-Hodgkin's lymphoma refractory to front-line chemotherapy were treated with etoposide, carmustine, bleomycin, and methotrexate with leucovorin rescue. Four patients achieved complete response and two achieved partial response. The durations of the complete responses were 4, 12, 24, and 32 months, respectively. Three of the four complete responses occurred in five patients who failed to respond to initial combination chemotherapy. The major toxic effects were severe myelosuppression in eight of 52 courses and pulmonary fibrosis in two patients. This regimen is useful in inducing durable remissions in patients with refractory, unfavorable, non-Hodgkin's lymphomas.

Adult↗