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Biomedical subjects

A M Lewis

Publications and source records attributed to A M Lewis.

At least 91 records · Page 5Linked to original sources

Suppression of the simian virus 40 tumorigenic phenotype in hybrid cells formed from simian virus 40- and adenovirus 2-transformed hamster embryo cells.

Hamster cells transformed by adenovirus 2 (Ad2) or simian virus 40 (SV40) have different tumorigenic phenotypes. In the present study, somatic cell hybrids formed from Ad2- and SV40-transformed hamster cells were used to determine whether possible interactions between the integrated viral genomes would influence the tumorigenic phenotype of hybrid transformed cells. These somatic cell hybrids were of two types, one expressing both Ad2 and SV40 T-antigens and the other expressing only SV40 T-antigens. Tumor induction by hybrid cells that expressed both Ad2 and SV40 T-antigens was reduced in adult syngeneic hamsters and abrogated in adult allogeneic hamsters. These results indicate that the tumorigenic phenotype of transformed somatic cell hybrids that contain both the Ad2 and SV40 genome is governed by the genetic expression of Ad2. This expression may alter the ability of SV40-transformed hamster cells to resist the immunologically nonspecific defenses of the host.

Adenoviridae↗

DNA virus-transformed hamster cell--host effector cell interactions: level of resistance to cytolysis correlated with tumorigenicity.

Spontaneously cytolytic hamster spleen cells and BCG-activated hamster macrophages were used to examine susceptibilities to nonspecific effector cell-induced lysis among 13 DNA virus-transformed hamster cell lines exhibiting four different tumorigenic phenotypes. Hamster cells transformed by adenovirus type 12 (an oncogenic adenovirus serotype) or simian virus 40 (an oncogenic papovavirus) readily induced tumors in immunocompetent syngeneic hamsters and were relatively resistant to spleen-cell-induced lysis compared to cells transformed by adenovirus type 2 (a non-oncogenic adenovirus serotype) which induced tumors only in immunoincompetent hosts. Simian virus 40-transformed cells, which possess the unusual property of efficient tumor induction in allogeneic hosts, were uniquely resistant to lysis by activated macrophages. These differential patterns of susceptibility to cytolysis suggest an association between the level of transformed cell resistance to lysis by nonspecific host effector cells and the oncogenicity of the transforming virus. Furthermore, these data suggest that tumor-cell properties, other than those commonly associated with neoplastic transformation, determine the level of susceptibility or resistance to host effector cell mechanisms.

Adenoviridae↗

Cardiovascular response to rapid phenytoin infusion during seizures in paralyzed rats.

The maximum rate at which phenytoin may be safely administered without inducing hypotension has been evaluated in nonconvulsing animals and man; no comparable information during convulsions of either animals or man is available. Comparison of blood pressure and ECG responses to rapid phenytoin infusion in nonconvulsing rats and in rats during bicuculline-induced status epilepticus suggests that the hypertensive response of convulsions may protect against phenytoin-induced hypotension, thus indicating that more rapid administration of phenytoin during convulsions might be possible with careful monitoring.

Animals↗

Spectrum of tumorigenic phenotypes among adenovirus 2-, adenovirus 12-, and simian virus 40-transformed Syrian hamster cells defined by host cellular immune-tumor cell interactions.

The tumor-inducing capacities of adenovirus type 2-, adenovirus type 12-, and SV40-transformed LSH hamster embryo cell define a spectrum of four distinct tumorigenic phenotypes: type I, nononcogenic for newborn hamsters but oncogenic for nude mice; type II, oncogenic for newborn hamsters but nononcogenic in syngeneic adults; type III, oncogenic for both newborns and syngeneic adults; and type IV, almost equally oncogenic for syngeneic and allogeneic adult hamsters. Modulation of the cellular immune response of the recipient hamster by immunosuppression or by alloimmunization alters tumor susceptibility, suggesting that dynamic transformed cell-host cellular immune interactions determine the tumorigenic phenotype of a transformed cell line. There is no correlation between the immunogenicities of the transformed cell lines tested and their tumor-inducing capacities. However, a strong correlation exists between the ability of transformed hamster embryo cells expressing phenotype IV to produce tumors in allogeneic CB hamsters and their resistance to cytolysis in vitro by activated macrophages. These data suggest that, in addition to transformation, DNA viruses may convey specific tumorigenic phenotypes to the cells that they infect by inducing cellular traits that determine the inherent susceptibility or resistance of a cell to host cell-mediated immune destruction.

Adenoviridae↗

Mexiletine in human blood and breast milk.

Twelve paired samples of breast milk and blood were obtained, between the 2nd and 5th days after she had given birth, from a 30-year-old woman who was a 8-hourly propranolol (20 mg) and mexiletine (200 mg). Propranolol was detected in 9 of the samples of blood and in only 4 of the milk samples. Mexiletine was measurable in all samples, and the milk : plasma ratio varied between 0.79 and 1.89 with a mean of 1.45. However, the large volume of distribution of mexiletine makes it unlikely that the small dose of the drug received from the milk would be detrimental to the health of infants.

Adult↗

Effect of age on serum immunoreactive parathyroid hormone and its biological effects.

Immunoreactive parathyroid hormone (iPTH) levels, nephrogenous cAMP (ncAMP), and tubular maximum phosphate reabsorption (TmP) were measured in 10 young and 12 healthy volunteers. The fasting urinary calcium to creatinine ratio (Ca:Cr) was also quantitated as an index of bone resorption. Aging was attended by increased iPTH levels (6.9 +/- 0.8 vs. 3.4 +/- 0.4 mu leq/ml; P less than 0.01) as well as increased ncAMP levels (2.48 +/- 0.28 vs. 1.12 +/- 0.21 nmol/100 ml glomerular filtrate; P less than 0.005) and decreased TmP (2.9 +/- 0.2 vs. 4.1 +/- 0.2 mg/100 ml glomerular filtrate; P less than 0.005), indicating that the increased iPTH levels reflected the biological effects of the hormone. A significant positive correlation of iPTH and ncAMP and a significant negative correlation of iPTH and TmP were observed. The Ca:Cr was increased in the older volunteers (0.10 +/- 0.02 vs. 0.05 +/- 0.01; P less than 0.05). The elderly subjects had significantly decreased daily calcium ingestion, serum phosphate and albumin, and creatinine clearance. Our findings suggest that the increased biological effects of PTH in the elderly subjects may contribute to the increases in Ca:Cr and bone loss that occur with age.

Adult↗

Diagnosis of twin zygosity by self-assessment and by genetic analysis.

For 173 pairs of like-sex adult twins, self-assessment of zygosity was verified by laboratory diagnosis. Seventeen percent of twins who were very likely monozygous (MZ) believed themselves dizygous (DZ), frequently citing two placentas at their delivery as "evidence." We suggest that twins be asked what leads them to their assessment of their own zygosity. For 93% of Caucasian and 89% of American Black like-sex twins in our sample, DZ twins could be differentiated based on six polymorphic markers retrievable from frozen sera. MZ twins who believe themselves DZ can be considered "environmentally DZ, genetically MZ" twins, and might be used to study genetic and environmental influences on the treatment of twins and on twins' choices of social characteristics.

Alleles↗

Resistance of simian virus 40-transformed hamster cells to the cytolytic effect of activated macrophages: a possible factor in species-specific viral oncogenicity.

Simian virus 40 (SV40)-transformed hamster cells were relatively resistant to the lytic effect of activated macrophages from animals with chronic intracellular infections. Conversely, SV40-transformed mouse and rat cells and adenovirus 2-transformed hamster cells were highly susceptible to destruction by tumoricidal activated macrophages. The pattern of resistance or susceptibility of SV40-transformed rodent cells was the same whether activated macrophage effectors were obtained from mice, random-bred hamsters, or the inbred LSH hamsters from which some of the SV40-transformed hamster lines were derived. The results suggest that resistance of transformed cells to macrophage-mediated cytolysis may explain in part the species-specific oncogenicity of this DNA virus.

Animals↗

Presence of allograft-rejection resistance in simian virus 40-transformed hamster cells and its possible role in tumor development.

LSH Syrian hamster cells transformed in vitro by simian virus 40, which is oncogenic for hamsters, are resistant to rejection by adult allogeneic CB hamsters. In contrast, simian virus 40-transformed cells from other species are usually not oncogenic in immunocompetent autologous or isologous hosts. The ability of simian virus 40 to convey resistance to an allograft-type host response to transformed hamster cells may be important in determining the tumor-inducing capacity of these cells and could, in part, explain the species-specific oncogenicity of this virus.

Animals↗

Oncogenicity of simian virus 40 deletion mutants that induce altered 17-kilodalton t-proteins.

Plaque-purified viable simian virus 40 deletion mutants containing deletions between map positions 0.54 and 0.59 induced tumors in 21--92% of LSH hamsters inoculated during the first 24 hr of life. HinfI restriction endonuclease digestion patterns of the genomes of virions rescued from the tumor cells and the distribution of simian virus 40 early proteins in these cells associated tumor induction with the inoculated mutants. These results imply that the DNA sequences comprising that portion of the early simian virus 40 genome between map positions 0.54 and 0.59 are not essential for simian virus 40 oncogenicity.

Antigens, Neoplasm↗

Free amino acid levels in the blood of patients undergoing parenteral alimentation.

Free amino acid levels were determined in the blood of patients undergoing parenteral alimentation. During amino acid infusions, alanine, valine, glycine, isoleucine, leucine, proline, threonine, serine, methionine, phenylalanine, and lysine levels increased. Bivariate regression analysis was then done to determine the average rise in each amino acid when 1 mmole/hr of that amino acid was infused and when 1 mmole/hr of glucose was infused. This analysis was done on both arterial plasma and arterial wh-le blood increments. The average rise in the amino acid level with 1 mmole of infusion per hour varied from 32 to 133 mumole/liter. Only alanine levels were positively correlated with glucose infusion, while the branched chain levels were all negatively correlated. In no instance could a significant positive arteriovenous difference across the forearm be correlated with the infusion of an amino acid, despite amino acid levels as much as five times normal. Methionine, proline, valine, threonine, and lysine showed the greatest rise in blood concentration per millimole of amino acid infused per hour suggesting that their degradation or use in protein synthesis was limited. While the blood concentration rise in glycine was only about half as much per millimole per hour infused as was found in the previously mentioned group of amino acids, high rates of infusion of this amino acid resulted in large increments inglycine levels. It may be desirable to reduce the amounts of these amino acids in parenteral amino acid formulations.

Amino Acids↗

Association of tumor induction by ultraviolet light-inactivated adenovirus 2-simian virus 40 recombinants with a specific segment of simian virus 40 DNA.

The nondefective (ND) adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid Ad2+ND4, which contains the segment of the SV40 genome between map positions 0.11 and 0.59, induced tumors in Syrian golden hamsters after inactivation by UV light. Ad2 and the Ad2+ND2 hybrid, which contains the segment of the SV40 genome between map positions 0.11 and 0.43, were not oncogenic after inactivation by UV light. These results showed that the incorporation of a specific segment of SV40 DNA into the Ad2 genome can alter the pathogenesis of the Ad2+ND4 virus by rendering it oncogenic for hamsters.

Adenoviridae↗