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Biomedical subjects

S Carpenter

Publications and source records attributed to S Carpenter.

At least 127 records · Page 7Linked to original sources
PubMed1991

Photosensitization is required for inactivation of equine infectious anemia virus by hypericin.

Hypericin, a photoreactive polycyclic quinone, was found to dramatically reduce infectivity of cell-free stocks of equine infectious anemia virus. However, the antiviral activity of hypericin was completely dependent on the presence of light. Short periods of photosensitization resulted in a partial loss of reverse transcriptase activity and complete inhibition of viral infectivity. These results suggest that the photodynamic effect of hypericin interferes with more than one stage in the virus replication cycle.

Anthracenes↗
PubMed1991

Identification of a hypervariable region in the long terminal repeat of equine infectious anemia virus.

An avirulent, field-derived isolate of equine infectious anemia virus (EIAV), designated MA-1, was molecularly cloned, and the complete nucleotide sequence was determined for the 3' half of the viral genome. Comparisons between MA-1 and the prototype Wyoming strain of EIAV identified a 66-nucleotide stretch between CAAT (-91) and TATAA (-25) in the U3 region of the long terminal repeat, where sequence divergence was as high as 39.3%. The polymerase chain reaction was used to amplify and clone long terminal repeat sequences from Th-1, the in vivo parental stock of MA-1. Results indicated that the nucleotide sequences of MA-1 and Th-1 clones were less variable than was observed between MA-1 and Wyoming. However, MA-1 and Th-1 markedly differed in the types of enhancer sequences located in the hypervariable region. These results suggest that variation in lentivirus regulatory sequences may be important in EIAV host cell tropism and pathogenesis.

Amino Acid Sequence↗
PubMed1991

Characterization of variable regions in the envelope and S3 open reading frame of equine infectious anemia virus.

The polymerase chain reaction was used to amplify and clone parts of the envelope gene and overlapping S3 open reading frame, thought to encode rev, of the virulent in vivo-derived Th-1 isolate of equine infectious anemia virus (EIAV). The results indicated that EIAV consists of a heterogeneous mixture of genotypes present at the first febrile cycle after initial infection. We showed that the Th-1 isolate apparently contains nondefective genotypes as well as types which have transmembrane protein truncations or are rev deficient. Furthermore, we could confirm the presence of a hypervariable region in the gp90 envelope glycoprotein. Taken together with earlier data on the heterogeneity of the regulatory motifs present in the long terminal repeat sequences of viruses from the same in vivo isolate (S. Carpenter, S. Alexandersen, M. J. Long, S. Perryman, and B. Chesebro, J. Virol. 65:1605-1610, 1991), our findings indicate that EIAV uses a complex system of diversity in biological phenotypes together with variation in regulatory and antigenic makeup to evade host response and to cause persistent infection and recurrent chronic disease.

Amino Acid Sequence↗
PubMed1991

In vivo muscle magnetic resonance spectroscopy in the clinical investigation of mitochondrial disease.

We have investigated the sensitivity and specificity of a rapid phosphorus magnetic resonance spectroscopy (MRS) protocol for detecting metabolic abnormalities in vivo in skeletal muscle of patients with mitochondrial disease. We examined 17 patients with mitochondrial myopathies. Sixteen had only mild or minimal myopathic signs and symptoms. Phosphorus magnetic resonance spectra from the resting gastrocnemius muscles showed an abnormal intracellular energy state (marked by an increased intracellular inorganic phosphate concentration) in 14/17. In 3/17, this was associated with a decreased phosphocreatine concentration. We also studied 20 patients with other diseases of muscle (inflammatory myopathies, metabolic myopathies, muscular dystrophies, and myasthenia gravis) that can present with similar clinical features. Spectra showed increased intracellular inorganic phosphate concentrations in 6/20. All of these muscle diseases were associated with evidence of muscle fiber necrosis. Abnormalities in the muscle energy state in these cases may be due to secondary mitochondrial dysfunction. Except for cases of polymyositis and dermatomyositis, these 6 other myopathies could be readily distinguished from the mitochondrial myopathies on the basis of the clinical examination and blood tests. We conclude that phosphorus MRS of resting muscle is practical in a clinical setting and has a useful sensitivity and specificity for mitochondrial myopathies when used in conjunction with standard noninvasive tests.

Adenosine Triphosphate↗
PubMed1991

Inhibition of myosatellite cell proliferation by gamma irradiation does not prevent the age-related increase of the number of dystrophin-positive fibers in soleus muscles of mdx female heterozygote mice.

In skeletal muscles of young mdx female heterozygote mice, there is a mosaic of dystrophin-positive and dystrophin-negative fiber segments. In older animals, there is a marked decline in the number of dystrophin-negative fiber segments. This phenomenon might be due to a fusion of dystrophin-competent satellite cells into the originally dystrophin-negative fiber segments during growth. To study this possibility, soleus muscles of 10-day-old mdx female heterozygotes were gamma irradiated (2000 rads) to inhibit subsequent myosatellite cell proliferation and fusion. In the irradiated soleus muscles of animals at 60 days, the relative amount of dystrophin measured by quantitative immunoblots was not significantly different from that of the contralateral nonirradiated muscles. The prevalence of dystrophin-negative fibers in the 60-day-old irradiated solei was not higher than in the nonirradiated contralateral muscles, implying that dystrophin-competent satellite cell fusion was not a significant factor in the observed conversion. A longitudinal expansion of the cytoplasmic domain of the original dystrophin-competent myonuclei during growth could explain the observed conversion phenomenon.

Aging↗
PubMed1991

Oxygen enhancement ratio as a function of dose and cell cycle phase for radiation-resistant and sensitive CHO cells.

There is still controversy over whether the oxygen enhancement ratio (OER) varies as a function of dose and cell cycle phase. In the present study, the OER has been measured as a function of survival level and cell cycle phase using volume flow cell sorting. This method allows both the separation of cells in different stages of the cycle from an asynchronously growing population, and the precise plating of cells for accurate measurements at high survival levels. We have developed a cell suspension gassing and sampling system which maintained an oxygen tension less than 20 ppm throughout a series of sequential radiation doses. For both radiation-resistant cells (CHO-K1) and a radiation-sensitive clone (CHO-xrs6), we could separate relatively pure populations of G1-phase, G1/S-boundary, S-, and G2-phase cells. Each cell line showed a typical age response, with cells at the G1/S-phase boundary being 4 (CHO-K1) to 12 (CHO-xrs6) times more sensitive than cells in the late S phase. For both cell lines, G1-phase cells had an OER of 2.3-2.4, compared to an OER of 2.8-2.9 for S-phase and 2.6-2.7 for G2-phase cells. None of these age fractions showed a dependence of OER on survival level. Asynchronously growing cells or cells at the G1/S-phase boundary had an OER similar to that of G1-phase cells at high survival levels, but the OER increased with decreasing survival level to a value near that of S-phase cells. These results suggest that the decrease in OER at high survival levels for asynchronous cells may be due to differences in the OERs of the inherent cell age subpopulations. For cells in one cell cycle stage, oxygen appears to have a purely dose-modifying effect.

Animals↗
PubMed1991

Radiobiology of alpha particles. III. Cell inactivation by alpha-particle traversals of the cell nucleus.

Cell inactivation after exposure to collimated 3.5-MeV alpha particles in three hamster cell lines, V79, CHO-10B, and HS-23, one mouse cell line, C3H 10T1/2, and a human skin fibroblast cell line were studied. Several parameters were investigated for each cell line. Theoretical calculations were performed to find the distribution of energy deposited in the nuclear volume for each cell line. The mean number of alpha-particle traversals required to induce a lethal lesion varied between two for HS-23 cells and six for C3H 10T1/2 cells. The number of traversals per unit area and the total track length of alpha particles that inactivated a cell were found to be nearly constant for the hamster and mouse cell lines. These quantities were found to be lower for the human skin fibroblast cell line. The RBE values for all cell lines were found to be about 3.8 at 10% survival. Thus cell lines that are more sensitive to alpha radiation are also more sensitive to gamma radiation. The average number of alpha-particle traversals producing a single lethal lesion is greater than one. The passages of alpha particles through the cell nucleus that do not kill the cell may lead to carcinogenic effects.

Alpha Particles↗
PubMed1991

Correlative multidisciplinary approach to the study of mitochondrial encephalomyopathies.

Mitochondrial encephalomyopathies can be caused by defects in the mitochondrial respiratory complexes. The clinical phenotypes are quite protean but in many instances a characteristic or suggestive clinical presentation permits a tentative bedside diagnosis. The diagnosis can be verified by laboratory investigations. The major laboratory hallmarks of mitochondrial encephalomyopathies include: ragged red fibers on muscle biopsy, a specific defect or deficiency in a mitochondrial respiratory enzyme complex, mtDNA abnormalities, reduced anaerobic threshold by bicycle ergometry, impaired cellular energy state by MRS and characteristic brain imaging abnormalities. Monitoring of some of these parameters along with the clinical phenotype will aid in the evaluation of therapeutic trials.

Brain Diseases↗
PubMed1991

Pregnancy and cystic fibrosis.

Despite reduced fertility, pregnancy is likely to occur with increasing frequency in cystic fibrosis in proportion to the number of patients reaching childbearing age. Thirty-eight pregnancies in 25 patients with cystic fibrosis are presented. Twelve of the 25 mothers were pancreatic-sufficient. Despite previous reports of the hazards of pregnancy in cystic fibrosis, we found that pregnancy was well tolerated by the vast majority of our patients and had little effect on their pulmonary and nutritional status. Therapeutic abortion for medical indications was required in two pregnancies. The incidence of prematurity and the neonatal mortality rate were low, and no congenital abnormalities occurred. We conclude that pregnancy can be tolerated by the majority of cystic fibrosis patients, particularly those who are pancreatic-sufficient.

Adolescent↗
PubMed1991

Response of X-ray-sensitive CHO mutant cells (xrs-6c) to radiation. II. Relationship between cell survival and the induction of chromosomal damage with low doses of alpha particles.

The induction of cytotoxicity, chromosomal aberrations, and sister chromatid exchanges (SCEs) was measured in CHO K-1c cells and in isogenic X-ray-sensitive mutant xrs-6c cells that had been irradiated with X rays and alpha particles in isoleucine-deficient alpha-minimal essential medium in G1 phase of the cell cycle. There was a noticeable shoulder region on the survival curve for CHO K-1c cells irradiated with very low doses of alpha particles, whereas this feature was absent for xrs-6c cells with alpha-particle doses as low as 0.5 cGy. Higher frequencies of chromatid-type aberrations were induced in G1-phase xrs-6c cells than in G1-phase CHO K-1c cells by both gamma- and alpha-particle irradiation. Induction of nonlethal chromosomal aberrations was observed following exposure to 2-6 cGy of alpha particles, doses yielding 97-100% cell survival. Irradiation with 0.5 cGy of alpha particles induced SCE; nearly 60% of irradiated cells contained significantly increased levels of SCE. However, only 3% of the nuclei of cells exposed to 0.5 cGy of alpha-particle radiation were actually traversed by an alpha particle. The observation that a large fraction of cells apparently survive exposure to very low doses of alpha-particle radiation with persistent genetic damage manifested by both chromosomal aberrations and SCEs may have important implications for the carcinogenic hazards of high-LET radiation.

Alpha Particles↗
PubMed1990

Antiretroviral activity of synthetic hypericin and related analogs.

Hypericin and pseudohypericin are naturally occurring polycyclic quinones which have recently been shown to inhibit the infectivity of several retroviruses, including human immunodeficiency virus. To better understand the antiviral mechanisms of these compounds, hypericin and a series of analogous quinones were synthesized and tested for anti-retroviral activity against equine infectious anemia virus (EIAV). Treatment of EIAV-infected cells with hypericin reduced the production of infectious virus by 99.99%. None of the analogs were found to inhibit virus replication. These results suggest that the complete ring structure of hypericin is required, but not sufficient, for antiviral activity.

Animals↗
PubMed1990

Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels.

In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption of mussels found to be contaminated with domoic acid, which is structurally related to the excitatory neurotransmitter glutamate. We studied the neurologic manifestations in 14 of the more severely affected patients and assessed the neuropathological findings in 4 others who died within four months of ingesting the mussels. In the acute phase of mussel-induced intoxication, the patients had headache, seizures, hemiparesis, ophthalmoplegia, and abnormalities of arousal ranging from agitation to coma. On neuropsychological testing several months later, 12 of the patients had severe anterograde-memory deficits, with relative preservation of other cognitive functions. Eleven patients had clinical and electromyographic evidence of pure motor or sensorimotor neuronopathy or axonopathy. Positron-emission tomography of four patients showed decreased glucose metabolism in the medial temporal lobes. Neuropathological studies in the four patients who died after mussel-induced intoxication demonstrated neuronal necrosis and loss, predominantly in the hippocampus and amygdala, in a pattern similar to that observed experimentally in animals after the administration of kainic acid, which is also structurally similar to glutamate and domoic acid. We conclude that intoxication with domoic acid causes a novel and distinct clinicopathologic syndrome characterized initially by widespread neurologic dysfunction and then by chronic residual memory deficits and motor neuronopathy or axonopathy.

Animals↗
PubMed1990

Dystrophin is localized to the plasma membrane of human skeletal muscle fibers by electron-microscopic cytochemical study.

Electron-microscopic immunoperoxidase technique revealed plasmalemmal localization of dystrophin in microscopically normal human skeletal muscle fibers obtained from nine routine diagnostic muscle biopsies. There was no evidence of periodicity of the immunoreactive product nor was there any evidence of immunostaining in any organelle besides the plasma membrane. Dystrophin appears to be a cytoskeletal protein associated with the plasmalemma. Its function is presumed to be the maintenance of the mechanical stability of the surface membrane so that it can withstand the normal contraction-induced stresses without disruption.

Biopsy↗
PubMed1990

Dystrophin-deficient mdx muscle fibers are preferentially vulnerable to necrosis induced by experimental lengthening contractions.

Lengthening contractions were induced in the right anterior tibialis muscles (ATM) of anaesthetized normal and mdx (dystrophic) mice by supramaximal, nonfatiguing stimulation of the sciatic nerve for 180 min. In the left ATM of the same animals identical stimulation caused shortening contractions because of a prestimulation Achilles tenotomy. The prevalence of recently necrotic fibers was determined in all stimulated ATM by demonstrating the presence of IgG in the necrotic fibers using immunoperoxidase staining of cryostat sections. The results were compared to unstimulated normal and mdx ATM. A significantly higher rate of necrosis was demonstrated after lengthening contractions in the mdx ATM than normal ATM. Unstimulated normal and mdx ATM have either no or extremely infrequent necrotic fibers. We suggest that the enhanced vulnerability of mdx muscle fibers to lengthening contractions is related to the deficiency of dystrophin, which renders the sarcolemma more susceptible to suffer focal breaks. A similar situation may occur in Duchenne muscular dystrophy.

Animals↗
PubMed1990

Cytogenetic effects of extremely low doses of plutonium-238 alpha-particle irradiation in CHO K-1 cells.

CHO K-1 cells were irradiated during the G1 phase with 0.5-6 rad of alpha particles. There was no appreciable cell killing in this low dose range. Significantly increased frequencies of sister-chromatid exchanges were induced by doses as low as 0.5 rad of alpha-particle irradiation, whereas increased numbers of chromosomal aberrations were observed following exposure to 2 rad. These results suggest that very low doses of alpha radiation may lead to radiation-induced genetic alterations.

Alpha Particles↗
PubMed1990

Attribution difficulty and memory for attribution-relevant information.

This research compared the processing and retrieval of attribution-relevant information when the attributional inference is easy or difficult to make. Subjects attributed behavioral events to the person or to the situation, based on several items of context information. Each context sentence implied either the person or the entity as causal agent. When the attributional inference was difficult to make (an equal number of context sentences implied actor and entity as the causal agent), subjects recalled more of the behavioral events, recalled more context sentences, and were less confident in their attributions than when the attributional inference was easy to make (most context sentences implied the same causal agent). Subjects also recalled context information that was implicationally incongruent with the majority of the other context sentences with a higher probability than when that same information was implicationally congruent.

Attitude↗
PubMed1990

Age-related conversion of dystrophin-negative to -positive fiber segments of skeletal but not cardiac muscle fibers in heterozygote mdx mice.

Immunoreactive dystrophin was examined in muscle fibers of quadriceps, extraocular muscles and cardiac ventricular muscles of female heterozygote mdx mice at 10, 35 and 60 days of age, with microscopic immunoperoxidase method and by immunoblots. In quadriceps muscle fibers there was a marked gradual diminution of the dystrophin-negative fiber segments between age 10 and 60 days. We suggest that this was partly due to a spontaneous fusion of dystrophin-competent satellite cells into the dystrophin-negative fiber segments and partly to an expansion of the cytoplasmic domain of dystrophin expression related to the original myonuclei. In cardiac muscle that lacks satellite cells, there was persistence of a large number of dystrophin-negative fiber segments even at age 60 days and probably beyond. The findings of this study have implications for the detection of heterozygote female carriers of Duchenne muscular dystrophy (DMD) and for the possible therapy of DMD muscles by myoblast transfer.

Aging↗