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Biomedical subjects

A C Lee

Publications and source records attributed to A C Lee.

At least 109 records · Page 6Linked to original sources
PubMed1985

Spontaneous occurrence of Staphylococcus aureus mutants with different pigmentation and ability to produce toxic shock syndrome toxin 1.

Spontaneous mutants that have pigmentation different than that of their parents were isolated from three Staphylococcus aureus strains associated with toxic shock syndrome. These mutants produced toxic shock syndrome toxin 1 in amounts varying from less than 0.05 to greater than 25 times that produced by the parents. The occurrence of nonpigmented variants may be overlooked if only one isolate from a patient with toxic shock syndrome is selected for analysis.

Bacterial Toxins↗
PubMed1985

Non-cross-reactive monoclonal antibodies to human chorionic gonadotropin generated after immunization with a synthetic peptide.

Noncross-reactive monoclonal antibodies specific for human chorionic gonadotropin (hCG) were obtained after pre-selection for submolecular specificity with a synthetic peptide immunogen. Mice were immunized with a synthetic peptide representing a segment unique to the beta-subunit of hCG (amino acid residues 109-145), conjugated to diphtheria toxoid. We then derived nine different hybridomas that secreted monoclonal antibodies reactive with both native hCG and isolated C-terminal peptide, after somatic cell hybridization of immune spleen cells with a nonsecretory myeloma cell line. None of the nine monoclonal antibodies, termed beta-hCG-CTPa1----a9, reacted with hLH, hFSH, or hTSH, although these pituitary hormones display extensive amino acid sequence homology with hCG. The noncross-reactive anti-beta-hCG monoclonal antibodies show apparent association constants on the order of 10(9) to 10(10) M-1. A sandwich-type enzyme-linked immunosorbent assay was set up with cut-off values of around 5 mIU/ml. These antibodies might have important implications for: a) improving the diagnosis and clinical management of pregnancy; b) monitoring the course of development of carcinomas which secrete the hormone, through in vitro assays or in vivo radioimmunodetection; c) evaluating the antibodies' therapeutic potential against such carcinomas; d) studying the biologic functions of the C-terminal segment of beta-hCG; and e) addressing the anti-fertility effect of antibodies raised against that segment.

Animals↗
PubMed1985

Some perspectives on cataractogenesis from heavy charged particles.

Two sets of observations on cataractogenesis in the New Zealand white (NZW) rabbit (Oryctolagus cuniculus) following localized exposure of optic and proximate tissues to heavy ions are reported. The experiments involved measurements of lenticular opacification in young (ca. 9 weeks old) rabbits caused by graded doses (0.5-5.0 Gy) of 460 MeV/u (incident energy) 56Fe ions and the effects of animal age (9 +/- 0.3 week, 1 +/- 0.5 year, and 4.5 +/- 1.3 year) on lenticular opacifications caused by 9 Gy of 400 MeV/u (incident energy) 20Ne ions. In substantiation of earlier results from NZW rabbits exposed to other low- and high-LET radiations, there was a dose-dependent onset of cataractogenesis following 56Fe-ion irradiation, with the highest doses causing the earliest appearance of cataracts. The level of stationary cataracts was also dependent on dose, and preliminary estimates of RBE yield values comparable to those found at similar doses (0.5-5.0 Gy) by others with populations of cultured cells. With increasing age at the time of exposure to 20Ne ions, the onset of lenticular opacification was delayed progressively and the level of stationary cataracts was reduced, but the onset and progression of late cataractogenesis was most rapid in the oldest group of animals. A discussion of the use of cataract measurements in risk assessment is included in this article.

Age Factors↗
PubMed1984

Late effects from particulate radiations in primate and rabbit tissues.

Optic tissues in groups of New Zealand white rabbits were irradiated locally at different stages throughout the median life span of the species with a single dose (9 Gy) of 425 MeV/amu Ne ions (LET infinity approximately 30 keV/micrometer) and then inspected routinely for the progression of radiation cataracts. The level of early cataracts was found to be highest in the youngest group of animals irradiated (8 weeks old), but both the onset of late cataracts and loss of vision occurred earlier when animals were irradiated during the second half of the median life span. This age response can have serious implications in terms of space radiation hazards to man. Rhesus monkeys that had been subjected to whole-body skin irradiation (2.8 and 5.6 Gy) by 32 MeV protons (range in tissue approximately 1 cm) some twenty years previously were analysed for radiation damage by the propagation of skin fibroblasts in primary cultures. Such propagation from skin biopsies in MEM-alpha medium (serial cultivation) or in supplemented Ham's F-10 medium (cultivation without dilution) revealed late damage in the stem (precursor) cells of the skins of the animals. The proton fluxes employed in this experiment are representative of those occurring in major solar flares.

Age Factors↗
PubMed1983

Cataractogenesis from high-LET radiation and the Casarett model.

Space radiations, especially heavy ions, constitute significant hazards to astronauts. These hazards will increase as space missions lengthen. Moreover, the dangers to astronauts will be enhanced by the persistence, or even the progression, of biological damage throughout their subsequent life spans. To assist in the assessment of risks to astronauts, we are investigating the long-term effects of heavy ions on specific animal tissues. In one study, the eyes of rabbits of various ages were exposed to a single dose of Bragg plateau 20Ne ions (LET infinity approximately equals 30 keV/micrometer). The development of cataracts has shown a pronounced age-related response during the first year after irradiation, and will be followed for two more years. In other studies, mice were exposed to single or fractionated doses of 12C ions (4-cm spread-out Bragg peak; dose-averaged LET infinity = 70-80 keV/micrometer) or 60Co gamma-photons (LET infinity = 0.3 keV/micrometer). Measurements of the frequency of posterior lens opacification have shown that the tissue sparing observed with dose fractionation of gamma-photons was absent when 12C-ion doses were fractionated. Development of posterior lens cataracts was also followed for long periods (up to 21 months) in mice exposed to single doses of Bragg plateau HZE particles (40Ar, 20Ne and 12C ions: LET infinity approximately equals 100, 30 and 10 keV/micrometer, respectively) or 225 kVp X-rays. Based on average cataract levels at the different observation times, the RBE's (RBE = relative biological effectiveness) for the ions were circa 5, 3 and 1-2, respectively, over the range of doses used (0.05-0.9 Gy). Investigations of cataractogenesis are useful for exploring the model of radiation damage proposed by Casarett and by Rubin and Casarett with a tissue not connected directly to the vasculature.

Age Factors↗
PubMed1983

Brain damage in the epileptic beagle dog.

Brain lesions associated with seizures in an epilepsy-prone colony of beagle dogs were studied in 68 dogs which died as a result of the disorder. Approximately 48.5% of the dogs had a relatively specific pattern of acute brain damage on microscopic examination. In all affected areas, there was a triad of lesions consisting of perineuronal and perivascular astrocytic swelling, perineuronal basophilic incrustations, and ischemic cell change in neurons. The most common areas of involvement were the cerebral cortex, basal nuclei, claustrum, amygdala, septal nuclei, dorsal thalamic nuclei, isthmus of the pyriform lobe, and hippocampus. The cerebellum was affected only rarely. In addition, intraneuronal inclusions identical to Lafora's bodies found in myoclonus epilepsy of man were detected in thalamic nuclei of six dogs.

Animals↗
PubMed1982

A case of leukemic reticuloendotheliosis responding to oxymetholone.

A 63-year-old man presented with fever, easy bruisability, splenomegaly and pancytopenia. Bone marrow aspiration was unsuccessful, and marrow biopsy revealed crowding by sheets of mononuclear cells; a diagnosis of leukemic reticuloendotheliosis (LRE) was made and the patient underwent splenectomy. There was no hematologic improvement, and the patient continued to have a significant requirement for erythrocytes and platelet transfusions. Within two months of beginning oxymetholone therapy (50 mg orally three times a day) the patient's platelet count had normalized, followed by improved erythrocyte and leukocyte counts. When the drug was discontinued, the peripheral blood counts deteriorated drastically; he again demonstrated hematologic improvement when oxymetholone therapy was reinstated. We feel that by demonstrating a hematologic response to oxymetholone, relapse when it was withdrawn, and another remission upon readministration, that we have provided stronger evidence than previously reported for the efficacy of this drug in LRE.

Adult↗
PubMed1982

Effects of heavy ions on rabbit tissues: cataractogenesis.

As part of an investigation of the responses of optic and proximate tissues to heavy-ion irradiation, the lenses of New Zealand white rabbits were exposed to the Bragg plateau regions of 530 MeV/amu Ar ions and 365 MeV/amu Ne ions and also to 60Co gamma-photons. The linear energy transfers (LET infinity s) for the radiations were 90 +/- 5, 35 +/- 3, and 0.3 keV/micrometer, respectively. After irradiation, lenticular opacities were monitored through their incipient and/or clinical stages (less than or equal to 5 years) by slit-lamp biomicroscopy and scored with subjective, but well-defined, indices. Cataractogenesis, which progressed according to the model proposed by Rubin and Casarett (1968), was modified by radiation quality in the following ways. (1) The rate of development of the early (acute) stage increased with the LET infinity of the incident radiation; (2) at the intermediate (plateau) stage, the values for the relative biological effectiveness (r.b.e.) of the heavy ions were similar to those reported for proliferating cells in culture; (3) for a given intermediate level, the onset of late cataractogenesis occurred earlier the higher the LET affinity of the radiation involved. As with alopecia, the r.b.e.s for cataractogenesis varied with post-irradiation time.

Animals↗
PubMed1982

Effects of heavy ions on rabbit tissues: damage to the forebrain.

As part of a study of progressive radiation effects in normal tissues, the forebrains of New Zealand white rabbits (Oryctolagus cuniculus) (about 6 weeks old) were irradiated locally with single acute doses of 60Co gamma-photons (LET infinity = 0.3 keV/micron), Ne ions (LET infinity = 35 +/- 3 keV/microns) or Ar ions (LET infinity = 90 +/- 5 keV/microns). Other rabbits received fractionated doses of 60Co gamma-photons according to a standard radiotherapeutic protocol. Irradiated rabbits and appropriately aged controls were sacrificed at selected intervals, and whole sagittal sections of their brains were examined for pathological changes. Forebrain damage was scored with subjective indices based on histological differences between the anterior (irradiated) and posterior (unirradiated) regions of the brain. Those indices ranged from zero (no apparent damage) to five (severe infarctions, etc.). At intermediate levels of forebrain damage, the relative biological effectiveness (r.b.e.) of each heavy ion was similar to that found for alopecia and cataractogenesis, and the early expression of the damage was also accelerated as the LET infinity increased. Late deterioration of the forebrain appeared also to be accelerated by increasing LET infinity, although its accurate quantification was not possible because other priorities in the overall experimental design limited systematic sacrifice of the animals.

Animals↗
PubMed1982

An enterotoxin-like protein in Staphylococcus aureus strains from patients with toxic shock syndrome.

An enterotoxin-like protein, tentatively labeled enterotoxin F, was isolated from Staphylococcus aureus strains taken from patients with toxic shock syndrome. Antibodies specific for enterotoxin F were prepared in rabbits. Use of these antibodies showed that 130 (91.5%) of 142 S. aureus strains from patients with toxic shock syndrome produced enterotoxin F. Strains from toxic shock patients in eight other countries were identified as enterotoxin F producers. Only a small number of S. aureus strains from sources other than patients with toxic shock syndrome were found to produce enterotoxin F. Twenty-one of 111 controls had low antibody titers (less than 1:100) to enterotoxin F whereas 86 of 92 toxic shock patients had low acute phase antibody titers (less than 1:100) to enterotoxin F. Eight of 52 patients had serum conversion as shown by an increase in antibody titer to enterotoxin F in sera taken 21 to 60 days after onset of the illness. It may be possible to identify persons susceptible to toxic shock syndrome by measuring their antibody titer to enterotoxin F.

Bacterial Toxins↗
PubMed1981

Antifertility effects of immunization of female baboons with C-terminal peptides of the beta-subunit of human chorionic gonadotropin.

Fifteen adult female baboons were immunized with a conjugate of tetanus toxoid coupled with a synthetic carboxy-terminal peptide of the beta-subunit of human chorionic gonadotropin and another 15 were immunized with tetanus toxoid. Freund's complete adjuvant was used in all immunizations. All females were placed with males of proven fertility during the third menstrual cycle after the primary immunization and those not sustaining pregnancy were mated in two additional consecutive cycles. Four pregnancies occurred following 42 matings in the conjugate-immunized group and 15 pregnancies resulted from 21 matings in the tetanus toxoid-immunized animals. Low levels of antibodies reactive to baboon chorionic gonadotropin were found in the pregnant animals in the conjugate-immunized group.

Animals↗
PubMed1980

Late degeneration in rabbit tissues after irradiation by heavy ions.

In 1974, using the rabbit as a model, we began long-term experiments designed to help in the evaluation of the hazards to man from extended exposure to heavy ions in space. Such exposure would occur, for example, during the construction of solar power stations in stationary orbits or on round trips to Mars. Our experiments with 400 MeV/nucleon Ne ions and 570 MeV/nucleon Ar ions have shown that true late effects of a degenerative nature are manifested only years after irradiation. At the appropriate doses (the high end of the experimental dose range), the magnitudes of the late effects are comparable with those encountered in human patients given radiation therapy with neutrons. Such comparisons show that the rabbit experiments are applicable to man. Given that basis, the results from the low end of the experimental dose range lead to the conclusion that astronauts subjected to the radiation fluxes anticipated during flights of the above duration could experience late radiation effects one or more decades after exposure. Late degenerative changes will occur in tissues of the central nervous system, terminally differentiating systems and stem cell populations. The studies also indicate that individual tissues may be "prematurely aged" by radiation in the sense that the "life spans" of those tissues can be decreased without the appearance of malignancies.

Alopecia↗
PubMed1980

Isolation of specific and common antibodies to staphylococcal enterotoxins B, C1, and C2.

Staphylococcal enterotoxins C1 and C2 elicit the production of antibodies in rabbits that give precipitin reactions with both toxins and gel diffusion plates. These enterotoxins also elicit the production of antibodies that are specific for each of the enterotoxins. Enterotoxin B elicits the production of antibodies in some rabbits that react with enterotoxins B, C1, and C2 in gel diffusion plates and in radioimmunoassay. Antibodies specific for enterotoxin B are produced also. Enterotoxin C1 elicits the production of antibodies that cross-react weakly with enterotoxin B, indicating that the antigenic sites involved in the cross-reactions are not identical in the two toxins. The antibodies have been isolated by affinity chromatography.

Animals↗
PubMed1978

Tumor and tumor-like lesions of perilimbal conjunctiva in laboratory dogs.

Review of records of 1,680 research colony Beagles revealed proliferative and neoplastic lesions in the nasal or temporal limbal conjunctiva of 8 male and 6 famale dogs. The mean age at observation was 5.2 years. The lesions ranged from acanthosis and squamous cell carcinoma of the conjunctival epithelium to vascular ectasia, hemangioma, and invasive hemangiosarcoma of the underlying lamina propria. The lesions developed under circumstances that suggested solar radiation was involved in the pathogenesis.

Animals↗
PubMed1978

Isolation of specific and common antibodies to staphylococcal enterotoxins A and E by affinity chromatography.

Specific and common antibodies to staphylococcal enterotoxins A and E (SEA and SEE) were isolated from anti-SEA and anti-SEE antisera by affinity chromatography. Anti-SEA and anti-SEE antisera were passed through a column with the cross-reacting enterotoxin coupled to a CNBr-activated Sepharose 4B matrix. Specifically bound common antibodies were eluted with NaSCN. The isolated specific antibodies reacted only with the homologous enterotoxin, whereas the common antibodies gave a reaction of identify with both enterotoxins in double gel diffusion plates. The common antibodies had a higher titer against SEE than against SEA. The significance of the isolation of antibodies common to two separate protein molecules is discussed.

Animals↗
PubMed1978

Echocardiographic assessment of normal and abnormal valvular function in Beagle dogs.

Echocardiograms were obtained from 5 young Beagles (4 to 5 years of age) and from 4 old Beagles (12 to 14 years of age). Ultrasound surface transducers and esophageal transducers were used on all animals during anesthesia. Triplicate studies were performed on the 5 young Beagles over a 2-week period. The left atrioventricular valve and aortic root were identified by both procedures, whereas the right atrioventricular valve dynamics could be viewed with difficulty by the transcutaneous approach. Suitable recordings of the pulmonary valve were not obtainable with either technique. Abnormal left atrioventricular valve dynamics, characterized by a decreased closing velocity of the left atrioventricular septal cusp and increased valve thickness, were observed in 2 of the 4 aged dogs, using echocardiography. Excellent correlation between the 2 methods was evident, and minimal variation in results from one recording session to another occurred.

Animals↗