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Biomedical subjects

M Lim

Publications and source records attributed to M Lim.

At least 109 records · Page 6Linked to original sources

Characterization of a major encephalitogenic T cell epitope in SJL/J mice with synthetic oligopeptides of myelin basic protein.

The C-terminal 89-169 amino acid fragment of myelin basic protein (MBP) causes experimental allergic encephalomyelitis (EAE) in SJL/J mice. In order to identify the encephalitogenic T cell epitope, we have examined the fine specificity of encephalitogenic SJL/J T cell clones with synthetic peptides derived from the C-terminal 89-169 amino acids of MBP. These peptides were examined for their immunogenic and encephalitogenic activity in the SJL/J mouse. The SJL/J-derived, encephalitogenic T cell clone, 4b.14a, was shown to be responsive to rat myelin basic protein synthetic peptides pR89-101 (VHFFKNIVTPRTP) as well as to intact MBP. Its response was effectively blocked by mAb 10-2.16 (anti-I-As) as was the response to intact MBP. Furthermore, pR89-101 was revealed to be highly immunogenic for the (PLSJ)F1 mouse in terms of lymphocyte proliferation, but not for the PL/J mouse, in spite of the fact that there exists a strong bias to H-2u restricted responses in the (PLSJ)F1 mouse at the T cell level. By using pR89-101, T cells of (PLSJ)F1 origin were revealed to recognize the peptide in association with the I-As molecule on (PLSJ)F1 antigen presenting cells (APC). When examined for encephalitogenicity for the SJL/J mouse, pR89-101 was found to be as encephalitogenic as intact rat MBP. These results demonstrated that MBP peptide pR89-101 is a major encephalitogenic determinant for the SJL/J mouse.

Amino Acid Sequence↗

Treatment of the chest wall.

Irradiation of the chest wall is sometimes given following radical or modified radical mastectomy. The aim of treatment planning in such cases is to deliver a uniform dose to a superficial layer of tissue a few centimeters thick with an acceptably low dose to underlying tissues, particularly the lung. Both tangential photon beams and appositional electron beams have been used for this purpose, the choice between them being determined by the radiation modalities available, the extent and thickness of the designated target volume and the curvature of the patient's contour in the region. In this paper we will consider a few examples of both types of treatment with emphasis on the use of multiple electron fields. Dose distributions for the following plans were calculated using the system developed at the Cross Cancer Institute in Edmonton. In this system electron dose calculations are based on the Fermi-Eyges theory of multiple Coulomb scattering using the programs developed by Hogstrom and his co-workers.

Breast Neoplasms↗

CT treatment planning of the liver.

The article deals with CT treatment planning of the liver to maximize the dose to the liver but minimize the dose to the right kidney, spinal cord, and bowels. (The left kidney is out of the field due to the oblique angles of the fields.) This is achieved by right kidney shielding reconstruction from multislice CT treatment planning and by the oblique angles of the fields. Without CT, it is not possible to utilize oblique fields to cover the liver. With conventional AP-PA fields, not only is the whole liver treated but also most of the right kidney, half of the left kidney, bowels and spinal cord. Tolerance dose to the kidneys is exceeded if adequate dose is delivered to the liver. Some new computer algorithms display a bird's eye view of the shielding but this paper presents for the first time, a technique for actual shielding reconstruction from multislice CT treatment planning for use by the radiation oncologist when shielding blocks are drawn on the simulator films.

Humans↗

Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model.

Using the chronic maternal-fetal sheep preparation, nine pregnant ewes were studied to determine the effects of intravenous dantrolene sodium on maternal and fetal physiology, with particular reference to its placental passage, and its effects on uterine blood flow and uterine tone. Two doses of dantrolene sodium were studied: 1.2 mg/kg and 2.4 mg/kg. After 2.4 mg/kg, maternal cardiac output increased 29% (P less than 0.05) after 1 min and returned to normal after 30 min. Maternal mean arterial pressure increased 13% after 1 min and remained significantly elevated (P less than 0.01) for 3 h. No significant changes (P greater than 0.05) were observed in maternal heart rate, uterine artery blood flow, or central venous pressure. Maternal arterial pH declined from 7.42 to 7.39 (P less than 0.01) after 1 min and returned to baseline values after 10 min. Fetal heart rate decreased 24% (P less than 0.01) after 3 min and returned to normal after 10 min; the mean fetal arterial pressure remained unchanged (P greater than 0.05). Fetal arterial pH declined from 7.29 to 7.27 (P less than 0.05) after 1 min and remained significantly decreased for 120 min. Similar changes of lesser magnitude and shorter duration were seen following the 1.2 mg/kg dose. Maternal levels of dantrolene were less than 3 micrograms/ml. Although an equilibrium between maternal and fetal plasma dantrolene concentrations was apparent at 5 min, the fetal levels of dantrolene were approximately 10% of the mother's. The results indicate that the administration of intravenous dantrolene at 1.2 mg/kg or 2.4 mg/kg has no clinically significant adverse effect on mother or fetus in the sheep model.

Acid-Base Equilibrium↗

Idiopathic hypereosinophilic syndrome with polymyositis.

We have reported a case of idiopathic hypereosinophilic syndrome (HES) with polymyositis, in which there was marked eosinophilic leukocytic infiltration of the myocardium and striated skeletal muscles, particularly of the diaphragm, with foci of necrosis and areas of fibrosis. We believe this to be the first detailed report of the involvement of the diaphragm in HES.

Aged↗

Anaesthesia for extracorporeal shock-wave lithotripsy. A comparison of propofol and methohexitone infusions during high frequency jet ventilation.

A continuous infusion of propofol 2.0-2.5 mg/kg for induction followed by 9 mg/kg/hour for the first 30 minutes and 6 mg/kg/hour thereafter, was compared with methohexitone 1.5 mg/kg for induction followed by 4.8 mg/kg/hour thereafter for maintenance of anaesthesia in a randomised study of 40 patients who underwent extracorporeal shock-wave lithotripsy using high frequency jet ventilation (HFJV). Systolic blood pressure was significantly lower in the propofol group after induction of anaesthesia, tracheal intubation, placement in the semirecumbent position in the hoist, bath immersion and after 5, 10 and 30 minutes of treatment. Diastolic blood pressure was significantly lower in the propofol group after intubation, placement in the hoist, bath immersion and after 5, 10 and 15 minutes of treatment. Heart rate was significantly lower in the propofol group after induction, intubation, placement in the hoist and bath immersion. There was no significant difference in the quality of induction between the two groups. Quality of maintenance of anaesthesia was judged to be poor in six out of 20 patients who received methohexitone compared with one out of 20 who received propofol but this difference did not reach statistical significance. There was no significant difference between the recovery times for the two groups but six out of 20 patients who received methohexitone were judged to have a poor recovery from anaesthesia compared with none in the propofol group (p less than 0.05). Propofol was associated with excellent induction, maintenance and recovery characteristics but it had a propensity to produce greater decreases in blood pressure, which were most marked when the patient was placed in the semirecumbent position in the hoist.

Adolescent↗

Comparative evaluation of general, epidural and spinal anaesthesia for extracorporeal shockwave lithotripsy.

The results of a prospective randomised evaluation of general anaesthesia (GA), epidural anaesthesia (EA) and spinal anaesthesia (SA) for extracorporeal shockwave lithotripsy are presented. GA provided speed and reliability but resulted in a high incidence of postoperative nausea, vomiting and sore throat. Both regional techniques conferred the advantages of an awake, cooperative patient, but EA required a longer preparation time than SA and more supplementary treatment with fentanyl or midazolam. A major drawback associated with the use of SA was a 42% incidence of postspinal headache. All three techniques were associated with hypotension on placement in the hoisl; bath immersion resulted in significant rises in blood pressure in the EA and SA groups and a more variable (overall non-significant) response in the GA group.

Adolescent↗

Effect of chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on sister chromatid exchange levels in peripheral lymphocytes of the rhesus monkey.

Frequencies of sister chromatid exchanges and chromosomal aberrations were examined in peripheral lymphocytes of Rhesus monkeys which had been fed a diet containing 25 parts per trillion 2,3,7,8-tetrachlorodibenzo-p-dioxin for a period of 4 years. When compared to non-exposed control animals, no significant differences were noted for either of these cytogenetic endpoints. In addition, there was not a significant difference in sister chromatid exchange response to a challenge dose of mitomycin C in cells from 2,3,7,8-tetrachlorodibenzo-p-dioxin exposed animals compared to controls. Our results confirm the lack of genotoxic effects associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

Animals↗

Treatment of lethal pertussis vaccine reaction with histamine H1 antagonists.

We studied mortality after pertussis immunization in the mouse. Without treatment, 73 of 92 animals (80%) died after injection of bovine serum albumin (BSA) on day +7 of pertussis immunization. After pretreatment with 3 mg of cyproheptadine, 2 mg mianserin, or 2 mg chlorpheniramine, only 5 of 105 animals (5%) died after receiving BSA on day +7 (p less than 0.001). Blockade of histamine H1 receptors may reduce mortality in pertussis immunization-induced encephalopathy in mice.

Animals↗

Induction of sister chromatid exchanges by inhibitors of topoisomerases.

To investigate the role of topoisomerases in the production of sister chromatid exchanges, the effects of inhibitors of type I and II topoisomerases on baseline and mutagen-induced sister chromatid exchanges were compared. V79 cells were treated with VM-26 and m-AMSA, known inhibitors of type II topoisomerase, or with camptothecin, the only known inhibitor of type I topoisomerase. We observed that inhibitors of both type I and II topoisomerases induced high levels of sister chromatid exchanges at 10(-6) M, and that the dose-response curves of these drugs were very similar. A clear heterogeneity in the distribution patterns of exchanges induced by inhibitors of topoisomerases was observed. We believe that this heterogeneity in response to these compounds is due to variation in sensitivity within the cell cycle. We also studied interactions of these agents with mitomycin-C and with PUVA (8-methoxypsoralen + UVA), both cross-linking agents and potent sister chromatid exchange inducers, and with x-rays, an agent that induces high levels of DNA strand breaks. No significant change in exchange levels was observed in interactions between topoisomerase inhibition and the levels induced by the agents studied. We conclude that double-strand break prevalence, known to be increased through inhibition of type II topoisomerase, is not the primary mechanism for induction of sister chromatid exchanges. We further conclude that acute inhibition of type I and type II topoisomerases does not influence substantially the induction of exchanges by other agents.

Amsacrine↗

Reversal of experimental allergic encephalomyelitis with monoclonal antibody to a T-cell subset marker.

Administration of a monoclonal antibody (GK1.5) that recognizes the L3T4 marker present on helper T cells prevented the development of experimental allergic encephalomyelitis (EAE) in mice. Furthermore, treatment with GK1.5 reversed EAE when the antibody was given to paralyzed animals. In vivo injection of GK1.5 selectively reduced the number of L3T4+ cells in the spleen and the lymph nodes. These results suggest that manipulation of the human equivalent of the murine L3T4+ T-cell subset with monoclonal antibodies may provide effective therapy for certain autoimmune diseases.

Animals↗

Pertussis toxin is required for pertussis vaccine encephalopathy.

A mouse model for encephalopathy induced by pertussis immunization has been described; it has features that closely resemble some of the severe reactions, including seizures and a shock-like state leading to death, occasionally seen after administration of Bordetella pertussis (whooping cough) vaccine. Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin. In this study we have investigated which bacterial determinant is responsible for the encephalopathy. Two lines of evidence implicate pertussis toxin as the active bacterial component. Single-site mutants of B. pertussis with single affected virulence factors were tested. A mutant that produces a defective pertussis toxin had greatly diminished capacity to induce encephalopathy, whereas a hemolysin- and adenylate-cyclase-deficient avirulent mutant had the same activity in the mouse model as a virulent strain. Purified pertussis toxin plus bovine serum albumin was tested and found to induce the lethal encephalopathy, demonstrating that the toxin was the critical constituent of B. pertussis responsible for encephalopathy.

Adenylate Cyclase Toxin↗

Murine model for pertussis vaccine encephalopathy: role of the major histocompatibility complex; antibody to albumin and to Bordetella pertussis and pertussis toxin.

A mouse model for pertussis immunization encephalopathy has been described with features that closely resemble the severe adverse reactions occasionally seen after pertussis vaccine administration,m including seizures and a shock-like state leading to death. These reactions are produced with nearly one hundred percent efficiency provided that the mice immunized with Bordetella pertussis have 1) the appropriate major histocompatibility (H-2) genotype, 2) have been sensitized to bovine serum albumin (BSA), and 3) that the injected B. pertussis contained sufficient amounts of pertussis toxin. Antibody titres were measured in mice with haplotypes H-2d.s.k. that are highly susceptible to encephalopathy as well as in H-2b mice, that are totally resistant. Mice with H-2d.s.k. haplotypes were high responders to BSA, while H-2b (B10) mice were non-responders to BSA. Both H-2d and H-2b mice responded well to B. pertussis. Encephalopathy was induced in resistant H-2b mice with B. pertussis and passively administered anti-BSA antiserum, but not with B. pertussis and anti-(T,G)-A--L antibody. This indicated that B. pertussis and anti-BSA were absolutely required for development of encephalopathy. Encephalopathy could be induced in mice decomplemented with cobra venom factor and given BSA and B. pertussis. Several single-site mutants of B. pertussis affecting single virulence factors were induced with transposon Tn5. One of these mutants, BP357, deficient in pertussis toxin production, had a greatly reduced encephalopathic potential in the mouse model compared to the virulent strain BP 338, or to BP348, an adenylate cyclase and hemolysin double mutant, or to BP 349, a hemolysin mutant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗

Arterial plasma potassium measured continuously during exercise in man.

Five continuous records of arterial plasma potassium were obtained from three normal subjects during brief periods (5-7 min) of exercise (100 W). In two of these subjects hepatic venous blood samples were withdrawn at 0.5-1.0 min intervals and analysed in vitro for plasma potassium. Arterial plasma potassium rose rapidly at the start of exercise from 3.8 +/- 0.3 mmol/l (mean +/- SD) to plateau levels of 5.4 +/- 0.1 mmol/l. One of the above subjects and a further subject were studied after beta-blockade with propranolol. This resulted in an exaggerated rise in arterial plasma potassium during exercise. Hepatic venous potassium measurements indicated that the liver probably had little effect on potassium changes during exercise. The changes in arterial plasma potassium during exercise are rapid and substantial. If transmitted to the extracellular fluid these changes would alter cell transmembrane potential and might as a result alter receptor sensitivity.

Adult↗