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Biomedical subjects

M M Fisher

Publications and source records attributed to M M Fisher.

At least 91 records · Page 5Linked to original sources
PubMed1986

Human IgA as a heterovalent ligand: switching from the asialoglycoprotein receptor to secretory component during transport across the rat hepatocyte.

Asialoglycoproteins are taken up by the rat liver for degradation; rat polymeric IgA is taken up via a separate receptor, secretory component (SC), for quantitative delivery to bile. There is negligible uptake of these ligands by the converse receptor, and only a low level of missorting of ligands to opposite destinations. The two pathways are not cross-inhibitable and operate independently (Schiff, J.M., M. M. Fisher, and B. J. Underdown, 1984, J. Cell Biol., 98:79-89). We report here that when human IgA is presented as a ligand in the rat, it is processed using elements of both pathways. To study this in detail, different IgA fractions were prepared using two radiolabeling methods that provide separate probes for degradation or re-secretion. Behavior of intravenously injected human polymeric IgA in the rat depended on its binding properties. If deprived of SC binding activity by affinity adsorption or by reduction and alkylation, greater than 80% of human IgA was degraded in hepatic lysosomes; radioactive catabolites were released into bile by a leupeptin-inhibitable process. If prevented from binding to the asialoglycoprotein receptor by competition or by treatment with galactose oxidase, human IgA was cleared and transported to bile directly via SC, but its uptake was about fivefold slower than rat IgA. Untreated human IgA was taken up rapidly by the asialoglycoprotein receptor, but depended on SC binding to get to bile: the proportion secreted correlated 1:1 with SC binding activity determined in vitro, and the IgA was released into bile with SC still attached. These results demonstrate that human IgA is normally heterovalent: it is first captured from blood by the asialoglycoprotein receptor, but escapes the usual fate of asialoglycoproteins by switching to SC during transport. Since the biliary transit times of native human and rat IgA are the same, it is probable that the receptor switching event occurs en route. This implies that the two receptors briefly share a common intracellular compartment.

Animals↗
PubMed1986

Detection of thiopentone-reactive IgE antibodies following anaphylactoid reactions during anaesthesia.

A radioimmunoassay was developed to detect IgE antibodies to the anaesthetic induction agent thiopentone. Significant levels of thiopentone-reactive IgE antibodies were found in the sera of two patients who had experienced life-threatening anaphylactoid reactions following administration of the drug. Inhibition experiments revealed that cross-reactivity occurs between the drug-reactive IgE antibodies and four barbiturate analogues pentobarbitone, phenobarbitone, barbitone and methohexital. The assay should supplement skin testing for the detection of patients with potentially lethal sensitivity to thiopentone.

Anaphylaxis↗
PubMed1986

Clinical observations on the pathophysiology and treatment of anaphylactic cardiovascular collapse.

Observations in 205 patients with cardiovascular manifestations of anaphylactic shock confirmed the belief that adrenaline is the drug of first choice in management and that colloid solutions are preferable to crystalloid solutions in volume replacement. Arrhythmias and elevated filling pressures are more common in patients with cardiac disease but the sympathetic response appears to override the cardiac effects of histamine in healthy patients.

Anaphylaxis↗
PubMed1986

Unexplained acute membrane pulmonary oedema related to anaesthesia.

Five patients developed severe pulmonary oedema in relationship to elective anaesthesia and surgery. The oedema was due to increased capillary permeability in four patients and probably due to increased capillary permeability in the other. No cause could be found in any patient.

Acute Disease↗
PubMed1986

Risk of fatty infiltration or cirrhosis of the liver in relation to ethanol consumption: a case-control study.

A case-control study was conducted to investigate the risk of either fatty infiltration of the liver or cirrhosis, in males and females, in relation to varying levels of ethanol consumption. Male and female cases of fatty infiltration of the liver (47 males and 43 females) and male and female cases of cirrhosis (85 males and 66 females) were identified during 1981-1982 as part of a liver biopsy study in 6 teaching hospitals in Toronto. All cases were confirmed by biopsy. Male and female controls (394 males and 225 females) were obtained from 7 different local industries during the same period as part of a study for the early detection of liver disease. Cases and controls were interviewed by a nurse practitioner using a standard questionnaire designed to elicit data on daily and cumulative alcohol consumption. In both males and females, a dose-response effect between increasing levels of both daily and cumulative alcohol consumption and increasing risk of either fatty liver or cirrhosis was demonstrated and was independent of effects of age and duration of consumption. In males, risk for fatty liver was 1.37 (95% CL = 0.47, 4.0) for those consuming 40-59 g absolute alcohol/day compared to males consuming less than 40 g/day, rising to 50 (95% CL = 15.0, 170.7) for males consuming 80 or more g/day. In females, risk for fatty liver appeared at lower levels and was 2.82 (95% CL = 1.02, 7.82) for females consuming 20-59 g/day compared to females consuming less than 20 g/day, rising to 8.53 (95% CL = 2.12, 34.31) for females consuming 60 or more g/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Assays for, and cross-reactivities of, IgE antibodies to the muscle relaxants gallamine, decamethonium and succinylcholine (suxamethonium).

Two radioimmunoassays have been developed to detect IgE antibodies to succinylcholine, decamethonium and gallamine in the sera of patients who have experienced life-threatening anaphylactoid reactions following administration of a muscle relaxant drug. They involve the coupling of choline and its ethyl analogue, triethylcholine to activated Sepharose. A high degree of cross-reactivity was shown to occur between drug-reactive IgE antibodies and 6 muscle relaxants as well as choline and triethylcholine. Results suggest that the specificities of the IgE antibodies are directed towards quaternary or tertiary ammonium ions on the drugs that bind the antibodies. Molecular models of these compounds support the structure-activity relationships determined in the inhibition studies.

Antibody Specificity↗
PubMed1985

Inhibition of histamine-N-methyltransferase activity by neuromuscular blocking drugs.

On the basis of previous findings that histamine-N-methyltransferase (HMT) activity can be significantly enhanced or inhibited by a number of analogues of histamine and drugs containing dialkylaminoalkyl moieties, we investigated whether the neuromuscular blocking drugs alcuronium, d-tubocurarine, decamethonium, succinylcholine, gallamine and pancuronium each of which contain quaternary ammonium groups, influence the activity of HMT. Our findings showed that all six drugs significantly inhibited HMT activity in the concentration range 10(-7)-10(-3) M with alcuronium being the most potent inhibitor (I.D.50 = 2 X 10(-6) M). Activities at these concentrations reveals that alcuronium, pancuronium, d-tubocurarine and gallamine are more potent inhibitors than two of the most potent histamine analogue inhibitors, N tau-methylhistamine and 2-methylhistamine. Alcuronium proved to be of similar potency to the dimaprit analogue, SKF 91488 regarded as one of the most potent HMT inhibitors known. The structurally similar and chemically least complex straight chain neuromuscular blocking compounds, succinylcholine and decamethonium proved to be the least potent inhibitors.

Alcuronium↗
PubMed1985

Nuclear magnetic resonance study of iron overload in liver tissue.

Whole-tissue and homogenized samples of human liver were studied in a NMR spectrometer, T1 and T2 relaxation times were measured as a function of added inorganic or organic iron. When inorganic iron (Fe+3) was added, pronounced T1 and T2 shortening was noted. However, when organic iron, in the form of ferritin, was added, the amount of T1 and T2 relaxation enhancement was much reduced for the same amount of added iron. The in vitro ferritin results model the situation found in clinical studies of hemochromatosis. Only in cases of severe iron overload were significant decreases in relaxation times observed. The T2 relaxation time was the more reliable indicator of excessive levels of iron in the liver. The large range of T1 and T2 values encountered in normal volunteers precludes the use of MR to quantitatively measure iron levels in the liver. The T1 and T2 relaxation times measured at intervals for one individual tend to fluctuate as well, making the use of MR to follow the course of treatment of iron overload disorders unreliable.

Hemochromatosis↗
PubMed1985

Role of IgE in anaphylactoid reactions during anaesthesia.

As diagnostic methods of detecting drug-specific IgE antibodies become more sophisticated, the evidence implicating specific IgE in anaesthetic allergy has increased. To implicate IgE in reactions, a history resembling anaphylaxis, the demonstration of drug-specific histamine release by intradermal testing and the demonstration of specific antibodies are necessary. Such evidence is seen in 70% of muscle relaxant reactors. Basophil histamine release studies suggest that histamine release is allergen-induced, not direct, and the final evidence necessary is to demonstrate the role of drug-specific antibodies in such histamine release.

Anaphylaxis↗
PubMed1985

In vitro diagnosis and studies on the mechanism(s) of anaphylactoid reactions to muscle relaxant drugs.

By covalently coupling alcuronium, d-tubocurarine and the pancuronium analogue, vecuronium, and using the resultant complexes in radioimmunoassays with patients' sera, we have found high levels of drug-reactive IgE antibodies in some subjects who reacted to these muscle relaxants. This is the first demonstration of IgE antibodies to such compounds. Assays were also developed for the detection of drug-reactive IgE antibodies to the muscle relaxant drugs succinylcholine, decamethonium and gallamine. They involved the coupling of choline and its ethyl analogue, triethylcholine to activated Sepharose. Results of direct binding and inhibition experiments and correlations with clinical findings demonstrated that the assays are relevant to the detection of succinylcholine-, decamethonium- and gallamine-reactive IgE antibodies in patients who experienced adverse reactions to these drugs. Quantitative inhibition studies revealed that IgE antibodies from most patients cross-reacted with all muscle relaxants tested, other quaternary ammonium compounds and some pharmacologically unrelated drugs including promethazine, morphine, neostigmine and pentolinium. Results showed that the specificities of the IgE antibodies are directed towards quaternary or tertiary ammonium ions on the drugs that bind the antibodies. As these ions occur widely in man's environment in drugs, cosmetics, disinfectants, foods and industrial materials, it seems possible that sensitization of patients may occur without previous exposure to muscle relaxant drugs. Thus, we now have assays that will detect antibodies to all six muscle relaxant drugs --alcuronium, d-tubocurarine, pancuronium, succinylcholine, decamethonium and gallamine-- and, for the first time since the work on penicillins, drug-specific IgE antibodies have been found in large numbers of patients and the allergenic determinants have been identified.

Anaphylaxis↗
PubMed1985

Skin testing in the preoperative diagnosis of anaesthetic allergy.

Intradermal testing is a valid manoeuvre for the determination of the drug responsible for an anaphylactoid reaction during anaesthesia. It does not fill criteria for a screening test and will have limited use in the preoperative diagnosis of anaesthetic allergy unless a high risk group is selected.

Anesthesia↗
PubMed1985

Cross-reactivity of metocurine, atracurium, vecuronium and fazadinium with IgE antibodies from patients unexposed to these drugs but allergic to other myoneural blocking drugs.

An inhibition assay was used to determine quantitatively the allergenic cross-reactivity of some myoneural blocking drugs not yet released for use in Australia, in the sera of patients who had experienced anaphylactic reactions to neuromuscular blocking drugs. Two of the compounds, metocurine and atracurium were highly cross-reactive with the currently used myoneural blockers; fazadinium was weakly cross-reactive and vecuronium intermediate in potency between these two extremes. From these results, we predict that anaphylactic reactions to these compounds, and particularly to metocurine and atracurium, will occur in some patients allergic to the currently used neuromuscular blocking agents.

Anaphylaxis↗
PubMed1985

Lymph cysts or lymphocoele: a case report.

A patient with a lymph cyst of the thigh following sulfuric acid burns of both feet is presented. It was diagnosed by percutaneous lymphangiography with Ethiodal. Omentopexy was performed with success. A complication of hernia of small intestine into the thigh was corrected by herniorraphy. Omentopexy is an excellent modality to improve lymph flow. Awareness of hernia post operatively may limit its use.

Female↗
PubMed1985

Hilar biliary plexus in human liver. A comparative study of the intrahepatic bile ducts in man and animals.

A comparative study of the hepatic bile ducts of man and laboratory animals was made by means of scanning electron microscopy of biliary tract casts. In man, the large intrahepatic bile ducts at the hilum have many irregular side branches and pouches which are all situated in one plane corresponding anatomically to the transverse fissure (porta hepatis). At the bifurcation, some of the side branches from two or three bile ducts communicate with each other. The anastomosing plexus so formed provides communications between the main bile ducts. Bile ducts of the rhesus monkey show a similar but less well developed structure. In the pig, many pouches are observed around not only large but also small bile ducts. No such structures are observed in dog, guinea pig, or rabbit bile ducts. These irregular side branches and pouches correspond to the "vasa aberrantia" and "parietal sacculi" described by L. S. Beale (The Liver. Lecture on the Principles and Practice of Medicine, p 47. London, Churchill, 1889), and they may store and modify bile. The plexus described in man in this report may provide an anatomical basis for incomplete biliary obstruction without cholestasis. A role in biliary atresia and in Caroli's disease is also raised.

Animals↗
PubMed1985

A role for the spleen in the appearance of IgM in the bile of rats injected intravenously with horse erythrocytes.

The i.v. injection of the particulate antigens horse red blood cells (HRBC) and Salmonella enteritidis into rats results in the appearance of high levels of IgM agglutinating antibody in the serum and bile. This is in contrast to the appearance of specific IgA antibodies in bile after the injection of antigen into the Peyer's patches. At the height of the response, a fivefold to 10-fold increase in total IgM was found in bile, whereas there was no increase in IgA or in total protein levels. The biliary IgM was not associated with secretory component. Studies aimed at revealing the source of the IgM showed that neither immunized nor nonimmunized rats were able to transport 131I-rat IgM, but both groups were equally efficient at transporting 125I-rat IgA. Furthermore, specific anti-HRBC antibody could not be detected in the bile of rats that were injected with a high titer serum, indicating that blood is unlikely to be the source. Splenectomy of rats at the time of the injection of antigen, at 3 days after immunization had abrogated the biliary response, and at 5 days resulted in rapid decline in existing specific antibody level. Involvement of the spleen was additionally implicated when it was shown that injection of animals with immune spleen cells gave rise to specific antibodies in serum and bile. On the basis of these experiments, it is proposed that antigen entering the blood stream can stimulate a population of cells in the spleen that emigrates to the liver, where the cells localize and secrete IgM into bile.

Animals↗