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Biomedical subjects

J Fung

Publications and source records attributed to J Fung.

At least 217 records · Page 12Linked to original sources

FK 506 for liver, kidney, and pancreas transplantation.

FK 506 was given for immunosuppression in 14 liver recipients. The drug was used in the first 10 cases because the recipients under conventional immunosuppression had rejection, nephrotoxicity, or both. This salvage therapy was successful in 7 of the 10 attempts. 2 of the 10 patients in the original salvage group as well as 4 new patients underwent fresh orthotopic liver transplantation under FK 506 plus low-dose steroids from the outset. None of these 6 patients had rejection although 1 with preexisting cor pulmonale and coronary atherosclerosis died of a myocardial infarction. In addition, 2 of the 14 liver recipients were given cadaveric kidneys, either from the same donor or from a different donor, and a third was given a pancreas as well as a kidney from the liver donor. There were no rejections of the kidney and pancreas grafts, and serious side-effects were not encountered.

Administration, Oral↗

A dynamic EMG profile index to quantify muscular activation disorder in spastic paretic gait.

Spasticity is a complex phenomenon that interferes with motor control. Existing clinical and physiological measures of spasticity have mainly focused on the evaluation of clonus and reflexes. Subjected to the limitation of testing in a resting position, the results may not necessarily reflect the extent of functional impairment caused by spasticity. To evaluate spasticity in a dynamic, voluntary movement such as locomotion, a task-specific approach is essential. A dynamic index, I, derived from the EMG activity obtained during treadmill walking in human subjects, is therefore proposed as a functionally relevant measurement of spasticity in locomotion. I, defined as the ratio of integrated EMG in the pre-determined 'off' window of the normalized gait cycle to that in the 'on' window, would indicate the degree of abnormal activation of locomotor muscles from their normally relaxed state as compared to the total recruitment in the active state during walking. The present study done on 5 normal and 8 spastic paraparetic subjects showed that I was homogeneously low in the normal group but abnormally high and variable in the spastic group. A case study has further demonstrated that I is sensitive to the alteration in locomotor spasticity with pharmacological intervention, and the change in I parallels the improvement in the kinematics observed. This preliminary study indicates that the proposed index appears to be a functionally relevant and dynamic measurement of spastic locomotor disorder.

Adult↗

Allospecificity of activated T cells grown from endomyocardial biopsies from heart transplant patients.

Studies were conducted to determine the functional characteristics of lymphocytes infiltrating human heart allografts. We have developed methodologies to generate lymphocyte cultures from endomyocardial biopsies. Thirteen biopsies from four heart transplant recipients, obtained at different days during a posttransplant period of less than two months, were cultured in interleukin-2 (IL-2)-containing medium supplemented with irradiated autologous peripheral blood lymphocytes as feeder cells. Lymphocyte cultures were obtained from all 13 biopsies and they exhibited a proliferative response to IL-2, suggesting the presence of activated T cells that express IL-2 receptors. Several cultures consisted of Leu 3 (helper/inducer) T cells, whereas others were primarily Leu 2 (cytotoxic/suppressor) T cells or a mixture of both types of cells. Cultured lymphocytes were also shown to be able to undergo secondary proliferation to donor-specific leukocytes as measured by primed lymphocyte testing (PLT). The PLT specificity of these cells was frequently toward class II HLA antigens of the donor, but certain cultures had PLT specificity associated with class I HLA antigens. These results demonstrate the feasibility of growing functionally active T cells from heart transplant biopsies. An analysis of the phenotypes and allospecificity, as well as a functional characterization of these cells, should generate useful information about the types of T cells involved in cardiac transplant rejection.

Antigens, Differentiation, T-Lymphocyte↗

Effect of different media on determination of novobiocin resistance for differentiation of coagulase-negative staphylococci.

Species identification of coagulase-negative staphylococci often requires the determination of novobiocin susceptibility. Although previous investigators have recommended the use of P agar for this purpose, most clinical laboratories do not routinely utilize this medium. For this reason, studies were performed to compare novobiocin susceptibility results obtained with 11 different species of staphylococci (10 isolates of each species), using P agar, Trypticase soy agar with 5% sheep blood, and Mueller-Hinton agar. Tests performed on 70 susceptible isolates (minimal inhibitory concentration less than 1.6 micrograms/ml) resulted in zones of inhibition around 5-micrograms novobiocin disks ranging from 19.6 to 33.9, 16.2 to 26.6, and 21.3 to 36.4 mm on P agar, Trypticase soy agar with 5% sheep blood, and Mueller-Hinton agar, respectively. Forty resistant isolates (minimal inhibitory concentration greater than or equal to 1.6 micrograms/ml) exhibited zones of inhibition ranging from 6.0 to 11.3 mm on P agar, 6.0 to 11.6 mm on Trypticase soy agar with 5% sheep blood, and 6.0 to 13.5 mm on Mueller-Hinton agar. Using the established cut off of 16 mm to define novobiocin resistance for the identification of coagulase-negative staphylococci, we correctly identified 100% of the strains tested, regardless of the media utilized.

Coagulase↗

Immune response to phosphorylcholine. VIII. The response CBA/N mice to PC-LPS.

CBA/N mice and F1 crosses of CBA/N X BALB/c with the CBA/N phenotype respond to immunization with PC-LPS with a PC-specific and an anti-bridge antibody production. The PC-specific response in defective CBA/N and NBF1 is devoid of the IgG3 subclass and is not T15 idiotype dominant, whereas normal BALB/c and nondefective NBF1 mice express the T15 dominantly in their anti-PC-LPS response. By the criteria of responsiveness to PC-LPS only and the absence of dominant T15 expression, the precursors in defective NBF1 mice for TI-1 antigen PC-LPS can be characterized as being immature B cells similar to those found in neonatal livers of normal BALB/c or in spleens of chronically idiotype suppressed BALB/c mice. This analogy suggests that the developmental defect in CBA/N mice becomes active during the maturation process before selection for clonal dominance occurs and specialization of precursors for the preferred expression of the IgG3 subclass is completed. Alterations in the T cell compartment may contribute to the immature nature of B cells in the sex-linked immunodeficiency of CBA/N mice.

Aging↗

Late clonal selection and expansion of the TEPC-15 germ-line specificity.

The maturation of the antibody response to phosphorylcholine (PC) in neonatal BALB/c mice was studied. A T cell-independent class 1 1 PC-antigen, 3-(p-azophenyl phosphorylcholine)-N-acetyl-L-tyrosylglycylglycine lipopolysaccharide, was synthesized and used to immunize neonatal mice of different ages. The earliest anti-PC hemolytic plaque-forming response could be induced in 1-d-old neonates. Idiotype analysis on these early anti-PC antibodies showed that the response was not TEPC-15 dominant although TEPC-15-positive plaque-forming cells were detected. However, idiotype analysis of the anti-PC-LPS response in 7 d or older animals indicated that clonal dominance had been established. Similar results were obtained in splenic fragment culture with cells from neonatal livers and spleens. PC-specific precursors were detected in the liver of 1-d-old neonates, whereas the spleen of those animals contained no precursors for PC. Precursors for PC residing in the neonatal liver are not TEPC-15 dominant, whereas the splenic PC precursors of 5- to 6-day-old animals express the TEPC-15 idiotype dominatly. These findings demonstrate that during ontogeny PC-specific B cells appear before the TEPC-15 clone becomes dominant. Thus clonal dominance in the adult anti-PC response and late acquisition of the TEPC-15 specificity during ontogeny do not signify a particularly unique or direct relationship to the expression of genes encoded in the germline.

Animals↗

Immune response to phosphorylcholine. VII. Functional evidence for three separate B cell subpopulations responding to TI and TD PC-antigens.

A T-independent PC antigen, the C-polysaccharide, was used to induce a primary response to PC in splenic foci containing precursors taken from normal, unprimed BALB/c mice. The precursor frequency for the TI response was compared with the frequency for a T-dependent PC antigen, PPC-TGG-Hy. Idiotype analysis of the precursors for TD and TI responses indicate that the TD responses are more diverse with respect to clonal dominance of idiotype, TEPC-15, than that of TI responses. If splenic fragments were doubly immunized with both TI and TD antigens, the combined PC-specific precursor frequency was superadditive. TD-antigen-induced responses were found resistant to tolerogen and anti-idiotype suppression, whereas TI responses were extremely sensitive to both manipulations. Since under limiting dilution conditions precursors sort out independently, the superadditive response seen in dual immunized fragments can only be interpreted as evidence for an additional subpopulation of B cells that responds to the combined signals of TD and TI antigens. This postulated third B cell population is also extremely sensitive to tolerogen and anti-idiotype suppression.

Animals↗

Mechanism of neonatal idiotype suppression. II. Alterations in the T cell compartment suppress the maturation of B cell precursors.

The cellular mechanism in neonatally suppressed BALB/c mice, which maintains the chronic suppressed state of the TEPC-15 idiotype in the antibody response to phosphorylcholine (PC), was investigated. Cells taken from these suppressed mice cannot transfer suppression to adult BALB/c or affect the in vitro response to PC of adult BALB/c spleen cells. However, spleen cells or T cells from neonatally suppressed mice given to neonatal animals induce chronic suppression of the TEPC-15 idiotype in the anti-PC response. Co-transfer of T cells from neonatally suppressed cells with normal T cells prevented the induction of suppression in neonates. Transfer of T cells from normal or keyhole limpet hemocyanin-primed BALB/c increased the expression of TEPC-15 idiotype in chronically suppressed mice, whereas T cells from neonatally suppressed were ineffective. These findings show that T cells in neonatally suppressed mice can affect the development of immature but not mature cells. The restoration of TEPC-15 expression in neonatally suppressed animals by normal T cells and the failure to induce suppression in neonates by co-transfers of T cells from normal and chronically suppressed mice demonstrate the profound role of an altered T cell compartment in sustaining chronic idiotype suppression.

Animals↗

Mechanism of neonatal idiotype suppression. I. State of the suppressed B cells.

Neonatal BALB/c mice, given small amounts of an anti-idiotype serum directed against the TEPC-15 idiotype, are chronically unresponsive to immunization with PC antigens. These mice recover from suppression slowly over a period of 10 mo, and their response is not of TEPC-15 idiotype. However, the PC-specific precursors, as analyzed by the splenic fragment culture technique, in 8-mo-old suppressed mice are normal with respect to their frequency and idiotype dominance. Furthermore, the PC-precursors in neonatally suppressed BALB/c are sensitive to tolerance induction, as are precursors from neonatal liver and spleen cells. When chronic suppressed mice are immunized with a novel TI-1 antigen, PC-LPS, shown to stimulate immature PC-specific precursors, their response to PC is 80% of TEPC-15 idiotype, whereas their response to a TI-2 PC antigen and to a TD PC antigen is not TEPC-15 dominant. These results indicate that the TEPC-15 positive B cells in neonatally idiotype suppressed mice are in a state of immaturity that resembles the developmental characteristics of normal neonatal BALB/c mice.

Animals↗

Role of murein lipoprotein in morphogenesis of the bacterial division septum: phenotypic similarity of lkyD and lpo mutants.

Phenotypes were compared in two different classes of mutants with defects in murein-lipoprotein (lkyD mutants of Salmonella typhimurium and an lpo mutant of Escherichia coli). Both mutations are associated with the same triad of phenotypic abnormalities, consisting of defective formation of the division septum, leakage of periplasmic proteins during growth, and increased sensitivity to several unrelated external toxic agents. The abnormality in septum formation consists of a defect in invagination of the outer membrane during formation of the nascent septum. The results suggest that formation of the murein-lipoprotein link plays an important role in differentiation of the division septum and perhaps also in maintaining the normal barrier function of the outer membrane.

Bacterial Proteins↗