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Biomedical subjects

R G Miller

Publications and source records attributed to R G Miller.

At least 253 records · Page 14Linked to original sources
PubMed1985

The tight junction as a barrier to cholesterol in canine epithelial cells.

Filipin has been used to test several models of continuity or flow of lipid components through the tight junction. Cultured canine kidney cells (MDCK) were fixed and incubated in the presence of filipin. Freeze-fracture replicas were analyzed and densities of filipin-cholesterol complexes measured. Fractures of membranes linked with tight junctions were compared statistically to determine whether filipin-cholesterol complexes (protrusions and pits, independently) were randomly distributed between the two membranes of cells separated by the tight junction. The results indicate that filipin-cholesterol complexes are not randomly distributed across the tight junction. If the density of filipin-cholesterol complexes is an accurate indication of membrane cholesterol concentration, then there is a difference in the cholesterol concentration between leaflets of membranes joined by tight junctions and models of the tight junction which suggest leaflet continuity across the junction are in error.

Animals↗
PubMed1985

Paraproteinemia associated with demyelinating polyneuropathy or myositis: treatment with plasmapheresis and immunosuppressive drugs.

Four patients with chronic, progressive demyelinating peripheral polyneuropathy were found to have paraproteinemia. Two of the patients had multiple myeloma [both immunoglobulin (Ig)G lambda]. The other two had benign gammopathies: one of IgG kappa type and the other one with marked polyclonal elevation of IgM. Immunofluorescence studies revealed deposits of the abnormal serum immunoglobulin along the myelin sheaths in two of the patients in whom sural nerve biopsies were performed. All four patients were treated with plasmapheresis in combination with immunosuppressive drugs. Favorable responses to the therapy was observed in all four patients, but the degree of response varied from patient to patient. Two patients who presented clinical and electromyographic findings consistent with polymyositis were found to have serum IgG kappa M components. Immunofluorescence studies performed on muscle biopsy material from both patients revealed deposits of the abnormal serum paraprotein along the sarcolemmal basement membrane. A treatment course of plasmapheresis and immunosuppressive drugs resulted in a sustained increase of muscle strength in both patients.

Azathioprine↗
PubMed1985

Emery-Dreifuss muscular dystrophy with autosomal dominant transmission.

A woman with early-onset, slowly progressive, humeroperoneal muscle weakness had marked restriction of neck flexion with contracture at the elbows. She developed exertional dyspnea at age 25, atrial fibrillation with slow ventricular rate was discovered, and a cardiac pacemaker was implanted. Her father had a similar disorder. There is at least one other report of autosomal dominant transmission of this clinical picture, which had previously only been reported as Emery-Dreifuss muscular dystrophy with X-linked recessive inheritance. Thus, more than one mode of inheritance is possible for this unusual and distinctive form of muscular dystrophy.

Adult↗
PubMed1985

Hereditary and acquired polyneuropathies. Electrophysiologic aspects.

The electrophysiologic evaluation of patients with polyneuropathy may, in an increasing number of disorders, provide data that are critical to both diagnosis and treatment, especially in acquired demyelinating neuropathies. In general, the data will permit the presence or absence of neuropathy to be determined, and provide information concerning etiology, severity, pathology, and prognosis of peripheral nerve disease.

Cockayne Syndrome↗
PubMed1985

Functional heterogeneity in allospecific cytotoxic T lymphocyte clones. II. Development of syngeneic cytotoxicity in the absence of specific antigenic stimulation.

Two out of four long-term murine allospecific cytotoxic T lymphocyte (CTL) clones tested could develop high levels of cytotoxicity against syngeneic target cells when cultured under appropriate conditions. All CTL clones maintained strict allospecificity so long as they were cultured with both appropriate allogeneic stimulator cells and growth factor (supernatant from secondary mixed lymphocyte cultures). In two of the clones, syngeneic reactivity rapidly developed when the allogeneic stimulator cells were replaced with syngeneic or third party stimulator cells, and when the supernatant from EL4 thymoma cells stimulated with phorbol ester was used as growth factor. In addition to killing the appropriate allogeneic target, clones with syngeneic reactivity could kill both syngeneic C57BL/6 targets and H-2-congenic BALB.B targets but not third party unrelated targets, suggesting that the self structure recognized was coded for within the major histocompatibility complex. Such clones did not kill the natural killer (NK) target YAC. The results obtained from cold target inhibition and from subcloning at limiting dilution of clones with syngeneic reactivity suggested that both allogeneic and syngeneic reactivity could be expressed by the same individual cell in the CTL clone. The specificity for syngeneic H-2 as opposed to third party H-2 and NK-sensitive target cells, and the observation that both allospecific and syngeneic killing could be partially blocked by anti-Lyt-2 antibody treatment of the CTL, strongly suggested that different recognition structures are involved in CTL-mediated syngeneic cytotoxicity and NK cytotoxicity.

Animals↗
PubMed1984

Functional heterogeneity in allospecific cytotoxic T lymphocyte clones. I. CTL clones express strong anti-self suppressive activity.

Five out of five allo-specific cytotoxic T lymphocyte (CTL) clones tested strongly suppressed the development of CTLs directed against the H-2 haplotype of the CTL clone and independent of the H-2 specificity recognized by the CTL clone. This was shown by including 100-1,000 cells from the five clones in one way mixed lymphocyte reaction (MLR) cultures in which the stimulator cells were of the same H-2 type as the CTL cells. When these cultures were assayed for cytotoxicity against the stimulator cell haplotype, the cytotoxic activity was decreased in a CTL cell dose-dependent manner by 50 to more than 90%. Suppression was usually not observed in MLR cultures where the CTL-H-2 type was identical with the responder cells or was different from both the responder or stimulator cells. Suppression was demonstrated not to be due to "cold" target inhibition at the time of cytotoxicity assay. Even if the added CTL were completely removed after 48-72 h of culture, significant suppression was obtained. Suppressive ability did not appear to be correlated with the level of allo-specific cytotoxic activity present in the CTL clones, but might involve direct killing of MLR precursor cells by cells in the added CTL clones. The suppression observed here, which is anti-self from the point of view of the added CTL clone, appears to be triggered by precursor cells in the MLR responder population recognizing MHC determinants on cells from the added CTL clone. This peculiar type of suppression, in which the regulator regulates on being recognized, has been christened the veto phenomenon and may play a role in maintenance of self tolerance.

Animals↗
PubMed1984

Polymyositis associated with monoclonal gammopathy.

Three patients presented with gradual onset of proximal muscle weakness. Electromyography and muscle biopsy were abnormal in each patient and typical of myositis. All three had an IgG kappa monoclonal paraprotein in the serum. Examination of muscle biopsy specimens by direct immunofluorescence revealed linear deposits of IgG kappa along the sarcolemmal basement membrane of individual fibres. Stains for lambda light chains, other immunoglobulins, and complement components were negative. Plasmapheresis and immunosuppressive drugs produced clinical improvement in all three patients. Muscle biopsies were taken from two of the patients after plasma exchange and drug therapy and showed no immune deposits. These observations suggest a possible cause-and-effect relation between the serum paraprotein and the inflammatory myopathy in these patients.

Aged↗
PubMed1984

Interactions between digitonin and bilayer membranes.

The morphology of interactions between digitonin and cholesterol has been investigated. When precipitated from ethanolic solutions, digitonin-cholesterol complexes form in flat lamellar sheets. In contrast, when the complex is formed in a bilayer membrane, the membrane is deformed into corrugations of hemitubules. The polarity of the deformations formed in bilayer membranes is highly correlated with the direction of entry of digitonin into the membrane. We suggest that the morphology of digitonin/cholesterol hemitubules is dependent upon the complex being formed within a bilayer and, in addition, is not correlated with asymmetry of cholesterol concentration across the membrane.

Animals↗
PubMed1984

Randomized comparison of intravenous versus intracoronary streptokinase for myocardial infarction.

The efficacy of intravenous (i.v.) thrombolytic therapy has not been firmly established in comparison with the intracoronary (i.c.) route of administration. In a randomized trial of 28 patients who underwent angiography before and during i.v. and i.c. administration of streptokinase (STK), recanalization was achieved in 73% of patients who received the drug by the i.c. route, compared with 62% of patients who received the drug by the i.v. route (difference not significant). Reopening took 28 minutes for i.c. STK and 39 minutes for i.v. STK. Patients in whom recanalization was successful using either route of administration had shorter euglobulin lysis times and lower fibrinogen levels than did patients in whom it was not successful (p less than 0.05). Bleeding complications were closely correlated with heparinization after thrombolysis rather than with STK itself. These results in a limited patient series suggest that early administration of i.v. STK in the emergency department may yield recanalization rates similar to those for the i.c. route and may benefit myocardial preservation by restoring flow much earlier.

Aged↗
PubMed1984

Differential binding of lectins to lymphopoietic and myelopoietic cells in murine marrow as revealed by flow cytometry.

Murine marrow cells were labeled with a panel of fluorescein-conjugated lectins and analyzed by flow cytometry. All lectins tested [concanavalin A (Con A), phytohemagglutinin (PHA), wheat germ agglutinin (WGA), pokeweed mitogen (PWM), soybean agglutinin (SBA), peanut agglutinin (PNA), lentil lectin (LL)], stained a fraction of marrow cells; the fraction was, over a defined concentration range, linearly related to the logarithm of the lectin concentration. The slope of this titration curve was characteristic of the particular lectin tested but independent of the nominal sugar specificity of the respective lectin. Con A-, PWM-, and PNA-labeled marrow cells showed brightly and dimly stained subsets in relative fluorescence intensity distribution histograms at high or intermediate staining concentrations. These subsets were composed of cells with restricted and characteristic size distributions as determined by forward light scatter. Lectin staining patterns of marrow cells from normal mice were compared with those of athymic nude mice and mice with severe combined immunodeficiency (SCID). Normal and nude mice lacked a subset of small cells, dimly stained by Con A and PWM, but brightly stained by PNA. This subset, uniquely defined by the above lectins, appears to correspond to the lymphopoietic marrow compartment.

Animals↗
PubMed1984

Irreversible inactivation of activated cytotoxic T lymphocyte precursor cells by "anti-self" suppressor cells present in murine bone marrow T cell colonies.

When added to a mixed lymphocyte culture, cells in T cell colonies grown from bone marrow (BM) suppressed the development of cytotoxic activity against H-2 antigens shared by the colony cells and the stimulator cells, apparently by inactivating cytotoxic T lymphocyte precursor cells (CTLP). From the point of view of the added suppressor cells, the suppression was against self-reactive cells. The suppressor cells were resistant to gamma irradiation (1500 rds) but sensitive to UV irradiation. Inactivated CTLP separated from the suppressor cells by cell sorting could not be reactivated on being recultured with fresh stimulator cells, suggesting the suppression is irreversible. There was a critical time window, extending roughly from 20 to 40 h after culture initiation, during which the suppressor cell had to be present if CTLP were to be inactivated. During the first 20 h and after 40 h of exposure to stimulator cells, CTLP were resistant to the suppressor cell. Direct experimental evidence is presented against the possibility that the suppressor cells derived from BM colonies act by augmenting the production of Lyt-2+ suppressor cells from the responder population which then produce the suppression, or that the suppressor cells interfere with an early interaction between CTLP and stimulator cells. We conclude that the suppressor cells in T cell colonies grown from BM act directly on activated CTLP and permanently inactivate them.

Animals↗
PubMed1984

Conduction block in compression neuropathy: recognition and quantification.

Previous reports of conduction block in compression neuropathy have used the amplitude difference of the compound muscle action potential (CMAP) comparing proximal with distal stimulation. The present study was undertaken to determine if area reduction of the proximal CMAP provides diagnostic information that is not included in amplitude reduction, particularly in distinguishing conduction block from temporal dispersion. Digitized, integrated area measurements were compared with amplitude and, as a convenient estimate of area, the calculated M-index (1/2 duration X amplitude). Amplitude reduction did not reliably distinguish conduction block from temporal dispersion in compression neuropathy. Both in the investigation of conduction block and in the management of compression neuropathy, integrated area measurement allows for the more accurate identification and quantification of conduction--a usually reversible cause for weakness in compression neuropathy.

Action Potentials↗
PubMed1984

A glycopeptide extract can inhibit cytotoxic T lymphocyte-target cell conjugation in an H-2-restricted manner.

Glycopeptides extracted from P815, a DBA/2 (H-2d) mastocytoma, were able to inhibit conjugate formation between anti-H-2d CTL and an H-2d target, but were not able to inhibit conjugate formation between anti-H-2k or anti-H-2b CTL and an appropriate target. This genetically specific effect was seen for CTL generated in primary bulk cultures and for long-term CTL lines, and was observed regardless of the strain combinations used to generate CTL. The phenomenon was quantitatively reproducible between independent experiments and between three separate preparations of P815 glycopeptide. These results suggest that recognition by CTL involves cell surface carbohydrate groups, and that the structure of these groups is influenced by H-2.

Animals↗
PubMed1984

Chancroidal ulcers that are not chancroid. Cause and epidemiology.

Hemophilus ducreyi was isolated from the ulcer of one of 33 patients in whom chancroid had been diagnosed clinically. Herpes simplex virus was isolated from 16 of these patients. A presumptive diagnosis of chancroid was made in one of three sexual partners of the only index patient with culture-proved chancroid. No chancroidal lesions were found in any of 39 sexual partners of the other 32 index patients. Genital cultures for herpes simplex virus were positive from four of 14 sexual partners of index patients with genital herpes simplex infection. The differential diagnosis of chancroidal genital ulcers is facilitated by herpes simplex virus cultures and a new selective H ducreyi culture medium.

Chancroid↗