Biomedical subjects

R H Lin

Publications and source records attributed to R H Lin.

At least 73 records · Page 4Linked to original sources

PubMed1991

Induction of autoreactive B cells allows priming of autoreactive T cells.

A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present the self protein mouse cytochrome c to autoreactive T cells in immunogenic form. This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen.

Animals↗

PubMed1991

Effects of elevated plasma magnesium concentration on cerebrospinal fluid levels of magnesium in neonatal swine.

To determine whether magnesium (Mg) can cross the blood brain barrier in developing swine, simultaneous measurements of [Mg] in plasma and cerebrospinal fluid (CSF) were made during experimental elevation of plasma [Mg] in 12 swine of differing postnatal age. All were anesthetized with Saffan and maintained at normal arterial blood gas composition. Aortic pressure and heart rate were monitored. Plasma and CSF samples, drawn at the beginning and end of a 60-min intravenous infusion of MgCl2 in all animals and every 10 min during the infusion in three, were analyzed for [Mg] and osmolality. CSF [Mg] increased in all animals as plasma [Mg] increased. There were no changes in CSF osmolality. The differences between plasma and CSF [Mg] was smallest in the youngest animals. These results indicate that Mg crosses the blood brain barrier in neonatal swine and suggest that the blood brain barrier is still maturing within the first postnatal month.

Aging↗

PubMed1990

Unusual observations on hypermagnesemic levels and cardiorespiratory effects in neonatal swine.

Mg is being used as a therapeutic agent in different clinical conditions, i.e. preeclampsia or eclampsia, and as a tocolytic agent to prevent premature delivery. For these reasons we decided to systematically investigate the cardiovascular and respiratory effects of excess Mg in 25 piglets less than 1 day to 3 months of age, lightly anesthetized with Saffan, tracheotomized, paralyzed with C-10 and artificially ventilated on 100% O2. A 1.0 M infusion of MgCl2 was given for 15-60 min, and arterial plasma samples were drawn before and at the end of the infusion for the determination of plasma Mg and Ca levels. Phrenic nerve activity was recorded monophasically simultaneously with arterial blood pressure, electrocardiogram, end-tidal CO2 and intratracheal pressure on a dynograph and on analog tape. In a subset of experiments (n = 6), spontaneous ventilation was monitored in piglets of different ages to determine the Mg concentration at which spontaneous ventilation ceased. Blood gases were measured at 45-min intervals, as well as both immediately before and after the MgCl2 infusion, and pCO2 and pH were maintained within normal limits. As a consequence of the high plasma concentration of Mg, mean arterial pressure and heart rate declined, and the inspiratory duration significantly decreased. Our results indicate that young piglets can survive high levels of plasma Mg (greater than 14 mM).

Animals↗

PubMed1989

A role of Ia-associated invariant chains in antigen processing and presentation.

Most native antigens require processing in a cellular compartment for efficient presentation to T helper cells. The cellular elements that permit processing are not known. We investigated a possible role of the class II MHC-associated invariant chains in antigen processing. Fibroblast cells that were transfected with class II genes were compared with fibroblasts supertransfected with the invariant chain gene for their capacity to present the fifth component of complement (C5) to C5-specific class II restricted T cell clones or influenza virus protein to a virus-specific T cell clone. Only fibroblasts supertransfected with the invariant chain gene were able to present native antigen, even at very low antigen concentration, whereas both fibroblast types could present cyanogen bromide-fragmented C5 or the virus peptide. Presentation of intact antigen but not of fragmented antigen was totally abrogated by treatment of fibroblasts with chloroquine. The invariant chain gene encodes two polypeptides, li31 and li41. Expression of either li31 or li41 was sufficient to render class II-expressing fibroblasts capable of presenting intact antigen.

Animals↗

PubMed1989

T cell immunity or tolerance as a consequence of self antigen presentation.

In this study we investigated the basis for immunity or tolerance to a mouse serum protein, the fifth component of complement (C5). In C5-deficient mice this protein is absent from serum and therefore they are not tolerized. Immunization of C5-deficient mice with C5-sufficient serum generates CD4+ T cells, which recognize C5 presented in the context of class II. No C5-specific responses were observed in T cells from C5-sufficient mice. We show that this self protein is processed and presented with class II by cells from C5-sufficient tolerant mice and can be recognized by C5-specific T cell clones and hybrids in the absence of exogenously added antigen. The stimulation of C5-specific T cells by C5-sufficient antigen-presenting cells is not a consequence of C5 secretion and subsequent processing in vitro but rather employs C5 peptide/class II complexes generated in vivo. We conclude that this self antigen is presented in normal mice in a form recognizable by T cells to induce and maintain immunological tolerance.

Animals↗

PubMed1989

Contribution between dorsal and ventrolateral regions of medulla oblongata in vasomotor function of cats.

In cats anesthetized with alpha-chloralose and urethane, the medulla oblongata was explored with electrical and/or chemical stimulation for vasopressor actions. Chemical stimulation included semimicroinjection of sodium glutamate or microinjection of dl-homocysteic acid (DLH). The dorsal (DM), particularly its dorsomedial (DMM) portion, and the ventrolateral (VLM) regions were found to be most sensitive to both electrical and chemical stimulation. In between these two regions there was an area in the ventral portion of the gigantocellular and the parvocellular reticular nuclei that was sensitive to electrical and somewhat sensitive also to chemical stimulation. The responses to chemical stimulation indicate the existence of perikarya in these three areas for vasopressor actions. The most active response of VLM followed microinjection of DLH into the region of nu. paragigantocellularis lateralis (PGL) and subretrofacial nu. These responses were about 30% greater than those from DM where the most active area was found in the DMM region including the nu. and tractus solitarius. When an extensive area of VLM was lesioned bilaterally with kainic acid (KA, 1 micrograms/100 nl), the resting systemic arterial blood pressure (SAP) fell 42% and the pressor response on DM stimulation fell by more than 80%. In contrast, after similar KA bilateral destruction of DM the resting SAP fell 38% and the pressor responses from 67%. When only a limited area in the PGL/subretrofacial nu. of the rostral VLM (3-4 pressor sites, 1 mm apart) on one side was lesioned, the resting SAP remained unaltered while the pressor response on the ipsilateral DMM decreased 76%. On the other hand, when a similar smaller KA lesion (3-4 sites) was made in the DMM, although the resting SAP did not change, the pressor response on stimulation of the ipsilateral rostral VLM decreased 28%. Further lesioning of the contralateral DMM then decreased the rostral VLM pressor response 62% without much alternation in the resting SAP. Results of the present experiments are in accordance with our previous results that neuronal perikarya for vasopressor action exist not only in VLM but also in DM (18,34) with the function of VLM slightly predominant over DM. It seems highly possible that reciprocal innervation exists between DM and VLM, at least between DMM and the PGL/subretrofacial nu. region.

Animals↗

PubMed1989

An intracellular self protein synthesized in macrophages is presented but fails to induce tolerance.

Mice deficient for the fifth component of murine complement (C5), unlike normal mice, do not possess the secreted form of C5 in their body fluids and can be readily immunized to serum-derived normal C5. Although macrophages from C5-deficient mice do not secrete C5, they synthesize the precursor form (pro-C5). Therefore contact of T cells with autologous pro-C5 presented by macrophages is theoretically possible. We show that macrophages from C5-deficient mice can indeed stimulate a class II restricted C5-specific T cell clone without addition of exogenous C5. Immunization of C5-deficient mice with autologous pro-C5 induces vigorous C5-specific T cell proliferation and pro-C5 is recognized by C5-specific T cells in vitro, demonstrating that this protein fails to induce tolerance under physiological conditions. Thus, intracellular pro-C5 is processed and presented by C5-deficient macrophages and can activate T cell clones in vitro, yet is neither immunogenic nor tolerogenic for T cells in vivo.

Animals↗

PubMed1988

Purification of the fifth component of murine complement from ascites fluid.

The murine complement component C5 was purified on an affinity column using a monoclonal anti-mouse C5 antibody. We describe in this paper that ascites fluid from normal (C5-sufficient) mice contains almost as much C5 protein as mouse serum. Since ascites fluid is much easier to obtain in large quantities it is a convenient source for the purification of this mouse serum protein.

Animals↗

PubMed1988

Presynaptic action of uranyl nitrate on the phrenic nerve-diaphragm preparation of the mouse.

The contraction of the diaphragm of the mouse, induced by nerve stimulation, can be potentiated by uranyl nitrate [UO2(NO3)2, 0.2-0.8 mM]. At concentrations greater than 0.8 mM, uranyl nitrate also directly enhanced the contractions induced by electrical stimulation of muscle. The effects of uranyl nitrate in potentiating the twitch were augmented by low calcium (0.25-0.5 mM) and antagonized by high levels of calcium (5-10 mM). Electrophysiological studies on the effects of uranyl nitrate on the diaphragm in the mouse have revealed that the frequency of miniature end-plate potentials (MEPP) but not the amplitude was increased; the amplitude and quantal content of end-plate potential (EPPs) were also markedly increased by uranyl nitrate. The most peculiar phenomenon induced by uranyl nitrate was that repetitive end-plate potentials, as well as repetitive action potentials, of the diaphragm of the mouse were triggered by single nerve stimulation in the presence of uranyl nitrate. The duration of muscle action potentials was significantly prolonged. Recordings of the evoked compound action potentials from nerve axons showed that uranyl nitrate not only prolonged the duration of the axonal compound action potentials but also induced antidromic activity with a single stimulation. This latter effect of uranyl nitrate was blocked by d-tubocurarine. All of these findings suggest that uranyl nitrate potentiated the contractions of the diaphragm of the mouse, possibly through the activation of stimulus-activated repetitive discharges which resulted in the repetitive end-plate potentials and muscle action potentials.

Action Potentials↗

PubMed1988

Paramedian reticular nucleus--sympathetic inhibition in spontaneously hypertensive rats.

The cardiovascular reactivity of various areas in the medulla related to sympathetic or parasympathetic activation, or to sympathetic inhibition, was compared in spontaneously hypertensive rats (SHR) and in normotensive rats Wistar-Kyoto (WKY) or Sprague-Dawley (SD). In SHR, which has an elevated resting systemic arterial blood pressure (SAP), the sympathetic pressor responses elicited from electrical stimulation of the dorsomedial medulla (DMM), parvocellular lateral nucleus (PVC) or ventrolateral medulla (VLM) were more profound than those in WKY and SD. The depressor and bradycardia responses elicited from electrical stimulation of the paramedian reticular nucleus (PRN) (which exerts both sympathetic and parasympathetic inhibitions) or from the area of the solitary nucleus/dorsomotor nucleus of vagus (NTS/DMV) (where stimulation leads to both parasympathetic activation and sympathetic inhibition) were also more intensive in SHR than in WKY and SD. The elicited pressor and depressor responses, however, were not significantly different between WKY and SD. Our results are consistent with previous findings (15) that in SHR an increased sympathetic activity of the pressor areas of medulla contributes to the pathogenesis of hypertension. Sympathetic inhibition (PRN and NTS/DMV areas) and parasympathetic activation (NTS/DMV area) from these areas, however, may not be critically involved.

Animals↗

PubMed1988

Pressor responses from electrical or glutamate stimulations of the dorsal or ventrolateral medulla.

In rats, rabbits, and cats anesthetized with alpha-chloralose and urethan, responses of the pressor areas of the dorsal portion (DM) and ventrolateral portion (VLM) of medulla and pons were compared. Electrical stimulation (monopolar square-wave pulses) on monosodium glutamate solution (Glu, 100-200 nl, 1 M) was delivered through an electrode-needle tubing connected to a Hamilton syringe for semimicroinjection. In all three of these species, pressor responses were elicited from both DM and VLM by either Glu or electrical stimulation. The most active parts of DM were found in the dorsomedial reticular formation of the rostral medulla to mid-medulla. In the pons and caudal medulla, the Glu-induced response was mild, although the electrically induced response was marked. Application of kainic acid (KA) to either DM or VLM produced an initial pressor response but was followed by a reduction of the pressure rise on subsequent electrical stimulation. Glu, unlike electrical stimulation, excites neural perikarya, not fibers of passage. KA initially excites the neural perikarya before causing damage that spares axons. These results thus suggest that both DM and VLM contain neural perikarya that mediate pressor effects.

Animals↗

PubMed1987

Study on the neuromuscular action of 4-aminopyridine in the mouse diaphragm.

4-Aminopyridine (4-AP), in concentrations ranging from 0.01 to 0.3 mM, increased indirectly evoked twitches of mouse diaphragm; directly evoked twitches were unaffected. 4-AP did not significantly affect the resting membrane potential, the amplitude and duration of muscle action potentials, the frequency and amplitude of m.e.p.p.s. or the half decay time of e.p.p.s. and m.e.p.p.s. However, e.p.p. amplitude and quantal content were increased by 4-AP in a concentration-dependent manner. On single stimulation of phrenic nerve 0.1 mM 4-AP induced repetitive e.p.p.s. Although 4-AP did not significantly affect compound action potentials evoked in the phrenic nerve, 4-AP caused repetitive firing to appear in phrenic nerve following single indirect stimulation of the nerve-muscle preparation. This repetitive firing was abolished by d-tubocurarine. In low Ca2+ (0.35 mM) Krebs solution 0.1 mM 4-AP induced muscle fasciculation accompanied by spontaneous giant e.p.p.s. and spontaneous muscle action potentials. In addition, 4-AP (0.1 mM) induced spontaneous repetitive firing of phrenic nerve axons; this was not inhibited by d-tubocurarine.

4-Aminopyridine↗

PubMed1987