Effect of purified heat-labile toxin of Bordetella bronchiseptica on the peripheral blood vessels in guinea pigs or suckling mice.
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Biomedical subjects
Publications and source records attributed to M Endoh.
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In vitro effects of the Bordetella HLT on the isolated perfused lung and some other tissue preparations from guinea pigs were examined. When HLT (30 to 300 MNDs/ml) was administered, an increase of the perfusion pressure was induced in the perfused lungs, indicating vasoconstriction. When 100 or 300 MNDs/ml of HLT was given, the pressure increase appeared after a lag period of 3.5 to 4 min, reached a maximum within 8 to 13 min, and then slowly decreased by 60 to 80% 25 min after exposure. In calcium-free medium, the pressure increase due to HLT did not occur, but these HLT-treated lungs manifested an increase without any lag period immediately after the calcium-free medium was replaced by normal medium containing calcium. No difference in the response of the perfused lungs to histamine was observed before and after exposure to HLT. The arterial strip did not respond to HLT, but after predigestion with a collagenase and elastase solution the contractive response to 100 MNDs/ml of HLT appeared with a lag period of 1 min. HLT had no effect on the pharmacological responses of the isolated atria, deferent canal or intestinal preparations, or on the ciliary movement of cultured tracheal rings.
A study of double immunofluorescence-staining of immunoglobulins and sialic acids in the glomeruli from patients with IgA nephropathy is described. Renal biopsy specimens from patients with IgA nephropathy were stained with rhodamine-labeled antihuman IgA, IgG or IgM antisera and then stained with FITC-labeled Limulus polyphemus (LPA), Tricum vulgaris (WGA) or antihuman C3 antisera. Marked positive stainings of IgA and C3 and positive binding of LPA or WGA were observed in the glomerular mesangial areas from patients with IgA nephropathy. LPA or WGA were not bound with glomerular capillary walls from patients with moderate and advanced stages of IgA nephropathy, although depositions of IgA and C3 were markedly observed in such walls. There was a significant inverse correlation between the deposition of IgA and the binding of LPA or WGA in glomerular capillary walls obtained from these patients with IgA nephropathy. The levels of proteinuria from patients with moderate and advanced stages of IgA nephropathy were significantly higher than those with minimal and slight stages of such disease. It is suggested that the decrease of sialic acids in glomerular capillary walls might be due to a deposition of IgA in some patients with IgA nephropathy. It is concluded that high levels of proteinuria might be due to the decrease of sialic acids in glomerular capillary walls from patients with moderate and advanced stages of IgA nephropathy.
The cytopathic effects of extracts of pharyngeal cells from patients with IgA nephropathy on fibroblasts were determined. Autoradiographical analysis of antigens in the fibroblasts was also described. Freeze and thawed extracts of pharyngeal cells obtained from patients with IgA nephropathy, other glomerular diseases and healthy adults were cultured with fibroblasts such as Vero or Hel cells at 37 degrees C for 1 or 2 weeks. The cytopathic effects of fibroblasts were examined with a light microscope. In addition, the eluate obtained from renal tissues of IgA nephropathy was labeled with iodine-125 by the chloramine-T method. These cultured fibroblasts were incubated with iodine-125-labeled eluate from the same or other patients with IgA nephropathy. The degree of cytopathic effects of extracts of pharyngeal cells from patients with IgA nephropathy on Vero or Hel cells was significantly increased compared with that from patients with other glomerular diseases or healthy adults without glomerular diseases. The cytopathic effects of such fibroblasts were not inhibited by filtration of extracts of pharyngeal cells obtained from patients with IgA nephropathy. It was shown that the antibodies eluted from renal tissues of patients with IgA nephropathy specifically bound with the nuclear regions of such fibroblasts. It was suggested that some antigenic substances might exist in the epithelial cells of the upper respiratory tracts of some patients with IgA nephropathy, and that such antigens were able to be transferred to cultured fibroblasts.
Using the basic equations for heat balance, a compartment model was constructed to simulate the physiological responses to heat and cold in rats. The model predicted steady-state situations of rectal temperature, skin temperature (pelt and tail), metabolic rate and evaporative heat loss.
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In isolated canine ventricular trabeculae and papillary muscles driven electrically at 0.5 Hz at 37 degrees C, the positive inotropic effects of milrinone, amrinone, MDL 17,043, MDL 19,205, OPC-8212, and forskolin were all associated with simultaneous elevations in tissue cyclic AMP levels. After the administration of sulmazole (AR-L 115 BS), the increase in force preceded that of cyclic AMP levels. Bay k 8644 increased the force of isometric contractions without producing any change in cyclic AMP levels. None of these agents affected the cyclic GMP level. Intracellular calcium transients were determined in similar preparations in which multiple superficial cells had been microinjected with the Ca++-sensitive bioluminescent protein aequorin. The aequorin signals increased in parallel with increases in force in response to cumulative administration of milrinone, amrinone, MDL 17,043, OPC-8212, forskolin, and low concentrations of sulmazole (less than or equal to 3 X 10(-4) M). Forskolin and sulmazole produced larger increases in the amplitude of the calcium transients than the other agents, and their inotropic effects were less variable in magnitude. High concentrations (greater than 3 X 10(-4)M) of sulmazole decreased the amplitude of the calcium transients while increasing further the force. The increases in cyclic AMP levels, calcium transients, and force produced by all of the inotropic agents except Bay k 8644 and high concentrations of sulmazole were effectively antagonized by carbachol. These results indicate that the accumulation of cyclic AMP resulting from the inhibition of cyclic AMP phosphodiesterase plays an important role in the action of new positive inotropic agents, milrinone, amrinone, MDL 17,043, MDL 19,205, OPC-8212, and sulmazole (less than or equal to 3 X 10(-4)M), on dog ventricular muscle.
Chronic relapsing experimental allergic encephalomyelitis was induced in SJL mice by adoptive transfer of long-term cultured T cell lines. The T cells which were activated with myelin basic protein (MBP) derived from various species, all induced chronic relapsing experimental allergic encephalomyelitis with a similar high incidence. During the relapsing stage, lymphocytes obtained from the spleen responded well to MBP and were capable of transferring experimental allergic encephalomyelitis, whereas thymus lymphocytes did not respond to MBP. There was no difference in the proliferative response of splenocytes to MBP when splenocytes were isolated either from mice with clinical relapse or from mice that did not relapse. Pathological examination revealed a transient appearance of inflammatory cells during the acute stage. Similar cell infiltrates were also observed at the relapsing stage. The I-region associated (Ia) antigens appeared on vessels and astrocytes in the acute inflammatory lesions which coincided with the appearance of inflammatory cell infiltrates. Ia antigen expression diminished with the disappearance of inflammatory cells. During the relapsing stage, the Ia antigens were also expressed on the vessels and astrocytes in the fresh lesions. Our data indicate that MBP-reactive T cells persist at least in the spleen, for a long time. They may be reactivated by certain mechanisms probably in the central nervous system associated with the Ia-antigen expression, which facilitates the effector phase again. The initial event that triggers the Ia-expression is not known as yet.
Intracellular Ca++ transients were monitored in preparations of mammalian heart muscle in which multiple superficial cells had been microinjected with the Ca++-sensitive bioluminescent protein aequorin. The relationship between changes in intracellular [Ca++] and changes in isometric tension development were studied under a variety of conditions in which experiments with "skinned" cardiac muscle preparations have indicated that alterations take place in the sensitivity of the myofilaments to Ca++. In each case (changes in muscle length, changes in intracellular pH, exposure to caffeine or theophylline, exposure to catecholamines, exposure to sulmazole), the relationship between the aequorin signal and the developed tension changed in ways that suggest that alterations in myofibrillar Ca++ sensitivity play an important role in the responses of intact myocardial cells to these inotropic interventions. Studies of the positive inotropic response of the rabbit papillary muscle to alpha-adrenoceptor stimulation indicate that an increase in myofibrillar responsiveness to Ca++ must play an important role in the genesis of this response as well.
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Clinical effects of dipyridamole and carbazochrome sodium sulfonate in patients with IgA nephropathy are described. Oral administration of 300 mg of dipyridamole and 180 mg of carbazochrome sodium sulfonate per day was employed in the present study. Urinalysis and renal function tests, i.e. serum creatinine (s-Cr), blood urea nitrogen (BUN), glomerular filtration rate (GFR) and phenolsulfonphtalein (PSP) tests, were performed before and after the administration of dipyridamole. It was demonstrated that the administration of dipyridamole was effective in reducing the level of proteinuria in the patients. The administration of carbazochrome sodium sulfonate was not effective in reducing the proteinuria level. It was concluded that the administration of dipyridamole may be useful for treatment of patients with IgA nephropathy.
Siblings with IgA nephropathy and diffuse proliferative glomerulonephritis without mesangial IgA deposits (PGN) who had identical HL-A antigens are described. A 21-year-old woman suffered from IgA nephropathy and her 27-year-old sister showed diffuse proliferative glomerulonephritis (PGN) distinct from IgA nephropathy. These siblings had identical HL-A alloantigens which were A2, Aw24; Bw16, Bw35; Cw4, Cw7; DR4. Microhematuria and increased serum IgA levels were shown in their father and other sister but renal biopsies were not performed. The serotypes for the HL-A antigens of their father and other sister were A2, Aw24; Bw27, Bw35; Cw4; DR4 and A2; Bw16; Cw7; Dr2, respectively. It is demonstrated that IgA nephropathy and PGN share a common HL-A phenotype including DR4. It is postulated that the presence of DR4 antigens is not directly related to the occurrence of IgA nephropathy.
Thermal response of rats to chlorpromazine (CPZ) was determined at low (15 degrees C) and high (28 degrees C) environmental temperature. Effects of CPZ at ambient temperature of 5-33 degrees C were estimated using a drug disposition-thermoregulation model reported previously. The simulation revealed that the hypothermic effect of CPZ is greater in cold environment and is suppressed in hot environment.
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A successful application of high-performance liquid chromatography for analysis of urinary C-peptide is described. Samples (1.0 ml of human urine) were first subjected to gel chromatography to remove interfering substances, and then applied to a reversed-phase column (LiChrosorb RP-18, 7 micron). The detection of C-peptide was performed using a highly specific radioimmunoassay. With the newly developed techniques, at least four forms of immunoreactive C-peptide were detected in human urine. One of these peptides was indistinguishable from authentic C-peptide. The present study has clearly demonstrated the heterogeneity of urinary C-peptide.
Two groups of immunoreactive insulin in human sera were reported by Kakita et al. (4), using gel chromatography after acid-alcohol extraction. These analogs were noted not only in circulating human sera but also in incubation medium and incubated human pancreas. The release of these insulin analogs was discussed in a previous report (5). The circulating C-peptide immunoreactivity was separated into two groups on a Bio-Gel column, and the early peak should not be proinsulin but an associated C peptide (6). These analogs of insulin were separated by the methods of ion-exchange chromatography, isoelectric focusing, gel electrophoresis, and gel chromatography. Immunoreactive insulin was also separated into two major bands by standard polyacrylamide gel electrophoresis. The fast migrating band corresponds to the rat insulin II position, and the slower corresponds to rat insulin I, which has one more basic amino acid residue in comparison with rat insulin II. Further studies have been performed in five healthy adults in order to elucidate the physiological relationship between analogs of insulin and C-peptide peak substances in human serum; the results are reported in this paper with a consideration of the mechanism of insulin secretion.
Titers of serum antibodies to myelin basic protein, cerebroside and ganglioside were determined in chronic relapsing experimental allergic encephalomyelitis in strain 13 guinea pigs at various intervals after inoculation with whole central nervous system (CNS) tissue. Levels of antibodies to cerebroside and ganglioside were higher in the animals with paralysis than those without paralysis during the early chronic stage. In the late chronic stage, these antibodies were still at high levels, but none of the levels correlated with clinical activity. Levels of antibody to cerebroside were significantly related to the amount of demyelination. The humoral response to the CNS antigens was monophasic, although the clinical course was polyphasic. Another factor seems to be required for clinical relapses in this animal model.
Detection of circulating IgA antibodies which are specific in patients with IgA nephropathy is described. Freeze and thawed extracts of pharyngeal cells obtained from patients with IgA nephropathy, other glomerular diseases, and healthy adults were cultured with fibroblasts such as Vero or Hel cells at 37 degrees C for 2 weeks. Serum samples were obtained from these patients and healthy adults. The cultured fibroblasts were fixed on slide glasses, and then incubated with the serum samples from the same or other patients with IgA nephropathy. The cells were stained with FITC-labeled heavy-chain specific anti-human IgA antiserum and then examined with a fluorescent microscope. It was demonstrated that the IgA antibodies in sera obtained from patients with IgA nephropathy or HSP nephritis were bound with the nuclear regions of such fibroblasts. It was suggested that IgA antibodies in sera could be bound with some antigenic substances which were transferred from pharyngeal cells of patients with IgA nephropathy to fibroblasts in vitro.