Biomedical subjects
Publications and source records attributed to R L Clancy.
A patient is described who presented with mixed obstructive and restrictive lung disease, shown to be due to deposition of amyloid in an alveolar-septal distribution. An association with a plasma cell dyscrasia and pulmonary tuberculosis is discussed, as is the need for early diagnosis and a trial of aggressive cytotoxic therapy in primary amyloidosis.
Exclusion diets may have a practical place in determining the precipitating dietary factors in certain clinical conditions. We present an exclusion diet which is based on the exclusion of food commonly known to cause food allergies, and the exclusion of food which contains salicylates, benzoates, tartrazine, yeast, and penicillin. This provided a basis for challenge with these additives and natural chemicals. Preliminary information in urticaria suggests a use for this diet in some allergic conditions.
A simple microtitration technique for the determination of total haemolytic complement levels in human serum is described. The method is fast and reproducible, and provides a routine screen of total complement activity for use in clinical medicine.
DBcAMP or crystalline glucagon was utilized to elevate the intracellular cyclic AMP concentration in isolated rat hearts. Butyric acid, a metabolite of DBcAMP, was also investigated. Their effect on the intracellular pH (pHi) as determined by the distribution of [14C]DMO was investigated. Rat hearts, perfused with a recirculated modified Krebs-Henseleit solution maintained at 30 degrees C, were exposed to respiratory acidosis by bubbling the perfusate with 20% CO2. alpha- and beta-receptor antagonists were used to block the effects of endogenous catecholamines. Hypercapnia decreased the pHi from 7.09 to 6.82. A similar degree of hypercapnia decreased the pHi to only 6.95 in the presence of DBcAMP and to only 6.96 in the presence of glucagon. The effective buffer values (delta[HCO-3]i/deltapHi) were: control, 19; butyric acid, 16; DBcAMP, 139; glucagon, 148. These data suggest that cAMP mediates the effect of norepinephrine, which has been shown to diminish the change in pHi accompanying respiratory acidosis.
Memory for previous immunologic contact with microbial antigens has been detected in lymphocytes from human bronchi as a secondary immune response, when tested in vitro. Antigens stimulated a predominantly proliferative response in blood lymphocytes that was significantly greater than the response in mucosal lymphocytes with purified protein derivative and Herpes simplex type 1 antigens. Co-culture experiments with autologous blood lymphocytes showed that cell-dependent suppression was one mechanism of the low response of bronchial lymphocytes. In the patient who inhaled a foreign body, a proliferative response to antigens was restricted to bronchus-associated lymphoid tissue lymphocytes, suggesting a recruitment of antigen-reactive cells from a circulating pool.
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Experiments were designed to determine the contribution of increased extracellular HCO3- concentration, [HCO-3e], to the net extracellular-to-intracellular HCO3- flux observed in hearts during hypercapnia. Isolated rabbit hearts were perfused by recirculating for 15-min periods a small volume of Ringer solution in which [HCO-3e] and carbon dioxide tension (PCO2) could be independently altered. A net HCO-3 flux was evidenced by a decrease in [HCO-3e] during recirculation. [HCO-3e] was randomly increased from 19 mM over a range of 19-42 mM at a constant PCO2 of 38.7 Torr. The resulting flux increased linearly with the [HCO-3e] existing at the start of recirculation. The same relationship was observed at 95.8 Torr PCO2. The disappearance of HCO-3 from the perfusate could not be explained by dilution in the interstitium or by lactate accumulation. When PCO2 was increased from 40 Torr over a range of 40-160 Torr at a constant [HCO-3e] of 20 or 30 mM, a small flux was observed only at the highest PCO2 levels. Essentially the same results were obtained when recirculation time was prolonged to 30 min. These results suggest that the major determinant of the HCO-3 flux is a change in extracellular HCO-3 concentration.
Experiments were performed to determine the relative effects of a net extracellular-to-intracellular HCO3- flux and of elevated carbon dioxide tension (PCO2) on cellular acid-base regulation. Isolated rabbit hearts were perfused by recirculating a small volume of Ringer solution in which the PCO2 and the HCO3- concentration could be independently altered. Net HCO3- flux was assessed by the disappearance of HCO3- from perfusate. Between 40 and 100 Torr PCO2, a HCO3- flux into the cell occurs only when perfusate HCO3- concentration is increased. Therefore, by selective manipulation of perfusate HCO3- and PCO2 it is possible to induce hypercapnia with or without an accompanying HCO3- flux. When perfusate HCO3- concentration was increased from 20 to 36 mM, cellular HCO3- concentration increased from 22.5 +/- 0.8 to 26.1 +/- 1.0 mM at 40 Torr PCO2 and from 27.8 +/- 0.7 to 34.1 +/- 1.4 mM at 98 Torr PCO2. These increases can be accounted for by the amount of HCO3- that disappeared from the perfusate. The results suggest that most of the initial cell CO2 buffering is provided by the net HCO3- flux in addition to the passive physicochemical buffering.
Passive immunotherapy was attempted in a patient with mast cell leukemia using antibody against IgE. The results of both in vitro and in vivo studies indicate that although receptor sites for IgE were retained by the malignant mast cell, a secretory defect was present characterized by the spontaneous release of histamine and an impaired secretory response to anti-IgE antibody. Anti-IgE antibody selectively and reproducibly reduced the number of circulating mast cells probably by facilitating their permanent uptake by the reticuloendothelial system. Tolerance was not achieved with high dose deaggregated sheep IgG, nor were we able to confirm the effectivity of immunochemotherapy based on linking chlorambucil to antibody directed against the tumor-associated "antigen" IgE.
Nephrectomized, open chested dogs were infused with 25-30 ml.kg(-1) body weight of 0.15 M NaCl (group I), 0.15 MHCl (Group II) or 0.3 M lactic acid (Group) III). Pulmonary ventilation was maintained constant in the three groups. Intracellular pH was calculated with the CO2 method. No significant intracellular or extracellular acid-base changes were produced in Group I. A similar degree of extracellular acidosis was achieved in Groups II and III. In spite of constant arterial PCO2, the PCO2 of mixed, coronary sinus and femoral vanous blood increased moderately after the infusion in Groups II and III. It was calculated that less than half of the HCl acid infused remained in the extracellular space. However, no significant changes were observed in the acid-base composition of skeletal muscle in either Group II or III. Comparison of the cardiac muscle cell acid-base composition of Group I with that of Groups II and III whows that metabolic acidosis of the degree and duration produced in these experiments does not produce appreciable myocardial acidosis.
Two patients with histologically diagnosed starch induced granulomatous peritonitis (SGP) have been shown to have cell mediated immunity to corn starch using the techniques of macrophage migration inhibition and lymphocyte DNA synthesis. Control groups of normal subjects, patients with uncomplicated laparotomy, and patients with Crohn's disease were negative in both tests. Lymphocytes from two patients with band adhesions, one of whom had biopsy evidence of a granulomatous reaction to starch, were sensitized to starch. Cell mediated immunity to starch may contribute to the pathogenesis of SGP, and some band adhesions may be a chronic low grade manifestation of this disorder.
Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell.
The effect of catecholamines on the intracellular pH of rat cardiac and skeletal muscle during varying extracellular acid-base states was determined. Intracellualr pH (pHi) was calculated from the distribution of [14C]DMO. Acid-base disturbances were produced by placing the animals in an environmental chamber containing 10 or 20% CO2 or by administering HCL or NaHCO3. Two hours later the animals were anesthetized with sodium pentobarbital and blood and tissue samples obtained. In one series of animals, the effects of catecholamines were attenuated by administering the beta-adrenoreceptor antagonist MJ 1999 (Sotalol). In animals breathing 20% CO2, cardiac muscle pH was lower in beta-blocked than unblocked animals (6.69 vs. 6.78). During metabolic acidosis, cardiac muscle pH of beta-blocked animals was lower than that of unblocked animals (6.75 vs. 6.84). The same relationship was observed for skeletal muscle during metabolic acidosis-beta blockade pHi, 6.66; unblocked pHi, 6.77. The pHi of beta-blocked versus unblocked animals was not significantly different under normal acid-base conditions or metabolic alkalosis for cardiac or skeletal muscle. The effective buffer value of both tissue over the normal acidotic range was decreased by the beta-blocking agent. These results indicate that catecholamine release accompanying acidosis attenuates the change in pHI and increases the effective buffer value of cardiac and skeletal muscle.
A cell wall deficient form of an alpha-haemolytic streptococcus was grown from a prolonged monolayer cell culture of a lymph node taken from a patient with Whipple's disease. Serological cross reactivity was shown between the organism and the material within Whipple's disease macrophages positive for diastase-resistant periodic acid-Schiff (D./P.A.S.). In vitro studies characterized the organism as a facultative intracellular parasite which caused the accumulation within cells of D./P.A.S.-positive material. These results suggest that a pathogenic bacterium is the essential aetiological agent and that the culture of Whipple's disease tissues in hypertonic media may have practical value.
Experiments in isolated, Ringer-perfused isovolumic rabbit hearts showed that metabolic acidosis resulted in a decrease in peak left ventricular pressure and dP/dt. Concomitantly, the decrease in extracellular pH from 7.28 plus or minus 0.02 to 6.82 plus or minus 0.02 at constant PaCO2 was associated with a negative av HCO3- difference that lasted throughout the duration of acidosis. This negative av HCO3- difference indicated that either HCO3- moved into the intravascular space or H+ moved in the opposite direction during acidosis. During perfusion with normal pH solution av HCO3- was not significantly different from zero. Washout of the extracellular space with the acid solution can account for only 32 percent of the total amount of HCO3-recovered in the venous perfusate during the 30 min of acidosis. The remaining 68 percent (10.7 plus or minus 3.1 mmol times kg-1 of cardiac tissue) must then have originated in the cellular fluid. When intracellular fluid volume is taken into account, it can be calculated that 21.3 plus or minus 6.1 mmol of HCO3- moved into the vascular space per liter of intracellular water. The magnitude of this HCO3- flux suggests that significant myocardial cellular acid-base changes are associated with metabolic acidosis.
The effect of norepinephrine (NE) on the intracellular hydrogen ion concentration [H+]i of isolated rat hearts perfused with a modified Krebs-Henseleit solution (SHS) was determined. The [H+]i was calculated with the [14C]-dimethyloxazolidinedione method. Respiratory or metabolic acidosis was produced by equilibrating the KHS with 20% C02 or decreasing the [HC03-] of the KHS, respectively. Three types of experiments were carried out: 1) beta blockade--MJ 1999 (Sotalol) was added to the KHS; 2) control--no pharmacological treatment; and 3) NE-norepinephrine was added to the KHS. The effective CO2 buffer values (delta[HC03-]i/deltapHi) during respiratory acidosis were: beta blockade, 11; control, 35; and NE, 84. The production of metabolic acidosis resulted in the following [H+]i changes: beta blockade, 52 mM; control, 60 nM; and NE 7 nM. These results suggest that NE markedly attenuates the changes in [H+]i accompanying respiratory and metabolic acidosis and may account in part for previous observations that the effective C02 buffer value of cardiac muscle in vivo is greater than that in vitro.
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