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Biomedical subjects

M Emmett

Publications and source records attributed to M Emmett.

At least 37 records · Page 2Linked to original sources

Role of vitamin D-dependent and vitamin D-independent mechanisms in absorption of food calcium.

We measured net calcium absorption and the calcium content of the digestive glands secretions in people with widely different serum concentrations of 1,25 dihydroxy vitamin D (hereafter referred to a 1,25-D). Patients with end stage renal disease on hemodialysis served as a model of human 1,25-D deficiency; they were also studied when they had abnormally high serum 1,25-D concentrations as a result of short periods of treatment with exogenous 1,25-D. Normal subjects were studied for comparison. The amount of calcium secreted into the duodenum by the digestive glands was found to be trivial compared to the calcium content of normal or even low calcium meals; therefore, values for net and true net calcium absorption differed only slightly. There was a linear correlation between true net calcium absorption and serum 1,25-D concentration. By extrapolating the short distance to a zero value for serum 1,25-D, D-independent true net calcium absorption was estimated. By subtracting D independent from true net calcium absorption, values for D-dependent absorption were obtained. For a given level of meal calcium intake, D-dependent calcium absorption was found to be directly proportional to serum 1,25-D concentration. At any given value for serum 1,25-D, absorption via the D-dependent mechanism was approximately the same with a low (120 mg) calcium meal as it was when meal calcium intake was increased to 300 mg. We interpret this to mean that the D-dependent mechanism is saturated or nearly saturated by low calcium meals. The D-independent absorption/secretion mechanism resulted in secretion (a loss of body calcium in the feces) when intake was low (120 mg per meal) and absorption when intake was normal. All of the increment in calcium absorption that occurs when low or normal calcium meals are supplemented with extra calcium is mediated by the D-independent mechanism.

Adult↗

Total enteral nutrition versus total parenteral nutrition after major torso injury: attenuation of hepatic protein reprioritization.

Reprioritization of hepatic protein synthesis, a process involving accelerated production of acute-phase proteins at the expense of constitutive proteins, accompanies major trauma. The impact of isocaloric, isonitrogenous total enteral nutrition (TEN) versus total parenteral nutrition (TPN) on hepatic reprioritization was investigated in a prospective, randomized trial. Of the 59 patients with an abdominal trauma index (ATI) greater than 15 but not more than 40, 45 evaluable patients were followed. Results from 36 (18 TEN, 18 TPN) evaluable patients revealed that mean serum levels of acute-phase proteins increased, whereas mean serum levels increased to a greater extent in the TPN group. The maximal increase from baseline for the acute-phase response in both groups occurred at postinjury day 5 and was significantly higher for alpha 1-antitrypsin (alpha 1AT, p = 0.03) and orosomucoid (p = 0.02) in the TPN group. Nonacute-phase proteins reached a nadir at day 10 in the TPN group and increased in the TEN group; significant differences between TEN and TPN groups appeared for albumin (p = 0.004) and retinol-binding protein (RBP, p = 0.03); alpha 2-macroglobulin (alpha 2M) approached significance at day 10 (p = 0.07). When change from baseline values was compared, day 10 increases in alpha 2M were significantly higher (p = 0.04) in the TEN group. These data suggest that postinjury TEN attenuates reprioritization of hepatic protein synthesis in patients sustaining major trauma.

Abdominal Injuries↗

Protein abnormalities in adult respiratory distress syndrome, tuberculosis, and cystic fibrosis sera.

Crossed immunoelectrophoresis (X-IEP) revealed several abnormalities in serum proteins from patients with adult respiratory distress syndrome (ARDS), tuberculosis (TB), and cystic fibrosis (CF). The two quite different kinds of pulmonary disease, one acute (ARDS) and the other chronic (TB and CF) exhibited serum changes specific for each disease and abnormalities associated with inflammation and pathogenesis, in general. In ARDS sera, most proteins were extremely low, presumably due to leakage into the lungs through damaged tissue, while the acute-phase proteins, orosomucoid, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, were markedly high when compared to the overall protein pattern. The extremely high alpha 1-antichymotrypsin values were not seen in corresponding TB and CF sera. Numerous TB patients had elevated alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, but only the alpha 1-antitrypsin population mean was significantly different from normal. Gc-globulin, ceruloplasmin, and beta-lipoprotein were higher and alpha 1-lipoprotein and inter-alpha-trypsin inhibitor lower than normal. All other quantitative serum changes were not statistically significant. Surprisingly, all TB patients belonged to the Gc-1-1 genotype in contrast to the Gc-1-1, Gc-1-2, Gc-2-2 polymorphisms of the other populations. CF homozygote sera revealed statistically significant increases in the acute-phase proteins, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and haptoglobin, while orosomucoid, transferrin, IgA, and IgG tended to be higher than normal. The tendency for higher levels of transferrin indicated possible iron deficiency in some patients. In contrast, prealbumin, alpha 1-lipoprotein, and inter-alpha-trypsin inhibitor were significantly depressed in CF patients. CF heterozygotes shared the decrease of alpha 1-lipoprotein with the patients while exhibiting small but significant depressions of alpha 2-macroglobulin and IgG. Though not statistically significant, lowered concentrations of alpha 1-antitrypsin were evident for the heterozygotes.

Acute-Phase Proteins↗

Crossed immunoelectrophoretic analysis of ARDS lavage proteins.

Serum proteins in normal and ARDS bronchoalveolar lavages were analyzed using crossed immunoelectrophoresis. Normal lavages demonstrated relatively few proteins (albumin, alpha 1-antitrypsin, transferrin, and haptoglobin) in low concentrations. In contrast, substantial amounts of all identifiable serum proteins were detected in ARDS lavages. IgA was apparently locally produced. Two of the largest proteins, beta-lipoprotein (mol wt greater than 2 million) and IgM (mol wt approximately 900,000) were found to be complexed as evidenced by their coprecipitation in a single spike in ARDS lavage. Electrophoretic modifications of ARDS albumin and alpha 1-antitrypsin precipitation peaks and partial identity spurring of the alpha 1-lipoprotein peak with other precipitation loops indicated possible complex formation between these proteins and other possibly pathogenic lung fluid constituents. Similarly, modifications of orosomucoid and Gc-globulin peaks indicated possible molecular alterations resulting from interactions with other components. The relatively few protein modifications exhibited in ARDS lavages together with alpha 1-antitrypsin-protease complex formation confirm the relative absence of substantial proteolytic activity in ARDS edema fluids obtained within 12 hr of the onset of the syndrome demonstrated in previous studies.

Albumins↗

Bowel infarction as a cause of death in dialysis patients.

Bowel infarction as a frequent occurrence in patients with end-stage renal disease has not been previously recognized. This report describes 12 dialysis patients with nonocclusive bowel infarction. All patients with bowel infarction had large weight losses secondary to vomiting, diarrhea, or ultrafiltration when undergoing dialysis, preceding the development of this disease. Of the potential risk factors analyzed, frequent and severe hypotension (systolic blood pressure, less than 100 mm Hg) when receiving dialysis occurred more commonly in patients developing bowel infarction. The weight loss was not often recognized initially as an important compromising problem. A fatal outcome was experienced in nine of the 12 patients. We conclude that bowel infarction may be a significant cause of morbidity and mortality in dialysis patients.

Body Weight↗

Carpal tunnel syndrome with cystic bone lesions secondary to amyloidosis in chronic hemodialysis patients.

Carpal tunnel syndrome (CTS) is increasingly recognized in patients undergoing chronic hemodialysis. Although the etiology remains obscure, angioaccess-related vascular engorgement and edema, and ischemic neuropathy are two likely possibilities. Amyloidosis is a relatively rare cause of CTS and had previously been thought to occur almost exclusively in patients with multiple myeloma. We report seven patients on chronic hemodialysis who developed CTS and were shown to have amyloid deposition within the synovium. Amyloid was demonstrated by characteristic staining with Congo red on polarizing microscopy and confirmed by electron microscopy. Six patients also exhibited radiolucent carpal bone cysts which were histologically shown to be due to bone replacement by an amyloid-positive synovitis. The average age of the patient and time on dialysis were 59.1 and 7.9 years, respectively. Serum and urine immunoelectrophoresis and bone marrow aspirates showed no evidence for plasma cell dyscrasia in six patients, while one patient did manifest a monoclonal IgA spike. Autopsies in three patients and liver biopsy in another showed no other evidence for disseminated amyloid. These hemodialysis patients exhibited a unique syndrome of CTS, lytic lesions of the carpal bones, and amyloid deposition in the synovium and within the bone cysts.

Adult↗

The absorption of dietary phosphorus and calcium in hemodialysis patients.

Absorption of dietary phosphorus plays a critical role in the development of metabolic bone diseases in patients with chronic renal failure. However, phosphorus absorption is difficult to quantitate in dialysis patients because the dialysis treatments complicate metabolic balance studies. Utilizing a recently developed technique which permits measurement of net absorption of dietary constituents after a single meal, we measured phosphorus absorption in dialysis patients. The following observations were made: A.) Following a meal containing approximately 300 mg phosphorus, mean phosphorus absorption in five hemodialysis patients (with severe vitamin D deficiency) was only slightly less than in matched controls (186 +/- 35 vs. 242 +/- 30). B.) After dialysis patients were treated with 1,25(OH)2-D3, phosphorus absorption increased from 186 +/- 35 to 272 +/- 16 mg (P less than 0.025). C.) The effect of three aluminum containing antacids on phosphorus absorption was studied; each slightly reduced the absorption of phosphorus compared to placebo (P less than 0.01), but there was no significant difference between them. D.) Aluminum hydroxide and calcium carbonate each reduced dietary phosphorus absorption to approximately the same extent. Calcium carbonate ingestion was associated with sharply increased calcium absorption. The absorption of dietary phosphorus is influenced only modestly by 1,25(OH)2-D3 and is inhibited to an equal but only modest degree by various aluminum antacids and by calcium carbonate.

Adult↗

Early protein alteration in blister fluid and serum associated with burn injury.

Since the most common site of infection in burned patients is the burn wound, we have previously studied the biologic effect of burn wound blister fluid (BF) on control lymphocyte and neutrophil activity. BF will not support the phagocytosis of Pseudomonas by normal neutrophils, and a subset of the BF samples suppressed the maximal mitogen response of control lymphocytes by more than 50%. The current work was carried out to analyze in depth the composition of BF using crossed immunoelectrophoresis. Twenty BF and six serum specimens collected from 20 patients between 6 and 18 hours postburn had 19 separate proteins measured. These proteins included immunologic proteins, antiproteases, acute-phase reactants, carrier proteins, and lipoproteins. A total of 546 protein measurements were made. The concentrations of all subgroups of proteins were significantly lower in the BF and burn serum specimens than in control serum. When the blister fluids were stratified according to their effect on normal lymphocyte activity, the suppressive blister fluid samples had higher levels of C3 and lower levels of I alpha I than the nonsuppressive samples. The elevation in C3 was secondary to the local activation of C3 and the generation of multiple C3 breakdown products. These changes in C3 are of potential biologic importance, since evidence has accumulated indicating that the various fragments of C3 can modulate both neutrophil and lymphocyte function. Thus, the results of this study suggest that local changes in the blister fluid may adversely affect local immunity and predispose the patient to burn wound sepsis.

Adolescent↗

Differential serum protein binding of benzidine- and benzidine-congener based dyes and their derivatives.

Environmental dyes and their derivatives, some of which are genotoxic, must be transported within the body to the tissues which they affect. One mechanism for this can be observed directly by crossed immunoelectrophoresis (X-IEP). Binding of these chemicals to certain serum proteins changes electrophoretic and immunoprecipitation morphology in X-IEP patterns. This is demonstrated here for four azo dyes derived from benzidine, 3,3'-dimethylbenzidine, and 3,3'-dimethoxybenzidine, and their parent aromatic amines. Direct Red 2 (a 3,3'-dimethylbenzidine-based dye), Direct Blue 15 (a 3,3'-dimethoxybenzidine-based dye), Direct Black 38 (a benzidine-based dye), and Evans Blue (a 3,3'-dimethylbenzidine-based dye) all bound to albumin, alpha 1-lipoprotein, beta-lipoprotein, and hemopexin. Direct Red 2 only slightly affected the mobilities of these proteins. Direct Blue 15 bound also to prealbumin and alpha 1-antichymotrypsin, and degraded C3 globulin. Direct Black 38 and Evans Blue bound to numerous additional proteins. Evans Blue bound variably to proteins of sera from different individuals, suggesting that there are individual differences in serum protein binding capabilities for these chemicals. Of the three derivatives of the benzidine dyes, only 3,3'-dimethylbenzidine caused changes in X-IEP patterns, indicating its binding to the serum proteins. This chemical differentially affected sub-populations of alpha 1-lipoprotein, either by altering its electrophoretic mobility or inhibiting its recognition by antibodies. Autoradiographic analyses demonstrated the binding of benzidine and 3,3'-dimethylbenzidine to both alpha 1- and beta-lipoproteins.

Azo Compounds↗

Crossed immunoelectrophoresis of rat serum.

A crossed immunoelectrophoresis (X-IEP) reference profile of normal (Sprague-Dawley) rat serum antigens was developed. Twenty-three antigens were detected; 13 were identified. These included inter-alpha-trypsin inhibitor, alpha 1-antichymotrypsin, and fibronectin, which had not previously been identified in rat serum. Many of the antigens were similar electrophoretically to their analogs in human and mouse serum, but some were substantially different. Inter-alpha-trypsin inhibitor, fibronectin, and C3 globulin were more anodic, while transferrin was more cathodic. Rat haptoglobin's mobility was between those of human and mouse haptoglobins. As in the mouse, but more so, alpha-macroglobulin in the rat had alpha 1 mobility rather than alpha 2 seen for this protein in human serum. Only rat alpha 1-antichymotrypsin exhibited a double peak. There were variations in haptoglobin and alpha 1-lipoprotein mobilities among different strains of rat. This establishment of a standard X-IEP map of rat serum will simultaneously permit multiple quantitative and qualitative analyses of rat serum antigens for various experimental and clinical purposes.

Alpha-Globulins↗

Lithium intoxication associated with acute renal failure.

Lithium can produce transient natriuresis, nephrogenic diabetes insipidus, and partial distal renal tubular acidosis. Lithium intoxication is commonly associated with mild renal insufficiency and may produce acute renal failure. We have described a case of acute renal failure in a patient with severe lithium intoxication, as well as cardiac arrhythmias and hypothyroidism, both of which have been reported to occur with lithium toxicity. Treatment with daily hemodialysis eventually produced complete recovery. Lithium clearance occurs quickly with hemodialysis, but a rebound effect occurs as lithium in intracellular water equilibrates with extracellular fluid. Prolonged dialysis may be required to reduce the blood lithium level to the therapeutic range. We conclude that lithium intoxication may produce severe reversible renal failure as a result of direct tubular epithelial damage.

Acute Kidney Injury↗

Immunological evidence for deficiency in an activator protein for sulfatide sulfatase in a variant form of metachromatic leukodystrophy.

Cultured skin fibroblasts from the patient described by Shapiro and co-workers as having a variant form of metachromatic leukodystrophy (MLD) [Shapiro, L.J., Aleck, K. A., Kaback, M.M., Itabashi, H., Desnick, R.J., Brand, N., Stephens, R.L., Fluharty, A.L. & Kihara, H. (1979) Pediatr. Res. 13, 1179-1181] were confirmed to have a partial deficiency (25-40% of controls) of arylsulfatase A activity in vitro and a severe inability to metabolize [14C]stearic acid-labeled sulfatide presented in the medium. When 150 micrograms of purified activator protein for GM1 ganglioside beta-galactosidase and sulfatide sulfatase was added in 4 ml of medium with the 14C-labeled sulfatide, correction of the sulfatide metabolism to the normal range was found. Monospecific antibodies to this activator protein were prepared in rabbits, and they were used to examine cultured cells for the presence of crossreacting material by Ouchterlony double immunodiffusion and rocket immunoelectrophoresis. Cell extracts from controls and from patients with GM1 gangliosidosis and MLD were found to have a single line of identity. By comparison to known concentrations of purified activator protein, cell extracts from controls were found to have 0.76 +/- 0.32 micrograms of activator protein (mean +/- 1 SD, n = 10) per mg of solubilized protein, whereas those from patients with type 1 GM1 gangliosidosis and late infantile MLD had 1.53 and 1.41 micrograms/mg, respectively. Cell extracts from the patient with a variant form of MLD had no visible precipitin line by Ouchterlony double immunodiffusion and only a diffuse nonspecific region of staining by rocket immunoelectrophoresis. These immunologic studies provide evidence for a deficiency in the activator protein required for normal catabolism of sulfatide in the cells from this patient and possibly provide a method for diagnosis of similar patients.

Cells, Cultured↗

Crossed immunoelectrophoresis: qualitative and quantitative considerations.

Invented 20 years age, crossed immunoelectrophoresis (X-IEP) today is a technique of unusual power and myriad application. It combines very high resolution with exquisite specificity by alloying 2-dimensional electrophoresis with immunoprecipitation for symbiotic new potentialities. The consequent matchless quantitative/qualitative capabilities of X-IEP for analyzing antigens in complex mixtures, particularly by their idiomatic internal comparison, are still not widely recognized. Because of this and the supposed complications of its use and interpretation, X-IEP is more rarely used than it should be. This essay discusses contemporary X-IEP with the particular aims of demonstrating that it is not difficult to use and of explaining with selected examples why it is peculiarly powerful for analyzing antigen mixtures like the body fluids, tissue and cell extracts, and microbial homogenates.

Analysis of Variance↗