Lowered Albumin Research Articles

Large-Scale Preparation and Function of Porcine Hepatocyte Spheroids

To obtain a large number of porcine hepatocyte aggregates (spheroids) that have great potential in a bioartificial liver (BAL), we performed spheroid formation at a high cell density in a 1-L-scale spinner flask fitted with a silicon tubing apparatus for oxygen supply. We thereby obtained, within 24 hours, approximately fifty times more porcine hepatocyte spheroids as compared with the results of previous reports. The amount obtained corresponds to 2.5x10(9) cells and to roughly one-sixth of the cell number required for a BAL for a human patient. When we cultured spheroids continuously in suspension, they expressed three times more albumin secretion and twice the ammonium removal as compared with conventional monolayers during 10 days culture. Collagen gel entrapment of spheroids particularly lowered albumin secretion. We therefore conclude that the supension culture vessel of porcine hepatocyte spheroids is one of the most promising module types.

Disposition and tumour concentrations of platinum in hypoalbuminaemic patients after treatment with cisplatin for cancer of the head and neck.

1 Platinum concentrations in the tumour reached a peak of 3.8 +/- 1.5 micrograms g-1 wet weight tissue at the end of an 8 h intravenous infusion of cisplatin. The tumour concentrations of platinum were higher than the corresponding plasma concentrations (2.5 +/- 0.9 micrograms ml-1) and declined more slowly. 2 Patients with squamous carcinoma of the head and neck had a significantly shorter median survival time if they had low plasma albumin concentrations (less than 40 g l(-1) compared with patients in the normal range, 133 days and 768 days respectively (P less than 0.05) after treatment with cisplatin. 3 No changes in the pharmacokinetics of platinum were detected to account for this poor response of hypoalbuminaemic patients, but plasma albumin concentration was found to be negatively correlated with the first order elimination rate constant. 4 The cumulative urinary excretion of platinum in the first 24 h was not altered by lowered plasma albumin. 5 The concentration of platinum in the tumour did not correlate with the survival time of the patient, but was found to be correlated with the volume of distribution in the post-distributive phase.

Clinical pathology of experimental Schistosoma curassoni infections in sheep and goats

The clinical pathology of Schistosoma curassoni infection in sheep and goats was studied for 22 weeks following experimental infection with 7000 and 4000 cercariae, respectively. Excretion of eggs began at week 7 after infection: in goats the numbers increased to 30 to 50 eggs per gram faeces (epg) at weeks 8 to 18, followed by a reduction. In a pregnant goat, epg values increased markedly before and after parturition. The mean faecal egg counts in sheep were lower than in goats, increasing to a maximum level of 30 epg at weeks 16 and 17 after infection. Infected sheep maintained growth rates roughly comparable with controls, whereas infected goats failed to gain as much weight as the controls. Infected goats and sheep produced eosinophil counts of about 3 x 10(3) mm-3, five and eight weeks after infection, respectively. Sheep developed a progressive anaemia from week 11 after infection, in goats blood values remained within normal limits. Differences in serum protein concentration were observed between infected and uninfected goats about nine weeks after infection, but not in sheep. Increased total protein values, hyperglobulinaemia and lowered albumin to globulin ratios were features of infected goats. Serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma-glutamyl transferase, total lactate dehydrogenase and bilirubin were not significantly changed. The mean recovery in sheep was 608 worms, in goats 428 worms, but the total tissue egg counts were higher in the latter. Of the total eggs deposited in the goats 92 per cent were found in the liver with 51.5 per cent in the ovine liver. The histopathological changes were studied.

The Nephrotic Syndrome and Its Complications

Modern views of the pathogenesis and natural history of nephrotic syndrome have changed substantially since the early studies by Cotugno and Bright. Contrary to beliefs held 20 years ago, we do not possess a unique satisfying explanation for the induction, maintenance, and resolution of nephrotic edema, and many concepts firmly established as "classic" are now being revised or reconsidered. These include the relationship between urinary protein losses and hypoalbuminemia, which is complicated by several factors such as daily protein intake, albumin catabolism, and the possible role of albumin loss at extrarenal sites. The influence of lowered plasma albumin on the decrease in plasma volume is also quite complex, due to technical difficulties in measuring plasma volume and turnover of radio-labeled albumin. The most contentious areas are how sodium and water retention are initiated and maintained and the relationship between hypoalbuminemia, plasma oncotic pressure, and edema. While aldosterone excretion and plasma concentrations are elevated in nephrotic patients, data on the renin-angiotensin system are controversial and the renal handling of sodium is related to a host of factors including glomerular filtration rate, altered proximal tubular reabsorption, and the role of vasodilators or vasoconstrictors. The complications of nephrotic syndrome are protean and relatively common. Among those are acute renal failure, thrombosis, infections, and hyperlipidemia. Since the introduction of percutaneous biopsy, the spectrum of lesions underlying nephrotic syndrome has widened considerably, the most common being minimal change, especially in children. There are very few prognostic indicators by which response to treatment may be predicted and these include persistent microscopic hematuria.

Acute effects of ethanol intake on albumin and total protein synthesis in free and membrane-bound polyribosomes of rat liver

Controversial results have been reported in the last few years concerning the effects of ethanol on hepatic protein synthesis. In most of the studies no distinction has been made between the synthetic capabilities of the poly-ribosomes and the secretory product of labelled protein by the hepatocytes. In order to assess the influence of a single feeding of ethanol on the synthesis of albumin and total protein by the polyribosomes of rat liver, free and membrane-bound polyribosomes were isolated quantitatively from rats given 4–8 g ethanol per kg body weight 3–5 h before killing. The following results were obtained: (1) No difference was found in yield and size of free and membrane-bound polyribosomes isolated from control and ethanol-treated rats. The abilities to synthesize albumin and total protein were also equal for polyribosomes from both groups. (2) Addition of 1% ethanol to the incubation mixture of protein synthesis lowered albumin and total protein synthesis by 20%. No effect was observed with 0.5% ethanol. (3) Cell sap prepared from ethanol-treated rats contains a factor or factors which stimulate protein synthesis (10–15%). (4) The albumin mRNA sequence content was not changed in free and membrane-bound polyribosomal RNA fractions of ethanol-treated rats as compared to the control animals.

Relationship of Free and Total Calcium in Hypercalcemic Conditions

An assessment of free and total calcium measurements was made in 691 patients with suspected hypercalcemia or disorders often associated with hypercalcemia. In 18.9% of the 1049 specimens analyzed from nine different patient groups, a different impression of hypercalcemia was obtained depending on whether the free or total calcium was considered. Analysis of the ratio of free to total calcium indicated that there are two main factors which influence the distribution of calcium in the serum of hypercalcemic patients: the concentrations of albumin and parathyroid hormone. A lowered albumin concentration accounted for the altered distribution of calcium in patients with malignancies and partially accounted for the altered distribution in patients postrenal transplantation. In patients with confirmed primary hyperparathyroidism a higher ratio of free to total calcium was found, which could not be explained by alterations in protein, albumin, pH, or CO2 content but was related to parathyroid hormone concentration. Free calcium appears to be a slightly better indicator of elevated calcium states than total calcium. Measurements of free calcium should be particularly useful in patients with altered albumin concentration, with multiple myeloma in whom a calcium-binding protein could be present, after renal transplantation, and with suspected hyperparathyroidism and normal or slightly elevated total calcium values.

Water filtration of the forearm in short- and long-term diabetes mellitus.

Blood flow and capillary filtration coefficient (CFC) were measured by strain-gauge plethysmography on the upper and lower third of the forearm in 9 normal subjects and 29 well regulated patients with diabetes mellitus of varying duration (less than 10 years, 10 to 20 years, and more than 20 years). There was no difference in blood flow in the four groups, but CFC was significantly increased in long-term diabetes (duration above 20 years) when measured at the distal part of the forearm near the wrist. Calculations showed that this was probably due to the relatively high contribution of connective tissue in this part of the forearm. Increased water filtration in connective tissue in long-term diabetics is in accordance with earlier findings of a lowered subcutaneous interstitial fluid albumin concentration in long-term diabetics, this being explained by an increase in net water outflux from the microcirculation.

Albumin synthesis (second of two parts).

Health and Disease (Table 2)Cirrhosis of the Liver113 114 115 116 117 118 119 120 121 122 123This disease is one of the most complex disorders to afflict man and it is becoming one of the most prevalent of the chronic disorders. For years the serum albumin level has been considered to be a reliable index of the functional status of the liver. In the early 1940's Patek and Post clearly showed that, in patients without ascites, a serum albumin level below 2 g per 100 ml was a bad prognostic sign, suggesting that impaired synthesis was the cause of this lowered albumin level. Yet, in patients with . . .

Correlation of liver function and structure of cirrhosis with and without hepatoma based on autopsy studies.

Fifty‐one cases of cirrhosis with hepatoma, 7 cases of hepatoma without cirrhosis and 70 cases of cirrhosis without hepatoma were studied in correlation of histologic findings and liver function tests.More than moderate lymphocytic infiltration in portal triads and in stromas is the best measure to correlate with abnormal liver function tests among cirrhosis. Hepatoma is associated more in cirrhosis with normal or only mild lymphocytic infiltration, meaning less active and slowly progressive cirrhosis. This histologic finding also reflects on liver function tests in that rather preseved liver function is more likely to be associated with hepatoma. Good level of total serum protein, particularly not lowered albumin seems to be an important factor in association with hepatoma in cirrhosis.Elevated serum alkaline phosphatase without obstructive jaundice is also an important measure in association to hepatoma in cirrhosis.

BCG接種マウスのインフルエンザウイルス静注毒性に対する抵抗性の変化について 〔第2報〕

BCG-injected mice showed an increase (30%) in the weight of the liver and increase (150%) in the weight of the spleen as compared with control mice, at the 11th day after BCG injection.In histological observations, in the liver of the mice were exhibited an infiltration with neutrophils and lymphocytes, multiplication of the Kupffer cells and degeneration of liver cells.In the spleen of the mice were showed a hypertrophy of follicles an proliferation of reticulo-endothelial cells.When the reticuloendothelial system of mice was blocked by Pelikan india ink, the mice showed a decrease (75%) in the LD50 for E. coli endotoxin, however showed no significant alteration of the LD50 for the PR8 strain of influenza A virus.In the peripheral blood picture of BCG-injected mice, an increase (120%) in the number of neutrophils was observed. An increase (20%) in the number of leucocytes was also observed.The results of cellulose acetate electrophoresis indicated a decrease in albumin, increase in α and β plus γ globulins and lowered albumin: globulin ratio (A/G ratio) in response to BCG infection in mice.A little increase in the serum protein concentration of BCG injected mice was observed.The hemagglutination inhibiting antibody titres of the sera of BCG injected and control mice were both lower than 1: 10.There were observed only a little permeability to Trypan blue of control mice's and rabbits' and also BCG-injected animals' skins after the administration with the PR8.This fact suggested that the more sensitive test of the permeability of blood vessel would be required.

Internal irradiation of dogs with radioactive colloidal gold: synergistic effect of iron.

When irradiation of the liver was accomplished in dogs by the intravenous administration of repeated doses of relatively massive amounts of radioactive colloidal gold (Au198) the effect was heightened by the previous administration of iron. This was particularly noticeable when the iron was given intravenously in particulate form, with resulant deposition in the reticuloendothelial system. Animals that were given iron in addition to Au198 developed ascites as well as moderately extensive cirrhotic changes in the liver. Transient but marked leukopeada was observed in the dogs that received Au198 alone. Erythropoiesis was not noticeably influenced, but precipitous drops in hematocrit levels that corresponded to massive internal hemorrhage were observed to occur terminally. Electrophoresis showed changes in the plasma protein constituents. There was a decided lowertng of the albumia-globulin ratio as a resudt of lowered albumin levels. The beta globulins were considerably increased, as were the gamma globudins. Total proteins were not markedly affected.

Relationship between concentrations of albumin and lipids in plasma of experimentally nephrotic rats.

Correlative studies were made of the concentrations of albumin and lipids in the plasma of rats made nephrotic by injection of antikidney serum. It was found that the increased concentrations of plasma triglycerides, cholesterol and phospholipid in such rats were inversely correlated with the magnitude of their lowered plasma albumin content, rather than with the amount of antikidney serum that was injected. The results are consistent with the belief that a causal relationship exists between the deficiency of albumin and the increased lipid content of nephrotic plasma.

Electrophoretic Studies on Serum and Plasma of Control and Vitamin Deficient Monkeys.

SummaryThe plasma or serum proteins of rhesus monkeys maintained on various vitamin deficient diets were studied by chemical and by electrophoretic analysis. Partial or complete deficiency of vit. B6 resulted in hypoalbuminemia and a significant increase in the gamma globulin component. On a niacin deficient diet 2 monkeys developed a lowered albumin and an increase in the gamma globulin. A low choline diet led to a decrease in the albumin and to an increase in the beta globulin. The addition of 1% cholesterol to the diet of control or vit. B6 deficient monkeys produced a significant increase in the alpha-3 component. The electrophoretic composition of the plasma did not appear to be altered by a state of early chronic scurvy. The mobilities of the plasma components appeared to be increased by an ascorbic acid deficient diet but were unaffected by the other regimens.

Effect of cortisone and adrenocorticotropin therapy on serum proteins in disseminated lupus erythematous.

SummaryThe electrophoretic distribution of the serum proteins of 20 patients with disseminated lupus erythematosus showed a lowered albumin content with a considerable increase in the α2- as well as γ-globulin concentration. The sera of 5 patients were studied before therapy with cortisone and adrenocorticotropin (ACTH). After a clinical remission had been produced by these agents, it was found that the albumin and γ-globulin components progressed towards normal levels whereas the α2-globulin fraction remained unchanged.Thanks are due to Dr. George Baehr and the members of the First Medical Service for their cooperation throughout this study. The technical help of Sheldon S. Gilbert and Harold Corey is acknowledged with appreciation.

A contribution to the study of malnutrition in Central Africa: A syndrome of malignant malnutrition

1. 1. Diets deficient in calories, protein and the vitamin B complex and other constituents produce a common syndrome of malnutrition in African adults and children. 2. 2. The syndrome manifests itself as a failure of growth, or loss of weight, oedema, a gastro-intestinal defect, changes in the skin and hair, anaemia, a fatty liver, and slight neurological signs. 3. 3. Detailed observations are offered of the failure to digest food, of the deficiency bowel pattern, of the lowered plasma albumin and the raised plasma globulin, and of two autopsies. 4. 4. This syndrome appeared to be distinct from pellagra and nutritional oedema, it is very resistant to any improvement in the diet and to supplements of all the common vitamins, and the disease has a high mortality. 5. 5. No satisfactory name has been proposed for this syndrome. Although “kwashiorkor” holds pride of place, as a description of the red-haired African babies, it has been proposed that it should be called “malignant malnutrition” ( Trowell 1944.