Carcinoembryonic antigen family of adhesion molecules in the cotton top tamarin (Saguinus oedipus).

Humans and the cotton top tamarin, a model for colitis and colorectal cancer, share carcinoembryonic antigen (CEA) moieties. We quantified CEA in colonic washings and extracts in both, and CEA bands were confirmed by Western blot. We compared CEA-family expression in tissues and serum in the tamarin with that of the common marmoset, which develops colitis but not cancer. CEA levels are higher in tamarin washings compared with humans, and higher than in marmosets extracts (P<0.005). CEA molecular species appear to be specific, and human CEA-family member epitopes are also found in these primates. The higher CEA levels in the tamarin may reflect the overall higher cancer prevalence.

Gastrointestinal tract antigenic profile of cotton-top tamarin, Saguinus oedipus, is similar to that of humans with inflammatory bowel disease.

As an animal model for human inflammatory bowel disease and colorectal cancer, the cotton-top tamarin remains controversial. Demonstration of antigenic similarity to the human would enhance its validity. Using colonic extracts and washings, we compared binding of seven monoclonal antibodies reactive with bowel and cancer antigens in both tamarins and humans with inflammatory bowel disease. Additionally, telomerase activity was tested for. Expression of a mucin antigen specific to human cancer was increased in tamarin colonic washings as well as aminoproteoglycans and EGFR in tamarin extracts, as compared to those of humans with inflammatory bowel disease (P < 0.005). An adenoma-associated antigen and k-ras p21 protein were negative in the tamarin. A trend to greater telomerase activity exists in tamarins. The antigenic similarity validates this model for human inflammatory bowel disease and colorectal cancer. A trend to increased telomerase activity in tamarins is consistent with the greater predisposition to cancer in these animals.

Predictive value of fetal serum beta 2-microglobulin for neonatal renal function.

When fetal urinary-tract malformations (UTM) are discovered, management is based on the prediction of postnatal renal function, currently made by fetal urinary biochemistry and sonography. Serum beta 2-microglobulin has been used postnatally to estimate renal function and does not cross the placenta. We investigated the relation between fetal serum beta 2-microglobulin and renal function by comparing 64 unaffected fetuses and 15 fetuses with UTM. A beta 2-microglobulin above a 5.6 mg/L cut-off gave cross-validated sensitivity of 80.0%, specificity of 98.6%, a positive predictive value of 88.9%, and a negative predictive value of 97.1% for our cohort study.

IgG Antibodies Against Factor VIII in Normal Individuals.

Previously, we found noninhibitory antibody against factor VIII in a hemophilic subject. We screened sera from normal and hemophilic individuals for the presence of similar antibodies. Sera from 18 normal individuals and 17 hemophilia A subjects were tested for the presence of factor VIII antibodies. We also tested two commercial immunoglobulin preparations for the presence of similar antibodies. Serum from two normal individuals were found to have IgG1 and IgG2 antibodies against factor VIII. The two commercial immunoglobulin preparations also contained IgG1 and IgG2 antibodies against factor VIII. Conclusions: Sera of apparently normal individuals contain antibodies to factor VIII with no inhibitory qualities. Such antibodies against factor VIII appear to be a common occurrence.

A new approach to immunologic identification of factor VIII antibodies.

We tested for antibodies against factor VIII by using monoclonal antibody-purified factor VIII preparation as a source of antigen. The factor VIII was adsorbed on nitrocellulose membranes and stored in a refrigerator until later use. Plasma or serum was incubated with the factor VIII containing strip and the antibody was detected by another incubation with peroxidase-labelled antihuman immunoglobulin antibodies. The test was efficient in detecting antibodies in haemophilic and normal subjects with acquired inhibitors to factor VIII. It also detected antibodies to the factor VIII protein in a haemophilic subject with no evidence of inhibitor. The technique is simple, readily applicable, and serves as a useful screening tool for detecting factor VIII antibodies. The stability of the antigen-containing strips in a refrigerator is a practical advantage with potential commercial application.

A putative CEA moiety is shared by the cotton-top tamarin (Saguinus oedipus) and humans.

CEA-like molecules immunologically distinct from those in humans have been described in non-human primates. These primates do not share the human predilection for colitis and subsequent development of colorectal cancer. CEA expression has not been fully evaluated in a lower-order primate, the cotton-top tamarin (Saguinus oedipus), an animal model for colitis and colorectal cancer. We found increased levels of CEA in both colonic washings and tissues of these animals using a commercially available kit, CEA AIA-PACK (Tosoh Medics, Foster City, CA). In contrast, we observed that other CEA kits failed to detect CEA in tamarins. To elucidate the nature of the CEA-like protein detected, we used the two component monoclonal antibodies used in the CEA AIA-PACK kit, and identified the reactive molecules by Western blotting. A band of approximately M(r) 50,000 was found to be common to samples from both humans and the tamarins. Minimal binding was observed with NCA antibody. We conclude that a CEA-like molecule shared by humans and tamarins may play a role in the pathogenesis of colitis and cancer in both species.

Developmental changes of adenocarcinoma-associated antigen.

The occurrence and serum concentrations of adenocarcinoma-associated antigen (ACAA) were studied during the fetal period of life, in newborns and in their mothers. The mean concentrations were significantly higher in fetal, newborn and maternal sera when compared with the mean concentration of ACAA in healthy, nonpregnant adults. Thus, ACAA appears to show fetospecific features as is known for other oncofetal proteins. ACAA should be recognized not only as a potential tumor marker, but also as a normal protein constituent of human serum.

Ontogeny of pancreatic oncofetal antigen.

Serum concentration of pancreatic oncofetal antigen (POA) was determined in human fetuses, newborns and pregnant women. The mean fetal concentration of POA (mean = 5.27 micrograms/ml) changed very little with gestational age. Also, only a weak correlation was found between POA concentration of newborns (mean = 5.15 micrograms/ml) and their birth weight. It appears that between the 19th and 40th weeks of gestation POA exhibits no fetospecific features, i.e. POA concentration did not exceed significantly the concentration of nonpregnant adults (mean = 6.10 micrograms/ml). A number of pathophysiological variables was correlated with POA concentrations of newborns. The most striking statistical differences were found between American black and white newborns and adults; the mean concentration of POA in sera of black full-term newborns was 5.38 micrograms/ml as compared to white newborns, where the mean concentration was 3.58 micrograms/ml. Similarly, black mothers had a mean concentration (mean = 12.21 micrograms/ml) significantly greater than white mothers (mean = 5.62 micrograms/ml).

Pancreatic oncofetal antigen and carcinoembryonic antigen in breast and colon carcinoma.

Pancreatic oncofetal antigen (POA) and carcinoembryonic antigen (CEA) were determined in plasma of 195 patients with breast cancer and 90 patients with colon carcinoma. Increased levels of POA and CEA were seen in 19.0 and 25.6% of patients with breast cancer, respectively. Some but not all patients showed an increase in both markers. The incidence of abnormal concentrations of POA and CEA increased with the progress of the disease. POA appears to be a useful marker in breast cancer, especially in patients who have normal CEA levels. On the other hand, colon carcinoma patients showed increased POA concentrations considerably less frequently than CEA levels.

The effect of steroids for shock on the immune response to tetanus toxoid.

The effect of corticosteroids on the immune response after severe injury and hemorrhagic shock was studied in 88 patients, who received an average of 13 blood transfusions for injury and hemorrhagic shock, which caused the systolic blood pressure to be below 80 torr for an average of 29 minutes. The immune response to tetanus toxoid was tested in the postoperative period. Besides the administration of blood, crystalloid solution, and plasma for coagulation factor deficiency, 42 patients also received methyl-prednisolone 1 g during additional resuscitation followed by an average of 15 mg/kg given daily for the next 2 days. The total dose of methylprednisolone averaged 3.9 g. The two groups of patients were similar for resuscitation needs and for insult. The immune response to tetanus toxoid was not significantly different between the two groups of patients. These data show that a short-term bolus of massive steroids does not appear to alter, significantly, the immune mechanism following severe hemorrhagic shock.

Effect of fresh-frozen plasma resuscitation on cardiopulmonary function and serum protein flux.

The adverse effects of albumin resuscitation on coagulation activity, cardiopulmonary function, and extravascular flux of nonalbumin protein have made fresh-frozen plasma (FFP) an attractive alternate volume expander for hemorrhagic shock. This study addresses the effects of FFP on cardiopulmonary hemodynamics and protein flux. Whole blood was collected three and six weeks before shock, separated into red blood cells (PRBCs) and FFP, and stored. In 24 conditioned splenectomized dogs, resuscitation from reservoir shock of two hours' duration consisted of autologous PRBCs and balanced electrolyte solution (BES) in control dogs and PRBCs, BES, and FFP in plasma-treated dogs. Hemorrhagic shock reduced serum albumin and IgG levels in both groups. Resuscitation with FFP led to a higher cardiac output, left ventricular stroke work (LVSW), and pulmonary capillary wedge pressure (PCWP). The PCWP/LVSW ratio was comparable for both groups. Postshock day 2 serum albumin and IgG levels and lymphatic albumin and IgG concentrations were increased in plasma dogs. Therefore, FFP supplement to PRBC and BES resuscitation does not derange the PCWP/LVSW ratio or reduce intravascular nonalbumin proteins.

Rapidly progressive glomerulonephritis and monoclonal gammopathy.

A case of rapidly progressive glomerulonephritis associated with nephrotic syndrome, hematuria, and edema is reported. Monoclonal IgG-lambda was found in the serum and urine. Renal biopsy revealed diffuse proliferative glomerulonephritis with crescent formation. Immunofluorescent study revealed IgG and lambda in a focal segmental distribution. Subepithelial humps were found on electron microscopic examination. A spectacular feature of the deposits was the presence of organized linear fibrils within the humps. Similar fibrils were found in the mesangium and urinary space. Renal function deteriorated rapidly, necessitating hemodialysis in eight months. In addition to the present case, 24 cases of glomerulonephritis associated with "benign" monoclonal gammopathy reported since 1970 are reviewed, and the potential causal relationship between monoclonal gammopathy and glomerular involvement is stressed.

In vitro neutrophil-erythrocyte rosette formation mediated by a serum factor (IgG).

In vitro neutrophil-erythrocyte rosette (NER) formation occurred in the peripheral blood of an elderly man. This caused problems in cross-matching for blood transfusion initially but was resolved by performing crossmatches at 37 degrees C because this phenomenon was temperature-dependent. NER formation was independent of complement and of the type of anticoagulant used. NERs were induced using normal control cells with the patient's plasma, serum, and the IgG fraction of serum. The rosetting factor was adsorbed by heterologous group-specific erythrocytes, but not by leukocytes. No neutrophil antibodies were identified.

Characterization of glomerular permeability and proteinuria in acute hypertension in the rat.

The effects of acute angiotensin II (AII) induced hypertension on renal hemodynamics, urinary excretory rates, and clearances of endogenous proteins, together with colloidal iron staining and numerical density of differently charged ferritins in glomerular basement membrane (GBM) have been studied. AII decreases para-aminohippurate clearance (63%) more than glomerular filtration rate (GFR) (42%), resulting in an increased filtration fraction (54%). Simultaneously, large increments in the excretory rates and clearances of albumin and IgG2a occur. The number of native ferritin particles per unit volume of GBM and its different layers increases significantly in both superficial and juxtamedullary glomeruli as a result of acute hypertension. In contrast, the number of cationized ferritin particles per unit volume of GBM as well as colloidal iron staining of GBM and adjacent cell membranes remain unchanged, irrespective of AII treatment. The results demonstrate that acute AII-induced hypertension enhances glomerular permeability to proteins of different size and shape in the absence of detectable alterations in the fixed negative charges of the GBM. Since both RBF and GFR are decreased, the increased transglomerular passage of proteins in acute hypertension appears to be due to an increase in the pore size of the glomerular filter, induced possibly by either high intracapillary pressure and/or a direct action of AII on GBM constituents.

Glomerular permeability in acute hypertension.

Acute hypertension induced by intravenous infusion of angiotensin II (AII) leads to enhanced transglomerular passage of albumin and IgG, as demonstrated by electronmicroscopic immunoperoxidase techniques. Although no morphological damage of the capillary wall was detected, significant amounts of macromolecules were present in the mesangial region. On a functional basis, a 42% decrease in glomerular filtration rate and a 63% decline in p-aminohippurate clearance were seen, resulting in a 54% increase in the filtration fraction. Quantitative measurements of albumin and IgG2a clearances showed a 90- and 15-fold increase, respectively. Similarly, the concentration of native ferritin particles in the glomerular basement membrane (GBM) increased 11-fold. On the other hand, the number of cationized ferritin particles and the staining properties of GBM to colloidal iron were not altered. These observations indicate that acute AII-induced hypertension affects glomerular permeability to proteins of different size and shape, possibly by increasing the pore size of the glomerular filter by either high intracapillary pressure and/or a direct action of AII on GBM constituents.

Natural killer and suppressor T-cell chronic lymphocytic leukemia.

A patient with low-grade lymphocytosis, splenomegaly, and neutropenia, but adequate myeloid leukogenesis, was found to have chronic lymphocytic leukemia, which represented a clonal proliferation of a distinct T-lymphocyte subset. The lymphocytes did not form E rosettes but had an OKT3+, OKT4+, OKT6+, OKT8+, OKT11+, HNK-1+, HNK-36+, OKIa1+, OKM1+ phenotype and functionally had suppressor and natural killer activity. Morphologically, they were large granular lymphocytes, which were strongly acid phosphatase positive and nonspecific esterase negative. They did not respond to mitogens, or to allogeneic cells. Initially, the spleen appeared to be the most involved organ and, judging from the high proportion of leukemic splenic lymphocytes in the S and G2/M phases of the cell cycle, was also the organ of origin of the leukemic cells. Only a few leukemic cells in the blood and bone marrow were in S and G2/M phases. After splenectomy, the lymphocyte count rose considerably and the bone marrow became progressively more infiltrated by tumor nodules. One year after diagnosis, the patient was started on chemotherapy because of progressive anemia. He responded to the chemotherapy by normalization of the hemoglobin and neutrophil count and had a moderate decrease in the bone marrow involvement and peripheral lymphocytosis.