Karel Kithier

Primary liver cancer. A review of the clinical features, blood groups, serum enzymes, therapy, and survival of 65 cases

A review of 65 patients with primary liver cancer was made. Of these, 53 had hepatocarcinoma. Primary cancer of the liver was most frequently found in patients aged 50 to 80 years, and was observed in three times as many males as females. There was an increased incidence of hepatocarcinoma in Negroes, especially those with blood group B. The most common symptoms with primary liver cancer were upper abdominal pain, weakness, and weight loss, while the most commonly found signs were hepatomegaly or an abdominal mass. Jaundice and ascites were also commonly found. Serum alkaline phosphatase, SGOT, SGPT, and LDH were elevated in most of these patients. In patients with hepatocarcinoma, 66% had histologically confirmed liver cirrhosis at autopsy. Serial alphafetoprotein tests were performed on 19 patients with hepatoma, in 14 of whom (73.6%) AFP was detectable. No Australia antigen was detected in 12 patients with hepatoma. In this study, 9 out of 16 patients (56%) had subjective and objective tumor responses with continuous 5‐FUdR hepatic artery infusion. None of 18 patients treated with systemic cytotoxic agents responded. The difference in response between hepatic artery infusion and systemic therapy is statistically significant (P < .0002). There was a statistically significant lengthening in survival of patients who responded to intra‐hepatic artery infusion as compared to non‐responders and patients who received systemic chemotherapy. In reviewing the autopsy findings on 30 patients with hepatocarcinoma and 9 with cholangiocarcinoma, there were differences in the incidence of metastases to the lungs or bones between these two types of primary liver cancer.

β2-Microglobulin: occurrence in fetal life and malignancy

Abstract The levels of β2-microglobulin in human fetal sera were found increased as compared with those in maternal and normal adult sera. Serum concentrations of β2-microglobulin in the course of intrauterine development parallel concentration changes of feto-specific proteins. Elevated serum levels of β2-microglobulin were also found in a number of pathological conditions, especially those of a neoplastic nature.

Binding of 17β-estradiol by variants of α-fetoprotein in rat amniotic fluid

Two variants of alpha-fetoprotein in rat amniotic fluid were separated by their different affinity for concanavalin A-Sepharose, which selectively binds alpha-D-manno-pyranosides and alpha-D-glucopyranosides. Both forms had the same mobility upon polyacrylamide gel electrophoresis. The binding of 17beta-estradiol per mg of alpha-fetoprotein, determined both immunologically and electrophoretically, was the same for both variants. These results indicate that a specific carbohydrate portion of the molecule is not necessary for steroid binding.

Biochemical characterization and cellular localization of serine protease in myopathic hamster

Abstract Purified serine protease was obtained from skeletal and heart muscle of 150-day-old myopathic hamsters. The skeletal muscle enzyme showed identical molecular weight and characteristics toward various reagents and inhibitors when compared with the cardiac muscle enzyme. In addition, no antigenic differences were detected between the two enzymes using double-immunodiffusion test. Further characterization of the properties of the two enzymes was carried out by using individual myofibrillar proteins as substrates. Both enzymes were capable of degrading myosin, tropomyosin and troponin but not actin. The divalent cations Ca 2+ or Mg 2+ were able to protect the myosin light chain 2 against proteolytic cleavage. The cellular localization of the serine protease of skeletal and cardiac muscle was studied by immunohistochemical techniques. The observations indicate that serine protease is contained within the cytoplasmic granules of cardiac and skeletal muscle mast cells of myopathic and control hamsters. The number of labeled mast cells is about three-fold greater in myopathic than in control tissues. This increase correlates with the increase in enzyme activity as detected by biochemical assay in tissue homogenates.

The value of serial carcinoembryonic antigen (CEA) in predicting response rate and survival of patients with gastrointestinal cancer treated with chemotherapy. A Southwest oncology group study

Elevated serum levels of carcinoembryonic antigen (CEA) were found in 70% of 141 patients with advanced gastrointestinal (GI) cancers. Serial CEA measurements were performed on 70 patients before and during chemotherapy. The majority were treated with 5‐FU and Methyl‐CCNU (33 patients), 5‐FU (19 patients), or 5‐FU and mitomycin‐C (8 patients). In 49 patients with colorectal carcinoma who had elevated serum CEA prior to chemotherapy, 18 had objective partial tumor remission, 16/18 (89%) showed definite decrease in CEA level, one had no change, and one had an increase CEA titer. Thirty‐one patients had either stable disease (10 patients) or increasing disease (21 patients) while on chemotherapy. Of these patients four showed decrease in CEA, eight had no change, and 19 had increase in CEA levels as compared to pretreatment value. The survival of patients with a decrease in CEA during chemotherapy was statistically significant (p = .03) as compared to survival of those with no change or increasing CEA levels. In 21 patients with other GI cancers, the correlation between the clinical response and change in CEA level observed was not as definite as in patients with colorectal carcinoma.

Serum β2-microglobulin levels in normal children and sex-linked agammaglobulinemia patients

Abstract β 2 -Microglobulin levels have been determined in cord blood sera and sera of healthy children of different ages, as well as in sera of patients with Brutons type of agammaglobulinemia. The results obtained showed the highest β 2 -microglobulin levels in cord blood sera and a gradual decrease in β 2 -microglobulin concentration with age; normal adult levels of β 2 -microglobulin are reached at the age of approx. 12 years. No correlation has been found between serum β 2 -microglobulin levels and immunoglobulin concentration. The results suggest that the production of β 2 -microglobulin does not depend solely on B-cell function. A simple and sensitive radioactive method for the quantitation of β 2 -microglobulin is described.

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

A prior prospective random study showed that supplemental albumin led to a significant (P ⩽ 0.05) fall in immunoglobulin (Ig) content of IgG, IgM, and IgA; no measurement was made on the immune response to a known antigen. Therefore, the immune response to tetanus toxoid, measured by antibody precipitation, was studied in 43 nonalbumin patients and 22 albumin patients from whom frozen sera were available. The 65 patients received an average of 16 units blood during resuscitation and 0.5 ml tetanus toxoid. Using single radial immunodiffusion technique, duplicate double-blind measurements of precipitants formed by the patients tetanus toxoid antibody and purified tetanus toxoid (TTA) incorporated in 1% agarose gel were made. TTA levels in the 22 albumin patients were compared with all nonalbumin patients and with two subgroups of 22 patients—one randomly chosen; the other matched for number of transfusions. TTA was also correlated with time after injury. TTA was significantly less in albumin patients (215 ± 100 units) than in the nonalbumin patients (387 ± 233 units) and both subgroups of nonalbumin patients. TTA correlated directly with time after injury in the nonalbumin patients (slope = −0.4). Albumin resuscitation for shock results not only in a fall in Ig content but also a reduction in the immune response to tetanus toxoid.

Alpha-fetoprotein in bovine hepatocellular carcinoma

Abstract The occurrence of bovine alpha-fetoprotein was studied in diseased cattle. Fetoprotein was found by the Ouchterlony test in two out of four cows with hepatocellular carcinomas. It was not detected in any of 105 animals with various other diseases, nor in healthy adults or calves, but it was found in all of 8 foetuses.

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.

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.