Alfred Gellhorn

Hypercalcemia in malignant disease without evidence of bone destruction

Abstract 1.1. Hypercalcemia with a tendency to hypophosphatemia is reported in ten patients with malignant disease and normal bones. 2.2. These patients exhibited symptomatology characteristic of hypercalcemic states, including mental confusion. 3.3. Removal of the primary tumor in three patients was associated with prompt return to normal of the serum values of calcium and phosphorus and the alkaline phosphatase, when elevated. 4.4. The parathyroid glands were invariably found to be normal at operation or at autopsy. 5.5. A possible mechanism for the hypercalcemia in this group of patients is discussed.

The intracellular localization of an enzymatic defect of lipid metabolism in diabetic rats

Abstract The conversion of stearic acid to oleic acid has been studied in homogenates and other subcellular fractions of adipose tissues and liver of untreated and insulin-treated diabetic rats and rats maintained on a fat-free diet. The synthesis of the monounsaturrated fatty acid is an oxygenase reaction requiring molecular oxygen and DPNH or TPNH. The site of the reaction has been localized to the microsomes. In diabetes, the microsomal enzymatic conversion of strearate to oleate stops. This defect in lipid metabolism, which is separable from the overall depression of lipid biosynthesis, is corrected by insulin therapy.

THE CLINICAL IMPLICATIONS OF HYPOGAMMAGLOBULINEMIA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND LYMPHOCYTIC LYMPHOSARCOMA

Excerpt Although many patients with agammaglobulinemia have been reported since 1952, there are few reports and surveys of serum gamma globulin depressions in association with chronic lymphocytic l...

The effect of massive prednisone and prednisolone therapy on acute leukemia and malignant lymphomas

Abstract 1.1. The administration of large doses of prednisone or prednisolone in eighteen cases of acute leukemia resulted in clear-cut complete remissions in five cases and partial remissions in six. Two of the partial remissions were not clearly related to administration of the steroid. The complete remissions occurred in adults whose ages were forty, thirty-six, thirty-five, twenty-six and fourteen. 2.2. In one patient with a subacute myelomonocytoid leukemia a brief and transient remission was obtained. 3.3. In three cases, including two of atypical or subacute leukemia, and one of acute leukemia there might have been some acceleration of the disease process by the administration of steroid. However in all these cases alternative possibilities in terms of infection or gastrointestinal perforation might have explained the accelerated downhill course. 4.4. Although objective remissions were produced by steroid administration in most of the ten patients with malignant lymphomas, the course of the disease was not significantly modified and side reactions were serious. 5.5. Complications of therapy included the development of diabetes, bacteremia, septicemia, local pyogenic infection and generalized fungus infection, psychoses, gastrointestinal ulceration and perforation.

Lysozyme activity in ulcerative alimentary disease: II. Lysozyme activity in chronic ulcerative colitis

Abstract 1.1. The stools of C.U.C. patients have a mean lysozyme content 27 times that of normal stools. 2.2. The mean twenty-four-hour output of lysozyme in C.U.C. stools is 168 times that of normal stools. 3.3. Upon purging the twenty-four-hour output of lysozyme in normal individuals is 6.7 times that of normal stools while the concentration of the enzyme decreases by about one-third. 4.4. The lysozyme content of regional enteritis stools is 6.1 times that of normals. 5.5. With clinical improvement, the lysozyme titers and daily outputs fall. 6.6. The colonic mucosa of individuals with acute C.U.C. shows an 8.5-fold increase in lysozyme content over that of normal colons. 7.7. These data, together with the experimental production by lysozyme of ulcerations in the canine alimentary tract, indicate that lysozyme is an etiologic agent which locally initiates the lesions of chronic ulcerative colitis.

LIPID BIOSYNTHESIS IN ADIPOSE TISSUE DURING AGING AND IN DIABETES

It is noteworthy that in our affluent American society in which science has been so handsomely supported, not only scientists but their invaluable assistants, the experimental rats and mice, tend to become obese as they all grow older. In an effort to gain additional understanding of this interesting phenomenon, a systematic study was undertaken of lipid metabolism in adipose tissue of the rat from the cradle to the grave. I shall not present our results’ on the depression of fatty acid release from, and fatty acid oxidation in, adipose tissue of old rats when compared to young, which may contribute to the accumulation of fat during aging, but rather emphasize changes in fatty acid biosyntheses in old adipose tissue and their similarity to the defects in experimental diabetes. Evidence will be presented which indicates a quantitative modification of two separable fatty acid synthetic processes during aging and in diabetes. These changes can be corrected by insulin administration to the intact animal but not by insulin in uitro. Our studies on the mechanism of insulin action will be summarized. FIGURE 1 demonstrates that the in uitro rate of incorporation of acetate into total lipids by adipose tissue from old rats is significantly slower than from young animals. This is considered a measure of the greater rate of de novo fatty acid biosynthesis in young adipose tissue. In rats fed a regular diet ad libitum (FIGURE 2) there is very little difference in the fatty acid composition of the adipose tissue between young and old animals save for the presence of short chain fatty acids in the young. These latter do not represent a difference in biosynthesis between young and old rats, but rather are residual from the mothers’ milk which has a high content of such acids. Although the fatty acid composition of young and old adipose tissue is quite similar, analysis of the incorporation of CI4 acetate into the individual fatty acids did reveal a marked difference in the labelling of the monoenes depending upon the age of the animal.’ Thus 10 per cent of the total fatty acid radioactivity was found in palmitoleic acid of the young animal compared to four per cent in the old and 17 per cent of the total radioactivity in young adipose tissue was found in oleic acid compared to 3.5 per cent in oleic of old animals. Since i t was felt that the regular rat diet, known to be rich in the various fatty acids found in the adipose tissue, was obscuring the effects of the depression in olefin synthesis in

Triethylene melamine in clinical cancer chemotherapy

F OLLOWING the introduction of nitrogen mustard (HN2) as a chemotherapeutic agent for the management of disseminated malignant lymphomas and inoperable bronchogenie carcinoma in 1943, hundreds of closely related compounds have been synthesized and studied experimentally. Although a small number of these demonstrated certain advantages over HN2 in the laboratory, clinical evaluation failed to justify their substitution for the commonly employed nitrogen mustard. Recently. however, a related chemical compound has been examined both in the laboratory and in clinical therapy which offers significant advantages over HN2 in selected cases. This drug, triethylene melamine, is effective after oral administration and the incidence of immediate toxic manifestations is appreciably less than with the intravenous nitrogen mustard. perience of this clinic in forty-four cases treated during the past two years. At the outset it can be stated that the drug does not cure any malignant disease. Emphasis will be placed on the indications, limitations, dosage and toxicity. The experimental observations which provided the basis for clinical trial have been reported by Rose’ and Philips, 2 and detailed discussion of the drug in cancer chemotherapy has been presented by Karnofsky et a1.3 and Wright et al.”

Amyloidosis in Hamsters with Leishmaniasis.

Summary Forty-six days after successful inoculation of L. donovani into hamsters, there appeared edema associated with amyloidosis. There was marked anasarca at 60 and 77 days after infection with extensive deposition of amyloid in the glomeruli and the adrenal cortex. The hypoalbuminemia, which coincided with the edema and a proteinuria, is believed to have been caused by the impairment of glomerular function.

Fatty acid biosynthesis and RNA function in fasting, aging and diabetes

Abstract 1. 1.Acetate incorporation into the total lipid of adipose tissue and mono-unsaturated fatty acid synthesis is markedly depressed in fasted rats. These observations have been associated with a depression in RNA synthesis. Refeeding a fasted animal leads to return of RNA synthesis to normal within 4 hr which precedes the increase of fatty acid biosynthesis. 2. 2.During aging, in the rat, there is a progressive decline in saturated and monounsaturated fatty acid synthesis in adipose tissue. These biosynthetic changes can be restored toward the pattern of young animals either by the feeding of a fat-free diet or by the administration of insulin. The RNA concentration of the adipose tissue from old rats is significantly lower than in young rats, but the specific activity of the RNA species isolated from adipose tissue after incubation with uridine-5-T is significantly greater in the old than in the young. This finding may be due to a decrease in the size of the precursor nucleotide pool. 3. 3.In alloxan diabetes, there is a decrease in acetate incorporation into total lipid and a defect in microsomal monoenoic fatty acid synthesis. These defects are repaired by the administration of insulin after a lag period of 6–12 hr. The coincident administration of actinomycin-D with insulin prevents the restoration of lipid biosynthetic activity but does not modify the hypoglycemic action of the hormone. These observations indicate that insulin stimulates the renewal of cellular RNA necessary for the synthesis of specific anabolic enzymes. The action of insulin on increasing the transport of glucose across cell membranes is not dependent on new enzyme synthesis. Following a single injection of insulin, the restoration of lipid biosynthesis to normal is maintained for more than 24 hr. Evidence has been obtained which indicates that the informational RNA-ribosome complex formed under the influence of insulin is more stable than the enzyme(s) synthesized on the template. 4. 4.From the direct and indirect evidence relating RNA function to fatty acid synthesis, it is proposed that the fundamental disturbances in fasting, aging, and diabetes affect RNA synthesis primarily and the enzymatic failures are secondary to this.

Lysozyme in chronic ulcerative colitis.

It has been previously shown in experimental animals that there is a low lysozyme content of the colonic mucosa in contrast to that of the stomach and in assays of apparently normal segments of 3 human large intestines, surgically removed for carcinoma, the lysozyme concentration was similarly low (mean = 3.5 units/g tissue). However, following the observation that lysozyme was able to remove the surface mucus from the dog stomach, 1 the present investigation was undertaken to determine whether abnormal concentrations of this mucolytic enzyme were present in the feces of patients with chronic nonspecific ulcerative colitis. Table I summarizes the results of the stool lysozyme determinations. It is to be noted that the concentration of the enzyme in the feces of the control individuals was low whether the determinations were made on specimens obtained following a normal bowel movement or after purging with magnesium sulfate or castor oil. Similarly, in 3 chronic ulcerative colitis patients whose disease necessitated ileostomy and colectomy, the lysozyme concentration of the ileal stools was uniformly low. Also, in the single patient with idiopathic diarrhea who failed to show any organic change in the mucosa of the gastro-intestinal tract, there was little lysozyme present in the stool. In marked contrast to the above noted findings was the elevated lysozyme concentrations in the fecal excretions of 12 patients in whom the diagnosis of nonspecific chronic ulcerative colitis was established by roentgen and proctoscopic examination and in whom exhaustive search for pathogenic bacteria and/or parasites was negative. Even more striking was the high titer of lysozyme found in specimens of mucus obtained from the rectosigmoid region of patients with this disease.