Daily subcutaneous injection of 6-dimethylamino purine, 3-amino-d-ribose, an aminonucleoside related to "puromycin."$ ( 1) into immature male rats for 10 to 12 days results in generalized edema, ascites? marked proteinuria, hypoproteinemia, hyperlipemia, and azotemia. The clinical complex and renal pathology closely resemble the nephrotic syndrome occurring in children. This initial report describes the renal lesions and electrolyte composition of edematous tissues in the rat. The observations indicate that the renal lesion involves both the glomerulus and the convoluted tubule: that skin, an essentially extracellular phase tissue, is the largest tissue reservoir for edema fluid; and that the electrolyte structure of muscle cells is only slightly altered during edema.Thirty-six 40 g male rats of Sprague-Dawley strain were caged individually and pair-fed on a standard synthetic diet containing 16% W AV vitamin-free casein. After a preliminary adjustment period, 18 rats (experimental group) were injected daily with 0.003 ml of a 0.5% aqueous solution of the drug per gram of body weight for 12 days. The control rats were injected with similarly calculated doses of distilled water. Twelve animals in each group were given an oral load of M / l NaC1 solution daily by stomach tube in a dose of 1 mM/100 g of body weight for the last 4 days of injection. All animals were sacrificed 24 hours after the last injection. At the time of sacrifice under Evipal anesthesia the hair was carefully Procedure.

No abstract

Small intestinal lactase activity in the health adult is either the same as in early infancy or may drop to very low levels. The behavior of the enzymatic state varies with the ethnic group studied. In those adults with low lactase activity little information is availalbe as to the age at which the lactase decreases. We attempted to determine a) the frequency of low intestinal lactase activity and b) the age at which the change occurs. For this purpose we reviewed in a large number of intestinal biopsies both histologically as well as for disaccharidase activities. The biopsies were obtained from a heterogeneous group of Caucasians, including patients, their siblings and parents. The patients were those with failure to thrive in whom no organic cause could be elicited, and those with the irritable colon syndrome. Patients ranged in age from 6 weeks to 50 years and out of a total of 1, 077 jejunal biopsies, 172 morphologically normal biopsies were selected. The milk drinking habits of 118 subjects and their families were elicited and 31 oral lactose tolerance tests performed. The mucosal lactase activity and sucrase-to-lactase ratio in those 172 individuals were plotted against age. In the first 3 years the mean lactase activity was 32.1 plus or minus 10.1 mumoles/g protein per min and the sucrase-to-lactase ratio was 1.7 plus or minus 0.5 with no change from year to year. However, after age 5 two separate groups emerge. A small group (24.6% of the population) with low lactase activity, and a second group possessing the same mean value for lactase activity as noted in the first 3 years. The low lactase activity group included children and adults with clinical lactose intolerance. These individuals consumed relatively small amounts of milk and when 12 of them were tested with an oral lactose tolerance test the result was a "flat" curve with a maximum rise in blood glucose of 9 plus or minus 3.2 mg/100 ml. The second group consumed more milk averaging 1 quart/day with no discomfort and when 19 were tested with oral lactose tolerance tests the values were normal. This study indicates that low lactase activity in the Caucasian population may make its appearance at the age of 5 years.

No abstract

Observations over a period of 6 years are reported on 10 children in whom the diagnosis of congenital sucrase isomaltase deficiency (SID) was confirmed by quantitative estimation of disaccharidase activity of the small intestinal mucosa. Repeat biopsies were performed on eight of the ten patients and showed no evidence that sucrase isomaltase activity is acquired. Sucrose tolerance tests (2 gm/kg) showed no significant rise in blood glucose in the seven patients in whom they were performed. This condition may appear in young infants with severe diarrhea resulting in a malabsorption syndrome and failure to thrive. It may also be manifest in a milder clinical presentation with bothersome diarrhea in spite of normal growth and development in the older infant or young child. The diagnosis in this latter group can be difficult, and is frequently missed.

No abstract

No abstract

ExtractSeven lysosomal enzymes and three mitochondrial enzymes were studied in cultured lymphoid cells from four patients with cystic fibrosis, three heterozygotes, one borderline patient, and six healthy controls. The lysosomes and mitochondria were isolated by differential and density gradient centrifugation. The activity of a-glucosidase, which is a lysosomal enzyme degrading glycogen, showed a marked increase in activity in the lysosomes of cultured lymphoid cells obtained from patients with cystic fi brosis as compared with the healthy controls. Two substrates were used for measuring the activity of this enzyme, the synthetic jfr-nitrophenyl-a-glucoside (p-NP-aglucoside), and the physiologic substrate glycogen. The values obtained with/>-NP-aglucoside were 32.6 (SD ± 8.6) and 13.8 (SD ± 12.2) ^moles/g lysosomal protein/hr and with glycogen 543.5 (SD ± 163.3) and 188.6 (SD ± 156.3) yumoles/g lysosomal protein/hr for patients with cystic fibrosis and controls, respectively. The values of a-glucosidase in the heterozygotes were also elevated, 17.2 (SD ± 5.5), controls 13.8 (SD ± 12.2) using/)-NP-a-glucoside as substrate. When glycogen was used as substrate, the values were 226.7 (SD =1= 85.3) in the heterozygote and 188.6 (SD ± 156.3) ^moles/g lysosomal protein/hr in the control.