The Transport Mechanism of an Organic Cation,Disopyramide, by Brush-border Membranes. Comparison Between Renal Cortex and Small Intestine of the Rat

Abstract— The characteristics of disopyramide uptake in brush-border membrane vesicles isolated from rat renal cortex and small intestine were investigated. Transport of disopyramide into an osmotically reactive intravesicular space was observed with notable binding to the membrane surface. An outwardly directed H⁺ gradient stimulated disopyramide uptake, resulting in a transient uphill transport in both brush-border membranes. As for the renal brush-border membrane, the H⁺ gradient itself appeared to be the driving force for this stimulation of uptake. These findings suggest that disopyramide-H⁺ antiport is the mechanism of disopyramide action in renal cell membrane. The initial uptake was saturable (K_m and V_max of 680 μm and 1·25 nmol (mg protein)^?1/30 s, respectively). The stimulation of disopyramide uptake by an outward H⁺ gradient in rat intestinal brush-border membrane was due to an interior negative H⁺-diffusion potential. A K⁺-diffusion potential (interior negative) enhanced disopyramide uptake. These results suggest that there are different mechanisms of disopyramide uptake for renal and intestinal brush-border membrane vesicles.     

Effect of weight loss on body fat distribution in obese children

The intra-abdominal visceral fat to subcutaneous fat ratio (V/S ratio) has been reported to be strongly related to disorders of glucose and lipid metabolism, and hypertension. It is a matter of concern as to whether weight loss causes an improvement of the V/S ratio or not in obese children. Changes in body fat distribution during weight loss in 23 obese children were quantified by weight, bioelectrical impedance analysis (BIA) and computed tomography (CT scan of the abdomen). Twenty-three patients were divided into two groups; six were in the inpatient group and 17 were in the outpatient group. Bodyweight, body fat percentage, subcutaneous fat and visceral fat were significantly higher in the inpatient group than in the outpatient group before weight loss. Whereas the V/S ratio was almost equal between the two groups before weight loss. Bodyweight, body fat percentage, subcutaneous fat and visceral fat were found to decrease significantly during weight loss in the two groups. The V/S ratio of the outpatient group did not change after weight loss. In contrast, the V/S ratio of the inpatient group decreased significantly during weight loss. These preliminary findings suggest that a large amount of body fat and a high obesity rate are not always accompanied by a high V/S ratio in obese children. The fat pattern changes during weight loss with strict dietary therapy and therapeutic exercise. A larger sample of obese children should be studied to test this conjecture.     

The interferon-α2b gene in Japanese patients with chronic viral hepatitis who developed antibodies after treatment with recombinant interferon-α2a

DNA was extracted from leucocytes of 23 Japanese patients with chronic viral hepatitis who received treatment with recombinant interferon-alpha 2a (IFN-alpha 2a) and nine healthy controls, as well as eight human cell lines of Caucasian or African origin. A part of the gene encoding IFN-alpha 2 was amplified by polymerase chain reaction and the sequence of nucleotides 1-231 was determined. Interferon-alpha 2a, -alpha 2b and -alpha 2c genes were tested for in five clones each from a patient or control, or a cell line, based on adenine or guanine at nucleotide positions 68 and 101. The IFN-alpha 2b gene was detected in all 160 clones from 23 Japanese patients and nine controls, but the IFN-alpha 2a or -alpha 2c gene was not found in any. Of five cell lines derived from Caucasians, four exhibited only the IFN-alpha 2b gene, while the remaining one exhibited both IFN-alpha 2a and -alpha 2b genes. Of three cell lines derived from Africans, one each showed only the IFN-alpha 2b or -alpha 2c gene, and the remaining one both IFN-alpha 2b and -alpha 2c genes. The 23 patients with the IFN-alpha 2b gene and chronic viral hepatitis included 10 who developed antibodies against IFN after treatment with recombinant IFN-alpha 2a. These results indicated a distinct geographical distribution of the three IFN-alpha 2 genes, and suggested the use of a recombinant IFN-alpha 2 preparation in agreement with the IFN-alpha 2 gene possessed by the recipient to avoid antibody responses.     

In Vitro Biological Activity of an Insulin-like Active Substance Extracted from the Tumor Tissue of a Patient with Primary Liver Cell Carcinoma Associated with Severe Spontaneous Hypoglycemia

Biological activity of an insulin-like active substance, extractedfrom the tissue of a tumor tissue of a patient with primaryliver cell carcinoma associated with severe spontaneous hypoglycemia,was studied in vitro. The substance was acid insoluble. It stimulatedglucose uptake and glucose oxidation by rat muscle and adiposetissue, and these effects were not suppressed by anti-insulinantibody. It stimulated glycogen synthesis in rat muscle tissuebut not in adipose tissue. Oxidation of glucose C-1 by adiposetissue was enhanced strongly by the substance, but it had noeffect on glucose C-6 oxidation. The biological activity ofthe substance resembled that of non-suppressible insulin-likeactivity-precipitated (NSILA-P) rather than that of pancreaticinsulin or nonsuppressible insulin-like activity-soluble (NSILA-S).