Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin.

Podocalyxin is a CD34-related sialomucin that is expressed at high levels by podocytes, and also by mesothelial cells, vascular endothelia, platelets, and hematopoietic stem cells. To elucidate the function of podocalyxin, we generated podocalyxin-deficient (podxl(-/)-) mice by homologous recombination. Null mice exhibit profound defects in kidney development and die within 24 hours of birth with anuric renal failure. Although podocytes are present in the glomeruli of the podxl(-/)- mice, they fail to form foot processes and slit diaphragms and instead exhibit cell--cell junctional complexes (tight and adherens junctions). The corresponding reduction in permeable, glomerular filtration surface area presumably leads to the observed block in urine production. In addition, podxl(-/)- mice frequently display herniation of the gut (omphalocele), suggesting that podocalyxin may be required for retraction of the gut from the umbilical cord during development. Hematopoietic and vascular endothelial cells develop normally in the podocalyxin-deficient mice, possibly through functional compensation by other sialomucins (such as CD34). Our results provide the first example of an essential role for a sialomucin in development and suggest that defects in podocalyxin could play a role in podocyte dysfunction in renal failure and omphalocele in humans.

[Prevention of urinary calculi with thiazides and allopurinol. A long-term study]. / Harnsteinprophylaxe mit Thiaziden und Allopurinol. Eine Langzeitstudie.

In 30 cases of recurring urinary calcium oxalate and calcium phosphate calculi, renal or absorptive hypercalciuria or hyperuricemia, long term controls of serum and urine electrolytes were made under hydrochlorothiazide and allopurinol therapy. By differentiating the type of hypercalciuria it could be determined, if thiazide-therapy is indicated in renal hypercalciuria only or in the absorptive cases as well. Statistic comparison of the patients with - and without increased urinary sodium excretion solved the question whether high sodium excretion diminishes or abolishes the hypocalciuric thiazide effect. The frequency of stones before and after treatment supports the efficacy of thiazide prophylaxis.

A study of the polymorphism and ethnic distribution differences of human serum paraoxonase.

The enzyme serum paraoxonase shows a polymorphism in Europeans which is governed by two alleles. The first allele has a gene frequency plow of 0.716-0.777, and is manifested as a low activity group in homozygotes. More than 50% of all European test subjects can be included in this group. A second allele with a gene frequency qhigh of 0.223-0.284 was found in typical European distributions and is manifested in both the form of a second heterozygotic and a third homozygotic group with high activities. The Hardy-Weinberg rule for a two-allele model is valid for the distribution. The gene frequency plow of the first allele decreases as one moves from Europe in the direction of Africa and Asia. In typical Mongoloid and Negroid collectives, less than 10% of the population can be included in the low-activity group, a group which is not even demonstrable in the Aborigines of Australia. The serum paraoxonase of the Aborigine population shows unimodal distribution. The validity of the Hardy-Weinberg rule for a three-allele model must be rejected in all examined collectives. Human serum paraoxonase shows neither age-related changes in activity nor sex-dependent activity differences.

[Sedentary occupation and recto-sigmoidal neoplasms]. / Sitzende Tätigkeit und Rektum-Sigma-Karzinom.

The aim of this study was to determine whether there is a relationship between sedentary occupation and the occurrence of rectal and sigmoid cancer. 105 patients with histologically proven rectal cancer were questioned. 55 patients with gastric carcinoma and 99 patients with cholelithiasis served as control groups. The percentage of patients with a sedentary occupation is significantly higher in the group with rectal cancer. In addition, the mean duration of the sedentary occupation is also longer. A direct relationship between the sedentary occupation and the tumor stage is obvious. It is concluded that a sedentary occupation-which leads to changes in the motility of the large bowel-had to be considered a risk factor in the occurence of rectal and sigmoid cancer.