We report the inactivation, via homologous recombination, of two of the three active mouse alkaline phosphatase genes, i.e., embryonic (EAP) and tissue nonspecific (TNAP). Whereas expression of the EAP isozyme was abolished in all tissues that express EAP developmentally (such as the preimplantation embryo, thymus, and testis), the EAP knock‐out mice show no obvious phenotypic abnormalities. They reproduce normally and give birth to live offspring, indicating the nonessential role of EAP during embryonic development. Mice deficient in the TNAP gene mimic a severe form of hypophosphatasia. These TNAP −/− mice are growth impaired, develop epileptic seizures and apnea, and die before weaning. Examination of the tissues indicates abnormal bone mineralization and morphological changes in the osteoblasts, aberrant development of the lumbar nerve roots, disturbances in intestinal physiology, increased apoptosis in the thymus, and abnormal spleens. Our results indicate that, in the mouse, TNAP appears not to be essential for the initial events leading to bone mineral deposition but that TNAP seems to play a role in the maintenance of this process after birth. The other phenotypic manifestations may be a consequence of the lack of TNAP in the developing neural tube between stages E8.5 and E13.5 of embryogenesis. We hypothesize that the autonomic nervous system is compromised in these TNAP −/− mice. Dev. Dyn. 208:432–446, 1997. © 1997 Wiley‐Liss, Inc.

A dramatic change in growth hormone secretion was demonstrated during the 3rd trimester of human pregnancy, when compared with the non-pregnant state. The pulsatile pattern, with intermittent high peaks, and low or undetectable levels between peaks, characteristic of normal men and non-pregnant women, was completely abolished. All the 10 pregnant women investigated had the same stable basal circulating growth hormone concentration. Values were in the range 6-10 mU/l and there was no evidence of pulsatile activity. Previously, in animal experiments, a continuous secretion of growth hormone has been shown to 'feminize' hepatic steroid metabolism, hepatic prolactin receptors, hepatic sulphatase activity and to stimulate pregnancy protein synthesis. The same biological principle could be valid also during human pregnancy and be related to maternal metabolic adjustment.

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Haptoglobin groups were investigated in 309 patients with primary lung cancer divided by sex, smoking habits and tumor type. Patients with squamous epithelial cancer and oat-cell cancer showed no significant difference from normal controls. Among patients with pulmonary adenocarcinoma the frequency of the Hp 2–2 type was significantly (p < 0.05) lower compared to the controls, with a corresponding increase of the Hp 1–1 and Hp 2–1 types. This difference was more pronounced (p < 0.025) among females with pulmonary adenocarcinoma.