Blood carbonic anhydrase activity in anemia,with a note on polycythemia vera

Measurements of blood carbonic anhydrase activity were made in patients witha variety of blood dyscrasias, using a new method. In patients with anemia dueto loss of blood, infection and uremia, and in most of those with anemia associatedwith liver disease and leukemia, a constant relation was found between bloodcarbonic anhydrase activity and the hematocrit; the same holds in polycythemiavera. In patients with pernicious anemia, and in some with "refractory" anemia,and anemias associated with hepatic disease and with myelogenous leukemia,blood carbonic anhydrase activity was in or near the normal range in spite oflowered hematocrit values. The possible relation between these differencesamong anemias and the tolerance of patients with various anemias to exercise isdiscussed.

     

Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease

The genetic defect in the p67phox-deficient form of chronic granulomatous disease (CGD) follows an autosomal recessive pattern of inheritance. When genomic DNA from normal individuals is digested with HindIII and probed with p67phox cDNA an allelic restriction fragment length polymorphism (RFLP) of 4.0 kb or 2.3 kb is detected. We cloned and characterized the p67phox gene using the cDNA and sequenced the exon/intron boundaries, mapping 16 exons on the 40-kb gene. The polymorphic region was then sequenced to identify the inheritance pattern of amniocentesis-derived fetal cells by genomic amplification. The proband, a 9-year-old female patient with p67phox-deficient CGD, and her phenotypically normal mother are homozygous for the RFLP marker, whereas the father and two brothers are heterozygous. The fetus was shown to be heterozygous as well, showing it had inherited at least one normal p67phox gene from the father and that it was predicted to have a normal phenotype. Cord blood samples at birth showed normal oxidative function. Amplification allows rapid detection of the inheritance pattern for fetal diagnosis in informative families. We report the genomic structure of p67phox and an amplification-based method for detection of the marker on chromosome 1q25, used here for prenatal diagnosis of CGD.     

Olfactory Mucosal Lesions in F344 Rats Following Inhalation Exposure to Pyridine at Threshold Limit Value Concentrations

Pyridine is a volatile solvent used as an intermediate in theproduction of insecticides, herbicides, pharmaceuticals, anddyes. Pyridine is also found in tobacco smoke. Because inhalationis a primary route of exposure to pyridine, we examined theeffect of inhaled pyridine on morphology at the portal of entry,the nose. Nasal tissues from F344/N rats exposed using a noseonlymode 6 hr/day for 4 days to either filtered air (controls) orone of two concentrations of pyridine vapor were examined histologically.The rats had been killed 18 hr after the last exposure. Thetwo pyridine concentrations were the current threshold limitvalue (TLV, 5 ppm) and a high concentration (444 ppm). Olfactoryepithelial lesions in rats exposed to both concentrations ofpyridine included vacuolar degeneration of sustentacular cells;focal, marked attenuation of the epithelium; loss of vacuolardegeneration of sustentacular cells; focal, marked attenuationof the epithelium; loss of neurons; and the presence of intraepithelialluminal structures. The lesions were only slightly more severein the rats exposed to 444 ppm compared to those rats exposedto 5 ppm pyridine. The results show that inhalation of pyridineat the current TLV concentration of 5 or 444 ppm causes lesionsin the olfactory epithelium of rats.     

Nitrous oxide in early human pregnancy

An analysis of the outcome of 375 cases (383 fetuses) of cervical cerclage and 58 other operations (59 fetuses) conducted under general anaesthesia, which included the administration of nitrous oxide, failed to reveal a single instance of which nitrous oxide could have been clearly indicted as a cause of fetal abnormality The incidence of inevitable abortion and of low birth weight babies in the series of cervical cerclage conducted under general anaesthesia was identical to that in a series conducted under regional analgesia (115 fetuses). This represents the first of a two-part test of the proposition that nitrous oxide should not be administered to women in the first or second trimester. Our interim conclusion is that the proposition is unacceptable.     

Growth and Differentiation of Transplanted W/Wv Marrow

This paper reports new data on the effect of the action of the mutant genesW and W^v on murine hemopoiesis. Our studies demonstrate that the presenceof these mutant genes produces: (1) a macrocytic anemia with neithergranulocytopenia nor thrombocytopenia; (2) a severe defect in the earlystages of hemopoietic repopulation manifested by (a) an apparent block inthe differentiation of immature cells into erythroid precursors, and (b) a greatly reduced rate of proliferation of differentiated hemopoietic elements.

These data demonstrate the existence of genetic influence on repopulationand differentiation of transplanted marrow and suggest that severe anemia mayresult not only from defects in the late stages of erythroid development butalso from abnormalities in the early stages of erythroid maturation andhemopoietic repopulation.

Submitted on February 15, 1967 Accepted on May 5, 1967     

In vivo behavior of human radioiodinated antithrombin III: distribution among three physiologic pools

It has recently been shown that antithrombin III (AT) distributes between plasma, a noncirculating vascular-associated pool and an extravascular pool in rabbit. Study of the in vivo behavior of autologous human 131I-AT demonstrates that in humans AT also distributes among three pools that are analogous to those found in rabbit. From the in vivo kinetic behavior of the 131I-labeled AT, the fractions of total-body AT in the plasma, noncirculating vascular- associated, and extravascular pools were calculated to be 0.393 +/- 0.015, 0.109 +/- 0.016, and 0.496 +/- 0.014, respectively. From three- exponential plasma radioactivity disappearance curves, an average plasma fractional catabolic rate, j3, of 0.576 +/- 0.034 day-1 was obtained for five healthy young men. This is almost identical to the result obtained if plasma 131I-AT disappearance is assumed to fit a two- exponential curve (0.546 +/- 0.038), where the constant C2 from *Ap(t) = C1e-a1t + C2e-a2t is assumed to be equal to 1 - C1. The fraction of the total vascular AT catabolized daily, j3.5, was calculated to be 0.457 +/- 0.034, and the fractional catabolic rate of total-body AT, jT, averaged 0.2271 +/- 0.0176. The results give further support to a model of in vivo behavior in which the vascular AT distributes between plasma and an endothelial receptor. Thus, the latter may serve to mediate activation of AT for its reaction with coagulation proteases and to mediate its entrance into the endothelial cell, where it is either transported to the extravascular fluids or is catabolized.