Hypertension from compression and/or enucleation of the adrenal glands in the rat.

Previos studies have shown that compression of the adrenal glands is as effective as adrenal enucleation in causing hypertension in rats. Unilateral adrenal enucleation is ineffective, however, if a normal contralateral adrenal gland is present. The studies reported herein demonstrate that unilateral compression also fails to cause hypertension in the presence of a normal contralateral gland. When present singly, either enucleate or compressed adrenals cause hypertension; when either is present with a normal contralateral gland, the blood pressure is unaffected. When compressed or enucleate glands constitute the pair, in any combination, hypertension ensues. However, whereas an enucleate gland remains extremely atrophic in the presence of a normal gland, compressed glands attain a much larger size under this circumstance. Furthermore, a compressed gland is less inhibitory to the regeneration of a contralateral enucleate gland than is a normal adrenal. Whereas enucleate glands, whether bilateral or unilateral, are always smaller than normal glands, compressed adrenals may be enlarged. The hypertensogenic function of compressed adrenals is, like that of enucleate glands, suppressed by the presence of a normal gland. The growth response of compressed or enucleate glands, whether bilateral or single, appears to depend upon the degree of injury inflicted upon them. There is a considerable discrepancy in the size of individual members of a pair when one or both have been injured, that members of a normal pair do not exhibit.     

Enzymological properties and immunological characterization of alpha-galactosidase isoenzymes from normal and Fabry human liver.

1. A method is described for the rapid isolation of alpha-galactosidases A and B (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) from normal human liver. 2. When the same method is applied to Fabry liver, most of the alpha-galactosidase activity is recovered in the fraction corresponding to normal alpha-galactosidase B. In agreement with Romeo, G., D'Urso, M., Pisacane, A., Blum, E., De Falco, A. and Ruffilli, A. (1975) Biochem. Genet. 13, 615-628) [18], a small amount of alpha-galactosidase activity is found in the fraction corresponding to normal alpha-galactosidase A. 3. The kinetic properties of the B-like activity from Fabry liver are similar to those of normal alpha-galactosidase B. In agreement with Romeo et al. [18], it was found that the kinetic properties of the A-like activity from Fabry liver are similar to those of normal alpha-galactosidase A. 4. Using antisera raised against normal alpha-galactosidase A and normal alpha-galactosidase B, it is shown that the normal alpha-galactosidase isoenzymes are immunologically distinct and that the B-like activity from Fabry liver is immunologically related to normal alpha-galactosidase B. Furthermore, the A-like activity from Fabry liver is immunologically related to normal alpha-galactosidase B and not to normal alpha-galactosidase A. 5. Normal alpha-galactosidase B is converted into an A-like form during storage. 6. It is concluded that the B-like alpha-galactosidase in Fabry tissues is identical to normal alpha-galactosidase B, and that the small amount of A-like activity found in Fabry material is due to a modified form of alpha-galactosidase B.     

Characterization of two new electrophoretic variants of human triosephosphate isomerase: Stability,kinetic, and immunological properties

Two new electrophoretic variants of human triosephosphate isomerase (TPI) have been partially purified and characterized. The TPI Manchester variant, a cathodally migrating electrophoretic allozyme identified in an individual with the phenotype TPI 1-Manchester, is associated with a normal level of enzyme activity in erythrocytes and normal kinetic properties. It is very thermolabile at 55 and 57° C, although it is not uniquely sensitive to either guanidine-HCl or urea denaturation. The TPI Hiroshima-2 variant is an anodally migrating allozyme (the phenotype of proband is TPI 1-Hiroshima-2) with normal activity and kinetic properties and also normal stability characteristics. It is inactivated less by antisera raised against normal human TPI than either the normal or the Manchester allozyme. Dissociation-reassociation experiments utilizing these allozymes have confirmed that normal human red blood cell TPI isozymes are produced by a sequence of reactions (presumably deamidations) involving alternating subunits.Financial support was derived from Contract EY-77-C-02-2828 from the Department of Energy.     

Antithrombin III Padua: a "new" congenital antithrombin III abnormality with normal or near normal activity, normal antigen, abnormal migration and no thrombotic disease

A "new" antithrombin III abnormality is described in four members of a family. The proposita is a 38 years old female who showed no thrombotic disease and the following laboratory pattern: normal routine clotting tests, normal or near normal AT III activity (chromogenic substrates S-2238 and Chromozym Th) both in plasma and in serum and in the presence or absence of heparin, slightly decreased antifactor Xa activity (chromogenic substrate S-2222), normal progressive antithrombin, normal AT III antigen but abnormal migration in the agarose-heparin bidimensional system. In the latter test, one major abnormal peak, less anodal than the normal counterpart, and a smaller, apparently normal peak, were seen. In agarose without heparin the pattern was similar to normal both in plasma and in serum. Heparin tolerance to heparin in vivo and in vitro was slightly increased but still within normal limits. The two sons and a paternal aunt showed the same pattern. The hereditary pattern seems therefore autosomal dominant. The abnormality described appears different from AT III Budapest. The toponym of antithrombin III Padua is proposed to define this peculiar abnormality.     

The increase in aneuploidy of embryos Is associated with pathological morphology of the sperm

Chromosomes of embryos of couples with reduced number of morphologically normal sperm cells (less than 4%) and couples with a normal level of morphologically normal sperm cells (over 4%) has revealed significant differences. In the group with a low level of normal spermatozoa, the frequency of embryos with normal chromosomes is significantly reduced and incidence of sex chromosome trisomies and autosomal monosomies and trisomies is increased; a tendency to decrease has been found for the frequency of male embryos. The obtained data may be useful to establish additional criteria for preimplantation genetic screening in the case of male infertility.     

Selective control of human glioma cell proliferation by specific cell interaction

Cells cultured from anaplastic astrocytoma (Kernohan and Sayre, grades III and IV) will proliferate on confluent monolayers of normal glia, while cells cultured from normal brain will not. The growth of a cell line containing a high proportion of well-differentiated glioma cells (G-CCM) was partially inhibited, though not as much as normal glia, while the growth of a cell line made up of less differentiated cells (G-UVW) was enhanced by the normal glia. Although non-glial confluent monolayers also inhibited the growth of normal glia, this was less specific, as one normal glial line (N-DUT) grew on fibroblasts and intestinal epithelium, although it was unable to do so on normal glia. It is suggested that this may be a useful method for examining reduced density limitation of growth, discriminating between normal and malignant glia, and for separating glioma cells from contaminating normal cells.     

DOES A NORMAL FOETUS REALLY HAVE A FUTURE OF VALUE? A REPLY TO MARQUIS

The traditional approach to the abortion debate revolves around numerous issues, such as whether the foetus is a person, whether the foetus has rights, and more. Don Marquis suggests that this traditional approach leads to a standoff and that the abortion debate 'requires a different strategy.' Hence his 'future of value' strategy, which is summarized as follows: (1) A normal foetus has a future of value. (2) Depriving a normal foetus of a future of value imposes a misfortune on it. (3) Imposing a misfortune on a normal foetus is prima facie wrong. (4) Therefore, depriving a normal foetus of a future of value is prima facie wrong. (5) Killing a normal foetus deprives it of a future value. (6) Therefore, killing a normal foetus is prima facie wrong. In this paper, I argue that Marquis's strategy is not different since it involves the concept of person--a concept deeply rooted in the traditional approach. Specifically, I argue that futures are valuable insofar as they are not only dominated by goods of consciousness, but are experienced by psychologically continuous persons. Moreover, I argue that his strategy is not sound since premise (1) is false. Specifically, I argue that a normal foetus, at least during the first trimester, is not a person. Thus, during that stage of development it is not capable of experiencing its future as a psychologically continuous person and, hence, it does not have a future of value.     

Two spatio-temporal filters in human vision

We have used the psychophysical methods described in the first paper of this series (Holliday and Ruddock, 1983) to determine selected spatial and temporal response characteristics of the ST1 and ST2 filters for subjects suffering visual defects. Data are given for 19 amblyopes, an albino and a hemianope, and comparison data are also given for a number of subjects with normal vision. The ST1 spatial responses for both the "normal" and "amblyopic" eyes of 12 convergent strabismic amblyopes are displaced to low spatial frequencies compared to the normal curve, which implies that there is a loss of fine spatial tuning. In all but one subject, the curve for the "amblyopic" eye peaks at a spatial frequency lower than that for the "normal" eye, thus the former deviates further from the normal pattern than the latter. The ST1 spatial responses of 6 refractive amblyopes are also displaced to the low frequency side of the normal curve, although on average the shift is smaller than in the case of the strabismic amblyopes. For each subject, the response curve of the "amblyopic" eye peaks at a lower spatial frequency than does that for the "normal" eye. ST1 spatial responses were measured for targets located up to 30 degrees off-axis along the horizontal meridian and sample data are given for one strabismic and one refractive amblyope and for two normal subjects. It is concluded from these data that the changes in the spatial responses associated with amblyopia do not simply reflect eccentric fixation of the target. The ST2 spatial response was measured for the "normal" and "amblyopic" eyes of 9 amblyopes (7 strabismic and 2 refractive). There is no significant difference between the average amblyopic response and that of normal subjects, and only in one case does the response for an "amblyopic" eye peak at a frequency lower than the peak frequency for normal vision. The ST2 temporal response for 9 amblyopes shows no systematic deviations from the normal response. For the albino, both the ST1 and ST2 spatial responses peak at around 0.3 cycles deg-1, and both curves are displaced considerably to the low spatial frequency side of the normal ST2 spatial response. The albino's ST2 temporal response is essentially normal. Measurements for the hemianope's "blind" hemifield under conditions appropriate to the isolation of the ST1 and ST2 spatial responses reveal no tuning curves. The ST2 temporal response for the "blind" hemifield, however, is of large amplitude, with a peak at 2 Hz, well below the normal frequency response peak. It is argued that the loss of fine spatial tuning which occurs in the ST1, but not the ST2, spatial responses of the amblyopes is consistent with the sequential organisation of these two filter classes proposed by Holliday and Ruddock (1983). Further, for the only two subjects whose ST2 spatial response curves are displaced to abnormally low frequencies (the albino and a strabismic amblyope) the ST1 spatial response is shifted to low spatial frequencies compared to the normal ST2 curve...     

COMPARATIVE STUDIES ON RESPIRATION : XI. THE EFFECT OF HYDROGEN ION CONCENTRATION ON THE RESPIRATION OF PENICILLIUM CHRYSOGENUM.

1. Variations in pH value between 4 and 8 produce practically no effect on the normal rate of respiration (the rate at neutrality is called normal). 2. Increasing the pH value to 8.80 causes respiration to fall to 60 per cent of the normal, after which it remains stationary for the duration of the experiment. 3. Decreasing the pH value to 2.65 causes a gradual rise and a gradual return to normal; at pH 1.10 to 1.95 the preliminary rise amounts to 20 per cent and is followed by a fall to below the normal. 4. The decrease in respiration brought about by solutions of a pH value of 1.95 or less are irreversible, while a similar decrease which occurs at pH 8.80 is reversible, the rate coming back to practically normal after the material is replaced in a neutral solution. 5. Determinations by means of Winkler''s method showed an increase in the consumption of oxygen in acid solutions and a decrease in alkaline solutions.     

Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia

Familial hypoalphalipoproteinemia (hypoalpha), characterized by a decreased high density lipoprotein level, is associated with an increased incidence of premature cardiovascular disease. Restriction fragment length polymorphism analysis of genomic DNA has detected a polymorphism for the PstI restriction endonuclease near the apoA-I gene, with either a 2.2 or a 3.3 kb fragment. The latter has been previously found to occur with significantly higher frequency in probands of families with familial hypoalpha. ApoA-I was isolated from three unrelated subjects with familial hypoalpha and the 3.3 kb PstI polymorphism of the apoA-I gene, and from normal control subjects. The apoA-I from the hypoalpha subjects was structurally normal as determined by amino acid analysis and by two-dimensional gel electrophoresis. When normal apoA-I and hypoalpha apoA-I were simultaneously injected into either normal controls or hypoalpha subjects, both forms of apoA-I were catabolized at the same rate in the same subject, indicating that the hypoalpha apoA-I is also metabolically normal. Analysis of the kinetics of metabolism of apoA-I in the hypoalpha subjects, compared to the normal controls, revealed that the reduced plasma levels of apoA-I were due to an increased apoA-I fractional catabolic rate, and that the synthetic rate was normal. Based on these results, we conclude that the apoA-I gene in these hypoalpha subjects is normal, and the PstI polymorphism near the apoA-I gene, which is associated with familial hypoalpha, is likely to be a marker for a mutant gene closely linked to, but not in, the apoA-I gene.     

Abnormal low density lipoprotein metabolism in apolipoprotein E deficiency

Apolipoprotein(apo) E deficiency is an inherited disease characterized by type III hyperlipoproteinemia and less than 1% normal plasma apoE concentration. The role of apoE in LDL metabolism was investigated by quantitating the metabolism of radiolabeled normal and apoE-deficient LDL in both normal and apoE-deficient subjects. ApoE deficiency resulted in an accumulation of plasma IDL, and a decreased synthesis of LDL consistent with a block in the conversion of IDL to LDL. The LDL isolated from the apoE-deficient patient was similar to normal LDL in hydrated density, size, and composition. However, the apoE-deficient LDL was kinetically abnormal with delayed catabolism in both normal subjects and the apoE-deficient patient. In addition, the catabolism of normal LDL in the apoE-deficient subject was increased. These results were interpreted as indicating that apoE is necessary for the conversion of IDL to LDL and the formation of kinetically normal LDL. The rapid catabolism of normal LDL in the apoE-deficient patient suggests an up-regulation of the hepatic LDL receptor pathway. Based on these results, apoE is proposed to play an important role in the conversion of IDL to LDL, the formation of kinetically normal LDL, and the regulation of LDL receptor function.     

The effect of extracellular matrix interactions on morphologic transformation in vitro

There is emerging evidence that the structure and function of a cell is dependent in part on the contacts that cells make with the extracellular matrix. We report here the effect of extracellular matrices secreted from both normal and tumor cells have on the structure of normal rat kidney epithelial cells. Normal rat kidney cells plated on the basement membrane secreted by tumor cells adopt a morphology and phenotype which closely resembles a Kirsten-ras transformed normal rat kidney cell. This morphologic transformation was not observed for cells plated on individual extracellular matrix components or on basement membrane secreted by normal placenta cells. This suggests that tumor derived basement membrane has unique characteristics which may cause morphologic transformation of normal rat kidney cells.     

Phospholipid composition and turnover in normal and SV40 transformed fibroblasts. Effect of cell density]

The phospholipid composition and turnover in normal and in SV 40 transformed hamster fibroblasts were studied. The amount of phospholipid phosphorus relative to protein is lower in transformed hamster fibroblasts than in normal fibroblasts. This amount decreases with increasing cell density until stationary growth is reached. The decrease is largest for the normal fibroblasts. In transformed cells, less sphingomyelin and more diphosphatidyl glycerol are found than in normal cells. The turnover of 32P in sphingomyelin is slower in transformed cells than in normal cells ; the contrary is observed with diphosphatidyl glycerol. On the other hand, in transformed cells, phosphatidyl ethanolamine has a faster turnover than phosphatidyl choline, whereas the contrary is observed in normal cells. Finally, the change to stationary growth slows down the turnover of 32P of all phospholipids, this decrease being more important in transformed cells.     

Derivation of the shrinkage estimates of quantitative trait locus effects

The shrinkage estimate of a quantitative trait locus (QTL) effect is the posterior mean of the QTL effect when a normal prior distribution is assigned to the QTL. This note gives the derivation of the shrinkage estimate under the multivariate linear model. An important lemma regarding the posterior mean of a normal likelihood combined with a normal prior is introduced. The lemma is then used to derive the Bayesian shrinkage estimates of the QTL effects.     

Polyamines--sickling red blood cell interaction.

The binding of polyamine as a function of concentration to normal and sickling rcc'. blood cells is analyzed by Langmuir type binding isotherms, based on the Gouy-Chapman model for an electrical double Iayer, where the zeta potential is a function of only the normal distance coordinate. For normal erythrocytes, the apparent exotropic binding constants are found to be 103, 110, and 130 dl/g at normal distance coordinates of 4, 5, and 6 Å, iezpectively. The esotropic binding constant is determined to be 420 dl/g at a distance of 7 Å. For sickling red blood cells, the apparent exotropic binding constants are 3.3, 3.8, 4.6, and 6-7 dl/g at a distance of 4 to 7 Å. The esotropic binding constant at a distance of 8 Å is found to be 12-9 dl/g. The apparent binding affinity of polyamines to the normal red blood cell. therefore, is approximately 30 times greater than to the sickling erythrocyte.The Praxis pulse nuclear magnetic resonance spectrometer is used to determine the spin-lattice relaxation time (T₁) for water in the presence of normal and sickling red blood cells. The spin-lattice relaxation time is found to be 540 ms for normal erythrocytes and 445 ms for sickling red blood cells in the oxy state. Differences in the spin-spin relaxation time (T₂) for the two types of erythrocyte are negligible, being within the range of normal experimental error.     

Transformations of osteoclast phenotype in ia rats cured of congenital osteopetrosis

The reduced bone resorption characteristic of osteopetrosis is accompanied in the incisors-absent (ia) rat mutation by a significant increase in osteoclasts of inactive (mutant) phenotype. Restoration of bone resorption in ia rats by transfer of spleen cells from normal littermates is preceded by a transformation of osteoclasts from mutant to normal phenotype. In this investigation the proportions of osteoclasts of normal phenotype have been determined by light microscopy in untreated ia and normal rats and in ia rats treated with various cell populations from normal rats. Significant increases in numbers of osteoclasts of normal phenotype were seen in the mutant skeleton soon after cell treatments that eventually restored bone resorption and cured the disease. No changes in osteoclast phenotype were seen after cell transfers that did not cure the disease. These data establish transformation of osteoclast phenotype as an early event in the recovery from osteopetrosis and suggest that determination of osteoclast phenotype is a reliable predictor of the success of normal cell populations to restore bone resorption in this mutation.     

Is intrauterine growth retardation with normal umbilical artery blood flow a benign condition?

OBJECTIVE--To determine whether intrauterine growth retardation associated with normal umbilical artery blood flow is a benign condition. DESIGN--A prospective comparative study of growth retarded fetuses with normal and abnormal umbilical artery blood flow. SETTING--The fetal assessment clinic of a large maternity hospital in Ireland. PATIENTS--179 Women with singleton pregnancies in which the fetal abdominal circumference, measured by ultrasonography, was below the fifth centile for gestation. MAIN OUTCOME MEASURES--Perinatal deaths, fetal distress requiring caesarean section, preterm delivery, cerebral irritation. RESULTS--Of 124 fetuses with normal flow, all physically normal fetuses survived but one baby had cerebral irritation; there were six preterm deliveries and four caesarean sections for fetal distress. Among 55 women with abnormal flow there were two midtrimester abortions, three perinatal deaths, and one case of cerebral irritation in physically normal fetuses. CONCLUSIONS--Intrauterine growth retardation associated with normal umbilical blood flow is a different entity from that associated with abnormal flow, normal flow being largely benign and abnormal flow carrying a serious risk of adverse outcome.