Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia

Silent cerebral infarcts and arteriopathy are common and progressive in individuals with sickle cell anemia. However, most data describing brain lesions in sickle cell anemia are cross-sectional or derive from pediatric cohorts with short follow-up. We investigated the progression of silent cerebral infarct and cerebral vessel stenosis on brain MRI and MRA, respectively, by describing the incidence of new or worsening lesions over a period of up to 25 years among young adults with sickle cell anemia and explored risk factors for progression. Forty-four adults with sickle cell anemia (HbSS or HbSβ⁰thalassemia), exposed to chronic transfusions (n = 12) or hydroxyurea (n = 32), median age 19.2 years (range 18.0–31.5), received a screening brain MRI/MRA and their results were compared with a clinical exam performed during childhood and adolescence. We used exact log-rank test to compare MRI and MRA progression among any two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated from Cox regression analyses. Progression of MRI and MRA occurred in 12 (27%) and 4 (9%) young adults, respectively, relative to their pediatric exams. MRI progression risk was high among participants with abnormal pediatric exams (HR: 11.6, 95% CI: 2.5–54.7) and conditional or abnormal transcranial Doppler ultrasound velocities (HR: 3.9, 95% CI: 1.0–15.1). Among individuals treated with hydroxyurea, high fetal hemoglobin measured in childhood was associated with lower hazard of MRI progression (HR: 0.86, 95% CI: 0.76–0.98). MRA progression occurred more frequently among those with prior stroke (HR: 8.6, 95% CI: 1.2–64), abnormal pediatric exam (P = 0.00084), and elevated transcranial Doppler ultrasound velocities (P = 0.004). Brain MRI/MRA imaging in pediatrics can identify high-risk patients for CNS disease progression in young adulthood, prompting consideration for early aggressive treatments.     

Seasonal reproductive cycle of the Galápagos tortoise (Geochelone nigra) in captivity

The reproductive physiology of nine Galápagos tortoises (Geochelone nigra) was studied from February 1988 to May 1989. The study encompassed the annual reproductive cycle to include complete mating and nesting sequences. Male (n = 4) and female (n = 5) seasonal reproductive changes were determined throughout the study with endocrine analysis and ultrasonographic examinations. Males displayed a prenuptial rise in serum testosterone (x― ±SE = 6.62 ± 0.92 ng/ml in August) during which gonadal maturation and spermatogenesis are thought to occur. The male reproductive cycle appears consistent with the prenuptial spermatogenic pattern exhibited by other tropical turtles. In the females, testosterone rose during the mating period (x― ± SE = 499.3 ± 124.6 pg/ml in October) prior to ovulation and is probably related to receptivity in the females. Progesterone was more variable, but also peaked during the mating period (x― ± SE = 1,017.2 ± 220.6 pg/ml in October) and appears related to ovulation. Estradiol rose several months prior to mating (x― ± SE = 75.5 ± 11.9 pg/ml in July) and was correlated with increased serum calcium levels. This increase in estradiol is thought to stimulate vitellogenesis several months prior to mating. Nesting occurred from November 1988 to April 1989, during which six clutches were laid. Clutch size ranged from eight to 17 eggs. Both male and female Galápagos tortoises display seasonal physiological changes that function to regulate annual reproductive patterns. Zoo Biol 17:505–517, 1998. © 1998 Wiley-Liss, Inc.     

Mode matches in hydrophobic free energy eigenfunctions predict peptide–protein interactions

The dominant statistical hydrophobic free energy inverse frequencies, amino acid wavelengths as hydrophobic modes, of neurotensin (NT), cholescystokinin (CCK), the human dopamine D₂ receptor [(DA)D₂], and the human dopamine transporter (DAT) were determined using orthogonal decomposition of the autocovariance matrices of their amino acid sequences as hydrophobic free energy equivalents in kcal/mol. The leading eigenvalues-associated eigenvectors were convolved with the original series to construct eigenfunctions. Eigenfunctions were further analyzed using discrete trigonometric wavelet and all poles, maximum entropy power spectral transformations. This yielded clean representations of the dominant hydrophobic free energy modes, most of which are otherwise lost in the smoothing of hydropathy plots or contaminated by end effects and multimodality in conventional Fourier transformations. Mode matches were found between NT and (DA)D₂ and between CCK and DAT, but not the converse. These mode matches successfully predicted the nonlinear kinetic interactions of NT-(DA)D₂ in contrast with CCK-(DA)D₂ on ³H-spiperone binding to (DA)D₂, and by CCK-DAT but not NT-DAT on [N-methyl-³H]-WIN 35,428 binding to DAT in (DA)D₂ and DAT cDNA stably transfected cell lines without known NT or CCK receptors. Computation of the dominant modes of hydrophobic free energy eigenfunctions may help predict functionally relevant peptide–membrane protein interactions, even across neurotransmitter families. © 1998 John Wiley & Sons, Inc. Biopoly 46: 89–101, 1998     

Sibling competition and the evolution of growth rates in birds

Variation among bird species in growth rates is traditionally attributed to differences in energy availability and developmental mode. However, the extent and form of competition among siblings for limited food resources may also be an important determinant. Kin-selection-based models of intrabrood competition suggest that nestling growth rates should be highest in those species in which siblings are likely to be less genetically related to one another (half-sibs rather than full-sibs). We test this novel prediction using the frequency of multiple paternity as an index of average sib relatedness within broods. As predicted, we find a significant positive association between the rate of multiple paternity within broods and nestling growth rates. Furthermore, this holds true when we control for the effects of variation in other factors that may be associated with variation in growth rate, such as body size, brood size, mating system and the form of parental care. We suggest, therefore, that variation in growth rate among bird species is not simply dependent on proximate ecological and developmental factors but is also strongly influenced by interactions, over an evolutionary time-scale, among kin.     

Acetoin production in growing Leuconostoc mesenteroides

Leuconostoc mesenteroides NCDO 518, provided with oxygen and pyruvate, preferentially used oxygen as accessory electron acceptor and converted pyruvate to acetoin. With glucose, 5.6 mM, as sole energy source only small amounts of acetoin were formed (0.08–0.21 mM). With glucose, 5.6 mM, and pyruvate, 20 mM, substantial amounts of acetoin were produced in growing, aerated cultures at pH 5 (2.8 mM, equivalent to 0.5 mol [mol glucose fermented]^–1). On exhaustion of glucose, growth ceased but metabolism of pyruvate continued with the formation of acetate and a little acetoin. In aerated cultures at pH 6 the general pattern was similar to that at pH 5 but less acetoin (0.6 mM) was formed during the growth phase and, after the exhaustion of glucose, pyruvate was converted very slowly to acetate only. Leuc. mesenteroides did not grow with pyruvate as sole energy source.     

Streptococcus iniae, a bacterial infection in barramundi Lates calcarifer.

The cause of ongoing mortality in barramundi Lates calcarifer (Bloch) in seawater culture was identified as Streptococcus iniae by biochemical and physiological tests. This is the first published record of this bacterial species in Australia and the first confirmed report of S. iniae causing mortality in barramundi. The bacterium was highly pathogenic for barramundi when challenged by bath exposure. The pathogen was found to have a LD50 of 2.5 x 10(5) and 3.2 x 10(4) colony-forming units at 48 h and 10 d respectively. Experimental challenge of barramundi resulted in high levels of mortality (> 40%) within a 48 h period. Ten days after the challenge, S. iniae could not be isolated from kidney, spleen, liver or eye of surviving fish. However, the organism was easily isolated from the brain of both moribund and healthy fish, indicating that barramundi can carry the bacterium asymptomatically.     

EFFECT OF AGING ON FLOWERING OF THE AXILLARY BUDS OF PHARBITIS NIL

In Pharbitis seedlings, aging is associated with definite trends in the pattern of flowering of the axillaries: 1) the locus of maximum flowering is displaced continuously upward, 2) there is a continuous loss of responsiveness to induction from the base of the plant, upward, 3) flowering of the axillaries is suppressed in general when the terminal bud fails to flower, and 4) flowering at the distal nodes regresses when the terminal bud fails to flower. Phenomena 1 and 2 start at the base of the plant and move progressively upward, whereas 3 and 4 are tied to the possibly rhythmic responses of the terminal buds to floral induction, with aging. Buds at axils that form after induction are capable of flowering. Buds at nodes that flower maximally range in development from those not visible with a stereomicroscope to those with enlarging apices ready to form the first leaf primordia at the time of induction. Axillaries that have formed leaf primordia fail to flower in response to one inductive night.     

Suppressor T cells, distinct from "veto cells," are induced by alloantigen priming and mediate transferable suppression of cytotoxic T lymphocyte responses in vivo

Primary and secondary cytotoxic T lymphocyte responses to minor alloantigens can be suppressed by priming host mice with a high dose (10(8) cells) of alloantigenic donor spleen cells (SC). Such suppression is antigen specific and transferable into secondary hosts with T cells. One interpretation of this is that antigen-specific host suppressor T cells (Ts) are activated. Alternatively, donor Lyt-2+ T cells, introduced in the priming inoculum, may inactivate host CTL precursors (CTLp) that recognize the priming (donor) alloantigens. Donor cells that act in this way are termed veto T cells. The experiments described here exclude veto T cell participation in transferable alloantigen-specific suppression, and demonstrate the operation of an alloantigen-specific host-derived T suppressor (Ts) cell. The origin of the Ts has been studied directly by using Thy-1-disparate BALB/c mice. The cell responsible for the transfer of suppression of a secondary CTL response to B10 minors was of the host Thy-1 allotype, and so originated in the host spleen and was not introduced in the priming inoculum. Secondly, antigen-specific Ts generated in CBA female mice against B10 minors could act on CTL responses to an unequivocally non-cross-reactive-third party antigen (H-Y), provided the two antigens were expressed on the same cell membrane. Such third-party suppression is incompatible with the operation of veto T cells. Depletion of Thy-1.2+ or Lyt-2+ cells from the suppression-inducing donor SC inoculum did not abrogate suppression induction in BALB/c mice; instead, suppression was enhanced. The demonstration of veto cell activity in similarly primed mice by other groups of investigators indicates that both types of suppression may operate. However, our results show that only antigen-specific Ts can mediate the transferable suppression of CTL responses to alloantigens.     

Thylakoid polypeptide composition and light-independent phosphorylation of the chlorophyll a,b-protein in Prochloron, a prokaryote exhibiting oxygenic photosynthesis

Thylakoids of the prokaryote Prochloron, present as a symbiont in ascidians isolated from the Red Sea at Eilat (Israel), showed polypeptide electrophoretic patterns comparable to those of thylakoids from eukaryotic oxygen-evolving organisms. Low temperature, fluorescence spectroscopy of Prochloron, having a chlorophyll a/b ratio of 3.8–5, and frozen in situ, demonstrated the presence of Photosystem II chlorophyll-protein complex emitting at 686 and 696 nm, as well as the emission band of Photosystem I at 720 nm which was so far not observed in Prochloron species. The latter emission was absent, if the cells or thylakoids were isolated prior to freezing. Energy transfer from chlorophyll b to chlorophyll a could be demonstrated to occur in vivo. The chlorophyll a,b-protein complex of Photosystem II, isolated by non-denaturing polyacrylamide gel electrophoresis, contained one major polypeptide of 34 kDa. The polypeptide was phosphorylated in vitro by a membrane-bound protein kinase which was not stimulated by light. A light-independent protein kinase activity was also found in isolated thylakoids of another prokaryote, the cyanophyte Fremyella diplosiphon. State I–State II transition could not be demonstrated in Prochloron by measurements of modulated fluorescence intensity in situ. We suggest that the presence of a light-independent thylakoid protein kinase of Prochloron, collected in the Red Sea at not less than 30 m depth, might be the result of an evolutionary process whereby this organism has adapted to an environment in which light, absorbed preferentially by Photosystem II, prevails.     

Expression of smooth muscle-specific alpha-isoactin in cultured vascular smooth muscle cells: relationship between growth and cytodifferentiation

The relationship between growth and cytodifferentiation was studied in cultured rat aortic smooth muscle cells (SMCs) using expression of the smooth muscle (SM)-specific isoactins (Vanderkerckhove, J., and K. Weber, 1979, Differentiation, 14:123-133) as a marker for differentiation in these cells. Isoactin expression was evaluated by: (a) measurements of fractional isoactin content and synthesis ([35S]methionine incorporation) by densitometric evaluation of two-dimensional isoelectric focusing sodium dodecyl sulfate gels, and (b) immunocytological examination using SM-specific isoactin antibodies. Results showed the following: (a) Loss of alpha-SM isoactin was not a prerequisite for initiation of cellular proliferation in primary cultures of rat aortic SMCs. (b) alpha-SM isoactin synthesis and content were low in subconfluent log phase growth cells but increased nearly threefold in density-arrested postconfluent cells. Conversely, beta-nonmuscle actin synthesis and content were higher in rapidly dividing subconfluent cultures than in quiescent postconfluent cultures. These changes were observed in primary and subpassaged cultures. (c) alpha-SM actin synthesis was increased by growth arrest of sparse cultures in serum-free medium (SFM; Libby, P., and K. V. O'Brien, 1983, J. Cell. Physiol., 115:217-223) but reached levels equivalent to density-arrested cells only after extended periods in SFM (i.e., greater than 5 d). (d) SFM did not further augment alpha-SM actin synthesis in postconfluent SMC cultures. (e) Serum stimulation of cells that had been growth-arrested in SFM resulted in a dramatic decrease in alpha-SM actin synthesis that preceded the onset of cellular proliferation. These findings demonstrate that cultured vascular SMCs undergo differential expression of isoactins in relation to their growth state and indicate that growth arrest promotes cytodifferentiation in these cells.