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Biomedical subjects

A Davidson

Publications and source records attributed to A Davidson.

At least 145 records · Page 8Linked to original sources

Absence of direct effect of beta-endorphin and calcitonin on human sperm motility.

Beta-endorphin and calcitonin are found in the male reproductive tract. To elucidate the role of these hormones in reproduction, we studied their effect on sperm motility in vitro. Eight semen specimens were obtained from healthy donors, washed, and incubated with different concentrations of human beta-endorphin and human calcitonin. After 30 min of incubation, percentage of motile sperm (% motility), mean progressive velocity (MPV), and lateral head displacement (LHD) were assessed by a computerized semen analyzer. There were no significant differences in any of the sperm motility parameters between control and treated sperm. There was also no correlation between the concentration of beta-endorphin or calcitonin and any sperm motility parameters. It would appear that beta-endorphin and calcitonin may not directly affect sperm motility parameters in vitro.

Calcitonin↗

A cross-reactive idiotype on anti-DNA antibodies defines a H chain determinant present almost exclusively on IgG antibodies.

We have previously reported two anti-idiotypic antibodies, 3I and 8.12, that recognize L chain determinants on anti-DNA antibodies. We have generated a new anti-idiotypic antibody, F4, that recognizes a H chain determinant on cationic anti-DNA antibodies. F4 reactivity is present in high titer in serum of approximately 60% of SLE patients and on 84 of 706 myeloma proteins. It is preferentially associated with 3I reactive L chains. Furthermore, antibodies bearing both the F4 and 3I idiotypic determinants preferentially bind DNA. Amino acid sequencing of H chains isolated from four F4-reactive myeloma proteins suggests that they derive from two currently identified VH gene families. F4 reactivity is restricted almost exclusively to Ig of the IgG isotype suggesting that F4 may recognize either a somatically mutated hypervariable region or a variable region used late in the immune response. F4, therefore, represents a new idiotypic family preferentially associated with auto-Ag specificity and having features of an Ag-driven immune response.

Amino Acid Sequence↗

Characterization of a cytoskeletal matrix associated with myelin from rat brain.

Extraction of rat brain myelin in a buffer containing Triton X-100 yielded a soluble fraction and an insoluble residue that was enriched in cytoskeletal elements. Immunoblot analysis of the detergent-soluble fraction and the insoluble cytoskeletal residue showed that all of the tubulin and more than half of the actin were found within the cytoskeletal fraction. The distribution of myelin-specific proteins was also examined, and revealed that 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) I and most of the myelin basic proteins (MBPs) were equally distributed between both fractions. By contrast, the large MBP (21.5 kDa) and CNPase II (50 kDa) were observed to partition almost entirely with the cytoskeletal fraction. Proteolipid protein was found predominantly in the detergent-soluble fraction, as was DM-20 protein. Analysis of the cytoskeletal fraction by sucrose-density-gradient centrifugation demonstrated that a distinct subset of lipids was tightly bound to the cytoskeletal protein residue. The cytoskeleton-associated lipid was considerably enriched in cerebroside and sphingomyelin by comparison with total myelin lipids. These results indicate that a cytoskeletal matrix is associated with multilamellar myelin, and suggest that this structure may play a fundamental role in myelinogenesis.

Animals↗

Acute effects of oxygen, nifedipine, and diltiazem in patients with cystic fibrosis and mild pulmonary hypertension.

The acute effects of oxygen, nifedipine, and diltiazem were studied in eight patients with cystic fibrosis and mild pulmonary hypertension, to assess the possibility of relieving the latter before the occurrence of irreversible vascular changes. Oxygen decreased pulmonary pressure (-23%) and resistance (-21%), while increasing systemic resistance (+23%). Nifedipine increased cardiac index (+30%), at the expense of augmented right ventricular work (+42%), resulting in a decreased calculated pulmonary resistance (-23%); pulmonary artery pressure remained unchanged, however. Nifedipine decreased arterial Po2 (-10%), suggesting ventilation-perfusion mismatch. Four of the eight patients responded to diltiazem. Their pulmonary pressure (-35%) and resistance (-43%) decreased, while systemic vascular tone remained unchanged. Oxygen in three patients, and diltiazem in two, returned pulmonary pressures and resistances to normal values. Early reversal of pulmonary hypertension is possible, and intervention is desirable before the establishment of chronic hypoxia, cor pulmonale, or right ventricular failure. Our data does not support the use of nifedipine in pulmonary hypertension, but shows that oxygen, and in some cases diltiazem, act as effective and selective pulmonary vasodilators.

Adolescent↗

Ovarian hyperstimulation inhibits embryo implantation in the mouse.

Embryo implantation is dependent on the synchronous development of the embryo and of the endometrium. Pharmacologic doses of estrogens change endometrial histology and are known to inhibit implantation. During controlled ovarian hyperstimulation, such as occurs during an in vitro fertilization cycle, serum estradiol levels may be elevated to as much as three to six times those found during spontaneous cycles. Serum progesterone levels are also increased and may counteract the elevated estradiol levels. The overall effect of ovarian stimulation on implantation is therefore not known. To study this question, we developed a mouse embryo donation model. Donor embryos were obtained in the late morula to early blastocyst stage from hyperstimulated mated mice. The donated embryos were then transferred to the uteri of two groups of recipient mice. The study group underwent ovarian hyperstimulation with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) (OHR group), while the controls were allowed to cycle spontaneously (SR group). All recipient mice underwent cervical stimulation to induce a pseudopregnant state. Five embryos were transferred to the left uterine horn of each of nine OHR mice and seven SR mice. A higher implantation rate was noted in the SR group than in the OHR group (50 +/- 12 vs 8 +/- 4%, P less than 0.001). Our data suggest that, in the mouse, ovarian hyperstimulation impedes implantation by causing adverse changes in uterine receptivity.

Animals↗

Possible mechanisms of autoantibody production.

Recent advances in the understanding of the ontogeny of the normal B cell response and of the molecular mechanisms that are used to generate a diverse B cell repertoire have resulted in new approaches to the study of autoimmune diseases. B cell lines with autoantibody specificity can easily be generated from normal individuals. These low affinity and generally polyspecific "natural autoantibodies" have features of a B cell response prior to antigenic stimulation and are encoded by germline or relatively unmutated genes. Pathogenic autoantibodies from autoimmune individuals on the other hand, appear to be higher affinity antibodies that have features of an antigen selected response. The relationship between these two different classes of autoantibodies remains to be determined. Our studies of anti-DNA antibodies in human SLE have revealed that anti-DNA antibodies from unrelated patients share dominant cross-reactive idiotypes. Analysis of monoclonal anti-DNA antibodies bearing two SLE related idiotypes, 3I and F4, have indicated to us that DNA binding activity is acquired by somatic mutation, suggesting that these autoantibodies are not germline encoded but require antigenic stimulation and T cell help. Molecular analysis of genes encoding 3I reactive light chains from a panel of EBV transformed B cell lines have revealed that 3I reactive light chains are nearly all encoded by a member of the VK 1 gene family. Thus for this idiotypic system, there is restricted gene usage to encode anti-DNA antibodies. Further molecular analysis may reveal the structural features that determine idiotype reactivity and autoreactivity and may help determine what features of these genes could account for their preferential expression in SLE patients and their family members.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Presence of immunoreactive beta-endorphin and calcitonin in human seminal plasma, and their relation to sperm physiology.

Opioid peptides and calcitonin are found in high concentrations in the male reproductive tract. To further elucidate their role in sperm physiology, we studied semen samples from 49 infertile men and 25 men with proven fertility. beta-endorphin and calcitonin were measured in each sample by radioimmunoassay and then were correlated with seminal plasma testosterone (T) and dihydrotestosterone levels as well as sperm count, total motile sperm/milliliter, and percentage of penetrated hamster eggs. The levels of beta-endorphin (308 +/- 22 pg/ml) and calcitonin (331 +/- 32 pg/ml) in seminal plasma were 10 and 20 times higher than levels found in venous plasma (32 +/- 2 and 14.5 +/- 1.2 pg/ml, respectively) (P less than 0.001). There was no difference between the levels of beta-endorphin and calcitonin in seminal plasma of fertile and infertile men. However, seminal plasma T was significantly higher in fertile than infertile men (19.4 +/- 2 versus 11.5 +/- 1 ng/dl; P less than 0.05). No correlation could be demonstrated between either beta-endorphin or calcitonin and any of the parameters studied. In conclusion, beta-endorphin and calcitonin are produced locally in the male reproductive tract; however, their role in male reproduction remains to be elucidated.

Calcitonin↗

rhs gene family of Escherichia coli K-12.

Two additional members of a novel Escherichia coli gene family, the rhs genes, have been cloned and characterized. The structures of these loci, rhsC and rhsD, have been compared with those of rhsA and rhsB. All four loci contain a homologous 3.7-kilobase-pair core. Sequence comparison of the first 300 nucleotides of the cores showed that rhsA, rhsB, and rhsC are closely related, with only 1 to 2% sequence divergence, whereas rhsD is 18% divergent from the others. The beginning of the core coincides with the initiation of an open reading frame that extends beyond the 300 nucleotides compared. Whether a protein product is produced from this open reading frame has not been established. However, nucleotide substitutions which differentiate the cores have highly conservative effects on the predicted protein products; this suggests that products are made from the open reading frame and are under severe selection. The four rhs loci have been placed on both the genetic and restriction maps of E. coli K-12. A fifth rhs locus remains to be characterized. In terms of size, number, and sequence conservation, the rhs genes make up one of the most significant repetitions in E. coli, comparable to the rRNA operons.

Amino Acid Sequence↗

The Nu1 subunit of bacteriophage lambda terminase.

The maturation and packaging of bacteriophage lambda DNA are catalyzed by the phage terminase enzyme. Terminase is composed of two protein subunits, gpNu1 and gpA. The holoenzyme is multifunctional in vitro; it binds to and cleaves lambda DNA at the cos site (where cos represents cohesive-end site), packages DNA into lambda proheads, and is also a DNA-dependent ATPase. The genes of the two subunits have been cloned separately into powerful expression vectors which allow for very high levels of protein overproduction. The gpNu1 protein has been purified to homogeneity and has a monomeric molecular weight of 21,200, in close agreement with the Mr of 20,444 expected from its amino acid sequence. Both gel filtration and sedimentation velocity centrifugation indicate that the native gpNu1 protein exists as a Mr greater than 500,000 aggregate. The sequence of the first 20 amino acids and the overall composition both match those predicted by the nucleotide sequence of the Nu1 gene. Purified gpNu1 is able to complement gpA-containing extracts in both lambda DNA packaging and cos cleavage assays. The Nu1 gene amino acid sequence predicts DNA binding by the protein, and gpNu1 does show specific binding to lambda DNA by filter binding assays. Also, as predicted from its sequence, gpNu1 exhibits ATPase activity; but in contrast to the holoenzyme, this activity is DNA-independent.

Amino Acids↗