Maturation of germinal center B cells after influenza virus vaccination in humans.

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination.

Humoral Correlates of Protection Against Influenza A/H3N2 Virus Infection.

Background: Influenza virus remains a threat to human health, but gaps remain in our knowledge of the humoral correlates of protection against influenza virus A/H3N2, limiting our ability to generate effective, broadly protective vaccines. The role of antibodies against the hemagglutinin (HA) stalk, a highly conserved but immunologically subdominant region, has not been established for influenza virus A/H3N2.

Methods: Household transmission studies were conducted in Managua, Nicaragua, across 3 influenza seasons.

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort.

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment.

SARS-CoV-2 BA.1 and BA.2 breakthrough infections boost antibody responses to early Omicron subvariants but not BQ.1.1 or XBB.1.5.

Subvariants of the Omicron lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficiently escape neutralizing antibody responses induced by both vaccination and infection with antigenically distinct variants. Here, we describe the potency and breadth of neutralizing and binding antibody responses against a large panel of variants following an Omicron BA.1 or BA.

Immunity to Seasonal Coronavirus Spike Proteins Does Not Protect from SARS-CoV-2 Challenge in a Mouse Model but Has No Detrimental Effect on Protection Mediated by COVID-19 mRNA Vaccination.

Seasonal coronaviruses have been circulating widely in the human population for many years. With increasing age, humans are more likely to have been exposed to these viruses and to have developed immunity against them. It has been hypothesized that this immunity to seasonal coronaviruses may provide partial protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been shown that coronavirus disease 2019 (COVID-19) vaccination induces a back-boosting effects against the spike proteins of seasonal betacoronaviruses.

Changes in oestrogen receptor protein, mRNA expression and localization in the endometrium of cyclic and pregnant gilts.

Conceptus secretion of oestrogen on Day 11 of gestation is involved with establishment of pregnancy in the pig. Changes in oestrogen receptor (ER) protein, mRNA and cellular localization in the endometrium were evaluated during the oestrous cycle and early pregnancy of the gilt. In nonpregnant gilts, concentration of nuclear ER in the endometrium increased from Days 0 to 12 followed by a decline on Day 15 of the oestrous cycle.

Effect of asynchronous transfer and oestrogen administration on survival and development of porcine embryos.

Results indicate that recovery of embryos on Days 11 and 13 of pregnancy was reduced for Day 5 embryos transferred to recipients on Day 6 of their oestrous cycle and was greatly reduced when embryos were transferred to recipients on Day 7 of the cycle (P less than 0.01). Administration of oestradiol-17 beta on Day 11 of the recipient's cycle did not appear to affect embryo development on Day 13.

An investigation of angiotensin II agonist and antagonist analogues with 5,5-dimethylthiazolidine-4-carboxylic acid and other constrained amino acids.

To probe the receptor-bound conformational requirements of angiotensin II (ANG II) octapeptide agonists and antagonists, the synthesis and biological activities of [Sar1]ANG II agonist and [Sar1,X8]ANG II antagonist analogues (X8 = Ile, D-Phe, or Aib) bearing conformational constraints in positions 3, 5, and 7 were investigated and compared with previous literature efforts. The conformational constraints that were examined include Pro, Dtc (5,5-dimethylthiazolidine-4-carboxylic acid), Aib, Cle, (NMe)Ala, (NMe)Ile, and the lactam modification, L,L-lactam-Phe, previously described by Freidinger et al. (J.

Endometrial surface and secretory alterations associated with embryonic mortality in gilts administered estradiol valerate on days 9 and 10 of gestation.

Administration of estrogen to gilts on Days 9 and 10 of pregnancy results in total embryonic loss by Day 18. The present study examined changes in the uterine endometrial surface and secretion during conceptus attachment in control and estrogen-treated (Days 9 and 10) pregnant gilts. Gilts were unilaterally hysterectomized on either Days 12 and 14 or Days 16 and 18 of gestation.

Development and infectivity of Anaplasma marginale in Dermacentor andersoni nymphs.

The development of Anaplasma marginale was studied in Dermacentor andersoni nymphs after they had fed on a calf with ascending Anaplasma infection. Gut tissues were collected on day 4 of tick feeding, from newly replete (fed) nymphs and on postfeeding days (PFD) 5, 10, 15, 20, and were processed for light and electron microscopy to determine density of A marginale colonies. Homogenates of gut tissues were prepared from nymphs collected on the same days and inoculated into susceptible, splenectomized calves to test for infectivity.

Embryonic steroids and the establishment of pregnancy in pigs.

In the pig, establishment of pregnancy begins about 11-12 days after the start of oestrus. The ability of pig conceptuses to synthesize and release oestrogens during this period, as well as the ability of exogenous oestrogens to induce pseudo-pregnancy when administered from Day 11-15 of the oestrous cycle, provide evidence for an involvement of oestrogen in the maternal recognition of pregnancy in the sow. Oestrogen derived from the conceptus or from administration to cyclic gilts stimulates uterine secretion of calcium and specific polypeptides on Day 11-12.

3-Amino-2-piperidinone-6-carboxylic acid. Molecular structures of cis and trans benzoyl derivatives.

The cis (2a) and trans (2b) isomers of methyl 3-benzamido-2-piperidinone-6-carboxylate (Apca) were prepared and separated by fractional recrystallizations. Proton n.m.

The role of position 4 in angiotensin II antagonism: a structure-activity study.

A number of [Sar1,(pX)Phe4]-ANG II and [Sar1,(pX)Phe4,Ile8]-ANG II analogues were prepared. A good correlation between pX structure in [Sar1,(pX)Phe4]-ANG II and antagonist activity could not be found. However, the data suggest a general trend: Position 4 para substituents that are hydrophilic and capable of donating a hydrogen atom in a hydrogen bond promote agonist activity, while para substituents that are hydrophobic and incapable of donating a hydrogen atom promote antagonist activity.

Potent angiotensin II antagonists with non-beta-branched amino acids in position 5.

Amino acids with lipophilic side chains that contain more than one functional group on the beta-carbon, i.e. a beta-branched hydrocarbon moiety, are required in position 5 of angiotensin II (AII) analogue with potent agonist activity.

Binding of growth hormone-releasing hormones and enkephalin-derived growth hormone-releasing peptides to mu and delta opioid receptors in forebrain of rat.

The purpose of this study was to compare the binding potency to opioid receptors of met-enkephalin-derived, hypophysiotrophic peptides with their reported growth hormone (GH)-releasing strengths in vitro and further, to determine the relative selectivity of each peptide for mu and delta opioid binding sites in the forebrain of the rat. A series of (GH)-releasing pentapeptides and hexapeptides (GHRP's), as well as rat (rGHRH) and human (hGHRH) growth hormone-releasing hormones were tested for preferential binding to specific opioid receptors. The site selectivity of each peptide was determined by its ability to compete for binding with synthetic ligands for mu (Tyr-D-Ala-Gly-MePhe-Gly-ol; DAGO) and delta ([D-Pen2,5]-enkephalin; DPDPE) opioid receptors.

The importance of residues 2 (arginine) and 6 (histidine) in high-affinity angiotensin II antagonists.

The structure-antagonist activity relationship is described for analogues of [Sar1,Ile8]angiotensin II substituted in position 2 (arginine) and position 6 (histidine). An extreme sensitivity of potency to alterations in these positions was observed, suggesting that both residues are important for binding. Evidence is presented suggesting that the position 6 histidine side chain in angiotensin II (AII) is not involved in receptor stimulation.

Effects of D-amino acid substitution on antagonist activities of angiotensin II analogues.

The synthesis and biological activities of angiotensin II (AII) analogues are described and compared to the literature. D-Amino acid substitution was employed to search for novel AII antagonists that would also display reduced partial agonist activity. Substitution of D-amino acids into the interior positions 2-7 of [Sar1,Ile8]-AII gave rise to inactive compounds or weak antagonists.

Differences in the interaction of histamine H2 receptor antagonists and tricyclic antidepressants with adenylate cyclase from guinea pig gastric mucosa.

The interaction of adenylate cyclase with histamine H2 receptor agents and with tricyclic antidepressants was studied in guinea pig gastric mucosal membranes. The H2 receptor antagonist tiotidine acted as a competitive inhibitor of histamine-stimulated adenylate cyclase. The tricyclic antidepressants imipramine and amitryptyline were also competitive inhibitors.

A radioimmunoassay for the histamine H2-antagonist, tiotidine.

A specific and sensitive radioimmunoassay (RIA) for the histamine H2-antagonist, tiotidine, has been developed. The assay is based upon competition of tiotidine with [3H]-tiotidine for antibody (Ab) obtained from immunized rabbits. The immunogen used was a glutaraldehyde coupled conjugate of the tiotidine derivative (ICI 147,655) and bovine serum albumin (BSA).

Morphology of colonies of Anaplasma marginale in nymphal Dermacentor andersoni.

Colonies of Anaplasma marginale Theiler were studied in midgut epithelial cells of nymphal Dermacentor andersoni Stiles that had become infected by feeding on splenectomized calves with anaplasmosis. Colonies of A marginale were not observed in nymphal ticks killed during the 6-day feeding period, but were present in sections of midgut epithelial cells of ticks killed as early as 5 days after repletion. Colonies of A marginale also were present in ticks examined throughout development to the adult stage.

Regulation by monovalent cations of histamine H2 receptor-coupled adenylate cyclase from guinea pig fundic gastric mucosa.

In thoroughly washed guinea pig fundic gastric mucosal membranes, NaCl markedly potentiates the maximal histamine-stimulated adenylate cyclase activity and increases the concentration of histamine required for half-maximal effect (EC50). The apparent dissociation constants for the antagonists cimetidine and metiamide are only slightly increased in the presence of NaCl. Potassium chloride does not change the histamine EC50 but does increase the maximal histamine-stimulated adenylate cyclase activity.

Histamine receptors in the myenteric plexus-longitudinal muscle of the guinea-pig ileum: H1- and H2-receptor-mediated potentiation of the contractile response to electrical stimulation.

The effect of histamine on the contractile response to low frequency-electrical field stimulation in the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum was investigated. By blocking the direct increase in smooth muscle tone caused by histamine with low concentrations of pyrilamine (10(-9)--5 x 10(-8) M) a dose-dependent, histamine-induced potentiation of the twitch response to electrical stimulation was observed. Blocking the direct actions of histamine with concentrations of pyrilamine greater than 10(-7) M resulted in a biphasic histamine dose-response curve: lower histamine concentrations produced a dose-dependent decrease of the twitch response; higher concentrations produced a potentiation.