Role of diameter differences among follicles in selection of a future dominant follicle in mares

Follicles > or = 5 mm were ablated in pony mares by a transvaginal ultrasound-guided technique on Day 10 (ovulation = Day 0). Follicle emergence (at 15 mm, experiment 1; at 6 mm, experiment 2) and development of the new wave was monitored by transrectal ultrasound. Deviation was defined as the beginning of a marked difference in growth rates between the two largest follicles. In experiment 1, mares were grouped (n = 4 per group) into controls, ablation-controls (ablations at Day 10 only), and a two-follicle model (periodic ablation sessions so that only the two largest follicles developed). There were no significant indications that the two-follicle model altered follicle diameters, growth rates, or time intervals of the two retained follicles at or between events (follicle emergence, deviation, and ovulation). In experiment 2, the two-follicle model (n = 14) was used for follicle and hormonal characterization and hypothesis testing, without the tedious and error-prone necessity for tracking many (e.g., 20) individual follicles. The future dominant follicle emerged a mean of 1 day earlier (p < 0.008) than the future subordinate follicle, the growth rates for the two follicles between emergence and deviation (6 days later) did not differ, and the dominant follicle was larger at the beginning of deviation (23.1 +/- 0.8 mm versus 19.6 +/- 0.9 mm; p < 0.0001). Mean FSH and LH concentrations increased (p < 0.05) concomitantly from emergence of the future dominant follicle and peaked 3 days later when the follicle was a mean of 13 mm. Thereafter, the two hormones disassociated until ovulation: FSH decreased and LH increased. Results supported the hypothesis that the future dominant follicle has an early size advantage over future subordinate follicles and indicated that the advantage was present as early as 6 days before deviation.     

Activation of protein kinase C modulates cell-cell and cell-substratum adhesion of a human colorectal carcinoma cell line and restores 'normal' epithelial morphology

Abnormal cell adhesion is an important contributing factor in invasion and metastasis. Here, we show that morphologically 'normal' cell-cell and cell-substratum adhesion can be restored to a poorly differentiated carcinoma cell line by activation of protein kinase C (PKC). This cell line, VACO 10MS, grows as multicellular aggregates loosely attached to the substratum. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, 7.5 nM) induces rapid adhesive changes with 2 components. First, within 15 min of TPA the cells become closely apposed, an event resembling the 'compaction' seen in the mouse early embryo. Next, over 2 hr, the cells spread, forming a monolayer. We show that compaction depends on extracellular calcium, E-cadherin-mediated adhesion and F-actin but not on protein synthesis, microtubules or substratum adhesion. By contrast, cell spreading is independent of cadherin and extracellular Ca2+ but involves the formation of focal contacts containing alpkha(v) integrin. TPA treatment causes rapid translocation of PKC-alpha to the insoluble fraction. During compaction, actin- and PKC-alpha-containing lamellae form over the entire aggregate surface, those adjacent to the substratum appearing to initiate spreading. Compaction does not involve increased phosphorylation of the cadherin/catenin complex. We conclude that activation of PKC-alpha restores 'normal' morphology to these poorly differentiated cells. Our results are of general interest in relation to the regulation of cell adhesion and, through further investigation, may lead to identification of novel targets for therapeutic suppression of invasion and metastasis.     

Flucytosine monotherapy for cryptococcosis

Medullary carcinoma is a recently recognized tumor of the kidney with distinctive microscopic features; the most notable are diffuse and glandular growth patterns, inflammatory infiltrates, and rhabdoid/plasmacytoid cells. It is a clinically aggressive tumor that occurs in relatively young patients. Moreover, this tumor shows a peculiar clinical association: it occurs in patients with sickle cell hemoglobinopathy. The case presented is that of a 37-year-old black woman with a history of bronchial asthma who died suddenly. Autopsy showed a 4-cm renal mass with extension to the inferior vena cava and metastases to the liver. Histologic evaluation showed the characteristic findings of medullary carcinoma of the kidney. This diagnosis prompted the investigation and subsequent detection of sickle cell trait in the deceased, alerting the family to the genetic nature of her illness. This case is the first report of this entity since the original described series of patients and shows the unique nature of this cancer as a marker of a genetic medical disease.     

Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.     

Prostaglandin E2 induction of labor for fetal demise

Intrauterine fetal demise is a source of anxiety to both patient and physician. Heretofore, the standard treatment was either careful observation until the patient went into labor or attempt at induction of labor with oxytocin. Unfortunately, oxytocin stimulation has not proven to be uniformly successful for this problem. Prostaglandin E2 suppositories have been shown to be effective in inducing uterine evacuation after intrauterine fetal demise. In the opinion of the authors, this approach will in the future replace the sometimes dangerous and emotionally laden convention of watchful delayed therapy.     

Aldosterone secretion during high sodium cerebrospinal fluid perfusion of the brain ventricles

Conscious sheep with permanent indwelling cannulae in the lateral ventricles and the cisterna magna were Na depleted and then perfused for 9 h with an artificial CSF solution. There were 3 experimental groups: Group I (n=5) received perfusion with aritifical CSF containing NA 170 MEq./1, Group II (n=7) received perfusion with artificial CSF containing Na 145 mEq./1, Group III (n=7) received no perfusion. In Group I the blood aldosterone level fell from 26.4 +/- 7.4 to 8.6 +/- 2.3 ng/100 ml by 9 h after perfusion. There was no significant change in plasma [Na] or [K], blood angiotensin II or plasma renin concentration. Blood cortisol and corticosterone levels rose. There was also a fall in post-perfusion. Group III showed no significant change in blood aldosterone concentration. Multivariate statistical analysis showed that the fall in aldosterone levels during 170 mEq./l Na perfusion could not be accounted for by changes, either alone or together, of ACTH as evidenced by alteration in blood cortisol or corticosterone, or by change of plasma [Na], [K] or renin concentrations. This data supports the hypothesis of an additional factor which may be of CNS origin being involved in the control of aldosterone secretion.