Subnormal Function Research Articles

Uterine influences on the formation of subnormal corpora lutea in seasonally anestrous ewes.

The hypothesis that subnormal luteal function after induced ovulation in anestrous ewes was the result of uterine influences exerted during the periovulatory period was tested. Crossbred ewes (n = 27) in seasonal anestrus were induced to ovulate by administration of 12 doses of 250 ng of LHRH at 2-h intervals, followed immediately by a bolus injection of LHRH (250 micrograms; d 0). Ewes were unilaterally hysterectomized on either d -3 (PRELHRH) or 2 (POSTLHRH). Daily blood samples were collected and assayed for progesterone (P4) and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM). All ewes were slaughtered on d 10, and corpora lutea (CL) were collected, weighed, and assayed for concentration of P4. All ewes that ovulated exclusively in the ovary ipsilateral to the remaining uterine horn had a transient increase in plasma P4 of 2 to 3 d (short luteal phase). In ewes with at least one CL in the isolated ovary, elevated plasma P4 was maintained after hysterectomy but was consistently lower (P less than .05) in POSTLHRH ewes than in PRELHRH ewes. Concentrations of PGFM did not differ between treatments. The CL ipsilateral to the remaining uterine horn weighted less (P less than .01) and contained less P4 (P less than .01) than contralateral CL. These data confirm the hypothesis that premature regression of subnormal CL is uterine-dependent in a local fashion. Presence of the uterus during the follicular and(or) early luteal phase inhibited subsequent luteal function in seasonally anestrous ewes.

The corpus luteum.

Normal corpus luteum function is determined by function in the follicular as well as the luteal phase. In the follicular phase adequate follicle-stimulating hormone (FSH) and oestrogen stimulation are required for granulosa cell mitosis and luteinizing hormone (LH) receptor synthesis. An increase in LH pulse frequency may also be necessary for adequate oestrogen synthesis and preparation of follicular cells for luteinization and secretion of progesterone. The nature of LH release may also influence luteal function and pre-ovulatory progesterone may increase the responsiveness of the follicle to gonadotrophins. The thecal vascular network becomes extensive around pre-ovulatory follicles and may influence access of gonadotrophins and/or the ability of follicular cells to respond to them. Further vascularization is an early feature of luteinization. Angiogenic factors are found in luteal tissue and prostacyclin increases luteal blood flow. The corpus luteum consists of large cells which secrete most of the progesterone and have prostaglandin F2 alpha receptors and small cells which are responsive to LH. In the luteal phase subnormal luteal function has not been associated with a reduction in LH concentration, pulse frequency or amplitude. The number and occupancy of LH receptors and adenylate cyclase activity do not appear to be altered by a reduction in luteal function. Low density lipoprotein provides the substrate and somatomedin C modulates among other hormones' influences, progesterone production. In addition to the cAMP second messenger system phosphatidyl inositol metabolism may also be associated with LH stimulation. Luteolysis is an active process; prostaglandin F2 alpha or lipoxygenase products and possibly an endogenous GnRH-like ovarian hormone may mediate it as also may oxytocin in some species.

Relationship of pre- and post-ovulatory gonadotropin concentrations to subnormal luteal function in postpartum beef cattle.

Early weaning of calves from anestrous cows results in formation of short-lived corpora lutea (CL) unless the animals are pretreated with a progestagen (norgestomet). This study was conducted to investigate the relationship between pre- and post-ovulatory gonadotropin secretion and luteal lifespan. Postpartum beef cows were assigned randomly into two groups, control (n = 5) and norgestomet (implant given at weaning for 9 d; n = 7). Calves from all cows were weaned 30 to 33 d postpartum. Coccygeal artery cannulas were placed into cows in the control group 1 d prior to weaning and 2 d before implant removal in cows in the norgestomet group. Plasma for determination of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol-17 beta (E) and progesterone (P) was collected daily at 10-min intervals for 6 h from weaning (control) or the day prior to implant removal (norgestomet) to estrus (d 0) and on d 2, 4 and 6 following estrus. Average interval (X +/- SE; P less than .05) from weaning to estrus or implant removal was 4.2 +/- .8 and 2.3 +/- .2 d for the control and norgestomet groups, respectively. Estrous cycle length for the control group was 12.4 +/- 1.8 d compared with 20.4 +/- .3 d for the norgestomet group (P less than .05). Four of five control cows had an estrous cycle length of 7 to 14 d; all cows in the norgestomet group and the remaining control cow had an estrous cycle of normal length (16 to 21 d).2+ estrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrodermal activity in antidepressant medicated and unmedicated depressive patients and in matched healthy subjects.

A group of 59 depressive in- and outpatients displayed statistically significantly subnormal electrodermal activity (EDA) according to the skin conductance level, the skin conductance response magnitude, the skin conductance response rate, and the index of nonresponding during neutral tone stimulation, compared to 59 mentally and somatically healthy subjects, individually matched for age and sex. Comparisons between 20 antidepressant medicated and 20 unmedicated patients, matched for age, and comparisons between 21 drug-free patients and 10 patients medicated exclusively with antidepressants yielded no statistically significant difference in any EDA variable. However, all the electrodermal central values were somewhat lower in the medicated patients, possibly an effect of greater severity of symptoms. The present and previous findings offer strong support to the hypothesis of a subnormal function of the electrodermal activity in groups of depressive patients.

Subnormal activation of phagocytes by complement in chronic inflammatory bowel disease? Neutrophil chemotaxis to complement split product C5a.

The capacity of circulating phagocytes for activation by complement was investigated in consecutive, untreated cases of chronic inflammatory bowel disease. The major complement derived chemotactic factor, C5a, served as chemoattractant in dose response studies of neutrophil chemotaxis. A similar, significantly decreased sensitivity and peak response was revealed in patients with Crohn's disease and ulcerative colitis. This subnormal function of neutrophils could be shown even in cases of complete clinical remission. Chemotactic response to casein and spontaneous motility was within the normal range showing an unaffected basic cell function of neutrophils in the patients. The study shows a dysfunction of phagocytic cells, related to potentially important phlogistic mediators, in chronic inflammatory bowel disease.

131I-19-iodocholesterol scintigraphy of the adrenal cortex.

131-I-19-iodocholesterol scintigraphy of the adrenal cortex has been carried out in 26 patients. In 4 patients with normal adrenocortical function the tracer was equally accumulated on the two sides. In 7 patients with untreated Cushing's syndrome, bilateral uptake was found in 4 patients with bilateral hyperplasia whereas unilateral visualization was obtained in three cases of cortisol producing adenomas. The side localization was confirmed at operation. Eight patients had been operated for Cushings syndrome prior to the scintigraphy. Remnant adrenocortical tissue with negligible or subnormal function (4 patients) could not be visualized. Normo- or hyperfunctioning remnant tissue was visualized in 3 patients. One patient had recurrent hypercorticism due to metastases from a previously removed adrenocortical carcinoma; a single pelvic accumulation was seen, whereas several metastases in the abdomen and thorax were not visualized. Four patients with aldosteronism were investigated. Three had primary aldosteronism due to an adrenocortical adenoma. In two of these, the site of the adrenal lesion was localized pre-operatively. In the third patient, equal bilateral accumulation of iodocholesterol was seen even after suppression with dexamethasone. At operation a small tumour was found. In 1 patient with indeterminate aldosteronism both glands were visualized and at a second examination the uptake was equally suppressed by dexamethasone.

Bacteriophage M13 gene 2 protein: Increasing its yield in infected cells, and identification and localization

M13 gene 2 protein, implicated in the introduction of single-strand nicks into double-stranded closed circular (RFI) DNA molecules, was previously found in only very small quantities in infected cells. We now find that the gene 2 protein can be readily identified and its yield can be increased manyfold if infections are carried out at high temperature with either a gene 2 temperature-sensitive mutant or with wild type M13. Mechanisms are suggested by which the increased yield could result from subnormal function of the protein in these infections. Under conditions of high yield, the gene 2 protein is found largely in a rapidly sedimenting particulate fraction of unknown nature, where it constitutes as much as 36% of the leucine-labeled protein. The gene 2 protein can be readily solubilized from this particulate fraction with the ionic detergent sodium dodecyl sulfate (SDS) but no satisfactory solubilization method was found which keeps the protein in its native state. Attempts to demonstrate in vitro activity of the gene 2 protein, that is, nicking of M13 RFI DNA, were not successful. On the basis of SDS-polyacrylamide gel electrophoresis, we estimate that the gene 2 polypeptide has a molecular weight of approximately 40,000. In the course of the experiments on gene 2 protein, it was observed that the gene 3, as well as the gene 8, virion protein molecules were found predominantly in the cell inner membrane, supporting the idea that virion assembly is carried out there. The gene 4, nonvirion, protein also proved to be in the inner membrane, as would be expected if this protein plays a role in virion assembly.

Serotyping and genetic analysis in the selection of related renal-allograft donors.

Thirty-two recipients of 33 renal allografts from related donors were divided into three groups by serotyping and genetic analysis. In the first group, eight patients inherited the same HL-A complexes as their donors. Seven have had excellent courses, with complete rehabilitation; one has recurrent glomerulonephritis. In the second group, seven patients inherited one HL-A complex in common with their donors and had very good serologic matches for the other. All had evidence of rejection, but six have had excellent courses; two have stable but subnormal function. In the third group 16 patients shared one HL-A complex with their donors but had poor serologic matches for the other; one differed by both complexes from his donor. Three patients have had excellent courses though two show decreasing creatinine clearances. Ten had unsatisfactory courses resulting in death, nephrectomy or poor rehabilitation; four have had intermediate courses. Intrafamilial donors can be selected so that the prognosis is excellent for rapid and complete rehabilitation.

Assessment of a test of adrenocortical function using beta1-25 corticotrophin.

SUMMARY In ten patients with a variety of rheumatic disorders the changes in plasma corticosteroid (11-OHCS) levels have been studied after adrenocortical stimulation by a continuous 5 hr. infusion of Synacthen (Ciba) or by a single i.v. injection of 200 i.u. (320 μg.) Pentacosactride (Sandoz). Comparable increases were obtained using both synthetic polypeptides. It is suggested that administration of Pentacosactride intravenously is a simple method of obtaining prolonged maximal stimulation of the adrenal cortex. A normal range of values of plasma 11-OHCS, obtained from 28 subjects, is given, and it is shown that the results are reproducible. The results of tests in six subjects with secondary adrenal atrophy due to long-term corticosteroid therapy indicate that the test can discriminate between normal and subnormal adrenocortical function.

Effect of Gestation and Dry Period on Deoxyribonucleic Acid and Alveolar Characteristics of Bovine Mammary Glands

Udders of 21 lactating and 26 dry cows were analyzed for deoxyribonucleic acid (DNA) concentration and amount. Right and left halves of 21 cows were dried off at different times to give comparisons between dry periods of 15, 45, 60, and 75 days. Udders of five dry cows with dry periods of 8 and 48 days for right and left halves, respectively, were obtained about a week before calving. Histological sections of 26 udders were used to record alveolar density and surface area. The correlation coefiicient between total DNA and milk yield per half udder (r = 0.34) was small but statistically significant (P<.05). Concentration of DNA and alveoli increased in dry udders compared to prepartum and laxtating udders. Involution of udders of nonpregnant or early gestation cows was evidenced by reductions in fresh weight, dry weight, alveolar surface area, and DNA. In prepartum half udders, six weeks’ difference in dry period did not significantly affect dry weight, DNA, or alveolar concentration. Lack of interference with either involution or alveolar development in the udder due to short dry periods indicates that subsequent subnormal lactation may be due to subnormal function rather than structure.

Cardiotoxic Thyroid and Radioactive Iodine

A study was made of 43 patients with heart disease who could not be restored to a comfortable state of ambulation by treatment with digitalis, diuretics, low-sodium diet, and other medication. In this group there were 5 men and 20 women with definite evidence of thyroid abnormalities. In none of the 25 was the hyperthyroidism diagnosed clinically, although it was looked for by both history and physical examination; the evidence was obtained in each case by the radioactive iodine (I131) tracer technique. The diagnostic and therapeutic use of I131is exemplified in the history of a 53-year-old man with angina pectoris. It is believed that by careful adjustment of I131dosage the patient can be brought to a state of normal rather than subnormal thyroid function. The procedure outlined gave marked improvement in all patients but two who died of myocardial infarction.