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Biomedical subjects

I Cooke

Publications and source records attributed to I Cooke.

33 records · Page 2Linked to original sources
PubMed1995

Inhibin as a marker for ovarian cancer.

Inhibin is a polypeptide hormone produced by the granulosa cells of the ovary, and is present in body fluids as dimers of various sizes each comprising an alpha- and beta-subunit. Free forms of the alpha-subunit also circulate, and the presently available radioimmunoassay (Monash assay) cannot distinguish these from biologically active dimeric inhibin. Recently we described a new two-site enzyme immunoassay able for the first time to measure the levels of dimeric inhibin throughout the human menstrual cycle. The sensitivity limit of this assay is 2 pg ml-1 in human serum with cross-reactivity against activin of 0.05%. The normal range of inhibin in post-menopausal women is < 5 pg ml-1, in pre-menopausal women 2-80 pg ml-1 (2-10 pg ml-1 in the follicular phase, 40-80 pg ml-1 in the luteal phase). This assay was used to determine inhibin levels in sera from 15 (five pre-menopausal and ten post-menopausal) patients with granulosa cell tumours of the ovary. It was raised in a pre-menopausal patient preoperatively (261 pg ml-1), in six post-menopausal patients (32, 43, 54, 66, 24 and 58 pg ml-1) and one pre-menopausal patient with recurrent tumour, (237 pg ml-1), all confirmed clinically. Inhibin was normal in six patients in remission. Oestradiol levels were normal in all patients. Serial levels of inhibin predicted recurrence before overt clinical relapse in two patients. In 29 patients with malignant epithelial ovarian tumours inhibin levels were modestly elevated in nine and normal in the rest. Three patients with endometrioid histology, two with undifferentiated tumours, three with mucinous adenocarcinoma and one with clear cell carcinoma had elevated inhibin levels. Functional inhibin is secreted by all granulosa cell tumours of the ovary studied and can be used as a tumour marker to determine response to therapy and predict recurrence and is superior to oestradiol. A more detailed analysis of the levels of inhibin, and its subunits in epithelial ovarian cancer is needed to identify the molecular forms of the immunoreactive material before optimised assays can be applied to this more common tumour.

Adult↗
PubMed1994

Fluorescence in situ hybridization analysis using cosmid probes to define chromosome 6q abnormalities in ovarian carcinoma cell lines.

Deletion of 6q is a frequent finding in ovarian carcinoma, which would suggest that this region contains one or more putative tumor suppressor genes. Chromosome 6q abnormalities in six ovarian carcinoma cell lines were analyzed by G-banding and fluorescence in situ hybridization (FISH). Using a variety of probes, including a chromosome 6 paint, a probe specific for the chromosome 6 centromere, and cosmids that map to q24 (cCI6-115), q25 (cCI6-4), q26 (cCI6-91, cCI6-119), and q27 (cCI6-13, cCI6-24, and cCI6-111), abnormalities of 6q were found in three cell lines. In cell line OAW42 (hypotetraploid), the sequences complementary to cCI6-119, cCI6-91, and cCI6-13 probes were lost in two homologues of chromosome 6, which indicates the deletion of genetic material from bands q26-27. The same bands were translocated in cell line PEO1 (hypertriploid). The probes from this region were absent on two copies of chromosome 6, but hybridized to two or three markers. In cell line 59M (hyperdiploid) an interstitial deletion proximal to q24 was detected in one chromosome 6. We conclude that it is very likely that a gene or genes localized in bands 6q26-27, and perhaps in the region proximal to 6q24, play a critical role in the development or progression of ovarian carcinoma.

Adenocarcinoma↗
PubMed1994

Detection of dimeric inhibin throughout the human menstrual cycle by two-site enzyme immunoassay.

OBJECTIVE: We have developed and validated a two-site immunoassay for the measurement of dimeric inhibin in plasma and subsequently measured dimeric inhibin levels in plasma through the normal female menstrual cycle. DESIGN: Recombinant inhibin added to plasma samples was quantitatively recovered in both follicular and luteal phase, and serial dilutions of samples were tested for parallelism to similar dilutions of recombinant 32 kDa inhibin. Daily samples were assayed from four women through a menstrual cycle. PATIENTS: (a) Four groups of six women who (i) were in the follicular phase of a normal menstrual cycle, (ii) were in the luteal phase of a normal menstrual cycle, (iii) were post-menopausal and (iV) who had received hMG to induce superovulation. (b) Four healthy female volunteers aged 25-33. RESULTS: Post-menopausal women had less than 2 ng/l of inhibin whereas six women treated with hMG had dimeric inhibin concentrations up to 1125 ng/l. During the early follicular phase, at the time of onset of menstruation, extremely low levels of dimeric inhibin were found (3.4 ng/l (CI 2.2-5.0)) while in the late follicular phase, there was a marked increase in dimeric inhibin concentration. The concentration of dimeric inhibin was maximal (65.6 ng/l (CI 53.1-81.1)) in the mid-luteal phase. The overall pattern of dimeric inhibin concentration during the menstrual cycle was similar to that observed with previous inhibin assays although the magnitude of change was considerably greater. CONCLUSION: The human ovary, in particular the corpus luteum, secretes significant amounts of dimeric and therefore biologically active inhibin.

Adult↗
PubMed1994

NEUROSECRETION OF CRUSTACEAN HYPERGLYCEMIC HORMONE EVOKED BY AXONAL STIMULATION OR ELEVATION OF SALINE K+ CONCENTRATION QUANTIFIED BY A SENSITIVE IMMUNOASSAY METHOD

A sandwich-type enzyme-linked immunosorbent assay (ELISA) was utilized to quantify crustacean hyperglycemic hormone (as Carcinus maenas equivalents) released by single X-organ&shy;sinus gland systems of the crab Cardisoma carnifex during continuous perifusion. Basal rates of secretion (20&shy;60 pg min-1) were stable for at least 4 h. Electrical stimulation (600 stimuli in 5 min) of the axon tract increased secretion two- to threefold, but only if it resulted in neural activity that was propagated to the terminals of the sinus gland. No difference was observable when stimuli were given repetitively or as a series of trains. Perifusion with saline having ten times the normal K+ concentration augmented secretion by as much as fivefold. Augmented secretion of crustacean hyperglycemic hormone evoked by either electrical or K+ stimulation appeared abruptly but declined slowly (over tens of minutes) after stimulation was stopped. K+-evoked secretion of crustacean hyperglycemic hormone was maintained without decrement for at least 1 h. Basal secretion increased in saline from which Ca2+ had been omitted, but decreased in saline containing Mn2+. Neither electrical stimulation nor high [K+] augmented secretion in Ca2+-deficient saline or if Mn2+ was present. Introduction of Mn2+ during K+-evoked secretion immediately reduced release to unstimulated levels; secretion resumed promptly upon removal of Mn2+. Tetrodotoxin reversibly blocked both electrical and secretory responses to axonal stimulation, but it did not block basal or K+-evoked secretion. Release of crustacean hyperglycemic hormone by isolated axon terminals was augmented two- to threefold by perifusion with saline having ten times the normal K+ concentration. The responses were similar to those of the intact systems, having a rapid onset, well-maintained secretion and a long 'tail' of secretion after removal of the K+ stimulus.

Journal Article↗
PubMed1993

The contribution of a hidden male factor to unexplained infertility.

OBJECTIVE: To assess sperm function in patients with unexplained infertility in comparison with normal fertile men. DESIGN: Prospective study. SETTING: Infertility outpatient clinic and donor insemination program, University Department of Obstetrics and Gynecology at the Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Nineteen patients with unexplained infertility and nineteen normal fertile men from a donor insemination program. MAIN OUTCOME MEASURES: Monitoring of reactive oxygen species generation; computerized assessment of the hyperactivated motility pattern of the spermatozoa under capacitating conditions, with and without the addition of follicular fluid (FF); evaluation of sperm-zona pellucida (ZP) binding. RESULTS: Reactive oxygen species generation was not significantly different between the study and control group. Follicular fluid-induced hyperactivation (HA) was significantly lower in patients with unexplained infertility than in the donors, but no difference was found comparing spontaneous HA (without FF) between the two groups. Follicular fluid-induced HA was completely absent in 39% of infertile men and only one fertile man. A low sperm-ZP binding ratio (< or = 0.3) was observed in 28% (5/18) of patients with unexplained infertility. In all, nine infertile men (47%) had 0% FF-induced HA and/or low sperm-ZP binding ratio. CONCLUSIONS: Assessing FF-induced HA and sperm-ZP binding may have clinical significance in distinguishing a subgroup of men with unexplained infertility with sperm function abnormalities in which the fertilizing capacity of the spermatozoa might be reduced. These patients cannot be identified by the conventional semen analysis. Both tests may also be useful in planning the appropriate treatment for couples with unexplained infertility.

Female↗
PubMed1993

Placental protein 14 levels in uterine flushing and plasma of women with unexplained infertility.

OBJECTIVES: To measure concentrations of placental protein 14 (PP14) in uterine flushings and plasma samples obtained from patients with unexplained infertility and to compare the results of those of normal fertile women. DESIGN: Prospective study. SETTING: Infertility and gynaecology outpatient clinics at the Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Sixteen patients with unexplained infertility and 12 normal fertile women who had been previously sterilized. INTERVENTIONS: Daily monitoring of luteinizing hormone (LH) to detect the LH surge; uterine flushings and blood samples were obtained on days 7, 10, and 12 after the LH surge. MAIN OUTCOME MEASURES: The measurement of PP14 concentration in uterine flushings and plasma samples throughout the luteal phase. RESULTS: Levels of PP14 in uterine flushings of patients with unexplained infertility were significantly lower than those of normal fertile women on days LH +10 and LH +12. No significant differences were observed between the two groups in PP14 levels in uterine flushings on day LH +7 and plasma samples on days LH +7, LH +10, and LH +12. CONCLUSIONS: Patients with unexplained infertility have reduced concentrations of PP14 in uterine flushings but not in plasma samples as compared with normal fertile women. Placental protein 14 measurement in uterine flushings may be a more valuable method of assessing endometrial function in infertile patients than plasma levels of the protein.

Adult↗
PubMed1991

Autoradiographic evidence that transport of newly synthesized neuropeptides is directed to release sites in the X-organ--sinus gland of Cardisoma carnifex.

Sections of isolated X-organ--sinus gland neurosecretory systems of the crab, Cardisoma carnifex, were studied by light- and electron microscopy with conventional and autoradiographic procedures. The somata only were exposed to a pulse of 3H-leucine (5 min-5 h) and the entire system perfused with chase medium for various times (1-72 h) before fixation. Within 1 h, radiolabel is concentrated in Golgi complexes and nascent granules of both large and small somata. Label is undetectable in the terminal region following a 10 h chase. It is found in the nerve tract near terminals at 14 h, while after a 19 h chase, label is concentrated in terminal profiles abutting blood sinuses of the neurohemal organ (sinus gland). Following a 72 h chase, label is distributed throughout the terminal region. Each of the six morphologically distinguishable terminal types shows labelling. These observations show that the vast majority of newly formed granules are initially transported to release sites of the perisinus terminals. They thus provide an explanation for previous analyses indicating that newly synthesized peptides are preferentially secreted.

Animals↗
PubMed1989

Crustacean peptidergic neurons in culture show immediate outgrowth in simple medium.

The survival and outgrowth of neurons in culture has usually required conditioning factors. We now report that crustacean neurons, taken from the peptidergic neurosecretory system of the eyestalk of crabs (Cardisoma carnifex) and lobsters (Panulirus marginatus), show immediate outgrowth, sustained for a week or more, in defined medium as simple as physiological saline with glucose and glutamine. The neurons show peptide hormone immunoreactivity that is prominent at growth cones, exhibit differences in form correlated with their immunoreactivity, release peptides to the medium, and have voltage-dependent currents, including a well-sustained Ca current. Cd blocks secretion, growth, and the Ca current. Peptidergic secretory neurons may be able to utilize existing membrane from their store of granules and already active synthetic, transport, and secretory mechanisms for immediate outgrowth.

Animals↗
PubMed1989

Tocolysis during cervical ripening with vaginal PGE2.

Forty-two primigravidae with unripe cervices (modified Bishop score less than or equal to 5) were pretreated with 8 mg of oral salbutamol 30 min before vaginal administration of 5 mg of PGE2. The proportion of patients in established labour after treatment (19%) was markedly less than results reported previously and cervical improvement occurred in 86% of the non-labouring patients. The improved outcome of labour associated with the prior administration of PGE2 when the cervix is unripe, including reduced induction-to-delivery intervals and higher rates of vaginal delivery was maintained. Apart from some minor side-effects, there were no adverse effects noted as a direct consequence of the tocolytic; blood loss was not increased, although one patient suffered an intrapartum abruption. This approach allows a greater control of induced uterine activity and timing of delivery which may be of particular importance in women with suspected placental insufficiency.

Administration, Intravaginal↗
PubMed1987

A comparison between two methods of chronological dating of human endometrial biopsies during the luteal phase, and their correlation with histologic dating.

This prospective study was performed on 61 infertile women to examine the correlation between histologic dating using the same criteria by two independent observers and chronological dating by two different methods: (1) determination of luteinizing hormone (LH) peak by daily LH assay, (2) calculation based on the onset of the next menstrual period (NMP). The correlation between histologic dating and chronological dating was found to be significantly better if the LH peak was used to determine the chronological date than if the NMP was used (r = 0.70 and 0.37, respectively).

Biopsy↗
PubMed1983

Immunocytochemically identified vasopressin neurons in culture show slow, calcium-dependent electrical responses.

From morphological characterization and intracellular recordings, monolayer cultures derived from fetal mouse hypothalami were found to include functionally differentiated peptide neurons, a number of which appear to contain vasopressin. These cells exhibited particular patterns of slow, calcium-dependent membrane depolarizations, resembling in their periodicity and duration the phasic activity of vasopressin neurons recorded extracellularly in vivo.

Action Potentials↗