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Biomedical subjects

D M Robertson

Publications and source records attributed to D M Robertson.

At least 163 records · Page 9Linked to original sources
PubMed1990

In vitro bioactive and immunoactive inhibin concentrations in bovine fetal ovaries and testes throughout gestation.

This study investigates the concentrations of inhibin in the bovine fetal ovary and testis throughout gestation (days 40 to 270/term) as determined by inhibin in vitro bioassay and RIA techniques. In addition, the expression of the inhibin alpha- and beta-subunits (beta A and beta B) in these tissues was evaluated by Northern blot analysis and in situ hybridization. Testicular concentrations of inhibin bioactivity and immunoactivity increased 2.5-fold (103 +/- 24.5 to 256 +/- 11.7 U/g wet weight; mean +/- SE) and 10.4-fold (139 +/- 56 to 1430 +/- 172) respectively, between 90 days and term. The corresponding ratio of inhibin biological: immunological activities (B/I ratio) decreased 8.3-fold (1.5 +/- 0.7 to 0.18 +/- 0.01). The concentration of ovarian bioactive inhibin increased significantly (P less than 0.05) 4.6-fold between 90 days and term (73.6 +/- 14.7 to 340 +/- 11.1 U/g wet weight), whereas the immunoactive inhibin concentration increased 10.3-fold between 120 and 210 days of gestation (7.2 +/- 1.9 to 40.0 +/- 8.7). The corresponding B/I ratio remained unchanged throughout gestation (8.3 +/- 2.4 to 12.5 +/- 4.0). Although the levels of alpha subunit mRNA in the testis and ovary increased over gestation, the levels of testicular beta A subunit mRNA remained low and unchanged. Ovarian levels of beta A subunit mRNA were also low but variable. Furthermore, no beta B subunit mRNA could be detected in gonadal tissue throughout gestation. alpha-Subunit mRNA was detected by in situ hybridization in the sex cords of the fetal testis and the granulosa cells of the fetal ovary while beta A subunit mRNA was detected only in the granulosa cells of the fetal ovary. It is concluded that inhibin is produced by the fetal testis and ovary and these tissue levels increase throughout gestation. The location of alpha- and beta A-subunit mRNA to the sex cords of the testis and granulosa cells of the ovary indicate that these cells are the primary source of inhibin production. The rapid fall in inhibin B/I ratio in testicular extracts over gestation is attributed to the production of an inhibin-related protein with limited or negligible biological activity.

Animals↗
PubMed1990

Inhibin and estradiol responses to ovarian hyperstimulation: effects of age and predictive value for in vitro fertilization outcome.

We have compared the time courses of serum inhibin and estradiol responses to ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer as well as their predictive value for outcome of intermediate variables and pregnancy in in vitro fertilization and embryo transfer. Blood samples (n = 749) were collected for up to 6 days before hCG administration in 100 consecutive treatment cycles, of which 44 resulted in pregnancy, as defined by elevated luteal phase serum hCG beta levels. Inhibin and estradiol levels increased markedly in parallel during hyperstimulation and were highly correlated (r = 0.89; P less than 0.001). Inhibin responses were significantly lower in women 35 yr of age or older (P less than 0.001), although estradiol responses were not influenced by age. Gravidity and tubal disease also had marginal effects on the time course of inhibin responses, but not on overall mean inhibin levels or estradiol responses. The time course of hormonal responses to hyperstimulation was not influenced by any other demographic or etiological factors. Peak values of both hormones correlated with the total number of follicles (inhibin, r = 0.70; estradiol, r = 0.65; P less than 0.001) and oocytes retrieved per cycle (inhibin, r = 0.49; estradiol, r = 0.39; P less than 0.001). The time course and peak values of inhibin and estradiol responses to hyperstimulation did not differ significantly between conception or nonconception cycles whether judged by biochemical (luteal hCG beta) or clinical (viable ongoing pregnancy) criteria. Luteal phase serum inhibin, estradiol, progesterone, and hCG levels were significantly higher in conception than in nonconception cycles (P less than 0.001). These data suggest that the rises in serum inhibin and estradiol levels during hyperstimulation have similar predictive properties for IVF-ET outcomes and could, therefore, be used interchangeably to monitor hyperstimulation regimens. The age-related reduction in inhibin, but not estradiol, responses suggests that these two hormones reflect different granulosa cell functions and that serum inhibin responses to maximal ovarian stimulation may be a sensitive and early index of declining ovarian function with advancing age.

Adult↗
PubMed1990

Current perspectives of inhibin biology.

Inhibin is generally considered to be a feedback regulator of FSH secretion, but significant progress in the field of inhibin biology over the past four years has widened our perspective of inhibin and its production, regulation and action. Firstly, inhibin is a member of a larger family of hormones, secondly it is produced by organs other than the gonads, and thirdly its action is not confined to the pituitary gland. In this review we will outline the isolation and characterization of inhibin related peptides and their production by the Sertoli and granulosa cells of the testis and ovary. With this information in mind, more recent studies concerning the measurement, production, regulation and action of inhibin and inhibin-related proteins will be discussed, in an effort to alert the reader to the contemporary and controversial issues concerning inhibin biology.

Animals↗
PubMed1990

Effects of bovine 35 kDa FSH-suppressing protein on FSH and LH in rat pituitary cells in vitro: comparison with bovine 31 kDa inhibin.

The mode of action of a recently isolated gonadal protein, termed FSH-suppressing protein (FSP) or follistatin, on basal and gonadotrophin-releasing hormone (GnRH)-stimulated release of FSH and LH and on pituitary cell content of FSH and LH was examined in rat pituitary cell cultures and compared with the previously reported effects of inhibin. Pituitary cells were cultured for 3-9 days in the presence of graded doses of FSP and the basal release rates and changes in cell contents of FSH and LH determined during this period. FSP suppressed both the basal release rate and the cell content of FSH with median inhibitory concentrations (IC50) of 135 and 161 pmol/l respectively. The corresponding effects of FSP on LH basal release rate and LH cell content (IC50 = 200 pmol/l) were limited compared with the effects on FSH. The effect of FSP on GnRH-stimulated release of FSH and LH during 4 h was determined in cells which had been preincubated with FSP for 3 days, and the GnRH-stimulated release of FSH and LH analysed as a percentage of the respective gonadotrophin available for release. FSP antagonized GnRH action with dose-related increases in the GnRH median effective (stimulatory) concentrations for FSH and LH release (EC50 values = 56 and 400 pmol/l respectively) and a suppression in the maximum release of FSH and LH by excess GnRH (IC50 values = 142 and 150 pmol/l respectively). The effect of FSP on FSH cell content after 3 days in culture was insensitive to the neutralizing effects of an inhibin antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Analysis of the ratio of biological to immunological LH secreted during the oestrogen-induced LH surge in the ewe.

Plasma concentrations of in-vitro biological and immunological LH were measured throughout the LH surge in cyclic ewes and in ovariectomized ewes treated i.m. with oestradiol benzoate. Both activities increased in parallel during the LH surge in both groups, although the ratio of biological to immunological activities (B/I ratio) was highest at the peak of the LH surge. The two activities were highly correlated (r = 0.86-0.92), with similar slopes from their regression analysis for the cyclic and ovariectomized groups (1.15 and 1.16 respectively). However, the intercepts of the regression lines did not pass through the origin, but intersected the y (radioimmunoassay) axis, suggesting that these serum samples contained immunoactivity not associated with LH bioactivity. In conclusion, an increase in the LH B/I ratio was observed during the LH surge in oestrogen-treated ovariectomized ewes and in cyclic ewes. This increase was not attributable to a change in the relationship between these two LH activities during the LH surge, but rather to the detection of bioinactive immunoactive material in plasma of unknown composition.

Animals↗
PubMed1989

Pigmentation of the eyelid margin accompanying conjunctival melanoma.

In a review of patients with histologically verified malignant melanoma of the conjunctiva, we found 17 patients who had heavy pigmentation of the ipsilateral eyelid margin that was visible on external examination. Among nine patients in whom the histologic characteristics of the skin pigmentation could be studied, the features ranged from an increase in pigmentation of melanocytes within the basal layer to invasive malignant melanoma. The presence of heavy skin pigmentation in association with conjunctival melanoma appeared to be an ominous sign, even when the eyelid did not show histologic features of malignancy. Twelve of the 17 patients (70%) died of metastases after histologic verification of the conjunctival melanoma.

Adult↗
PubMed1989

Malignant melanomas of the conjunctiva, nasal cavity, and paranasal sinuses.

Four patients had malignant melanoma involving the conjunctiva, nasal cavity, and paranasal sinuses. In each patient, the conjunctival melanoma preceded recognition of the lesion in the nasal cavity by months or years. Each patient had one or more conjunctival biopsy specimens that documented melanoma, and in each patient the melanomas evolved in primary acquired melanosis of the conjunctiva. Histologic examination of the epithelium adjacent to the tumor in the nasal cavity failed to show either atypia or diffuse melanosis. We believe that these melanomas in the nasal cavity and paranasal sinuses are most likely to evolve as regional metastases, although it is possible that they arise de novo or as related foci in accordance with the multicentric characteristics of conjunctival melanoma. If a patient with a conjunctival melanoma has symptoms referable to the nasal cavity or paranasal sinuses, ophthalmologists should refer the patient to an otolaryngologist.

Conjunctival Neoplasms↗
PubMed1989

Ocular surgery on patients receiving long-term warfarin therapy.

We analyzed data of 50 patients receiving long-term warfarin sodium therapy who underwent ocular surgery between 1982 and 1986. The frequency of hemorrhagic and thrombotic complications was compared in patients in whom anticoagulants were continued, those in whom the anticoagulants were discontinued in the perioperative period, and a group of matched control patients. There were six perioperative hemorrhagic complications in the warfarin-treated group (12%) compared to none in the control group. This difference was significant (P less than .03). However, no significant difference in hemorrhagic complications was seen between patients in whom warfarin sodium was continued and those in whom it was discontinued.

Adult↗
PubMed1989

Photic retinopathy from the operating room microscope. Study with filters.

A patient's blind phakic eye with clear media, the subject of previous light exposure studies, was exposed for 60 minutes to light from a standard operating room microscope (Zeiss OpMi-6) filtered through an infrared filter. A typical acute photic retinopathy lesion was produced. Two and a half months later, the eye was exposed for 60 minutes to light filtered simultaneously through an ultraviolet filter and an infrared filter. Despite blocking both the ultraviolet and infrared light, and despite reducing the overall light energy by approximately one fourth because of the combination of filters, a typical acute photic retinopathy lesion was produced by the transmitted light, the energy of which was essentially all within the visible spectrum.

Adult↗
PubMed1989

Inhibin as an oocyte meiotic inhibitor.

The effect of inhibin on oocyte maturation division was studied in vitro. Inhibin inhibited spontaneous division in both cumulus enclosed and denuded rate oocytes obtained from immature rats. The inhibition was dose-dependent (15-5000 units/ml) with an ED50 of 45.8 units/ml (4.00 nM). Follicle stimulating hormone (FSH) suppressing protein (FSP) which has inhibin-like activity accelerated the rate of meiotic maturation of rat oocytes in culture (P less than 0.05, at a dose of 0.7 microgram/ml) while activin, which has opposite biological effects to inhibin in many systems did not significantly stimulate oocyte maturation at a dose of 1.12 micrograms/ml. The actions of the three proteins studied were reversible.

Activins↗
PubMed1989

Immuno- and bioactive inhibin and inhibin alpha-subunit expression in rat Leydig cell cultures.

The rise in serum immunoactive inhibin levels in male rats following hCG stimulation raised the possibility that Leydig cells may produce inhibin. This study therefore evaluated whether Percoll-purified Leydig cells from adult male rats synthesized and secreted inhibin in vitro as measured by Northern blot analysis, radioimmunoassay and in vitro bioassay. Northern blot analysis demonstrated the presence of alpha-inhibin subunit mRNA in the Leydig cell and inhibin bioactivity was detected in Leydig cell culture media. Levels of immunoactive inhibin increased in culture over 20 h and were directly dependent on the number of Leydig cells in culture. rLH (NIADDK-rLH-I-6) and not rFSH (NIADDK-rFSH-I-6) stimulated immunoactive inhibin levels in a dose-dependent manner. This study demonstrates that Leydig cells express mRNA for the alpha-subunit of inhibin and produce inhibin which is biologically and immunologically active prompting a re-evaluation of our concepts of testicular inhibin production.

Animals↗
PubMed1989

Inhibin and activin regulate [3H]thymidine uptake by rat thymocytes and 3T3 cells in vitro.

[3H]Thymidine incorporation by adult rat thymocytes, in the presence of phytohaemagglutinin (PHA), was stimulated by bovine inhibin (ED50 0.7 nM), and inhibited by bovine activin (ID50 0.4 nM) and porcine transforming growth factor-beta (TGF-beta) (ID50 4 pM); inhibin opposed the actions of activin and TGF-beta. Bovine 35 kDa follicle stimulating hormone (FSH) suppressing protein (FSP) had no effect on either unstimulated or PHA-stimulated thymocytes. Inhibin also stimulated thymocytes in the presence of a submaximal dose of concanavalin A (ConA), and in the absence of either lectin. Thymocytes which had been maximally stimulated by ConA were inhibited by TGF-beta (ID50 0.02 nM), but not affected by inhibin and activin. Both activin and TGF-beta stimulated [3H]thymidine uptake by 3T3 fibroblasts, but inhibin and FSP had no effect, alone or on activin-stimulated 3T3 fibroblasts. The results indicate that inhibin and activin have opposing, cell type-specific effects on the proliferation of T-lymphocytes, while activin also stimulates fibroblast proliferation in vitro.

Animals↗
PubMed1989

Follitropin (FSH) stimulation of inhibin biological and immunological activities by seminiferous tubules and Sertoli cell cultures from immature rats.

Seminiferous tubules from 20-day-old rats were isolated by mechanical dissection and the conditions to produce optimal inhibin secretion over a 5-day period of culture were established. Inhibin was measured by a specific heterologous radioimmunoassay and by an in vitro bioassay using rat pituitary cells in culture. The tubule production of biologically and immunologically active inhibin was stimulated by ovine follitropin (FSH); however, the ratio of biological to immunological (B:I) activity fell significantly with increasing dose. A similar stimulation of both B and I inhibin activity with a corresponding decrease in B:I ratio with increased FSH dose was also observed using isolated immature Sertoli cells in culture. Fractionation of seminiferous tubule and Sertoli cell culture media by reverse-phase high-performance liquid chromatography (HPLC) revealed the presence of two peaks (I and II) with inhibin biological and immunological activity both of which increased following FSH stimulation. However, while the B:I ratio for peak I remained unchanged following FSH stimulation, the B:I ratio for peak II significantly fell. The molecular weights of peak I and II immunoactivity, determined following fractionation on preparative polyacrylamide gel electrophoresis were 30 kDa and 27 kDa respectively. The 30 kDa peak, based on its inhibin in vitro biological and immunological activity, molecular weight and retention position on HPLC most likely represent 30-32 kDa inhibin. The 27 kDa material remains to be identified.

Animals↗
PubMed1989

External beam irradiation for retinoblastoma: patterns of failure and dose-response analysis.

Eighteen children with retinoblastoma (25 eyes) were treated with external beam radiation at the Mayo Clinic between January 1977 and January 1987; 15 eyes were in groups I to III and 10 were in groups IV and V (Reese-Ellsworth classification). The median number of tumors per eye was 3. Radiation therapy consisted of 4- or 6-MV photons. Doses varied from 39 to 51 Gy in 1.8- to 3.0-Gy fractions. Fourteen eyes were treated through lateral fields by anterior segment-sparing techniques, and 11 eyes were treated by an anterior approach with no attempt at anterior segment sparing. All patients survived (median follow-up, 31.5 months). Cataracts developed in five eyes at a median of 23 months, four in eyes treated with anterior segment-sparing techniques. Of the 15 group I to III eyes, 6 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation and 2 were enucleated. Of the 10 group IV and V eyes, 8 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation, 1 with persistent disease is being followed closely, and 3 were enucleated. Ten (71%) of the 14 eyes treated with anterior segment-sparing techniques required additional treatment (9 of the 10 for tumors anterior to the equator). Four (36%) of the 11 eyes treated with an anterior approach required additional treatment (3 of the 4 for tumors in the posterior pole of group IV or V eyes). Ninety percent of the tumors 10 disc diameters or smaller (1 disc diameter = 1.6 mm) were controlled independently of dose and fractionation used when they were not in the low-dose area of the anterior retina of an eye treated with an anterior segment-sparing technique. We find that use of lateral, anterior segment-sparing techniques has a high risk of anterior retinal tumor development and cataract formation and should be abandoned in favor of techniques that treat the entire retina. A dose of 45 Gy in 1.8-Gy fractions appears to be adequate for local control of tumors smaller than 10 disc diameters. Larger tumors may require additional treatment.

Child, Preschool↗
PubMed1989

Temporal relationships of neuropathologic conditions caused by perinatal asphyxia.

The neuropathologic conditions in 120 perinatal deaths attributed to fetal or newborn asphyxia were examined. Central nervous system necrosis was present in 16 of these deaths. The approximate time of asphyxial insult was established by determining the duration of the process, based on the findings of neuronal necrosis, macrophage response, or an astrocyte response, in conjunction with clinical data. The time of the asphyxial insult for the 16 perinatal deaths was as follows: antepartum fetal asphyxia, two cases; antepartum-intrapartum fetal asphyxia, five cases; intrapartum fetal asphyxia, four cases; and neonatal asphyxia, five cases. These observations indicate that an asphyxial insult may occur in the antepartum period, in the prodromal period of preterm labor, in the intrapartum period, and in the neonatal period. Five to ten percent of the asphyxial insults in each reproductive time period were initially sublethal, allowing necrosis of the brain of the fetus or newborn to develop.

Asphyxia Neonatorum↗
PubMed1989

The isolation and physiology of inhibin and related proteins.

Inhibin, a glycoprotein that preferentially suppresses follicle-stimulating hormone (FSH) secretion, has been isolated from follicular fluid as a heterodimer of two dissimilar subunits linked by disulphide bonds. The larger subunit is termed alpha and the smaller is designated beta. Two forms of inhibin termed A and B have been isolated, the differences being due to variations in the amino acid sequence of the beta-subunit; Inhibin A consists of alpha-beta and Inhibin B of alpha-beta B. Dimers of the beta-subunit, termed activins, have also been found in follicular fluid; these stimulate pituitary FSH secretion. Inhibin is produced in the female by the granulosa cell and corpus luteum under the control of FSH and luteinizing hormone (LH), respectively. The levels in serum rise to peak at mid-cycle and in the mid-luteal phase of the human menstrual cycle, and decline prior to menstruation. In pregnancy, the late-luteal phase decline in inhibin does not occur and the levels increase slowly. Studies suggest that the levels in pregnancy arise from an embryonic source, particularly the placenta. In the male, inhibin is produced by the Sertoli cells under the control of FSH by mechanisms involving cyclic adenosine 3', 5'-monophosphate. Testosterone exerts a minor inhibitory control at supraphysiological levels (10(-5) M), but human chorionic gonadotropin stimulation results paradoxically in a rise in serum inhibin levels. Disruption of spermatogenesis in the rat by cryptorchidism, heat treatment, or efferent duct ligation results in a decline in inhibin levels and a rise in FSH levels, findings consistent with the negative feedback action of inhibin on FSH secretion. As well as their roles in the reproductive system, inhibin and activin have more widespread actions in the haemopoietic, immune and nervous systems as evidenced by the finding of mRNA for its subunits in a range of tissues. Other studies have shown actions on erythroid differentiation and on mitotic activity in thymocytes. These actions suggest that inhibin and activin may function as growth factors as well as regulators of FSH.

Animals↗
PubMed1989

Epiretinal membranes and cystoid macular edema in gyrate atrophy of the choroid and retina.

A 26-year-old woman with gyrate atrophy of the choroid and retina and hyperornithinemia lost central visual acuity because of cystoid macular edema associated with epiretinal membrane formation. Dietary manipulation over a 5-month interval reduced the plasma ornithine levels 37% but did not halt the progression of the gyrate atrophy nor influence the cystoid edema or visual acuity.

Adult↗