Metacognition, social cognition, and symptoms in patients with first episode and prolonged psychoses.

While it has been documented that persons with prolonged schizophrenia have deficits in metacognition and social cognition, it is less clear whether these difficulties are already present during a first episode. To explore this issue we assessed and compared metacognition using the Metacognition Assessment Scale-Abbreviated (MAS-A) and social cognition using the Eyes, Hinting and Bell-Lysaker Emotional Recognition Tests (BLERT) in participants with first episode psychosis (FEP; n=26), participants with a prolonged psychosis (n=72), and a psychiatric control group consisting of persons with a substance use disorder and no history of psychosis (n=14). Analyses revealed that both psychosis cohorts scored lower than controls on the MAS-A total and all subscales except metacognitive mastery. Compared to the FEP group, the persons with prolonged psychosis demonstrated greater metacognitive capacities only in those MAS-A domains reflective of the ability to understand the mental state of others and to see that others may have motivations and desires separate from their own. Other domains of metacognition did not differ between psychosis groups. The Eyes, Hinting and BLERT scores of the two psychosis groups did not differ but were poorer than those produced by the control group. Exploratory correlations in the FEP group showed a pattern similar to that previously observed in prolonged psychosis. Taken together, these findings suggest that while certain domains of metacognition could improve with prolonged psychosis, difficulties with global metacognition and social cognition may be stable features of the disorder and perhaps unique to psychosis.

The prognostic significance of day 3 embryo cleavage stage on subsequent blastocyst development in a sequential culture system.

PURPOSE: To determine prognostic significance of blastomere number on Day 3 of culture upon subsequent blastocyst (BL) development. METHODS: A retrospective analysis was conducted in 37 IVF subjects undergoing standard protocols and BL transfer after sequential embryo culture in P1 and BL media. RESULTS: Of Day 3 embryos containing 7 or more blastomeres, 68.9% (186/270) developed into BL compared to embryos containing 4-6 blastomeres, 38.1% (56/147), P < 0.0001. The majority of BL, 68.9% (168/244), were observed on Day 5. Extended Day 6 culture represented 31.1% (76/244) of all BLs. CONCLUSIONS: The observation of 7 or more blastomeres on Day 3 yielded a significantly greater likelihood of BL development. Embryos containing 4-6 blastomeres are still relatively likely to progress to a BL. Extended culture to Day 6 still yields a significant proportion of BL. Cell cleavage stage on Day 3 appears to be a useful prognostic indicator of subsequent BL development.

Specific activation of the alpha 7 nicotinic acetylcholine receptor by a quaternary analog of cocaine.

Effects of cocaine and cocaine methiodide were evaluated on the homomeric alpha 7 neuronal nicotinic receptor (nAChR). Whereas cocaine itself is a general nAChR noncompetitive antagonist, we report here the characterization of cocaine methiodide, a novel selective agonist for the alpha 7 subtype of nAChR. Data from (125)I-alpha-bungarotoxin binding assays indicate that cocaine methiodide binds to alpha 7 nAChR with a K(i) value of approximately 200 nM while electrophysiology studies indicate that the addition of a methyl group at the amine moiety of cocaine changes the drug's activity profile from inhibitor to agonist. Cocaine methiodide activates alpha 7 nAChR with an EC(50) value of approximately 50 microM and shows comparable efficacy to ACh in oocyte experiments. While agonist effects are specific for the alpha 7 neuronal nAChR and are not observed with heteromeric neuronal or skeletal muscle nAChR, antagonist effects are present for heteromeric nAChR combinations. Studies of PC12 cells transiently transfected with human alpha 7 cDNA and expressing a variety of functional nicotinic receptor subtypes confirm the specificity of cocaine methiodide agonist effects. Our results indicate that a quaternary structural derivative of cocaine can be used as a specific agonist for the alpha 7 subtype of neuronal nicotinic receptor.

The activation and inhibition of human nicotinic acetylcholine receptor by RJR-2403 indicate a selectivity for the alpha4beta2 receptor subtype.

Human nicotinic acetylcholine (ACh) receptor subtypes expressed in Xenopus oocytes were characterized in terms of their activation by the experimental agonist RJR-2403. Responses to RJR-2403 were compared with those evoked by ACh and nicotine. These agonists were also characterized in terms of whether application of the drugs had the effect of producing a residual inhibition that was manifest as a decrease in subsequent control responses to ACh measured 5 min after the washout of the drug. For the activation of alpha4beta2 receptors, RJR-2403 had an efficacy equivalent to that of ACh and was more potent than ACh. RJR-2403 was less efficacious than ACh for other human receptor subtypes, suggesting that it is a partial agonist for all these receptors. Nicotine activated peak currents in human alpha4beta2 and alpha3beta2 receptors that were 85 and 50% of the respective ACh maximum responses. Nicotine was an efficacious activator of human alpha7 receptors, with a potency similar to ACh, whereas RJR-2403 had very low potency and efficacy for these receptors. At concentrations of <1 mM, RJR-2403 did not produce any residual inhibition of subsequent ACh responses for any receptor subtype. In contrast, nicotine produced profound residual inhibition of human alpha4beta2, alpha3beta2, and alpha7 receptors with IC(50) values of 150, 200, and 150 microM, respectively. Co-expression of the human alpha5 subunit with alpha3 and beta2 subunits had the effect of producing protracted responses to ACh and increasing residual inhibition by ACh and nicotine but not RJR-2403. In conclusion, our results, presented in the context of the complex pharmacology of nicotine for both activating and inhibiting neuronal nicotinic receptor subtypes, suggest that RJR-2403 will be a potent and relatively selective activator of human alpha4beta2 receptors.

Subtype-selective inhibition of neuronal nicotinic acetylcholine receptors by cocaine is determined by the alpha4 and beta4 subunits.

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels of the central and peripheral nervous system that regulate synaptic activity from both pre- and postsynaptic sites. Nicotine binding to brain nAChRs is thought to underlie the induction of behavioral addiction to nicotine, probably as a result of desensitizing/inhibitory effects. Here, another commonly abused drug, cocaine, is shown to selectively inhibit particular nAChR subtypes with a potency in the low micromolar range by interacting with separate sites associated with the alpha4 and beta4 nAChR subunits. Chimeric receptor subunits and site-directed mutants were used to localize sequence determinants of cocaine affinity to: 1) a region of alpha4 located between residues 128 and 267 and 2) a site within the pore-lining M2 domain of beta4 that includes the 13' phenylalanine residue. The voltage dependence for inhibition associated with each site is consistent with these results. Analysis of the effects of incorporation of mutant and chimeric subunits also permitted identification of sequence elements important in receptor activation. For alpha3-containing receptors, a region or regions contained within the N-terminal extracellular domain of neuronal beta subunits influence the time course of responses to acetylcholine. Conversely, the 13' residue of the beta4 subunit M2 region is important in determining acetylcholine potency, indicating a role for this residue in agonist binding/gating processes. In summary, the present work describes sequence elements critical in both cocaine inhibition and acetylcholine activation of nAChRs and indicates that nAChRs may provide a site of interaction for the effects of nicotine and cocaine in the nervous system.

Biodegradation of dicyclopentadiene in the field.

Dicyclopentadiene (DCPD) is formed during the pyrolysis of alkanes to produce olefins suitable for manufacturing synthetic polymers. DCPD has an irritating odor with a 5 ppb detection level that provides the impetus for remediation efforts. One method of destroying odors is to alter the structure of the chemical. This can be accomplished by biological oxidation using microorganisms. Field studies at two sites, where DCPD was a soil contaminant, indicated that biodegradation contributed significantly to DCPD removal. DCPD degradation was stimulated by decreasing bulk soil density and adding nitrogen and phosphorous nutrients. The presence of other easier degradable aromatic hydrocarbons may also be beneficial, suggesting that the process is cometabolic.

Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain.

We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function. The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine. Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage. Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field. An analysis of point mutations indicates that the residues at the 6' position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10' position are not sufficient to produce effects, but 6' 10' double mutants show more effect than do the 6' single mutants.

Immature oocyte retrieval: lessons from unstimulated IVF cycles.

OBJECTIVE: To describe retrieval of immature oocytes during unstimulated IVF and assess the in vitro maturation and fertilization rates. DESIGN: Retrospective analysis. SETTING: The USC program for assisted reproduction. PATIENT(S): Spontaneously ovulatory women with predominantly pelvic factor as their principal cause of infertility, under the age of 40, and no male factor. INTERVENTION(S): HCG administration in mid-cycle, aspiration of all visible follicles, in vitro maturation of immature oocytes in culture media versus 50% follicular fluid in media, IVF, and embryo transfer. MAIN OUTCOME MEASURE(S): Rates of in vitro maturation, fertilization, and implantation after embryo transfer. RESULT(S): A total of 101 immature oocytes were obtained during 59 follicle aspirations. Thirty percent of prophase I oocytes matured to metaphase II in vitro compared with 44% of metaphase I oocytes. Fertilization rates for matured prophase I oocytes were 62% for those cultured in standard culture media (controls) and 87% for follicular fluid culture media. Two pregnancies resulted from the transfer of embryos derived from immature oocytes when no other embryos were transferred. CONCLUSION(S): Immature oocytes may be retrieved successfully during the mid-cycle aspiration of the dominant follicle in unstimulated IVF cycles. Maturation of immature oocytes in vitro with follicular fluid results in similar maturation and fertilization rates as for control incubation. Immature oocytes thus retrieved contribute to the overall pregnancy success of unstimulated IVF cycles. It may be better to retrieve immature oocytes during unstimulated cycles than during the follicular phase of natural cycles.

Factors influencing sperm-zona pellucida binding in vitro using the intact zona model.

The zona pellucida binding assay assesses the ability of spermatozoa to bind to the zona pellucida. The present study investigated the influence of: (i) prior oocyte exposure to spermatozoa on subsequent sperm-zona pellucida binding in vitro; and (ii) cryopreservation of oocytes. Only oocytes obtained from fertile donors were used and the binding capacity of non-inseminated, cryopreserved oocytes was compared with both inseminated/unfertilized, cryopreserved oocytes and inseminated/unfertilized, non-cryopreserved oocytes recovered from in-vitro fertilization cultures on sperm-zona pellucida binding using an intact zona model. There was no statistically significant difference in sperm-zona binding between non-inseminated, cryopreserved oocytes (range 9.6-23.2), inseminated/unfertilized, cryopreserved oocytes (range 15.0-16.0) and inseminated/ unfertilized, non-cryopreserved oocytes (range 3.3-23.0). The coefficient of variation for sperm binding to all oocyte groups was very large (range 37-121%). We conclude that neither prior exposure of human oocytes to human spermatozoa nor cryopreservation of human oocytes influences the subsequent binding of a different population of spermatozoa to the zona pellucida. However, large oocyte-to-oocyte variation of sperm-zona binding may diminish the usefulness of this assay in clinical practice and as a research tool.

Sensitivity to voltage-independent inhibition determined by pore-lining region of the acetylcholine receptor.

Some noncompetitive inhibitors (e.g., ganglionic blockers) exhibit selectivity for the inhibition of neuronal nicotinic acetylcholine receptors (nAChRs). This study characterizes the mechanism of selective long-term inhibition of neuronal and muscle-neuronal chimeric nAChRs by bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (bis-TMP-10 or BTMPS), a bifunctional form of the potent ganglionic blocker tetramethylpiperidine. Long-term inhibition of neuronal nAChRs by bis-TMP-10 has been previously demonstrated to arise, at least in part, from the binding of the bis compound to neuronal beta-subunits. In this study, long-term inhibition is demonstrated to be dependent upon the presence of sequence element(s) within the pore-lining second transmembrane domain (tm2) of neuronal beta-subunits; however, the inhibitor binding site itself does not appear to be contained within the segment of the channel pore influenced by the membrane electric field. Specifically, our results imply that bis-TMP-10 interacts with an activation-sensitive element, the availability of which may be regulated by a sequence in the tm2 domain. Furthermore, we demonstrate a compound length requirement for long-term inhibition that would be consistent with binding to multiple sites located on the extracellular portion of the receptor.

Successful pregnancy in a 63-year-old woman.

OBJECTIVE: To report the occurrence of an unusual case of successful pregnancy achieved by oocyte donation in a woman > 60 years of age. DESIGN: Case report. SETTING: University-based assisted reproductive technology program. PATIENT(S): Sixty-three-year old nulligravida, married for 16 years to her 60-year-old husband. Throughout her infertility treatment, the patient was believed to be 10 years younger, as she claimed. She revealed her true age of 63 only upon being referred for obstetric care at 13 weeks of gestational age. INTERVENTION(S): Oocyte donation, IVF, embryo cryopreservation, and ET. MAIN OUTCOME MEASURE(S): Attainment of pregnancy and subsequent delivery. RESULT(S): The patient underwent two cycles of oocyte donation. During the second attempt, the fresh transfer resulted in a clinical miscarriage at approximately 8 weeks of gestational age. A subsequent transfer of three frozen-thawed embryos resulted in an ongoing singleton gestation. The pregnancy was complicated by gestational diabetes (controlled by diet) and mild pregnancy-induced hypertension. Delivery by cesarean section at 38 weeks of gestational age resulted in the birth of a healthy female infant weighing 2,844 g with Apgar scores of 9 and 9. CONCLUSION(S): This case demonstrates that the uterus is capable of supporting nidation and subsequent gestation for many years beyond natural menopause. It shows that other aspects of human physiology are capable of adapting to the stresses and changes of pregnancy sufficiently well to achieve a normal birth at the age of 63 years. This case also exemplifies the difficulty in attempting to regulate the age of recipients in oocyte donation. As in other aspects of human life, when age limits are applied to the provision of certain services, human beings whose age falls outside of these limits become motivated to deceive the providers of those services to avail themselves of the services.

The utility of a midcycle follicle-stimulating hormone boost in addition to human chorionic gonadotropin for timing of follicle aspiration in unstimulated in vitro fertilization cycles.

PURPOSE: To analyze the effects and potential benefits of a single midcycle dose of follicle-stimulating hormone (FSH) prior to human chorionic gonadotropin (hCG) administration during unstimulated in vitro fertilization (IVF) cycles. METHODS: Twenty-five cycles from 20 patients receiving 150 IU of FSH 42-44 h and 10,000 IU of hCG 34-36 h prior to follicle aspiration were compared to 110 cycles triggered with hCG alone. RESULTS: Serum E2 levels were significantly lower on the day of hCG treatment in the FSH-treated group (266 vs. 297 pg/ml). On the day after hCG administration, serum E2 was similar in both groups. Maximum follicular diameters the day of and the day after hCG treatment were similar as were the number of oocytes aspirated and embryos transferred, and clinical pregnancy rates in both groups. The number of cycles dropped due to premature luteinizing-hormone (LH) surge was 8% in the FSH group compared to 20% in the group treated with hCG alone. CONCLUSIONS: A midcycle FSH boost does not increase pregnancy success of unstimulated IVF cycles but does enhance the increase in serum E2 levels after hCG, thereby potentially allowing earlier hCG administration while incurring decreased cycle cancellation rates due to premature LH surges.

The significance of elevated early follicular-phase follicle stimulating hormone (FSH) levels: observations in unstimulated in vitro fertilization cycles.

OBJECTIVE: Our objective was to determine the effect of elevated early follicular-phase serum follicle stimulating hormone (FSH) levels on follicle growth and oocyte maturity in unstimulated in vitro fertilization (IVF) cycles. STUDY DESIGN: We compared cycles with elevated day 3 FSH levels (> 20 mIU/ml) to subsequent cycles in the same patients when day 3 FSH returned to normal and to cycles among women with normal day 3 FSH levels. PATIENTS: Seven cycles in seven patients had an elevated day 3 FSH (high-FSH group). These were compared to 11 subsequent cycles in which there was a return to a normal baseline FSH and to 13 cycles in 13 patients that entered the unstimulated protocol with a normal baseline day 3 FSH. RESULTS: The day of human chorionic gonadotropin (hCG) administration was similar in all groups as were the serum estradiol (E2) levels. Although the high-FSH group tended to have smaller maximum follicular diameters, the difference was not statistically significant. The highest FSH level on cycle day 3 in a completed cycle was 56.2 mIU/ml. The total number of oocytes aspirated and the number of embryos obtained was similar in all groups. Whereas there were no pregnancies in the high-FSH group, 2 of the subsequent 11 normal day 3 FSH cycles resulted in clinical pregnancies. Two of the 13 patients in the normal day 3 FSH values also achieved pregnancies. CONCLUSIONS: We conclude that cycle day 3 serum FSH levels as high as 56.2 mIU/ml may be associated with apparently normal follicular growth, oocyte fertilization, and embryo cleavage in unstimulated cycles. However, pregnancies are not observed. In addition, FSH levels vary widely from cycle to cycle and elevated levels in one cycle do not necessarily imply that pregnancy may not occur in a subsequent cycle when FSH levels return to normal.

Muscle-type nicotinic acetylcholine receptor delta subunit determines sensitivity to noncompetitive inhibitors, while gamma subunit regulates divalent permeability.

Heterologous expression of nicotinic acetylcholine receptor (nAChR) RNAs in Xenopus oocytes was used to examine the structural basis for pharmacological and physiological differences between muscle-type and neuronal nAChRs. Neuronal nAChRs have a higher permeability to calcium than muscle-type nAChRs and display inward rectification. while muscle-type nAChRs have a linear current-voltage relation. In addition, neuronal nAChRs are more sensitive to inhibition by a class of compounds known as "ganglionic blockers". It has been shown previously that neuronal-muscle hybrid receptors show increased sensitivity to the use-dependent inhibitor of neuronal nAChRs, BTMPS, based on the presence of a neuronal beta subunit. In this study, we report that omission of gamma subunit RNA has a similar effect. alpha beta delta receptors exhibit prolonged inhibition by BTMPS; show a significant permeability to divalent ions, display inward rectification and are more sensitive to mecamylamine. However, while pharmacological effects are associated with the presence of an additional delta subunit, the physiological changes described seem to be associated with the presence or absence of a gamma subunit. These results suggest that, for nAChRs, as is also the case for non-NMDA ionotropic glutamate receptors, the crucial functional property of limiting calcium permeability can be served by a single subunit.

Preimplantation adoption: establishing pregnancy using donated oocytes and spermatozoa.

The experience of transferring embryos produced through in-vitro fertilization (IVF) utilizing donated oocytes and spermatozoa is described. Recipients (n = 28; aged 38-59 years) received oral micronized oestradiol and i.m. progesterone and were synchronized to donors undergoing ovarian stimulation. Reasons for selecting therapy included advanced reproductive age (> 42 years; n = 21) or hypergonadotrophic hypogonadism (n = 7), combined with severe male factor infertility in 23 couples. Five women were single and without partners. Oocytes were fertilized by cryopreserved spermatozoa designated for use by the recipient. Up to five embryos were transferred transcervically. Supernumerary embryos were cryopreserved. A total of 36 aspirations produced 15.6 +/- 7.3 oocytes per retrieval. In 10/36 cycles (27.8%), embryos were available for cryopreservation. Using fresh embryos, the overall pregnancy rate was 38.9% (14/36), clinical pregnancy rate 33.3% (12/36), and ongoing/delivered pregnancy rate 30.6% (11/36). Three ongoing pregnancies were later established by transferring cryopreserved embryos. Adjusting for these events, the per aspiration overall pregnancy rate per retrieval was 47.2%, clinical pregnancy rate 41.7%, and ongoing/delivered pregnancy rate 38.9%. Implantation rates per individual embryo transferred were 16.6% following fresh embryo transfer. A viable pregnancy was achieved by 14 of 28 women (50% cumulative pregnancy rate). We conclude that using donor oocytes and donor spermatozoa is efficacious and allows couples of whom both members suffer from severe gamete abnormalities and single functionally agonadal women an effective means of achieving pregnancy.

A new long shelf life formulation of modified Ham's F-10 medium: biochemical and clinical evaluation.

PURPOSE: To evaluate biochemically and clinically a new formulation of modified Ham's F-10 medium made without the inclusion of hypoxanthine. The medium was formulated for long-term storage and use by separately preparing a stable liquid ("basal") portion and a freeze-dried "supplement" containing the labile medium components. RESULTS: Following 18 months of storage the basal medium was biochemically analyzed for its amino acid (aa's) and vitamin content. Cysteine and tryptophan were decreased to less than 30% of their starting theoretical concentrations (STCs). Asparagine, serine, tyrosine, histidine and lysine were present at 50% to 70% of their STC. The remaining aa's were all within 90% of their STCs except arginine which was at 77%. All of the vitamins were present at 90% or more of their STCs except inositol, riboflavin and thiamine which were present at 70% of their STCs. IVF with the new formulation resulted in 13 deliveries from 51 aspirations (25%) as compared with 10/39 (26%) in 1991, when standard medium preparation was used. Oocyte donation resulted in 30 deliveries from 84 cycles (36%) with the new formulation as compared with 21/65 (32%) in 1991. CONCLUSIONS: (1) The new basal with lyophilized supplement formulation produces similar clinical results in the IVF laboratory as medium prepared in the standard fashion, (2) certain amino acids and vitamins are not stable in the liquid basal medium, and (3) the separate formulation of a liquid basal medium with lyophilized supplement is convenient, viable alternative to modified Ham's F-10 medium prepared in the standard manner (i.e., from powder) and may decrease the need for frequent medium preparation.

Factors affecting pregnancy success of human in-vitro fertilization in unstimulated cycles.

Successful pregnancies have recently been reported in cycles of unstimulated in-vitro fertilization (IVF) which is a simplification of the standard IVF approach utilizing ovarian stimulation. The purpose of this study was to analyse retrospectively the results of the first 3 years of unstimulated IVF cycles at our institution in order to identify factors which predispose these cycles to success or failure. All patients (n = 57) underwent serial monitoring with transvaginal ultrasound and serum oestradiol determinations. Human chorionic gonadotrophin (HCG) 10,000 IU was administered when follicles were felt to be mature and aspiration undertaken (n = 98) 34-36 h later. Among nine patients aged > or = 40 years, 13 aspirations resulted in nine embryo transfers and no pregnancies. In one completed cycle in this group, the patient, who was 42 years old had a baseline follicle stimulating hormone (FSH) concentration of 35.3 mIU/ml. The cycle progressed uneventfully and follicle aspiration yielded two oocytes and two morphologically normal embryos which, however, did not implant. In six patients < 40 years with male factor, seven aspirations yielded 18 oocytes of which 15 were inseminated and did not fertilize. One of the immature oocytes was allowed to mature in vitro and was fertilized and cryopreserved. Its transfer in a subsequent cycle yielded a live birth. Among 78 cycles in 42 patients aged < 40 years without male factor, 63 resulted in embryo transfer with 14% clinical pregnancy rates per aspiration and 17% per embryo transfer. Pregnancy was associated with higher oestradiol concentrations at the time of HCG administration and multiple embryos available for embryo transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II (AII) modulation of steroidogenesis by luteinized granulosa cells in vitro.

PURPOSE: The purpose of the present study was to evaluate the effect of angiotensin II and its inhibitor, saralasin, on steroid production by luteinized human granulosa cells in vitro. Granulosa cells were obtained from follicular fluid aspirations from human in vitro fertilization. Cultures were established in supplemented Ham's F-10 medium. Human chorionic gonadotropin and angiotensin II were added to culture media and the effect on steroid production was measured. RESULTS: Human chorionic gonadotropin alone stimulated production of progesterone, estradiol, and testosterone. The addition of angiotensin II resulted in a dose-dependent increase in progesterone production (428% increase compared to baseline). No effect was seen on estradiol or testosterone. However, a large increase (700%) in estradiol was seen with the addition of the competitive inhibitor of angiotensin II, saralasin. CONCLUSION: We conclude that angiotensin II modulates progesterone production by human luteinized granulosa cells in vitro. The observed enhancement of estradiol production by angiotensin blockade suggests a tonic inhibition of estradiol secretion by endogenous angiotensin II.

Disposal of slop oil and sludges by biodegradation.

These pilot tests indicate that immobilized microbial populations can degrade a wide range of crude oils absorbed into a properly prepared peat matrix with surprising speed and flexibility. Depending on the hydrocarbon composition, ultimate disposal by landfarming or landfilling of the residues is possible. In the former case, performance of the landfarm will be enhanced and environmental concerns related to its operation reduced. In terms of ease of operation, capital and operating costs and reduced environmental concerns, the novel bioreactor presented here meets the requirements and cost constraints associated with on-site slop oil and sludge disposal for the sorts of volumes normally encountered. A patent has been applied for (Francis and Jack, 1991). The technological issues in this development process largely arose from requirements and constraints associated with the target application. Scientific issues surrounding the enhanced biodegradation, seen especially for absorbed heavy oil, remain unresolved. These may or may not be picked up in further development and optimization as need and cost allow.

A prospective controlled evaluation of TEST-yolk buffer in the preparation of sperm for human in vitro fertilization in suspected cases of male infertility.

OBJECTIVE: To evaluate sperm preincubation in tes and tris (TEST)-yolk buffer as a potential enhancing agent of fertilizing capacity of sperm during human in vitro fertilization (IVF). DESIGN: Oocytes obtained during IVF were divided into two groups: one group fertilized with TEST-yolk buffer-treated sperm and the other group with standard-prepared sperm. SETTING: The University of Southern California IVF Program. PATIENTS: Thirty-nine couples with suspected male factor infertility undergoing IVF. INTERVENTIONS: Preinsemination incubation of sperm in TEST-yolk buffer for 24 hours. MAIN OUTCOME MEASURES: Fertilization rates in vitro. RESULTS: TEST-yolk buffer-treated sperm fertilized 140 of 241 oocytes (58%), whereas control sperm fertilized 108 of 251 oocytes (43%). Of four couples who had previously failed to fertilize during IVF, one fertilized with both specimens and three fertilized with TEST-yolk buffer-treated sperm only. CONCLUSIONS: TEST-yolk buffer pretreatment of sperm for 24 hours results in higher fertilization rates during IVF among suspected male factor patients.