Evidence for the presence of pro-oxytocin/neurophysin-converting enzyme in the human ovary

The activity of pro-oxytocin/neurophysin (pro-OT/Np)-processing enzymes was determined in human granulosa cells, follicular fluids and purified secretory granules of corpora lutea. We detected the presence of an endoprotease which releases OT-Gly10-Lys11-Arg12 on cleavage of the synthetic pro-OT/Np(1-20) peptide after the dibasic Lys11-Arg12 doublet. This endoprotease was inhibited by EDTA, but was not affected by phenylmethanesulfonyl fluoride and pepstatin. Enzymatic activity was markedly reduced by replacement of L-Arg by D-Arg in the basic amino acid doublet of the substrate. The molecular weight of this enzyme was estimated to be 60 kDa. These features closely resembled those of the endoprotease identified in the bovine pituitary. The endoprotease is a metalloenzyme, specific for the Lys-Arg doublet. We also detected a carboxypeptidasic activity, inhibited by guanidinoethane-mercaptosuccinic acid. In the light of our previous detection of the processing intermediates, OT-Gly-Lys-Arg, OT-Gly-Lys and OT-Gly, in human ovary, these observations are in favour of a pro-OT/Np-processing pathway in the human ovary comparable with that in the bovine ovary. Moreover, these results confirm that oxytocin post-translational processing occurs in the human ovary and strongly suggest that pro-OT/Np is synthesized locally.     

Influence of molybdenum on passivation of polarised stainless steels in a chloride environment

Polarised specimens of AISI 304L and 316L stainless steels (SS) were studied using X-ray photoelectron spectroscopy in conjunction with Ar⁺-ion sputtering. A 5% NaCl test solution was used at room temperature. The polarised passive films formed consist mainly of chromium oxide and hydroxide and a small proportion of iron oxides. The composition of the films depend strongly on the potential. Chloride and molybdenum ions appear when the AISI 316L SS alloy is polarised at a potential close to pitting potential.     

Loss of heterozygosity and overexpression of the p53 gene in ovarian carcinoma

Eight anticonvulsant drugs-including clonazepam, diazepam and phenobarbital-were tested for their effects on GABA-stimulated chloride uptake in rat cerebral cortical microsacs (unfiltered synaptoneurosomes). "Mid" and "high" therapeutic concentrations were screened, and, if significant enhancement was found, full concentration-response tests were done. In the initial screens, enhancement of GABA-stimulated uptake was found only with phenobarbital, clonazepam and diazepam. In subsequent concentration-response tests, the effects of phenobarbital were found to occur throughout the range of normal, anticonvulsant concentrations, whereas the effects of clonazepam and diazepam were observed only above the concentrations normally used for the chronic control of seizures or anxiety. These data suggest that phenobarbital's anticonvulsant effects are mediated via the GABAA receptor complex, but that the low-dose effects of the benzodiazepines may be mediated via some other mechanism.     

In vivo fluorescence microscopy for the assessment of microvascular reperfusion injury in small bowel transplants in rats

With the use of in vivo fluorescence microscopy we have analyzed microvascular reperfusion injury of small bowel isograft transplants in rats. Following 1 hr cold storage in University of Wisconsin solution, the small bowel was transplanted heterotopically, and the intestinal microcirculation was quantitatively analyzed 20-60 min after onset of reperfusion. The intestinal grafts' capillary perfusion of both the mucosa and the circular and longitudinal muscles was not found altered when compared with the intestinal capillary perfusion of sham-operated controls. In contrast, leukocyte-endothelial cell interaction, including leukocyte rolling (40 +/- 5%) and sticking (280 +/- 100 mm-2) in submucosal postcapillary venules, was significantly increased when compared with nontransplanted controls (12 +/- 8% and 20 +/- 10 mm-2, P < 0.01 and P < 0.05, respectively). Leukocyte-endothelial cell interaction was associated with a marked alteration of lymphatic capillary drainage, as indicated by the low functional density of lymphatic microvessels of 10.2 +/- 6.1 cm-1 (P < 0.01 vs. sham-operated controls (39.2 +/- 6.1 cm-1)). From these results we propose that leukocyte-endothelial cell interaction, not capillary "no-reflow," is the primary step in the manifestation of microvascular reperfusion injury following a short period of cold ischemia in small bowel grafts.     

Phosphofructokinase from mantle tissue of Mytilus galloprovincialis. Purification and effects of phosphorylation on the enzymatic activity

Phosphofructokinase purified from mantle tissue of the sea mussel Mytilus galloprovincialis, was phosphorylated "in vitro" by the catalytic subunit of cyclic AMP-dependent protein kinase. The incorporation of phosphate gave rise to an activation of the enzyme by increasing its affinity for fructose-6-phosphate, by decreasing its sensitivity to the inhibition by ATP and by enhancing the effect of allosteric activators (5'-AMP and fructose-2,6-bisphosphate). In addition, the effects of phosphorylation on the catalytic activity are pH-dependent.     

Introduction to the special section on contemporary issues in human sexuality: research and practice

Critical issues in human sexuality have changed markedly during the past decade and so have the contributions of psychology to the evaluation and treatment of sexual behavior problems. Some of the greatest challenges facing psychologists today include the increasing emphasis on medical interventions for the male sexual disorders and the relative decline of traditional behavioral sex therapies, the recalcitrance of sexual desire disorders, the prevention of "unsafe" sexual behavior, and the limited understanding of female sexuality. This overview introduces a series of 5 articles that examine these selected critical issues in human sexuality. Guidelines for clinical practice and directions for future research are highlighted.     

Arthroscopic Bankart repair with the Suretac device. Part I: Clinical observations

Although arthroscopic Bankart repair has become an accepted surgical stabilization technique for anterior shoulder instability, the failure rate remains unacceptably high. Little information is available concerning healing of the Bankart repair. The purpose of this article is to clarify this issue by analyzing a cohort of 15 patients who underwent a "second-look" arthroscopy to evaluate and treat pain or recurrent instability following arthroscopic Bankart repair with the Suretac device (Acufex Microsurgical, Mansfield, MA). "Second-look" arthroscopy was performed at an average of 9 months following the index surgical procedure. The reasons for this second surgery were recurrent instability in 7, pain in 6, and pain and stiffness in 2. In the 7 patients with recurrent instability, the Bankart repair was found to be completely healed in 3 (43%), partially healed in 1 (14%), and had recurred in 3 (43%); however, 6 of 7 were observed to have lax capsular tissue. In 4 of these cases, retrospective review of the index surgical procedure showed that a technical error had been made during the repair. Two cases had biopsy of the repair site on "second-look" at 6 to 8 months, and this showed residual polyglyconate polymer debris surrounded by a histiocytic infiltrate. In the remaining 8 cases with stable shoulders, the Bankart repair had completely healed in 5 cases (62.5%) and partially healed in 3 cases (37.5%). The higher failure rate with this approach compared with open approaches appears to result from improper patient selection and errors in surgical technique. There is some question concerning healing strength of the Bankart repair, although complete healing of the Bankart does not seem to be a prerequesite for shoulder stability. Success of the procedure might be expected to improve by selecting only patients with unidirectional, posttraumatic, anterior instability who are found to have a discrete Bankart lesion and well-developed ligamentous tissue.     

Is Down syndrome a risk factor for poor outcome after repair of congenital heart defects?

Down syndrome is commonly associated with significant congenital heart disease with the potential for early development of pulmonary hypertension. As such, children with Down syndrome may be at increased risk for both perioperative and long-term mortality. The purpose of this study, using data collected from a population-based outcomes study, is to analyze the potential role that Down syndrome plays in the outcome of surgically "corrected" congenital heart disease. Data were collected from a registry of all Oregon residents who, in the period 1958 to the present, had a reparative operation for one of 14 congenital cardiac malformations when younger than 18 years (N = 3965 patients). Down syndrome was present in 289 (7%) of the total registry patients. In evaluating the cardiac mortality associated with Down syndrome for each of the repaired cardiac malformations, only complete atrioventricular septal defect was associated with significantly higher perioperative (13% vs 5%) as well as higher overall late cardiac mortality through 20 years after the operation (20% vs 5%; p = 0.04). The survival outcomes for each of the other cardiac malformations were similar for children with and without Down syndrome.     

Juvenile myoclonic epilepsy

CONCLUSION: We conclude that despite inevitable variability the clinical picture of JME is characteristic. It is easy to diagnose JME if one thinks of it while the history should be thoroughly analyzed. An EEG recording during sleep confirms the diagnosis. An early diagnosis of JME permits adequate prognosis of the subsequent course of epilepsy, and adequate therapy brings remission in most of the patients. If treatment starts following the large number of severe GTC seizures, the response to therapy is incomplete. The persistency of the illness throughout the life, the need for continuous medication and therapeutic unresponsiveness in cases with late diagnosis, do not justify the increasing misconception that JME is of benign nature. Diagnosis of JME is rare because of insufficient familiarily of physicians with the illness. BACKGROUND: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epileptic syndrome characterized with the combination of myoclonic, generalized tonic-clonic (GTC) and absence seizures that are readily provoked by sleep deprivation. PATIENTS: Forty-three patients, aged from 14 to 51 years, participated in a 5-year follow-up study. Diagnosis was made according to the criteria (Table 1) for diagnosis of JME set by Panayiotopoulos et al. (1994). Nineteen patients made their first contact with a neurologist at the Institute of Neurology and were diagnosed as JME, while the remaining 24 were referred to from other medical institutions with a diagnosis of therapy resistant to focal epilepsy. All patients underwent a somatic and neurological examination, "mini mental test," EEG in waking and CT scan of the brain. Some patients had EEG performed during sleep and some had MRI of the head. RESULTS: JME began between 9 and 26 (average 17) years. All patients had myoclonic seizures, 98% had GTC and 23% absence seizures. The first myoclonic seizure occurred between 9 and 24 years while the frst GTC seizure occurred between 10 and 32 years. Myoclonic seizures (83% of patients) and GTC seizures (70% of patients) occurred most often immediately after awaking. The most frequent provocative factors were insufficient sleep, alcohol abuse and tiredness. Epilepsy in the family was present in 39%, focal neurological deficiency in 9% and pathological findings on of CT and MRI in 7% of patients. Waking EEG was pathological in 77% of patients; it included generalized spike-wave discharges in 73%, multiple spike-wave complexes in 33% and focal discharges in 12% of patients, respectively. In all 26 patients tested, sleep EEG was pathological most often with multiple spike-wave complexes in 85% and 3-4 Hz spike-wave complexes in 57% of patients. The correct diagnosis of JME following a comprehensive examination was made in 24 (56%) patients after a delay of 1 to 35 years. In 24 patients with delayed diagnosis of JME the replacement of earlier medication with valproic acid (VPA) induced remission in 18 patients (75%) while 1 patient (4%) experienced a reduction in the number of seizures. Five patients (21%) did not respond to VPA medication: 2 due to a weak compliance, another 2 due to inefficient medication and 1 because of the preexistent malabsorption syndrome. In 19 patients (44%) with initial diagnosis of JME, VPA was introduced immediately upon diagnosis. Of them, 15 (79%) had excellent response to VPA, 1 refused therapy and for 3 patients there is no information. In 2 patients VPA was substituted due to side effects (hepatotoxicity and alopetia) with lamotrigine (low doses), which brought about decrease in frequency and mitigation in myoclonic seizures.     

The "first generation" of endovascular stent-grafts for patients with aneurysms of the descending thoracic aorta

OBJECTIVE: Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta. METHODS: Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure. RESULTS: Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors. CONCLUSIONS: This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future.