Intrafollicular oocyte transfer in the horse: effect of autologous vs. allogeneic transfer and time of administration of ovulatory stimulus before transfer.

PURPOSE: To assess meiotic and developmental competence after transfer of immature cumulus-oocyte complexes (COCs) to the preovulatory follicles of mares (intrafollicular oocyte transfer (IFOT)). METHODS: In Experiment 1, mares received an ovulatory stimulus at IFOT. Thirty hours later, COCs were recovered from the follicle, and mature oocytes underwent ICSI and embryo culture. In Experiments 2 and 3, autologous vs. allogeneic COCs were used. The mares were inseminated and embryos were recovered. In Experiment 3, the ovulatory stimulus was administered 9 h (autologous) and 15 h (allogeneic) before IFOT. In Experiment 4, only allogeneic COCs were used; the ovulatory stimulus was administered 9 or 15 h before IFOT. Excess embryos (autologous) and parentage-verified embryos (allogeneic) were considered IFOT-derived. RESULTS: In Experiment 1, 36/54 IFOT oocytes (67%) were recovered, of which 56% were mature, vs. 49% of in vitro matured oocytes (P > 0.1). After ICSI, blastocyst rates were 25% and 18%, respectively (P > 0.1). In Experiment 2, 0/6 autologous and 2/6 allogeneic IFOT yielded IFOT-derived embryos. In Experiment 3, 0/7 autologous and 2/5 allogeneic IFOT yielded IFOT-derived embryos. The proportion of mares yielding IFOT-derived embryos was lower after autologous vs. allogeneic IFOT (0/13 vs. 4/11; P < 0.05). In Experiment 4, 1/8 9-h and 1/7 15-h IFOT yielded IFOT-derived embryos. CONCLUSIONS: Transferred oocytes mature within the follicle and can maintain developmental competence. Allogeneic IFOT was more efficient than was autologous IFOT. The time of ovulatory stimulation did not affect embryo yield. The IFOT procedure is still not repeatable enough to be recommended for clinical use.

Megalin is an endocytic receptor for insulin.

Renal clearance is a major pathway for regulating the levels of insulin and other low molecular weight polypeptide hormones in the systemic circulation. Previous studies have shown that the reabsorption of insulin from the glomerular filtrate occurs by binding to as yet unidentified sites on the luminal surface of proximal tubule cells followed by endocytosis and degradation in lysosomes. In this study, an insulin binding site was identified in renal microvillar membranes by chemical cross-linking procedures. By immunoprecipitation it was demonstrated that this binding site is megalin, the large multiligand binding endocytic receptor that is abundantly expressed in clathrin-coated pits on the apical surface of proximal tubule cells. Moreover, using cytochemical procedures, it was also shown that megalin is able to internalize insulin into endocytic vesicles. In ligand blotting assays, megalin also bound several other low molecular weight polypeptides, including beta2-microglobulin, epidermal growth factor, prolactin, lysozyme, and cytochrome c. These data suggest that megalin may play a significant role as a renal reabsorption receptor for the uptake of insulin and other low molecular weight polypeptides from the glomerular filtrate.

Mapping rat megalin: the second cluster of ligand binding repeats contains a 46-amino acid pathogenic epitope involved in the formation of immune deposits in Heymann nephritis.

Megalin (gp330), an epithelial endocytic receptor, is a major target antigen of Heymann nephritis (HN), an autoimmune disease in rats. To elucidate the mechanisms of HN, we have mapped a pathogenic epitope in megalin that binds anti-megalin antibodies. We focused our attention on four clusters of cysteine-rich, low density lipoprotein receptor (LDLR) ligand binding repeats in the extracellular domain of megalin because they represent putative ligand binding regions and therefore would be expected to be exposed in vivo and to be able to bind circulating antibodies. Rat megalin cDNA fragments I through IV encoding the first through fourth clusters of ligand-binding repeats, respectively, were expressed in a baculovirus system. All four expression products were detected by immunoblotting with two antisera capable of inducing passive HN (pHN). When antibodies eluted from glomeruli of rats with pHN were used for immunoblotting, only the expression product encoded by fragment II was detected. This indicates that the second cluster of LDLR ligand binding repeats is directly involved in binding anti-megalin antibodies and in the induction of pHN. To narrow the major epitope in this domain, fragment II was used to prepare proteins sequentially truncated from the C- and N-terminal ends by in vitro translation. Analysis of the truncated translation products by immunoprecipitation with anti-megalin IgG revealed that the fifth ligand-binding repeat (amino acids 1160-1205) contains the major epitope recognized. This suggests that a 46-amino acid sequence in the second cluster of LDLR ligand binding repeats contains a major pathogenic epitope that plays a key role in pHN. Identification of this epitope will facilitate studies on the pathogenesis of HN.

Stability of beta-lactamase inhibitors and beta-lactam antibiotics in parenteral dosage forms and in body fluids and tissue homogenates: a comparative study of sulbactam, clavulanic acid, ampicillin and amoxycillin.

The beta-lactamase inhibitors and the beta-lactam antibiotics differ appreciably in chemical stability. A comparative study of four different infusion solutions at 4, 25 and 37 degrees C yielded the following descending sequence of stability: sulbactam (CAS 68373-14-8), ampicillin (CAS 69-53-4), amoxycillin (CAS 61336-70-7) and clavulanic acid (CAS 58001-44-8). Especially noteworthy was that the two beta-lactamase inhibitors, sulbactam and clavulanic acid, behaved very differently. Moreover, sulbactam is markedly more stable than clavilanic acid even when incubated at 37 degrees C in body fluids or tissue homogenates. The differences in the chemical stability of these pharmacological agents should be taken into consideration in the therapeutic use of combination preparations such as sulbactam/ampicillin (Unacid(R)) and clavulanic acid/amoxycillin.

[Are there predictors for impulsive, homicidal-suicidal acts of violence]. / Gibt es Prädiktoren für impulsive, homizidal-suizidale Gewalttaten?

Patient's statements or fears that they may "go crazy" and harm themselves or persons around them are rare, but extremely difficult for all participants to deal with. On the basis of the existing, unsatisfactory literature as well as an analysis of 196 incidents of homicidal-suicidal violence designated by German media as "running amok" and fulfilling defined criteria, we examined whether or not there are predictors for the degree of potential danger inherent in such threats. Impulsive, homicidal-suicidal acts of violence among patients with psychiatric disorders often occur in environments characterised by chronic psychosocial estrangement and isolation. Extremely distressing situations may trigger the course of violence, but the actual act is often planned during a seemingly peaceful interval. Personalities with a high affinity to weapons and a tendency toward acting out seem to increase the potential risks. Such events should be treated analogous to suicidal crises, with a strategy that takes the individual disorder into consideration. The parameters investigated in this paper are not sufficient, even in different combinations, to offer a satisfactory explanation or predict the occurrence of this extremely rare behaviour; further research is necessary.

A structural and functional comparison of the latency-associated transcript promoters of herpes simplex virus type 1 strains KOS and McKrae.

The promoters of the latency-associated transcripts (LATs) of herpes simplex virus type 1 (HSV-1) strains KOS and McKrae were compared to examine their influence upon the reactivation phenotypes of these two strains. Unlike strain KOS, McKrae is readily reactivable using in vivo reactivation models. We found greater than 96% sequence conservation between KOS and McKrae in the LATs promoter region, and both promoters showed equivalent basal and inducible activities. An inter-strain recombinant (termed MK13) was constructed in which the LATs promoter of HSV-1 McKrae was recombined into the background of HSV-1 strain KOS. In a murine u.v. light-induced reactivation model, virus shedding was detected by eye swabbing in two of 44 (5%) mice infected with KOS, 20 of 42 (48%) mice infected with McKrae and none of 45 (0%) mice infected with MK13. These data show that the LATs promoters of these viruses are structurally and functionally similar and that transfer of the LATs promoter from McKrae into KOS is insufficient to confer a reactivatable phenotype.

["Running amok"--content analytic study of 196 news presentations from industrialized countries]. / "Amokläufer"--kontentanalytische Untersuchung an 196 Pressemitteilungen aus industrialisierten Ländern.

We performed a content analysis study based on 196 reports in the German press published during the last decade on acts of violence designated as "going berserk" or "running amok (amuck)" and meeting defined criteria. With less than one person per one million men per year running berserk or amok, this is a very rare act of violence, albeit a very dangerous one involving 1.3 deaths and 1.7 injuries per case. Offenders differ from the normal population in regards to the small percentage of women (5%) and high unemployment (40%), and from other violent offenders in that they are normally occupationally well-qualified. Severe psychiatric disorders are overrepresented. A total of 108 cases were classified according to specific syndromes either by specialists or experts on the spot, or on the basis of a description of the signs and symptoms. Of the syndrome-related acts, the most dangerous offences were committed by 10 delusionally ill and 2 psychopathic individuals. 30 less dangerous offenders suffered from paranoid-hallucinatory syndromes. 28 crimes committed in a state of intoxication and 11 "crimes of passion" were the least dangerous. Another 25 persons with an extensive incidence of suicide in the family, without any apparent pre-existing psychiatric disorder, may have gone berserk in the course of a depressive syndrome. Although psychotically ill individuals tend to overreact more often following a minimal slight, under delusions or with no apparent reason at all, on the whole the causes for both the psychotic and other offenders are of a serious nature. Object loss and private disputes on the one hand and social conflicts on the other were of approximately equal significance. The relationship between the offender and his victim is more essential for the course of the occurrence than motives or the type of the psychopathological syndrome. If only family members are attacked, the offenders have usually been inconspicuous, elderly individuals, two thirds of whom can not be allocated to a given syndrome and may be depressive. They kill deliberately and on-target, do not merely injure their victims--hardly ever, in fact--and then commit suicide practically without exception. If strangers are the target of violence, the crimes are generally committed by younger, passive-aggressive, psychopathic, paranoid or intoxicated offenders. They kill only about half of their victims, but injure many, also causing a great deal of damage. They rarely commit suicide.(ABSTRACT TRUNCATED AT 400 WORDS)

In vivo characterization of site-directed mutations in the promoter of the herpes simplex virus type 1 latency-associated transcripts.

Transient expression assays in PC12 cells showed that the cAMP response element (CRE) and the TATA box of the herpes simplex virus type 1 latency-associated transcripts (LATs) promoter are essential for basal expression. Recombinant viruses were generated containing site-specific mutations in these motifs. The abilities of these recombinants to replicate, express LATs and reactivate from latency were compared with wild-type and marker-rescued viruses in a murine ocular model. The acute replication of these TATA and CRE mutant viruses was at a level equivalent to their respective marker-rescued viruses. The reactivation of virus was unaffected by mutation in the TATA box as compared with wild-type or marker-rescued viruses. In situ hybridization of TATA box mutant virus-infected ganglia, however, showed threefold fewer LAT-positive neurons than wild-type virus-infected ganglia, with consistently weaker hybridization signals. Thus, this TATA box is required for normal expression of the LATs but not for efficient reactivation. The LATs CRE mutant reactivated with slightly but reproducibly reduced frequency and delayed kinetics relative to marker-rescued virus. By in situ hybridization, however, the percentage and intensity of LATs-positive neurons were found to be comparable for the CRE mutant- and wild-type virus-infected ganglia, suggesting that the CRE is dispensable for abundant LATs expression but that a reactivation function of the LATs may depend upon the presence of the CRE. Finally, using a modified assay for examining the timing of reactivation, we showed that the induction of viral reactivation by addition of exogenous cAMP can occur independently of the LATs.

["Endogeniform" affective psychoses and normal pressure hydrocephalus]. / "Endogeniforme" affektive Psychosen und Normaldruckhydrozephalus.

Four patients with neuroradiological evidence of normal pressure hydrocephalus and psychiatric diagnosis of affective psychoses with major depression--like characteristics are presented. Three patients underwent shunting operations following an observation period of 2 to 6 years. During the post-operative follow-up of 3 to 7 years, resp., no clinical changes were noted. In our opinion, and following critical evaluation of the available literature, major depression--like affective disorders in normal-pressure hydrocephalus are not influenced by shunting operations, unless they occur simultaneously as an additional symptom in an Adams-Hakim syndrome with definite progression.

[Anorectic reactions in low intelligence]. / Anorektische Reaktionen bei Intelligenzminderung.

Six female in-patients suffering from anorectic reaction are described. Difficulties in diagnosis and differences between these patients and anorectic patients of normal intelligence are discussed. The main finding is that in all six cases there was an extremely close and symbiotic mother-child relationship and a weak or absent father. Relevant life events in the nuclear family (new partner for the mother, illness in the father) then triggered the eating disorder.

[Validity of the Beck Depression Inventory for cross-cultural comparisons. A study of German and Egyptian patients]. / Zur Validität des Beck-Depressionsinventars (BDI) für interkulturelle Vergleiche. Eine Untersuchung an deutschen und ägyptischen Patienten.

The present study compares self-rated depressive symptoms of 95 inpatients with depressive syndromes: 45 in Germany and 50 in Egypt. In each country, 50 patients suffering from acute internal diseases served as controls. Psychiatric patients were selected according to DSM-III criteria for major depressive disorder (MDD). Depressive symptoms and depth of depression were scored by the Beck Depression Inventory (BDI). The self-rating of depressive symptoms proved sufficient for transcultural comparison, provided controls are used, and was more practicable than observer rating scales. The results indicate higher BDI total scores for Egyptian than for German inpatients. This appear to be due to cultural differences, presumably mostly in language performance ("tendency to hyperbole"). Moreover, Egyptians complained more about somatic symptoms, as has already been frequently suggested on the basis of clinical observations.

[Inpatient management of adolescent psychiatric patients. A single day study]. / Die stationäre Versorgung jugendpsychiatrischer Patienten. Eine Stichtagsuntersuchung.

The distribution of disorders in a one-day sample of 1806 adolescents receiving inpatient psychiatric care and classified with the diagnostic system ICD-9 is described. Of the inpatient psychiatric facilities for adolescents in the Federal Republic of Germany and West Berlin, 85% responded to our questionnaire. The main findings were: 1) More of the inpatients were male than female (1:0.8); 2) 80% of the patients were being treated at non-university facilities; 3) differences in diagnose between university and other hospitals were small and concerned only psychosis, eating disorders and oligophrenia; 4) the most frequent diagnoses were psychosis and neurosis (20% each), followed by special symptoms/syndromes and conduct disorders (between 10% and 15% each) and emotional disorders (10%); 5) other disorders were less common (under 10% each); 6) a comparison of the different Länder in the Federal Republic indicated that some regions do not have enough inpatient facilities.

[Stability of beta-lactamase inhibitors and beta-lactam antibiotics in parenteral formulations as well as in body fluids and tissue homogenates. Comparison of sulbactam, clavulanic acid, ampicillin and amoxicillin]. / Stabilität von beta-Lactamase-Inhibitoren und beta-Lactam-Antibiotika in parenteralen Darreichungsformen sowie in Körperflüssigkeiten und Gewebehomogenaten. Vergleichende Untersuchung von Sulbactam, Clavulansäure, Ampicillin und Amoxicillin.

Stability of beta-Lactamase Inhibitors and beta-Lactam Antibiotics in Parenteral Formulations as Well as in Body Fluids and Tissue Homogenates/Comparative studies with sulbactam, clavulanic acid, ampicillin and amoxicillin. The beta-lactamase inhibitors and the beta-lactam antibiotics are markedly different in chemical stability. The comparative examination of 4 different infusion solutions at 4 degrees C, 25 degrees C and 37 degrees C gives the following sequence of decreasing stability: sulbactam (CAS 68373-14-8), ampicillin (CAS 69-53-4), amoxicillin (CAS 61336-70-7) and clavulanic acid (CAS 58001-44-8). It is particularly striking that the two beta-lactamase inhibitors, sulbactam and clavulanic acid, behave very differently. Sulbactam is also much more stable than clavulanic acid to incubation at 37 degrees C in body fluids or in tissue homogenates. The differences in the stability of the individual drugs should be born in mind during clinical use of combination formulations such as sulbactam/ampicillin (Unacid) and clavulanic acid/amoxicillin.

[Differentiation of suicide and parasuicide. A study of the last letters of suicidal patients]. / Zur Differenzierung von Suizid und Parasuizid. Eine Untersuchung an Abschiedsbriefen suizidaler Patienten.

The paper presents a content-analytical comparison between "last letters" of suicidals (SUI) and parasuicidals (PARA). So far studies on this topic are mostly performed by "external" parameters, e.g. sociodemographic or anamnestic data. The content-analytical approach provides to describe the presuicidal situation on base of "internal" variables. Compared with the suicidal notes the parasuicidal communication can be evaluated as more ambivalent, emotionally disturbed, and cognitively restricted. The successful reclassification of the notes into the two samples by a stepwise discriminant analysis supports the hypothesis, that both groups are distinct even on base of internal variables.