[Mechanisms regulating the selective release of follicle-stimulating hormone].

Selective secretion of FSH, involving no apparent changes in LH secretion, was studied in cycling rat females in the late proestrus and early estrus stages. The preovulatory wave of LH and FSH secretion, observed in the second half of the day of proestrus was associated with elevation of the levels of nuclear estrogenic and androgenic receptors. High concentrations of both receptor types were seen during a secondary elevation of FSH secretion early in the morning in the estrus stage. Administration of phentolamine (alpha-adrenoreceptor blocker) did not influence blood levels of FSH and LH in the estrus stage early hours. Administration of a dopamine blocker haloperidol inhibited the second wave of FSH secretion, this being paralleled by a reduction of the number of estradiol nuclear receptors. The authors suggest that estrogenic and androgenic receptors of adenohypophysis and dopaminergic systems of the brain contribute to the mechanism of regulation of the second phase of FSH increased secretion observed in the early morning hours of the estrus stage, the dopamine effect on FSH release being mediated via estradiol receptors.


Babesia ovata: isolation from erythrocytes and development of an enzyme-linked immunosorbent assay for detection of antibodies.

A method of isolating Babesia ovata merozoites from infected erythrocytes and an enzyme-linked immunosorbent assay (ELISA) for the detection of anti-B. ovata antibodies were developed. After B. ovata-infected erythrocytes had been lysed using the nitrogen cavitation method, the merozoites were separated from erythrocyte components by differential centrifugation and density-gradient centrifugation. The light microscopic examination showed that the purified merozoites were morphologically intact and contained few contaminants. Sodium dodecyl sulfate-polyacrylamide electrophoretic (SDS-PAGE) analysis revealed that the merozoite fraction contained very little contamination with erythrocyte components. The merozoites thus obtained were sonicated and treated with Triton X-100 and then used as an antigen to measure anti-B. ovata antibodies in ELISA. The ELISA was more sensitive in detecting anti-B. ovata antibodies than was either the indirect fluorescent antibody test or the complement fixation test on sera from cattle infected with B. ovata.


Characterization of anti-Neospora caninum hyperimmune rabbit serum by western blot analysis and immunoelectron microscopy.

The antigens recognized by hyperimmune rabbit serum raised against tachyzoites of the NC-1 isolate of Neospora caninum were characterized using chemiluminescent Western blotting, immunogold-silver staining and immunoelectron microscopy. Approximately 20 immunodominant antigens whose relative rates of migration were 16-80 kDa were recognized by the serum in Western blots using reduced or nonreduced parasite antigen preparations. The nonreduced parasite antigens were more strongly recognized by the serum than were the reduced antigen preparations. Immunoelectron microscopy revealed that the rabbit-serum-labeled antigens were localized to some organelles of N. caninum tachyzoites and to the parasitophorous vacuole surrounding them. In particular, antigens found in the dense granules, in the micronemes, and in the posterior portion of the rhoptries were strongly labeled by an indirect immunogold-labeling technique.


Stage-associated risk of transmission of the Lyme disease spirochete by European Ixodes ticks.

To more closely define the risk of infection by the agent of Lyme disease in Europe, we determined whether spirochetal prevalence increases throughout the development of the Ixodes ricinus vector tick. Of all ticks that could be flagged from vegetation, I. ricinus were by far the most abundant. Spirochetal infection rates in the adult stage of this tick (15%) are no higher than those in nymphs (18%) but greatly exceed those in larvae (0.7%). This tick therefore appears to attain infection mainly from the host of its larval stage, generally feeds on hosts that are noncompetent as reservoirs in its nymphal stage, and rarely inherits infection. Risk of human infection mainly derives from contact with the nymphal stage of the vector tick because the larva is rarely infected and the adult is large enough to be noticed and promptly removed.


Demonstration of extrachromosomal DNA from Babesia equi merozoites.

An extrachromosomal nucleic acid element was detected in high-molecular-weight DNA preparations form Babesia equi merozoites. This extrachromosomal element was shown to be DNA rather than RNA and had an apparent fragment size of about 9 kilobase-pairs (kb). Hybridization experiments using purified 9-kb DNA as a probe revealed sequence homologies with extrachromosomal DNA from two other Babesia species.


Site-directed mutagenesis and X-ray crystallography of two phospholipase A2 mutants: Y52F and Y73F.

Tyr52 and Tyr73 are conserved amino acid residues throughout all vertebrate phospholipases A2. They are part of an extended hydrogen bonding system that links the N-terminal alpha-NH3(+)-group to the catalytic residues His48 and Asp99. These tyrosines were replaced by phenylalanines in a porcine pancreatic phospholipase A2 mutant, in which residues 62-66 had been deleted (delta 62-66PLA2). The mutations did not affect the catalytic properties of the enzyme, nor the folding kinetics. The stability against denaturation by guanidine hydrochloride was decreased, however. To analyse how the enzyme compensates for the loss of the tyrosine hydroxyl group, the X-ray structures of the delta Y52F and delta Y73F mutants were determined. After crystallographic refinement the final crystallographic R-factors were 18.1% for the delta Y52F mutant (data between 7 and 2.3 A resolution) and 19.1% for the delta Y73F mutant (data between 7 and 2.4 A resolution). No conformational changes occurred in the mutants compared with the delta 62-66PLA2, but an empty cavity formed at the site of the hydroxyl group of the former tyrosine. In both mutants the Asp99 side chain loses one of its hydrogen bonds and this might explain the observed destabilization.


3-D structure of a mutant (Asp101-->Ser) of E.coli alkaline phosphatase with higher catalytic activity.

Mutagenesis of the absolutely conserved residue Asp101 of the non-specific monoesterase alkaline phosphatase (E.C. 3.1.3.1) from E. coli has produced an enzyme with increased kcat. The carboxyl group of the Asp101 residue has been proposed to be involved in the positioning of Arg166 and the formation of the helix that contains the active site Ser102. The crystal structure of the Asp101-->Ser mutant has been refined at 2.5 A to a final crystallographic R-factor of 0.173. The altered active site structure of the mutant is compared with that of the wild-type as well as with the structures of the mutant enzyme soaked in two known alkaline phosphatase inhibitors (inorganic phosphate and arsenate). The changes affect primarily the side chain of Arg166 which, by losing the hydrogen bond interaction with the carboxyl side chain of Asp101, becomes more flexible. This analysis, in conjunction with product inhibition studies of the mutant enzyme, suggests that at high pH (> 7) the enzyme achieves a quicker catalytic turnover by allowing a faster release of the product.


The structural consequences of exchanging tryptophan and tyrosine residues in B. stearothermophilus lactate dehydrogenase.

A mutant Bacillus stearothermophilus lactate dehydrogenase has been prepared in which all three tryptophan residues in the wild-type enzyme have been replaced by tyrosines. In addition, a tyrosine residue has been mutated to a tryptophan, which acts as a fluorescence probe to monitor protein folding. The mutant enzyme crystallizes in the same crystal form as the wild-type. The crystal structure of the mutant has been determined at 2.8 A resolution. Solution studies have suggested that there is little effect upon the mutant enzyme as judged by its kinetic properties. Comparison of the crystal structures of the mutant and wild-type enzymes confirms this conclusion, and reveals that alterations in structure in the region of these mutations are of a similar magnitude to those observed throughout the structure, and are not significant when compared with the errors in atomic positions expected for a structure at this resolution.


A new approach to the design of a sequence with the highest affinity for a molecular surface.

We describe an algorithm to design the primary structures for peptides which must have the strongest binding to a given molecular surface. This problem cannot be solved by a direct combinatorial sorting, because of an enormous number of possible primary and spatial structures. The approach to solve this problem is to describe a state of each residue by two variables: (i) amino acid type and (ii) 3-D coordinate, and to minimize binding energy over all these variables simultaneously. For short chains which have no long-range interactions within themselves, this minimization can be done easily and efficiently by dynamic programming. We also discuss the problem of how to estimate specificity of binding and how to deduce a sequence with maximal specificity for a given surface. We show that this sequence can be deduced by the same algorithm after some modification of energetic parameters.


Detection of secondary structure elements in proteins by hydrophobic cluster analysis.

Hydrophobic cluster analysis (HCA) is a protein sequence comparison method based on alpha-helical representations of the sequences where the size, shape and orientation of the clusters of hydrophobic residues are primarily compared. The effectiveness of HCA has been suggested to originate from its potential ability to focus on the residues forming the hydrophobic core of globular proteins. We have addressed the robustness of the bidimensional representation used for HCA in its ability to detect the regular secondary structure elements of proteins. Various parameters have been studied such as those governing cluster size and limits, the hydrophobic residues constituting the clusters as well as the potential shift of the cluster positions with respect to the position of the regular secondary structure elements. The following results have been found to support the alpha-helical bidimensional representation used in HCA: (i) there is a positive correlation (clearly above background noise) between the hydrophobic clusters and the regular secondary structure elements in proteins; (ii) the hydrophobic clusters are centred on the regular secondary structure elements; (iii) the pitch of the helical representation which gives the best correspondence is that of an alpha-helix. The correspondence between hydrophobic clusters and regular secondary structure elements suggests a way to implement variable gap penalties during the automatic alignment of protein sequences.


Potential of genetic algorithms in protein folding and protein engineering simulations.

Genetic algorithms are very efficient search mechanisms which mutate, recombine and select amongst tentative solutions to a problem until a near optimal one is achieved. We introduce them as a new tool to study proteins. The identification and motivation for different fitness functions is discussed. The evolution of the zinc finger sequence motif from a random start is modelled. User specified changes of the lambda repressor structure were simulated and critical sites and exchanges for mutagenesis identified. Vast conformational spaces are efficiently searched as illustrated by the ab initio folding of a model protein of a four beta strand bundle. The genetic algorithm simulation which mimicked important folding constraints as overall hydrophobic packaging and a propensity of the betaphilic residues for trans positions achieved a unique fold. Cooperativity in the beta strand regions and a length of 3-5 for the interconnecting loops was critical. Specific interaction sites were considerably less effective in driving the fold.


Protein secondary structure prediction using logic-based machine learning.

Many attempts have been made to solve the problem of predicting protein secondary structure from the primary sequence but the best performance results are still disappointing. In this paper, the use of a machine learning algorithm which allows relational descriptions is shown to lead to improved performance. The Inductive Logic Programming computer program, Golem, was applied to learning secondary structure prediction rules for alpha/alpha domain type proteins. The input to the program consisted of 12 non-homologous proteins (1612 residues) of known structure, together with a background knowledge describing the chemical and physical properties of the residues. Golem learned a small set of rules that predict which residues are part of the alpha-helices--based on their positional relationships and chemical and physical properties. The rules were tested on four independent non-homologous proteins (416 residues) giving an accuracy of 81% (+/- 2%). This is an improvement, on identical data, over the previously reported result of 73% by King and Sternberg (1990, J. Mol. Biol., 216, 441-457) using the machine learning program PROMIS, and of 72% using the standard Garnier-Osguthorpe-Robson method. The best previously reported result in the literature for the alpha/alpha domain type is 76%, achieved using a neural net approach. Machine learning also has the advantage over neural network and statistical methods in producing more understandable results.


Molecular mechanics analysis of inhibitor binding to HIV-1 protease.

Crystallographic structures of HIV protease with three different peptide-mimetic inhibitors were subjected to energy minimization using molecular mechanics, the minimized structures analyzed and the inhibitor binding energies calculated. Partial charge assignment for the hydrogen bonded catalytic aspartic acids, Asp25 and -25', was in good agreement with charge calculations using semi-empirical molecular orbital methods. Root mean square deviations on minimization were small and similar for both subunits in the protease dimer. The surface loops, which had the largest B factors, changed most on minimization; the hydrophobic core and the inhibitor binding site showed little change. The distance-dependent dielectric of D(r) = 4r was found to be preferable to D(r) = r. Distance restraints were applied for the intermolecular hydrogen bonds to maintain the conformation of the inhibitor binding site. Using the dielectric of D(r) = 4r, the calculated interaction energy of the three inhibitors with the protease ranged from -53 to -56 kcal/mol. The psi groups of the inhibitors were changed to add or remove a 'transition state analogue' hydroxyl group, and the loss in energy on the removal of this group was calculated to be 0.9-1.7 kcal/mol. This would represent 19-36% of the total measured difference in binding energy between the inhibitors JG365 and MVT-101.


The T<-->R structural transition of insulin; pathways suggested by targeted energy minimization.

The transition of insulin between its crystallographically defined states T and R is connected with considerable change even of backbone structure: the N-terminal B chain (residues B1-B8) refolds from extended conformation in T into helical in R, and vice versa. Although hitherto observed only in hexamers the transition of the monomer was adequate for developing and testing the method of 'targeted energy minimization' (TEM), capable of coping with conformational changes of such extent at moderate computational expenditure. The simulation is performed in a predetermined number of steps consisting of two atomic displacements each, one by force in the direction of the target structure, the second by energy minimization releasing the constraint caused in the first. The transition pathway is represented by the string of energy minimized transient structures. Due to the directedness of the algorithm the simulated pathway for R-->T is not the reversal of that for T-->R. It is, therefore, not pretended that the minimum energy pathway was identified. In the T-->R direction the N-terminal B chain first swivels while remaining largely stretched and then winds up extending the pre-existing helix B9-B19. The A chain advances into the space abandoned and withdraws from it in the R-->T simulation. In the latter the extended helix first kinks at B8/B9, and then the B1-B8 segment is unwound and stretched. The helical H-bonds of that segment are formed late in T-->R and are maintained during almost half of R-->T. The AN helix is less stable and more involved in the transitions than helix AC.(ABSTRACT TRUNCATED AT 250 WORDS)


Site-saturation mutagenesis and three-dimensional modelling of ROB-1 define a substrate binding role of Ser130 in class A beta-lactamases.

Site-saturation mutagenesis was performed on the class A ROB-1 beta-lactamase at conserved Ser130, which is centrally located in the antibiotic binding site where it can participate in both protein-protein and protein-substrate hydrogen bonding. Mutation Thr130 gave a beta-lactamase hydrolysing penicillins and cephalosporins but which showed a 3-fold lower affinity (Km) for ampicillin and cephalexin, and a 30-fold lower hydrolytic (Vmax) activity for ampicillin. In contrast, the hydrolytic activity for cephalexin was similar to the wild-type for the Thr130 mutation. Mutation Gly130 gave a beta-lactamase hydrolysing only penicillins with an affinity and hydrolysis activity for these compounds approximately 15-fold lower than the wild-type, but no detectable activity against cephalosporins. Mutation Ala130 produced an enzyme capable of hydrolysing penicillins only at a low rate. Modelling the ROB-1 active site was done from the refined 2 A X-ray structure of the homologous Bacillus licheniformis beta-lactamase. Ampicillin and cephalexin were docked into the active site and were energy minimized with the CVFF empirical force field. Dockings were stable only when Ser70 was made anionic and Glu166 was made neutral. Interaction energies and distances were calculated for fully hydrated pre-acylation complexes with the Ser, Thr, Gly and Ala130 enzymes. The catalytic data from all mutations and the computed interactions from modelling confirmed that the Ser130 has a structural as well as a functional role in binding and hydrolysis of penicillins. This highly conserved residue also plays a substrate specificity role by hydrogen binding the carboxylic acid group of cephalosporins more tightly than penicillins.


A molecular dynamics simulation of bacteriophage T4 lysozyme.

An analysis of a 400 ps molecular dynamics simulation of the 164 amino acid enzyme T4 lysozyme is presented. The simulation was carried out with all hydrogen atoms modeled explicitly, the inclusion of all 152 crystallographic waters and at a temperature of 300 K. Temporal analysis of the trajectory versus energy, hydrogen bond stability, r.m.s. deviation from the starting crystal structure and radius of gyration, demonstrates that the simulation was both stable and representative of the average experimental structure. Average structural properties were calculated from the enzyme trajectory and compared with the crystal structure. The mean value of the C alpha displacements of the average simulated structure from the X-ray structure was 1.1 +/- 0.1 A; differences of the backbone phi and psi angles between the average simulated structure and the crystal structure were also examined. Thermal-B factors were calculated from the simulation for heavy and backbone atoms and both were in good agreement with experimental values. Relationships between protein secondary structure elements and internal motions were studied by examining the positional fluctuations of individual helix, sheet and turn structures. The structural integrity in the secondary structure units was preserved throughout the simulation; however, the A helix did show some unusually high atomic fluctuations. The largest backbone atom r.m.s. fluctuations were found in non-secondary structure regions; similar results were observed for r.m.s. fluctuations of non-secondary structure phi and psi angles. In general, the calculated values of r.m.s. fluctuations were quite small for the secondary structure elements. In contrast, surface loops and turns exhibited much larger values, being able to sample larger regions of conformational space. The C alpha difference distance matrix and super-positioning analyses comparing the X-ray structure with the average dynamics structure suggest that a 'hinge-bending' motion occurs between the N- and C-terminal domains.


Immunological manipulation of adiposity.

Although hormonal regulators of adiposity are available they as yet have not been licensed for use. Withdrawal periods and delivery systems are still potential problems in maximizing their effectiveness. Immunization techniques, on the other hand, suffer none of the problems of withdrawal periods or requirement for frequent injection/implantation. As such they are clearly perceived as safe, economic and should have a positive animal welfare image. They are, however, not without their problems. Active immunization in particular involves an autoimmune response and this is typically difficult to evoke and virtually impossible to regulate. In addition, the fact that antibodies may have immunoneutralizing and immunoenhancing properties may explain the apparently contradictory results obtained in various studies as, for example, in the case of immunization against somatostatin. As our knowledge of immune responsiveness and its control increases, however, the possibilities for immune intervention should increase considerably. We may then be faced with ethical rather than practical limitations as to how far we should manipulate growth and body composition.


A process of mutual support. Establishing a support network for nurses caring for dying patients.

Caring for dying patients and their families is demanding and stressful. In order to help patients in their time of greatest need, nurses themselves require support from management and colleagues. A support network can provide nurses with a structured programme of support and guidance.


Positive use of a traumatic reawakening. Therapy with incest survivors.

A wide range of triggers can reawaken long suppressed memories of childhood sexual abuse. Analytic psychotherapy can bring such memories out into the open, often enabling clients to reassess both their past and present relationships.


Taking the heat out of burns. Nursing management of burns.

Burns constitute a serious and distressing injury. It is essential that nursing care takes on an holistic approach, focusing jointly on the physical and psychological effects.


Treatment leads to significant improvement. Effect of conservative treatment on pain in lymphoedema.

Pain is a common complaint in patients with secondary upper limb lymphoedema related to breast cancer. This study shows how standard conservative treatment of lymphoedema can result in a significant reduction in pain and decreased limb volume.


A safe way to reduce the symptoms? Advising women on hormone replacement therapy.

Hormone replacement therapy (HRT) counters the symptoms associated with the menopause, and can improve quality of life. As with any form of treatment, HRT has both advantages and disadvantages, and women must be told about these so they can make an informed choice.


The hydration question. Hydration or dehydration of terminally ill patients.

Hydration of terminally ill patients is a controversial issue. This study assesses the reasons why doctors and nurses in hospital and hospice settings do or do not undertake this procedure.


Surgical intervention for oesophageal atresia with tracheo-oesophageal fistula.

1. This condition is a congenital condition occurring in 1:3,500 births. 2. The condition can be diagnosed in utero, then delivery can be arranged at a hospital with a neonatal unit. 3. Most cases can be easily treated with surgical intervention. 4. Most TOF babies thrive after surgery, and good nursing care increases their chances of healthy development.


Greater understanding enhances control. Maintaining pharmacological control of asthma.

1. Asthma is a syndrome--not a disease--which affects the bronchi in the lungs. 2. Asthma is a cause of substantial ill-health, and economic loss (due to sick leave) to both clients and society. 3. Agreed systems of management (protocols) between client and practitioner may help clients gain control over their condition.


Setting an example to improve quality of life. Care in the community for people with physical disabilities.

Care in the community is much lauded as a concept, but has yet to be fully implemented. A community care nursing service set up in Cambridgeshire provides one example of how community care can be effectively employed to benefit clients and carers.


Histamine analogues. 36th communication. Basically substituted histamine derivatives with H1-agonistic activity.

Piperidinoalkyl-, morpholinoalkyl- or [(pyrid-2-yl)methylthio]alkyl-substituents were introduced into position 2 of the essential histamine structure. These 2-substituted histamine derivatives were prepared via reaction of imidate hydrochlorides in liquid ammonia under pressure with 1,3-dihydroxypropanone followed by a stepwise build-up of the side chain in position 4 of the imidazole nucleus (route I) or by cyclization with 2-oxo-4-phthalimido-1-butyl acetate (route II) followed by deprotection of the primary amine function. The novel compounds were screened for H1-activity on the isolated guinea-pig ileum and for H2-activity on the isolated guinea-pig right atrium. While 10a, c-e proved to be weak partial H1-agonists, 10b, f were very weak H1-antagonists.


Thieno[2,3-d]pyrimidin-4(3H)-one derivatives and 1,2-dihydrogenated homologues: synthesis, enhanced in vitro antiaggregant activity for reduced compounds.

Some derivatives of thieno[2,3-d]pyrimidin-4(3 H)-one A and their 1,2-dihydrogenated homologues B were synthesized. The study of their in vitro antiaggregating activity showed that the first compounds exhibited significant inhibiting power when aggregation was induced with ADP. Their reduction to derivatives of 1,2-dihydrothieno[2,3-d]pyrimidin-4(3 H)-one led to a new series of molecules possessing a large antiaggregant activity. When compared to that of acetylsalicylic acid under the same conditions, this activity was the same with collagen or arachidonic acid-induced aggregation, but greater when aggregation was induced by ADP. Serotonin release was also inhibited.


[Anti-arrhythmic action of some amidinohydrazone substituted benzophenones. 1. Synthesis of new amidinohydrazone and N-phenylamidinohydrazone substituted benzophenones].

The title compounds are synthesized as a rule by condensation of substituted benzophenones and derivatives of aminoguanidine in the presence of up to 2.5 moles of an anorganic acid. They can be obtained alternatively via corresponding hydrazones, thiosemicarbazones or methylthiothiocarbonylhydrazones.


[Potential cardiotonics. 14. Synthesis and in vitro positive inotropic actions of 4-morpholino-5-(4-pyridinyl)pyridine derivatives].

By the reaction of 2-chloro-5-(4-pyridinyl)pyridines 1-6 with morpholine as well as by derivation of the 2-morpholino-pyridine-3-carboxamide 8 the 3-substituted 2-morpholino-5-(4-pyridinyl)pyridines 7-14 were prepared. The evaluation for positive inotropic properties in spontaneously beating isolated guinea pig atria gave for the 3-cyano derivative 7 (AWD 122-14) the best activity. The potency is comparable to that of milrinone and is due to partial by inhibition of phosphodiesterase III (PDE III).


Synthesis, structure and biological activity of 1,2,4-triazolo-1,3-thiazine derivatives.

A group of condensed triazole-thiazine derivatives (2a-i, 3b, 3j) was obtained in reaction of the corresponding 5-substituted 1,2,4-triazole-3-thiones (1a-j) with epichlorohydrin in alkaline medium. The structure of the compounds synthesized was confirmed by spectral and roentgenographic methods. Tuberculostatic and circulatory activities of the compounds were also studied.


Reactivity and microbiological activity of 2-methyl-3-carboethoxy-5-pyrrolinone derivatives.

This work describes the synthesis of 2-methyl-3-carboethoxy-5-pyrrolinone which was then allowed to react with aromatic aldehydes, nitromethines, benzendiazonium salts, hydrazine and amines. Several of the products have shown good results in preliminary antimicrobial and antifungal tests.


[Potential cardiotonics. 15. Crystal modifications of 3-cyano-2-morpholino-5-(4-pyridinyl)pyridine (AWD 122-14)].

The preparation and X-ray crystallographic characterisation of 10 polymorphic or pseudo-polymorphic forms of the novel cardiotonic AWD 122-14 are described. Thermic transformations of some polymorphic forms into the alpha-form was proved by thermogravimetric analysis and powder diffraction pattern. In dissolution behaviour no significant differences were found between the crystalline modifications but with regard to galenic processing compact alpha-, gamma- and epsilon-forms show advantages.


[Solid phase-sample preparation of ifosfamide and chloroethyl metabolites in biological material. 1. Determination in plasma and urine].

The cytostatic drug ifosfamide (IFF) and its main metabolites 2-dechloroethyl ifosfamide (2-D-IFF) and 3-dechloroethyl ifosfamide (3-D-IFF) were isolated from the plasma matrix with high recovery by solid phase extraction using Bakerbond C18-cartridges. A further cleaning of the extracts is not necessary. An effective separation of IFF and metabolites from interfering compounds present in urine samples prior gc was performed with Extrelut-1 and dichloromethane/isopropanol (95:5, v/v). The described assays may be used for pharmacokinetic studies as well as drug monitoring in the clinical laboratory.


[Mucus models for investigation of intestinal absorption mechanisms. 4. Comparison of mucus models with absorption models in vivo and in situ for prediction of intestinal drug absorption].

Intestinal absorption with an in vitro model using pig intestinal mucus was examined by means of in vivo and in situ experiments in the rat. With 10 compounds of different structure, in vitro, in situ, and in vivo models were tested. The in vitro model in the present form can only simulate the first step of intestinal absorption, namely diffusion through the mucus layer. Indeed, we found that one function of the intestinal mucus can be described being a molecular sieve with a molecular mass (MM) cut off within the range of about 600 to 700 [g/mol]. Absorption of substances with higher molecular mass remains at a low level. With the mucus model prediction of intestinal absorption of hydrophilic substances with MM < 600 to 700 [g/mol] will be possible, if the mass transport in the mucus layer is rate limiting. Independent of polarity, it is also valid for substances of MM > 600 to 700 [g/mol]. Estimation however, is not valid for lipophilic substances and MM < 600 to 700 [g/mol], when mass transport from the mucus to the adjacent compartments is rate limiting. Further optimization of the mucus model for a more extensive application seems possible and reasonable with respect to saving in vivo experiments with animals.


[Intuitive prognostic assessment in rehabilitation of long-term psychiatric patients].

The significance of intuitive prognostic assessments by the nursing staff and the examining female doctor is studied with regard to the course and results of "late rehabilitation" of 30 psychiatric patients who had been hospitalised for many years. Using standardised assessment criteria and catamnestic data on readmission as inpatients (covering a period of 20 months) patients were compared who had been discharged from the psychiatric hospital, transferred to long-term residential quarters, and assessed before discharge as likely or unlikely to be readmitted to the hospital. The group of patients who had been given an unfavourable prognosis--most of them women--proved in course of time to be readmitted as inpatients more often and to be significantly more disturbed than the patients who had been discharged with a more favourable prognosis. These results are discussed with regard to sociopolitical and medical care aspects and to approaches for further research in this direction.


[Follow-up options in institutional protection--"patient careers" in a comprehensive community psychiatric care system].

The recommendations for the reorganization of German psychiatry were associated with the expectation that institutional protection can be reduced in a comprehensive community care system on the longterm basis and that a stabilization can be achieved during treatment with a minimum share in full and partial hospitalization. To test this assumption we studied the institutional pathways of 136 chronic, mainly schizophrenic patients within the comprehensive care system of the Department of Social Psychiatry over two years. A cluster analysis of sequence and intensity of institutional care showed three major types of use of the system: as a rehabilitation system, as an alternative and flexible care system, and as a traditional "dual-care-system". These patterns of institutional pathways were analyzed regarding predictors from patient's history. Consequences are discussed concerning further development of community mental health, coordination of services and continuity of care.


[Occupational rehabilitation of psychiatric patients--results of a study of workshops for handicapped patients].

The situation of persons with mental illness, who work in workshops for the handicapped, and the problems they have to deal with, are discussed. Concepts of the psychology of work, which nearly have not been recognized in the field of vocational rehabilitation are described. In a study in several workshops the relationship between job conditions and social support at the workplace and the personnel development of the mentally ill was investigated. The results show that above all the perceived job characteristics as well as social support are important for a positive development of the personality--both at the workplace and during leisure time.


[Poverty on the psychiatric unit--a central problem in mental health treatment].

72 patients of the psychiatric department of the general hospital in Berlin Neukölln were interviewed unselectedly to the subjects of lodging and income with the help of a semistructured interview. Only 16 (22%) patients still had a job, 17 (24%) were without job and 31 (43%) were on pension. 10 patients (14%) were homeless, 12 patients (17%) lived in insufficient conditions of housing. Only 11 patients (15%) earned their own wage/salary. All together 25 patients (36%) were in some way dependent on support by social security. Half of the patients had a regular income of less than DM 1000.--a month. The everyday dealing with the problem of poverty on the ward is pointed out and discussed. Obviously this theme is not integrated enough in the therapeutic process. This subject can not only be delegated to the responsibility of the social worker.


[What must the community contribute to the managements of chronic psychiatric patients?--Reflections from England].

Chronically disabled psychiatric patients who are living outside hospital still need help. The degree of disability they show and the support which they receive from family or friends differs greatly. How they manage will depend on their ability to adapt and one can recognize the difference between those who adapt well in spite of disability and those for whom this is very difficult. In consequence their need for support from others varies. In England some national voluntary agencies traditionally offer support. However, today the combined work of voluntary organisations, hospitals and statutory community authorities in local areas is often impressive and two examples are described. Even so families are perhaps still the most important form of support although some are unable or unwilling to help. Other alternative forms of help noted are two-patient marriages, long-term hospital support of discharged patients and regular employment. Examples of innovations in Australia and the U.S.A. are also described.


[Multiple admissions to the psychiatric hospital--a study of the status of so-called "revolving door patients"].

The graph of the frequency distribution of rehospitalization shows a constant exponential decline without demarking a particular population of so-called "revolving-door" patients. Patients with at least four admissions to a regional psychiatry hospital within a time span of two years are compared to a control group of the total clinic population. Multiple admission patients suffer significantly more often from diseases with an unfavourable prognosis, the illness has started earlier in their lives, and the course of illness is marked by unstable dynamic states with frequent crises of suicide. A demographic analysis shows the group under survey to be younger and less often married; participation in the world of labour has been lost more often, schizophrenics who have frequently stayed in hospitals even loose their former autonomy in housing. Guardianships are significantly more often installed, but they have not proved to be an efficient form of help. The therapeutic care of this problem patients is rather unsatisfactory. The offered ambulatory services are not claimed and in hospital the special treatment units fail to reach these patients. Lack of therapeutic continuity and compliance determines the course of treatment and complicates therapeutic strategies.


[Delusion of possession in a Korean patient and therapy].

Through a Korean freechristian priest, who brought about an atmosphere of syncretism, a Korean patient was introduced by withdrawal of sleep into a shortterm state of artificial psychosis which lead to her attempting suicide. The therapeutic intervention based on the ideas of Rogers was successful in creating a basis of confidence between the patient and the doctor. Through this process it was possible to obtain further personal information, in particular concerning the patient's grandmother, who was a shamanistic mudang. In connection with the knowledge about the patient's cultural background and its ties to shamanism, and respecting the cultural content without evaluating it, a good presupposition was given for an effective therapy.


Clinical picture and long-term course of epileptic seizures that occur during clozapine treatment.

Clozapine is an atypical neuroleptic drug that has proved to be effective in alleviating psychotic symptoms refractory to treatment with standard neuroleptic drugs. In addition to hematological side effects, an increased susceptibility to epileptic seizures during clozapine treatment has previously been described. In this report, we describe the clinical picture and electroencephalographic findings of 12 schizophrenic patients who have had from one to six clozapine-associated epileptic convulsions.


Altered interleukin-2 production in schizophrenia: association between clinical state and autoantibody production.

Mitogen-stimulated interleukin-2 (IL-2) production was measured in 122 patients who met Research Diagnostic Criteria for schizophrenia and 98 normal control subjects. The presence of autoantibodies against seven common antigens was also determined. There was no relationship between the presence of circulating autoantibodies and IL-2 production in control subjects. In patients, however, autoantibody-positive, acutely ill patients had significantly lower IL-2 production as compared with other patients and control subjects. Never-medicated patients showed the same trends for decreased IL-2 production in association with autoantibodies. These data suggest that decreased IL-2 production is associated with acute illness in schizophrenic patients who produce autoantibodies, a trait known to be associated with increased vulnerability to autoimmune disease.


Attention, cognition, and motor perseveration in adolescents at genetic risk for schizophrenia and control subjects.

Twenty-three offspring of schizophrenic parents (mean age = 12.1 years, SD = 3.2) and 61 adolescent control subjects (mean age = 12.3 years, SD = 3.3) were compared in their performance of the following psychometric tests: simple reaction times (RTs), warned RTs in a monomodal and cross-modal design, d2 concentration test, a motor perseveration test, and a cognitive performance measure (Wechsler Intelligence Scale). The results were validated in a second analysis in which a subgroup of the control subjects were matched to the high-risk subjects for the following characteristics: age, gender, education, and environmental background. Significant deficits were found in the high-risk group in tests that required sustained attention and information processing under high perceptual load (RT measures and d2 concentration test). Deficits were particularly prominent for the processing of visual stimuli; sensory incongruence might also have been a contributor to this deficit. The attentional dysfunction of high-risk subjects might explain their tendency to show less structured behavior and distractibility as reflected by their higher entropy scores in a motor perseveration test. Cognitive evaluation showed a significant deficit in the high-risk group, primarily as reflected in the verbal IQ score.


Empirical assessment of the factorial structure of clinical symptoms in schizophrenic patients: formal thought disorder.

Male schizophrenic patients (n = 142) were examined with a clinical assessment of their language dysfunctions with the Scale for the Assessment of Thought, Language, and Communication (TLC). Confirmatory factor analyses were conducted to test the relative fit of several differential theoretical models of the factorial structure of thought disorders. The models examined were positive-negative thought disorder, a three-factor model based on the results of an earlier exploratory factor analysis, and a simpler verbal productivity-disconnection model that can be extracted from other exploratory analyses and empirical studies. The positive-negative thought disorder model failed to fit the data, while the three-factor model fit the data, but no better than the simpler verbal productivity-disconnection model.


Empirical assessment of the factorial structure of clinical symptoms in schizophrenia: negative symptoms.

The factor structure of the Scale for the Assessment of Negative Symptoms (SANS) was examined in a confirmatory factor analysis that used the LISREL procedure. Four models of negative symptom factors were tested in 130 hospitalized schizophrenic patients. A three-factor model of diminished expression, social dysfunction, and disorganization generated by the authors yielded a superior fit to the data relative to the two-factor model of Liddle (1987b) and a unifactorial severity model. A four-factor model based on the original subscale formulation of the SANS failed to fit the data.


Plasma tryptophan levels and plasma tryptophan/neutral amino acids ratio in patients with mood disorder, patients with obsessive-compulsive disorder, and normal subjects.

Fasting plasma tryptophan (TRP) levels and ratios of total plasma tryptophan to the sum of five large neutral amino acids (LNAAs)--tyrosine, phenylalanine, leucine, isoleucine, and valine--that compete with tryptophan for passage across the blood-brain barrier were found to be significantly lower in a group of 28 patients with major depression compared with 29 normal subjects and 21 patients with obsessive-compulsive disorder (OCD). The OCD group was divided in two subgroups: patients with OCD alone and patients with a co-diagnosis of major depression. Since it has been considered that these biological parameters reflect brain tryptophan and serotonin levels, our results suggest their importance in relation to the presence or absence of depressive symptoms. The values of the other LNAAs and their sum did not differ significantly among the groups.


Differential validity of psychometric tests in dementia of the Alzheimer type.

Forty-nine patients with a clinical diagnosis of probable dementia of the Alzheimer type underwent an extensive test battery designed to evaluate cognitive deficits according to NINCDS/ADRDA criteria. All patients demonstrated signs of impairment on this test battery. One day later, they were administered a second test battery that consisted of the Mini-Mental State Examination (MMS), the Alzheimer's Disease Assessment Scale (ADAS), the SKT test (SKT), and the Brief Cognitive Rating Scale (BCRS) to assess the construct validity, sensitivity, and possible shortcomings of these tests. A control group of 47 age-matched persons was administered the same test battery to allow a comparison with reference values from other studies. Due to the design of the study, values of controls and patients did not overlap. Intercorrelations in patients were above 0.65 (p < 0.05 after Bonferroni correction) for all four cognitive tests. The ADAS and BCRS appeared to document the whole course of the disease in patients studied. The best differentiation with the SKT test could be obtained in mild to moderate dementia; however, due to the test's construction, a floor effect demonstrated its limitations in the case of severe dementia. Results obtained with the MMSE indicated the contrary: a ceiling effect showed its lack of differentiation in mild dementia. Therefore, a combination of tests should be used in the evaluation of cognitive deficits in the course of dementia of the Alzheimer type.


Correlates of Tridimensional Personality Questionnaire Scales with selected Minnesota Multiphasic Personality Inventory Scales.

The pattern of correlations between selected MMPI scales and the scales of the Tridimensional Personality Questionnaire were examined in a convenience sample of 88 patients who had received both tests. Time between tests (usually less than one year) did not affect the correlations, but MMPI response-set variables (L, F, K, F-K) did. The Tridimensional Personality Questionnaire harm avoidance scale and subscales had many correlates on the MMPI. The Novelty seeking scale and subscales showed a number of moderate correlations with a smaller number of MMPI scales; these correlations did not significantly exceed the correlations with MMPI response-set variables. The Tridimensional Personality Questionnaire reward dependence scale and subscales had few, if any, significant MMPI correlates. It was also noted that no Tridimensional Personality Questionnaire scales were related to MMPI repression factor scores.


The fractal nature of the development of the self.

This paper provides a discussion of the life cycle using a framework constructed from ideas in chaos theory. Building upon psychodynamic ideas from Freud, Jung, and Erikson, the integration of the Self is discussed from the viewpoint of Analytical Psychology. It is proposed that throughout our lives we encounter crisis points that fractionate the ego and necessitate use of more complex and adaptive psychic structures to contain or handle the seemingly disparate qualities that arise. We may say that eventually one aspires to realize Analytical Psychology's goal of integrating the superior and the inferior functions of the psyche into a cohesive Self. Jung seemed to state that the Self could never be attained, but it is argued in this paper that a form of transitory self may be realized periodically during the course of the life cycle.


Existential anxiety as related to conceptualization of self and of death, denial of death, and religiosity.

82 students completed a questionnaire which measured their existential anxiety as described by Yalom, conceptualization of self and of death, denial of death, and religiosity. For these students, scores on existential anxiety correlated with identity confusion, feeling responsible toward others but fearing emotional closeness with them, seeing people as fundamentally different and not seeing oneself as living on in one's tasks or projects. Their existential anxiety scores were not related to a particular concept of death, but death was more likely to be seen as cold and denied. Their existential anxiety seemed symptomatic of adjustment problems for which religiosity was not helpful. Specific suggestions for further research are made.


Personality differences of sex offenders referred for treatment.

Personalities of 64 sex offenders (rapists, molesters, and incestuous types) referred for treatment were compared. No significant differences on MMPI scores or IQ were noted among subgroups of molesters. Significant trait anxiety indicated that molesters of both males and females had higher anxiety than incestuous offenders. Also, a significant difference was noted on state anxiety; all groups decreased scores over treatment. A significant effect of brief therapy also occurred for trait anxiety. All groups but incestuous offenders decreased on trait anxiety over 5-wk. therapy. Male and female molester groups decreased in self-esteem whereas incestuous types and rapists increased in self-esteem. Implications are provided for these results.


A multivariate analysis of weight-loss behavior.

This study used a theoretical framework with multiple variables in multivariate analyses (factor, multiple regression, and path analyses) to investigate the sociopsychological predictors of weight loss. Responses from 309 participants of a comprehensive weight-loss program indicated that self-assurance was the most significant predictor of actual weight loss, followed by weeks completed. Other factors, such as program satisfaction and perceived importance, indirectly predicted weight loss through the intervening variables of self-assurance and weeks completed. Differences in the factors predicting weight loss were observed between completers and dropouts. The implications of these results for professionals concerned with weight control are discussed.


Gender-related motivational differences in participation in an organized seniors fitness program: moving beyond sex-role stereotypic motives.

Primary reasons for senior adults' participation in a fitness program were examined in two groups to assess gender-related differences. 30 senior adults or "beginners" had just enrolled in the program, while 43 "veterans" had participated for about three years. Among "beginners" women were more likely to participate because "daytime meetings were offered" and "people I trust recommend it" but there were no gender differences among "veterans." Close examination of responses indicated that differences among "beginners" no longer obtained because "veteran" men's motivations increased to resemble those of women. Examination of these motivational shifts as well as those which approached significance is in progress with a larger sample.


Personality factors in monozygotic and dizygotic twins: a comparative study.

To explore similarities or differences on a number of psychological variables relating to personality for members of 16 pairs of monozygotic and 16 pairs of dizygotic twins and between the two groups, the Rorschach, Luscher, Cattell 16 PF, Bem Sex-role Inventory, and Symptom Distress Check List were given to 64 subjects. Analysis confirms data in the literature concerning significant similarities on some personality traits for monozygotic and dizygotic pairs, but with some differences between the groups tested. The particular similarity between the twins may be more attributable to the type of relationship developed early between the twins and the mother than to a greater genetic than environmental influence.


Social support and suicidal ideation in college students.

The present study examined the link between social support and suicidal ideation among 305 university students (90 men and 215 women) whose ages ranged from 18 to 24 years. Social support was significantly correlated with suicidal ideation (r = -.38), but social support did not contribute to the variation in suicidal ideation scores beyond the joint contribution of scores on the Beck Depression Inventory and scores on the Hopelessness Scale. A stronger relationship between social support and suicidal ideation might be found if investigators assessed different aspects of social support and if they examined the interaction of social support and level of reported stress.


Sustained attention deficit in young schizophrenic and schizotypic men.

We studied groups of 39 schizophrenic subjects, 35 schizotypic subjects, and 33 control subjects, comparing them on a standard sustained attention task called the Continuous Performance Test (identical pairs version). The expected negative relationship between performance on sustained attention and psychopathology was confirmed by differences among the three groups which were in the direction predicted, although only the difference between the schizophrenic group and the other two groups was significant. This finding adds evidence to the view from research on high risk and attention with schizophrenic subjects that subtle attention deficits are present among subjects within the schizophrenia spectrum. Consequently, our results can be understood as supporting a dimensional theory of psychopathology.


A measure of positive health-related quality of life: the Satisfaction with Illness Scale.

The Satisfaction with Illness Scale measures the extent to which chronic or acute physical illness has had positive consequences for patients. In a sample of 52 persons with chronic bronchitis, the scale was shown to have good internal consistency and to correlate .42 with another scale of positive life satisfaction.


Mothers of children with asthma: perceptions of parenting stress and the mother-child relationship.

In a study of 41 mothers of asthmatic children ranging from 8 to 13 years of age, perceived parenting stress was greater and the quality of the mother-child relationship more problematic than for a comparison group of mothers with healthy children. These mothers also perceived certain areas of behavioral difficulty in their asthmatic children that were greater than those of children in a comparative sample of mothers. The findings suggested that mothers and their asthmatic children may be at risk for a variety of individual and relational problems.


Relationship between knowledge of and attitudes towards AIDS.

202 subjects completed a questionnaire concerning their knowledge of and attitudes towards AIDS. The knowledge questionnaire had three sections, general knowledge, knowledge of spread and symptoms. Intercorrelations of the sections of the attitudinal measure were factor analysed, and five interpretable factors identified. As in two previously reported studies the correlations among the three knowledge and five attitudinal factors were low and nonsignificant. Implications for health education and attitude change are considered.


Short forms of the Marlowe-Crowne Social Desirability Scale.

Three short forms of the Marlowe-Crowne Social Desirability Scale were constructed from the results of principal components analysis (N = 399). Those subscales were compared with short forms developed by previous researchers who used the same methodology. Examination of the subscales indicated that 13 of the scale's 33 items were isolated by at least two of the three reported studies. Those items were used to construct a composite subscale, which appeared to offer a useful alternative to the full scale. Further analysis of the subscale's contents, however, raised questions about the dimensionality of the Marlowe-Crowne scale. Caution was urged in the use and interpretation of both the full inventory and the short form until the meaning of scale scores can be clarified.


Mental disorder and the perception of family characteristics: an assessment of the relationships in childhood and adolescence.

To assess whether the presence or absence of symptoms of mental disorder in childhood and adolescence is associated with perception of the family of origin in early adulthood, 168 undergraduates completed a questionnaire containing a checklist of symptoms of mental disorder and two family assessment instruments. Respondents who had never experienced symptoms of mental disorder rated their families of origin as more cohesive and reported less confusion of kinship relations. No significant differences were found between the two groups on the perceived adaptability of the family.


Psychometric properties of the Social Interaction Self-Statement Test in a college sample.

The psychometric properties of the Social Interaction Self-statement Test were investigated with a sample of 321 college students. Factor analysis of the 30 items gave two factors, similar to the positive and negative self-statement subscales. The internal consistency coefficients of the factor scales were high and adequate. Correlations between the subscales and independent measures of social anxiety and psychological distress from the Symptom Checklist-90--Revised were examined. Data provided opportunity for evaluating the construct validity and psychometric adequacy of the test.


Relationship between optimism and coping strategies in the work environment.

The work environment is often stressful; however, the specific coping strategies used by individuals to deal with such stress have received limited attention. While the benefits associated with optimism have long been touted, little insight has been developed regarding the mechanism(s) that may contribute to optimists' superior job performance. It is possible that optimism is associated with higher performance because it influences the coping strategies used by salespeople. This possibility was addressed in a cross-sectional study of 101 salespeople. Dispositionally optimistic salespersons were observed to rely more on problem-focused coping strategies, while pessimists engaged in emotion-focused coping. But the specific coping tactics that emerged and the extent to which these tactics were used differed substantially from those which research conducted in other, nonsales settings would have predicted.


What is stressful about in vitro fertilization?

The present work was designed to explore whether psychological stress is more related to concerns about the actual physical pain or fear of treatment during in vitro fertilization. Analysis of data for 12 middle-class women from Iran showed that the greatest psychological stress during treatment was associated with worries about the outcome of different stages of treatment rather than fear and pain of the actual procedure.


Death depression versus death anxiety: exploration of different correlates.

Possible differences between death depression and death anxiety were explored for 182 students, 81 church members, and 41 employees of an air terminal. Both female gender and older age were more highly associated with greater death anxiety than with greater death depression. Living without a significant other was associated with greater death depression than with death anxiety.


The marriage and family therapist: graduate preparation of a mental health professional.

To better acquaint mental health professionals with the educational background of marriage and family therapists, this study examined degree-objective programs offered by 55 academic units in US colleges and universities. Through mailed questionnaires supplemented by telephone follow-ups, information was obtained regarding location of units, enrollment, faculty, admission requirements, program requirements, and therapy models taught. In addition to describing available programs, units with and without accreditation by the American Association of Marriage and Family Therapy's Commission on Accreditation for Marriage and Family Therapy Education were compared.


Construction of the Hyman-Baker Mammography Questionnaire, a measure of health belief model variables.

Despite its considerable promise as a screening tool, mammography has thus far not been as widely used as seems warranted. One conceptualization of patient-related factors or motivation useful in previous research on use of services is the Health Belief Model, which postulates that health behavior can be predicted by people's perceptions of the seriousness of the disease, their susceptibility to the disease, and their perceptions of the benefits of and barriers to the health behavior. Yet no psychometrically sound measure of these variables as related to mammography was found in a search of the literature. This study reports the construction and preliminary validation of such an instrument. Factor analysis, moderate or zero correlation of the subscales, and a higher mean score on the Barriers subscale for women referred for mammography as compared to those actually presenting for mammography support the validity of the questionnaire. Although reliability coefficients for Benefits were low, those for Susceptibility and Barriers were adequate. The questionnaire appears to be a promising measure awaiting further validation.


Psychological androgyny and the NEO Personality Inventory.

The hypothesis that the personality profile of androgynous individuals is different from those of the other sex-role groups was tested by giving the Personal Attributes Questionnaire and the NEO Personality Inventory to 113 male and 135 female undergraduates. Results strongly supported the hypothesis.


Effect of reading a summary of research about biological bases of homosexual orientation on attitudes toward homosexuals.

The effect of exposure to information regarding the development of homosexual orientation on attitudes toward homosexuals was investigated. Testing was conducted in five regularly scheduled undergraduate classes. 105 volunteer subjects from college classes were exposed to one of three treatment conditions. Subjects in the experimental group read a summary article of current research emphasizing a biological component of homosexual orientation. Subjects in one control group read a summary article of research focusing on the absence of hormonal differences between homosexual and heterosexual men. Subjects in another control group were not exposed to either article. All subjects completed the Index of Attitudes Toward Homosexuals. As predicted, subjects in the experimental group had significantly lower scores than subjects in the control groups. There was a significant interaction between treatment condition and sex of subject. Scores on the index were significantly lower for women, but only in the experimental group. These results show that exposure to a research summary can significantly affect immediately assessed scores on the Index of Attitudes Toward Homosexuals. Also, the pattern of effects of these experiences was different for women and men.


Scores of Spanish smokers on Fagerström's Tolerance Questionnaire.

Nicotine may be the agent responsible for tobacco addiction. A non-invasive, easy measure for evaluating addiction is Fagerström's 1978 Tolerance Questionnaire. Present results are based on responses of 732 Spanish smokers to the Spanish version of the questionnaire. The questionnaire has a moderate reliability, and some items are more important than others. Among the Spanish smokers, the questionnaire differentiated the groups of 327 light, 275 normal, and 130 heavy smokers.


Effects of erotica upon men's and women's loving and liking responses for their partners.

We replicated the essential features of the 1978 Dermer and Pysczinski study in two investigations with 70 and 197 subjects, respectively. The primary question was whether the reading of erotic texts (vs neutral texts) affects only scores on the 1970 Love scale of Rubin or also scores on the liking scale. We tested men and women, both individually and in groups. We found no significant effects due to the experimental treatment on either of the scales for women and men. Present moods of the subjects yielded a double interaction with gender and the experimental treatment for scores on the Love scale, but not those on the Liking scale. We interpreted the interaction in relation to the discriminant validity of the two scales.


Construct validity of the Commitment to Career Choices Scale among late adolescents: another look.

In response to Stead and Watson (1992), we reassessed the construct validity of the Commitment to Career Choices Scale using an age-constrained sample from our aggregate data base. A confirmatory factor analysis yielded findings comparable to Stead and Watson's results, thereby suggesting that their findings were likely due to using a homogeneous sample with truncated scores. Given the theoretical importance of measuring the full range of the two commitment to career choices continua, it seems premature to delete items from the scales for research with South African university students. Alternatively, we encourage the use of norms to interpret scores from the scales.


Stress profiles for mothers and fathers of children with autism.

Stress profiles in 18 mothers vs 12 fathers of children with autism were compared on three measures, the Questionnaire on Resources and Stress, the Coping Health Inventory for Parents, and the Beck Depression Inventory. Mothers showed significantly more stress than fathers on each inventory, with a pattern suggesting stress may be related to the differing responsibility assigned to child rearing for each parent.


Cognitive style as a factor in accounting students' perceptions of career-choice factors.

Since prior studies of individuals' perceptions of career-choice factors have not considered the effect of cognitive styles of subjects, this study, using 68 accounting students, investigated the mediating effects of the field dependent-independent cognitive dimension on perceptions of the importance of career-choice factors. The results, in general, show that cognitive style affected individuals' perceptions of career-choice factors, suggesting that future studies of individuals' perceptions should take into account individual cognitive differences.


Beyond gender: the basis of sexual attraction in bisexual men and women.

The construct of sexual orientation has typically considered the gender of the sexual partner as defining whether the individual is homosexual, bisexual, or heterosexual, and the Kinsey scale conceptualises bisexuality as a point midway between homosexuality and heterosexuality. We propose an alternative model which places homosexuality and heterosexuality at one end of a continuum as gender-linked choices of sexual partner, and bisexuality at the other as nongender-specific. As a test of this model, we administered repertory grids to nine bisexual men and women to investigate the characteristics of sexual attraction in individuals for whom gender of partner was not a critical variable. Results supported the hypothesis that gender is not a critical variable in sexual attraction in bisexual individuals. Personality or physical dimensions not related to gender and interaction style were the salient characteristics on which preferred sexual partners were chosen, and there was minimal grid distance between preferred male and preferred female partners. These data support the argument that, for some bisexual individuals, sexual attraction is not gender-linked.


Burnout and stress, depression and self-esteem of teachers.

33 teachers from one institutional school setting and 59 teachers from three north central school districts volunteered to complete and return Beck's Depression Scale, the Coopersmith Self-esteem Inventory--Adult Form, Stress Profile for Teachers, and the Staff Burnout Scale for Mental Health Professionals. Analysis of variance (2 x 2) for teaching level (grade and high school) by sex showed those teaching regular classrooms is grade school experienced less burnout and stress than did high school teachers. There was no sex difference. In the institutional setting there was a significant difference on burnout scores between men and women who taught high school; their scores were higher than those of the male grade school teachers. Burnout lie scores were also significantly higher for female high school teachers than for both male and female grade school teachers. Scores on stress were significantly higher for male high school teachers than for both female high school teachers and male grade school teachers.


Myths about aggression and attitudes about the death penalty.

165 college students completed a survey containing a measure of misconceptions about human aggression and attitudinal items on the death penalty from a 1985 Gallup report. Analysis did not provide strong support for the hypothesis that subjects with relatively high numbers of misconceptions about human aggression are more likely than better informed subjects to support the death penalty.


Effects of narcissistic personality organization on causal attributions.

The present study addressed a central, although neglected, aspect of research into narcissism and attributions, the role of cognitive-perpetual processes and cognitive styles of individuals with narcissistic personality disorder in their causal explanation of events. The extent to which narcissistic personality organization may be a determinant of attributional style was examined. The sample consisted of 20 individuals with narcissistic personality disorders and 20 with neurotic disorders. Participants completed the Narcissistic Personality Inventory-40 and the Attributional Style Questionnaire. A significant association between narcissistic personality disorder and internal, stable attributions for positive outcomes was observed. The reformulated learned helplessness model of depression was used to interpret the attributional style of the narcissists as means to obliterate experience of helplessness. The results are discussed in terms of the role of self-esteem and maintenance of self-presentation in the skewed attributional biases of narcissists.


Computerized cognitive training with learning disabled students: a pilot study.

The effects of practicing computerized exercises in class by 59 learning disabled students who received an 8-hr. training program, 30 min. per week, were evaluated. Six exercises designed to facilitate basic cognitive skills development were used. Twelve subjects were assigned to a control group without any form of intervention. Covariance analysis (pretest scores used as covariates) showed a significant effect of training on mental arithmetic. These results suggest that practicing a computerized exercise of mental arithmetic can facilitate the automatization of basic arithmetic skills (addition, subtraction, and multiplication). The nature, progress, and evaluation of such types of intervention are discussed.


Relationship of pharmacologic compliance to long-term prophylaxis in recurrent depression.

This report examines the relationship of long-term medication compliance (as measured by stability of level/dose ratios and total blood level averages) to prophylaxis in recurrent unipolar patients. Of the 53 patients assigned to active imipramine conditions in a long-term maintenance treatment protocol, 42 were evaluated as clearly compliant, 8 were clearly noncompliant, and 3 were not classifiable. We examined a number of demographic and clinical variables in an attempt to find possible predictors of compliance. No differences were observed between compliant and noncompliant patients with respect to sex, age at screening, age at the onset of their recurrent unipolar illness, duration of the index episode, number of previous episodes, bipolar II vs. recurrent unipolar subtype, endogenous vs. nonendogenous subtype, or baseline severity of depression as assessed by the Hamilton Rating Scale for Depression. However, medication compliance was found to be significantly associated with effective prophylaxis. There was a significantly larger proportion (6 of 12) of noncompliant patients among those experiencing a recurrence in one of the two active medication conditions than among those who remained well for 3 years (2 of 28). The value associated with this difference was p = .04. We conclude that effective prophylaxis is strongly related to stability of medication blood levels which fall within the therapeutic range.


Psychosocial strategies for maximizing the effects of psychotropic medications for schizophrenia and mood disorder.

This paper reviews strategies for dealing with psychosocial processes underlying resistance to compliance with psychotropic agents in schizophrenic and bipolar patients. The nature of those processes are described and methods for resolving them are suggested. The strengths and limitations of a narrow psychoeducational approach are discussed. Conditions in which other psychotherapeutic approaches are needed to buttress psychoeducation are illustrated.


Acquisition and retention of skills training methods in chronic schizophrenic outpatients.

Forty-one DSM-III-R schizophrenic subjects on constant, low-dose maintenance neuroleptic drug therapy (5-10 mg of fluphenazine decanoate intramuscularly every 2 weeks) were randomly assigned to structured and modularized skills training or to supportive group psychotherapy. The skills training was designed by using cognitive and behavioral methods to compensate for the learning disabilities that plague many schizophrenic patients. Skill acquisition was assessed by using quantified performance on standardized role-play tests. Subjects who received skills training made significant gains in each of the areas taught, whereas those who participated in the control psychotherapy group did not. The knowledge and skills learned during training were retained without significant erosion over a 1-year followup period. These results suggest that the use of structured principles of learning and cognitive therapy can effectively train schizophrenics in skill areas pertinent to the self-management of their illness.


Antiglucocorticoid strategies in hypercortisolemic states.

Major depressive illness is frequently associated with cortisol hypersecretion. The pathophysiologic significance of this is unknown, although it is possible that hypercortisolemia exacerbates or perpetuates depressive symptoms. In both depression and Cushing's syndrome, certain depressive symptoms are correlated with cortisol levels and, in the latter condition, therapeutic lowering of cortisol levels is associated with remission of psychiatric symptomatology. We review the behavioral effects of anticortisolemic drug administration in Cushing's syndrome and major depression. Preliminary data from small-scale studies suggest that ratings of depressive symptoms in hypercortisolemic major depression may be lowered by such interventions. Such results, if confirmed in larger scale, double-blind studies, might help clarify the role of endocrinologic disturbance in psychiatric symptomatology and might lead to the development of a novel class of antidepressant agent for hypercortisolemic depressed patients.


Are patients who are intolerant to one SSRI intolerant to another?

One hundred patients with major depression who had discontinued fluoxetine because of side effects were enrolled in a multicenter, open, 8-week study of sertraline. After a washout period of at least 3 weeks following fluoxetine discontinuation and an additional 1-week, single-blind, placebo washout period, patients began treatment with 50 mg sertraline once daily. Based on the clinician's judgment of patient response, doses were titrated upward if necessary. The maximum daily dose of sertraline was 200 mg. Depressive symptoms and adverse events were assessed weekly. An interim analysis was conducted of the first 93 patients who completed the study. Of 91 evaluable patients, 69 sertraline-treated patients (75.8%) experienced significant improvement in depression. Only 8 of 93 patients (8.6%) discontinued sertraline because of side effects.


Effectiveness in psychiatric care: IV. Achieving effective medication management for major affective disorder.

Although effective medications for the treatment of Axis I disorders have been developed, achieving adequate, let alone, optimal medication regimens has been difficult. This hypothesis-generating study had the objective of dissecting the process of medication-management among 24 previously hospitalized affective disorder patients, their families, and their doctors in Italy, Japan, and the United States as well as identifying their outcomes. The data demonstrated significant positive associations between outcome and delivery of adequate medication as well as psychoeducation (about the illness and its treatment) to both patient and family. These results suggested that, regardless of country, medication was necessary but insufficient without the practitioner delivering a family intervention and psychoeducation.


Neuroanatomical circuits in depression: implications for treatment mechanisms.

We previously investigated the functional neuroanatomy of familial pure depressive disease (FPDD) using positron emission tomography (PET) measurements of regional blood flow and obtained evidence that flow is increased in the left prefrontal cortex, amygdala, and medial thalamus and is decreased in the medial caudate. These data along with other evidence suggested that circuits involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus are involved in the pathophysiology of FPDD. One of these circuits, the limbic-thalamo-cortical circuit, which includes the amygdala, the medio-dorsal thalamus, and parts of the ventral and medial prefrontal cortex, may be engaged in abnormal reverberatory activity that maintains the cognitive and emotional set of depression. Using this hypothesis as a neural model to investigate antidepressant treatment mechanisms, we review evidence that the changes in dopaminergic, serotonergic, and noradrenergic function induced by somatic antidepressant therapies may yield modulatory effects on limbic-thalamo-cortical activity. We also discuss preliminary findings of treatment-associated changes in this circuit in studies comparing PET images acquired before and during antidepressant treatment.


Effects of amfonelic acid and GBR 12909 on the haloperidol- and clozapine-induced activation of dopamine neurons.

The purpose of the present study was to establish the extent to which dopamine uptake inhibitors, for example, amfonelic acid (AFA) and GBR 12909, differentially affect the haloperidol- and clozapine-induced activation of dopamine neurons. In the striatum and nucleus accumbens, the haloperidol-induced increases in dopamine synthesis and metabolism, as well as striatal dopamine release, were either potentiated or unaffected by AFA or GBR 12909. In contrast, AFA or GBR 12909 markedly attenuated the clozapine-induced increases in dopamine synthesis, metabolism, and release. However, the clozapine-induced increase in dopamine synthesis within tuberoinfundibular dopamine neurons was not significantly altered by AFA treatment. AFA and GBR 12909, appear to differentially affect the haloperidol- and clozapine-induced activation of nigrostriatal and mesocorticolimbic dopamine neurons. However, the inhibitory effect of AFA on the clozapine-induced activation of dopamine neurons does not extent to the stimulatory effect of clozapine on tuberoinfundibular dopamine neurons.


Transient neutropenia induced by clozapine.

Blood dyscrasias are frequently reported to be induced by the atypical antipsychotic clozapine. Next to agranulocytosis, a potentially lethal form of these side effects, hematologic disturbances include leucocytosis, eosinophilia, and neutropenia. Neutropenia is of considerable clinical relevance because it can be a sign of incipient agranulocytosis. In an analysis of our clozapine drug monitoring program, we have analyzed the data from 68 patients receiving clozapine for the first time. Neutrophil granulocytes dropped to 290 and 660/mm3 in 2 patients, both recovered after the discontinuation of clozapine. Another patient with a granulocyte count of 1800/mm3 was stopped because regular white blood cell monitoring was not possible. Eight additional patients demonstrated a transient decrease of granulocytes during ongoing clozapine administration. This amounts to a cumulative incidence of transient neutropenia of 22 percent (95% confidence interval 7.5%-36.5%).


Effect of anticholinergics on positive and negative symptoms in schizophrenia.

Anticholinergic drugs have been assumed to have no effects on schizophrenic symptomatology. Some studies suggest, however, that anticholinergic agents may antagonize the beneficial effect of neuroleptics on positive symptoms and partially ameliorate negative symptoms. Virtually all studies have been conducted in patients receiving concomitant neuroleptic treatment, raising the possibility that neuroleptics may obscure or modify any "true" anticholinergic effect on schizophrenic symptoms. To evaluate the hypothesis that anticholinergics may increase positive and decrease negative schizophrenic symptoms, we assessed the effect of biperiden on symptoms in the medication-free state. We studied the effect of biperiden 8 mg/day for 2 days on positive and negative symptoms in 40 otherwise drug-free schizophrenic inpatients. Biperiden produced a significant increase in positive symptoms (t = 6.7, p < .001) and reduction in negative symptoms (t = -3.4, p < .01). These data indicate that cholinergic modulation significantly affects positive and negative schizophrenic symptoms and suggest the need for systematic trials of cholinergic and anticholinergic agents in the treatment of positive and negative symptoms of schizophrenia, respectively.


Continuation treatment with adjunctive imipramine in schizophrenia.

An open continuation treatment trial was undertaken for schizophrenic and schizoaffective patients with postpsychotic depressions who had manifested favorable responses to initial treatment with adjunctive imipramine added to their fluphenazine decanoate and benztropine regimen. Of 27 patients enrolled, none had a psychotic or depressive relapse, and 23 completed the 6-month study. The patients did well; completers' Global Assessment Scale scores improved with statistical significance during the trial. Side effects also appeared to improve during the trial. The results therefore support continuation treatment with adjunctive antidepressant medication for those patients with postpsychotic depressions who initially respond favorably to this regimen.


Adjunctive desipramine in the treatment of cocaine abusing schizophrenics.

Because schizophrenic patients have a lifetime prevalence rate for cocaine abuse between 15 and 50 percent, the use of adjunctive pharmacotherapy should be considered in cocaine-abuse treatment programs. This 12-week, open-label outpatient study compares 12 cocaine-abusing schizophrenic patients treated with desipramine (DMI) 100 to 150 mg and antipsychotic agents to 15 patients treated with only antipsychotic agents (no DMI). All 27 patients participated in a Dual Diagnosis Relapse Prevention (DDRP) program, which integrates traditional substance-abuse relapse prevention and psychiatric social skills training. The DMI group was more likely to complete the study (83% vs. 60%, odds ratio = 3.3, NS) and had fewer cocaine-positive urines during the last 6 weeks (20% vs. 50%, odds ratio = 4.0, p < .01). In the context of a specialized dual diagnosis treatment program, patients receiving DMI substantially decreased cocaine usage and had improved psychiatric symptoms.


The convergent validity of the Drug Impairment Rating Scale for Cocaine.

The Halikas-Crosby Drug Impairment Rating Scale for Cocaine (HAL DIRS-C) is designed to measure improvement in drug treatment through interval assessment of impact of cocaine use on daily functioning, relationships with other people, other alcohol and drug use, cocaine withdrawal symptoms, adverse effects associated with cocaine use, and personal outlook over the previous week. The scale is a 25-item clinical rating scale administered in the context of a semistructured interview (modeled after and similar to the Hamilton Rating Scale for Depression). The HAL DIRS-C was administered weekly to 147 subjects participating in a 12-week, double-blind medication trial with a psychosocial treatment component. Without breaking the pharmacologic blind, the HAL DIRS-C score was found to be significantly related to study retention, ongoing psychosocial treatment participation, urinalysis results, and other measures of outcome. The results support the validity of the HAL DIRS-C as a standardized measure of improvement or outcome in clinical research involving the treatment of cocaine abuse.


Side effects associated with lithium and placebo administration in aggressive children.

This study represents a secondary data analysis of two double-blind and placebo-controlled clinical trials of lithium, performed to contrast side effects associated with lithium administration to those associated with placebo. The sample consisted of 91 hospitalized children, aged 5.12 to 12.92 years (mean 9.16), diagnosed as having conduct disorder characterized by severe aggressiveness and explosiveness. Daily doses of lithium ranged from 250 to 2100 mg. During the entire treatment period, more side effects were seen in the lithium group than in the placebo group, whereas during the therapeutic dose period, the difference between side effects in the two groups diminished. The most common side effects seen exclusively with lithium administration included enuresis, fatigue, and ataxia. Increased aggressiveness was observed in 4 children who received placebo. Vomiting, headache, and stomachache were the most common side effects experienced by patients in both lithium and placebo groups. However, more patients experienced these side effects in the lithium group than in the placebo group.


Myocardial infarction in patients over 75 1982-1990.

Admissions to hospital of patients aged 75 or over with symptoms suggestive of acute myocardial infarction have increased markedly since 1982. Patients over 75 present to hospital as soon after the onset of symptoms as do younger patients; they require more treatment with diuretics and digoxin than do younger patients and their fatality rate is higher. Despite this, the chance of patients over 75, especially women, being admitted to a Coronary Care Unit, and so being treated with a thrombolytic and being monitored closely for the complications of acute infarction are much less than those for patients under 75. If we are confident that we can influence the outcome of and reduce fatality from acute myocardial infarction, we should be prepared to offer elderly patients the same opportunities for treatment that we currently afford to younger patients.


Possible mechanism and treatment of o,p'DDD-induced hypercholesterolaemia.

Ortho,para,dichlorodiphenyl dichloroethane (o,p'DDD, Mitotane (Roussell)) is used as an adrenolytic drug to reduce adrenocortical mass and circulating cortisol levels in Cushing's syndrome but has the unwanted side-effect of inducing hypercholesterolaemia. This paper examined the mechanism of that effect in 30 patients with Cushing's syndrome treated with o,p'DDD during the past 10 years. o,p'DDD increased serum cholesterol by 68 per cent, mainly by increasing LDL-cholesterol. The latter effect was not due to impaired binding of LDL to its receptor, as shown in vitro using cultured fibroblasts. Increases in plasma mevalonic acid during o,p'DDD administration were suggestive of increased cholesterol synthesis, this effect being reversed by simvastatin. These findings suggest that o,p'DDD causes hypercholesterolaemia by increasing cholesterol synthesis. It is proposed that this effect is due to the drug's known ability to block cytochrome P450-mediated reactions, thus impairing the formation of oxysterols responsible for down-regulating hepatic cholesterol synthesis. Treatment with simvastatin, an inhibitor of cholesterol synthesis, reverses the hyperlipidaemia and enables o,p'DDD therapy to be maintained without increasing cardiovascular risk.


Clinical status of patients after 10 years of lupus nephritis.

Little information is available about the clinical status and outcome of patients with a long history of lupus nephritis. We have reviewed the dossiers of 25 patients (23 women and two men) who have been monitored by our Unit for more than 10 years after the diagnosis of lupus nephritis. At presentation the mean age was 28.5 +/- 10.33 (SD) years, the mean plasma creatinine was 136.1 +/- 144.7 (SD) nmol/l, the mean proteinuria was 3.02 +/- 2.7 (SD) g/day. At initial renal biopsy 18 patients showed diffuse proliferative glomerulonephritis, six patients showed membranous glomerulonephritis and one showed focal proliferative glomerulonephritis. All patients but one were treated with corticosteroids and 18 were also given immunosuppressive agents. At the last observation (16 +/- 4.6 (SD) years after presentation), 19 patients have normal plasma creatinine (11 of them show proteinuria less than 0.2 g/day) and six patients show increased plasma creatinine (mean 203.3 +/- 61.9 (SD) mmol/l). Eleven patients have been without any treatment for 88 +/- 64 (SD) months. The incidence of lupus flare-ups fell significantly after the tenth year (0.31/patient/year between 0 and 10 versus 0.11 between years 11 and 27; p = 0.01). No case of pericarditis or cerebritis occurred after the tenth year. Only one case of cerebral thrombosis occurred before the tenth year, but ten severe atherosclerotic cardiovascular and cerebrovascular complications were seen after the tenth year (two cardiac infarcts, three angina pectoris, four cerebral thrombosis, one cerebral haemorrhage). Two cases of cancer (thyroid and lung) occurred after the tenth year. The professional rehabilitation was good in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Biological activity of autoantibodies from patients with thyroid-associated ophthalmopathy: in vitro effects on porcine extraocular myoblasts.

To determine whether antibodies to orbital tissue have a pathogenic role in thyroid-associated ophthalmopathy, the in vitro effects of IgG from patients with thyroid-associated ophthalmopathy on porcine extraocular myoblast growth were studied. Growth of primary extraocular myoblast cultures and extraocular myoblast clones was stimulated by patients' IgG, as measured by [3H]thymidine uptake and bromodeoxyuridine incorporation. Myoblasts responded in a dose-related fashion to increasing concentrations of patients' IgG, and the response was reversed by anti-human IgG. The growth stimulating effect of patients' IgG was relatively specific to extraocular myoblasts, compared to skeletal myoblasts. Individual IgG samples from 36 patients with ophthalmopathy gave rise to higher growth responses of cloned extraocular myoblasts, than either 31 normal controls (p < 0.005), or IgG from 10 patients with Graves' disease without evidence of ophthalmopathy (p < 0.001). Myoblast growth-stimulating antibody did not correlate with thyroid autoantibody levels (thyrotrophin receptor antibody or thyroid microsomal antibody levels), but correlated significantly with binding to extraocular muscle membranes (r = 0.524, p < 0.001). Eye-muscle stimulating antibodies were demonstrable in sera of patients with thyroid-associated ophthalmopathy, and may be responsible for the enlargement of eye muscle in this disease.


Major neurological disease and occupational exposure to organic solvents.

Five patients are described who presented with major organic brain disease affecting one or more of pyramidal and extrapyramidal tracts, cerebellum, and higher cortical functions. All had a history of 10 years or more of regular occupational exposure to solvents in confined spaces, three in painting inside ships and the others in weapons maintenance and printing. All had been regularly exposed to high air vapour peaks as well as to skin contamination. Four showed some evidence of improvement after the exposure ceased. None was initially suspected of having a toxic encephalopathy by the consultant to whom he was referred. The spectrum of neurological disease presented by these men mirrors closely that described in solvent abusers. All were forced by illness to retire from their work, a circumstance which might have in the past have led to such conditions being missed in cross-sectional studies, which in general have not shown evidence of major disease. We suggest that when such disease occurs nowadays, its cause is usually not suspected. Further epidemiological study of the problem is necessary.


Pre-natal development of a hypothalamic biological clock.

The available evidence indicates that a biological clock oscillates in the mammalian fetus and that the fetal clock is entrained by redundant circadian signals from the mother. An entrainable biological clock during fetal life helps the developing mammal more readily prepare for life in the outside world. In humans, the early establishment of maternal-infant synchrony may help the infant maximize its responsiveness to the outside world.


Circadian rhythms and the suprachiasmatic nucleus in perinatal development, aging and Alzheimer's disease.

Circadian rhythms are already present in the fetus. At a certain stage of pre-natal hypothalamic development (around 30 weeks of gestation) the fetus becomes responsive to maternal circadian signals. Moreover, recent studies showed that the fetal biological clock is able to generate circadian rhythms, as exemplified by the rhythms of body temperature and heart rate of pre-term babies in the absence of maternal or environmental entrainment factors. Pre-term babies that are deprived of maternal entrainment and kept under constant environmental conditions (e.g., continuous light) in the neonatal intensive care unit run the risk of developing a biological clock dysfunctioning. However, the fact should be acknowledged that at least in mice the development of the circadian pacemaker (i.e., SCN) does not depend on environmental influences (Davis and Menaker, 1981), although other data suggest that severe disruption of the maternal circadian rhythm indeed abolishes the circadian rhythm of the fetal SCN (Shibata and Moore, 1988). During aging and in particular in AD circadian rhythms are disturbed. These disturbances include phase advance and reduced period and amplitude, as well as an increased intradaily variability and a decreased interdaily stability of the rhythm. Among the factors underlying these changes the loss of SCN neurons seems to play a central role. Other contributory factors may be reduced amount of light, degenerative changes in the visual system and the level of activity and decreased melatonin.


The human hypothalamus: comparative morphometry and photoperiodic influences.

The concept of the hypothalamus as a distinct neurological entity concerned with a variety of regulatory processes dates back to the end of the 19th century. Before 1900 there were only vague intimations of the function of the brain surrounding the third ventricle and these were based primarily on various pathological and assorted clinical observations. Since then a large body of evidence has been derived implicating that the hypothalamus contains the control systems which are critically involved in many physiological, endocrine and behavioral processes. Among these are feeding and drinking, reproduction and the regulation of the sleep-wake cycle and temperature. Although the human hypothalamus accounts for only 4 cm3, or 0.3% of the adult brain volume, it contains the integrative systems critical for all these processes. A comparative morphometric analysis of the hypothalamus among mammals revealed that the volume of this part of the brain is highly correlated with brain size, irrespective of the ecological strategy or evolutionary history of the species considered. It appears that the human hypothalamus has just the size we may expect of such a large-brained mammal, but it is considerably larger than would be predicted from its body size. In mammals the preoptic region of the hypothalamus is implicated in the neural control of endocrine functions and in the temporal organization of a wide spectrum of biological rhythms. In recent years, the pivotal role of two hypothalamic cell groups have been considered in this context: the sexually dimorphic nucleus (SDN-POA) as part of the neural circuitry underlying masculine sexual behavior and reproductive functions and the suprachiasmatic nucleus (SCN) as the principal component of the central clock mechanism. Consistent with its role in the temporal organization of circadian processes, investigations in rodents and non-human primates suggest that the SCN is also involved in the seasonal control of reproductive and metabolic phenomena. Since the environmental light-dark cycle is the main Zeitgeber for circadian and seasonal rhythms in most species, including man, photic information could have substantial effects, not only on the neural activity of the biological clock, but also on its underlying structure. Our observations on the human SCN in relation to photoperiod indeed revealed a marked seasonal variation in the morphology of the human SCN. The volume of the SCN was, on average, twice as large in the autumn as in the summer and contained more than twice as many vasopressin immunoreactive neurons.(ABSTRACT TRUNCATED AT 400 WORDS)


LHRH neurons: functions and development.

Examination of the properties of developing LHRH neurons, by in situ hybridization procedures or LHRH immunocytochemistry, showed that these cells (1) are unique among neuroendocrine cells in their origin from the epithelium of the medial olfactory pit, and (2) express LHRH mRNA. LHRH neurons, visualized by either method, tended to be clustered when seen along the migration route in the nasal mesenchyme. Neural cell adhesion molecule (NCAM) is present on the central processes of the olfactory, vomeronasal and terminalis nerves, which form the scaffold along which LHRH neurons migrate into the brain. Injection of a small amount (1 microliter) of antiserum to NCAM into the olfactory pits of 10-day-old embryonic mice, while not sufficient to break up the NCAM scaffolding, appeared to decrease the number of LHRH-immunoreactive cells in the epithelium of the medial olfactory pit, and retarded their migration in the nasal mesenchyme. This suggest that NCAM is important for LHRH cell migration. Never found actually colocalized with LHRH in the same neurons, NCAM nevertheless may be required for the migration of LHRH-expressing cells.