Complete uterine septum, double cervix, and longitudinal vaginal septum: an integrated approach for one-stop diagnosis and ultrasound-guided endoscopic treatment.

Background: A complete uterine septum, double cervix and vaginal septum is a complex and rare congenital genital tract anomaly. The diagnosis is often challenging and based on the combination of different diagnostic techniques and multiple treatment steps. Objective: To propose a combined one-stop diagnosis and an ultrasound-guided endoscopic treatment of complete uterine septum, double cervix, and longitudinal vaginal septum anomaly. Materials and Methods: Stepwise demonstration with narrated video footage of an integrated approach management of a complete uterine septum, double cervix and vaginal longitudinal septum treated by expert operators combining minimally invasive hysteroscopy and ultrasound. The patient was 30 years old and was referred to our clinic because of dyspareunia, infertility and the suspicion of a genital malformation. Results: A one-stop complete evaluation of uterine cavity, external profile, cervix, and vagina was made through 2D, and 3D ultrasound combined with hysteroscopic assessment and a U2bC2V1 malformation (according to ESHRE/ESGE classification) was diagnosed. The procedure consisted in a totally endoscopic removal of the vaginal longitudinal septum and the complete uterine septum, starting the uterine septum incision from the isthmic level, and sparing the two cervices, under transabdominal ultrasound guidance. The ambulatory procedure was performed in the Digital Hysteroscopic Clinic (DHC) CLASS Hysteroscopy in Fondazione Policlinico Gemelli IRCCS of Rome - Italy, under general anaesthesia (laryngeal mask). Main outcomes: Surgical time of procedure was 37 minutes; no complications occurred; patient was discharged three hours after the procedure; the hysteroscopic office control after 40 days showed a normal vagina and a normal uterine cavity with two normal cervices. Conclusion: An integrated ultrasound and hysteroscopic approach allows an accurate one-stop diagnosis and a totally endoscopic treatment option for complex congenital malformations using an ambulatory model of care with optimal surgical results.

Hereditary spastic paraplegia: More than an upper motor neuron disease.

Hereditary spastic paraplegias (HSPs) are a group of rare inherited neurological diseases characterized by extreme heterogeneity in both their clinical manifestations and genetic backgrounds. Based on symptoms, HSPs can be divided into pure forms, presenting with pyramidal signs leading to lower-limb spasticity, and complex forms, when additional neurological or extraneurological symptoms are detected. The clinical diversity of HSPs partially reflects their underlying genetic backgrounds. To date, 76 loci and 58 corresponding genes [spastic paraplegia genes (SPGs)] have been linked to HSPs. The genetic diagnosis is further complicated by the fact that causative mutations of HSP can be inherited through all possible modes of transmission (autosomal-dominant and -recessive, X-linked, maternal), with some genes showing multiple inheritance patterns. The pathogenic mutations of SPGs primarily lead to progressive degeneration of the upper motor neurons (UMNs) comprising corticospinal tracts. However, it is possible to observe lower-limb muscle atrophy and fasciculations on clinical examination that are clear signs of lower motor neuron (LMN) involvement. The purpose of this review is to classify HSPs based on their degree of motor neuron involvement, distinguishing forms in which only UMNs are affected from those involving both UMN and LMN degeneration, and to describe their differential diagnosis from diseases such as amyotrophic lateral sclerosis.

High cellularity and mitotic activity in a primary ovarian fibro-thecomatous tumor of a young patient: a diagnostic and clinical challenge.

Purpose ofInvestigation: Solid ovarian tumors represent a clinical challenge, in particular in case of young patients who require a fertility sparing treatment. The authors report a case of hypercellular mitotically active ovarian fibrothecoma in a very young woman, successfully treated with a fertility sparing surgery. MATERIALS AND METHODS: A 21-year-old nulliparous woman presented at the present hospital with a 14-cm right ovarian mass, consisting of solid and pseudo-cystic components. There was neither an elevation of tumor markers nor evidence of metastatic disease. A laparotomic right salpingo-oophorectomy was performed. Uterus and left adnexa were preserved. RESULTS: The neoplasm consisted of a prevalent population of spindle-shaped elements and of a minor component of cells with wider cytoplasms, attributable to a thecomatous differentiation. The mitotic activity was focally elevated. Cytological atypia was mild to focally moderate. Clear areas of coagulative necrosis were not observed. At present 48 months after surgery, the patient is alive with no evidence of recurrence. CONCLUSIONS: The authors reported the lesion as a hypercellular and mitotically active fibrothecoma. The uneventful follow-up confirms the low malignant potential of the lesion. Caution is required reporting hypercellular stromal ovarian tu- mors, in order to avoid overdiagnosis and overtreatment, particularly in young patients.

The fine line between 'brave' and 'reckless': amygdala reactivity and regulation predict recognition of risk.

BACKGROUND: High sensation-seekers (HSS) pursue novelty even at the cost of self-harm. When challenged, HSS are less anxious, show blunted physiological (cortisol, startle) and neurobiological (prefrontal-limbic) responses, and devalue aversive outcomes. Here, we investigate how these features interact under conditions of physical danger, in distinguishing between adaptive and maladaptive approaches to risk. METHODS: We recruited a cohort of individuals who voluntarily sought out recreational exposure to physical risk, and obtained serial cortisol values over two time-locked days. On the 'baseline' day, we scanned subjects' brains with functional and structural MRI; on the 'skydiving day,' subjects completed a first-time tandem skydive. During neuroimaging, subjects viewed cues that predicted aversive noise; neural data were analyzed for prefrontal-limbic reactivity (activation) and regulation (non-linear complexity), as well as cortical thickness. To probe threat perception, subjects identified aggression for ambiguous faces morphed between neutral and angry poles. RESULTS: Individuals with prefrontal-limbic meso-circuits with less balanced regulation between excitatory and inhibitory components showed both diminished cortisol/anxiety responses to their skydives, as well as less accurate perceptual recognition of threat. This impaired control was localized to the inferior frontal gyrus, with associated cortical thinning. Structural equation modeling suggests that sensation-seeking is primarily mediated via threat-perception, which itself is primarily mediated via neural reactivity and regulation. CONCLUSIONS: Our results refine the sensation-seeking construct to provide important distinctions (brain-based, but with endocrine and cognitive consequences) between the brave, who feel fear but nonetheless overcome it, and the reckless, who fail to recognize danger. This distinction has important real-world implications, as those who fail to recognize risk are less likely to mitigate it.

A disposition to reappraise decreases anterior insula reactivity during anxious anticipation.

Across individuals there is variability in one's inherent tendency to reappraise emotional events in everyday life, which may be related to how worried one becomes in the presence of an anticipated aversive event. The extent to which this natural tendency to reappraise has neurobiological correlates during anxious anticipation is unknown. Neuroimaging research indicates that responses in the anterior insula precede anticipated aversive events and appear to represent one's affective feeling state of anxious anticipation. Successful cognitive reappraisal should weaken this anticipatory insula response. Here, functional magnetic resonance images were acquired while participants completed an anticipation task. We found increased anterior insula activation during aversive anticipation and a negative association between anxious anticipatory right anterior insula reactivity and dispositional reappraisal. Thus, even without the instruction to reappraise, individuals high in dispositional reappraisal tended to have a reduced anticipatory insula response to aversive stimuli, thereby down-regulating a neural substrate for aversive anticipation.

Higher body fat percentage is associated with increased cortisol reactivity and impaired cognitive resilience in response to acute emotional stress.

OBJECTIVE: Cortisol is elevated in individuals with both increased emotional stress and higher percentages of body fat. Cortisol is also known to affect cognitive performance, particularly spatial processing and working memory. We hypothesized that increased body fat might therefore be associated with decreased performance on a spatial processing task, in response to an acute real-world stressor. DESIGN: We tested two separate samples of participants undergoing their first (tandem) skydive. In the first sample (N=78), participants were tested for salivary cortisol and state anxiety (Spielberger State Anxiety Scale) during the plane's 15-min ascent to altitude in immediate anticipation of the jump. In a second sample (N=20), participants were tested for salivary cortisol, as well as cardiac variables (heart rate, autonomic regulation through heart rate variability) and performance on a cognitive task of spatial processing, selective attention and working memory. RESULTS: In response to the skydive, individuals with greater body fat percentages showed significantly increased reactivity for both cortisol (on both samples) and cognition, including decreased accuracy of our task of spatial processing, selective attention and working memory. These cognitive effects were restricted to the stress response and were not found under baseline conditions. There were no body fat interactions with cardiac changes in response to the stressor, suggesting that the cognitive effects were specifically hormone mediated rather than secondary to general activation of the autonomic nervous system. CONCLUSIONS: Our results indicate that, under real-world stress, increased body fat may be associated with endocrine stress vulnerability, with consequences for deleterious cognitive performance.

A systems approach to prefrontal-limbic dysregulation in schizophrenia.

INTRODUCTION: Using a prefrontal-limbic dysregulation model for schizophrenia, we tested whether a dynamic control systems approach in conjunction with neuroimaging might increase detection sensitivity in characterizing the illness. Our analyses were modeled upon diagnostic tests for other dysregulatory diseases, such as diabetes, in which trajectories for the excitatory and inhibitory components of the negative feedback loops that reestablish homeostasis are measured after system perturbation. We hypothesized that these components would show distinct coupling dynamics within the patient population, as compared to healthy controls, and that these coupling dynamics could be quantified statistically using cross-correlations between excitatory and inhibitory time series using fMRI. METHODS: As our perturbation, we activated neural regions associated with the emotional arousal response, using affect-valent facial stimuli presented to 11 schizophrenic patients (all under psychotropic medication) and 65 healthy controls (including 11 individuals age- and sex-matched to the patients) during fMRI scanning. We first performed a random-effects analysis of the fMRI data to identify activated regions. Those regions were then analyzed for group differences, using both standard analyses with respect to the time series peaks, as well as a dynamic analysis that looked at cross-correlations between excitatory and inhibitory time series and group differences over the entire time series. RESULTS: Patients and controls showed significant differences in signal dynamics between excitatory and inhibitory components of the negative feedback loop that controls emotional arousal, specifically between the right amygdala and Brodmann area 9 (BA9), when viewing angry facial expressions (p = 0.002). Further analyses were performed with respect to activation amplitudes for these areas in response to angry faces, both over the entire time series as well as for each time point along the time series. While the amygdala responses were not significantly different between groups, patients showed significantly lower BA9 activation during the beginning of the response (0.000

The d3/fl-growth hormone (GH) receptor polymorphism does not influence the effect of GH treatment (66 microg/kg per day) or the spontaneous growth in short non-GH-deficient small-for-gestational-age children: results from a two-year controlled prospective study in 170 Spanish patients.

CONTEXT: The d3/fl-GH receptor (d3/fl-GHR, exon 3-deleted/full-length GHR) has recently been associated with responsiveness to GH therapy. OBJECTIVE: The objective of the study was to evaluate whether the d3/fl-GHR genotypes influence the intensity of spontaneous and/or GH therapy-stimulated growth in small-for-gestational-age (SGA) patients. DESIGN: This was a 2-yr prospective, controlled, randomized trial. SETTING: Thirty Spanish hospitals participated. Auxologic and GH secretion evaluation was hospital based, whereas molecular analyses and auxologic data computation were centralized. PATIENTS: Patients included 170 short SGA children: 140 remained prepubertal and 30 entered puberty during the second follow-up year. INTERVENTION: Eighty-six were treated with GH (66 microg/kg.d) for 2 yr and 84 were not treated. MAIN OUTCOME MEASURES: Previous and 2-yr follow-up auxologic data were recorded at each hospital, d3/fl-GHR genotypes determined, and data analyzed for patients who remained prepubertal (group 1, 68 GH treated and 72 non-GH treated) and for all the patients (group 2). RESULTS: In group 1 GH-treated patients, growth velocity, and height-sd score during the first and second years, total 2-yr height gain (18.5 +/- 2.4 cm in d3/d3; 18.4 +/- 2.6 in d3/fl; 19.5 +/- 2.3 in fl/fl), Delta 2-yr height increase (9.1 +/- 2.4 cm in d3/d3; 9.4 +/- 3.0 in d3/fl; 10.4 +/- 2.1 in fl/fl), first-year growth prediction and studentized residual values (0.08 +/- 1.26 in d3/d3; 0.28 +/- 1.21 in d3/fl; 0.67 +/- 0.95 in fl/fl) did not differ among the d3/fl-GHR genotypes. In group 1 non-GH-treated patients, neither growth velocity nor height-sd score changed significantly, and values were similar in each d3/fl-GHR genotype. Results in all patients (group 2) were similar to those in group 1. CONCLUSIONS: In short non-GH-deficient SGA children, both spontaneous growth rate and responsiveness to 66 microg/k.d GH therapy were similar for each d3/fl-GHR genotype carried.

Nonlinear complexity and spectral analyses of heart rate variability in medicated and unmedicated patients with schizophrenia.

OBJECTIVE: Heart rate variability (HRV) reflects functioning of the autonomic nervous system and possibly also regulation by the neural limbic system, abnormalities of which have both figured prominently in various etiological models of schizophrenia, particularly those that address patients' vulnerability to stress in connection to psychosis onset and exacerbation. This study provides data on cardiac functioning in a sample of schizophrenia patients that were either medication free or on atypical antipsychotics, as well as cardiac data on matched healthy controls. We included a medication-free group to investigate whether abnormalities in HRV previously reported in the literature and associated with atypical antipsychotics were solely the effect of medications or whether they might be a feature of the illness (or psychosis) itself. METHOD: We collected 24-hour ECGs on 19 patients and 24 controls. Of the patients, 9 were medication free and 10 were on atypical antipsychotics. All subject groups were matched for age and gender. Patient groups showed equivalent symptom severity and type, as well as duration of illness. We analyzed the data using nonlinear complexity (symbolic dynamic) HRV analyses as well as standard and relative spectral analyses. RESULTS: For the medication-free patients as compared to the healthy controls, our data show decreased R-R intervals during sleep, and abnormal suppression of all frequency ranges, but particularly the low frequency range, which persisted even after adjusting the spectral data for the mean R-R interval. This effect was exacerbated for patients on atypical antipsychotics. Likewise, nonlinear complexity analysis showed significantly impaired HRV for medication-free patients that was exacerbated in the patients on atypical antipsychotics. CONCLUSIONS: Altogether, the data suggest a pattern of significantly decreased cardiac vagal function of patients with schizophrenia as compared to healthy controls, apart from and beyond any differences due to medication side effects. The data additionally confirm earlier reports of a deleterious effect of atypical antipsychotics on HRV, which may exacerbate an underlying vulnerability in patients. These results support previous evidence that autonomic abnormalities may be a core feature of the illness (or psychosis), and that an even more conservative approach to cardiac risk in schizophrenia than previously thought may therefore be clinically appropriate.

Protein S deficiency. Description of a case associated with chronic inflammatory bowel disease.

Thrombotic disease is one of the most relevant clinical problems for morbility and mortality. We can differentiate congenital and acquired forms. In this short communication we describe 1 case observed by us that seems interesting for the association of a congenital and acquired form [Protein S deficiency and inflammatory bowel disease (IBD)] and for the dramatic events suffered before receiving a complete diagnosis and therapy, indicating the importance of recollection of information from the patients, starting from anamnestic data.

Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication.

Interleukin-18 (IL-18), previously known as interferon-gamma (IFN-gamma)-inducing factor (IGIF), is a proinflammatory cytokine expressed by activated macrophages that acts in synergy with IL-12 as an important amplifying factor for IFN-gamma production and Th1 development. To study the effect of IL-18 on a lentiviral infection, we cloned the IL-18 gene from a rhesus macaque and constructed replication-competent simian immunodeficiency virus (SIV) that expressed either the precursor pro-IL-18 (SIV(IL-18)) or the mature form (SIV(mIL-18)) of IL-18. The predicted amino acid sequence for rhesus IL-18 had 96% homology with the human one, differing in only 8 of 193 residues. SIV(IL-18) and SIV(mIL-18) replicated more slowly than control viruses in the CEM x 174 cell line and resulted in the development of chronically infected cell lines that expressed high levels of infectious SIV. The cell line generated by SIV(IL-18) released large quantities of IL-18 into the supernatant, whereas the one obtained from SIV(mIL-18) showed the accumulation of IL-18 in the cytoplasm. Similarly, SIV(IL-18) and SIV(mIL-18) replicated more slowly than the unmodified viral vector in rhesus peripheral blood mononuclear cells (PMBC), but only SIV(IL-18) expressed biologically active IL-18. These experiments show that the precursor form of IL-18 is necessary for the efficient release of the cytokine and that IL-18 does not promote increased replication of SIV in rhesus PBMC.

Logical processing, affect, and delusional thought in schizophrenia.

Deficits of logical reasoning have long been considered a hallmark of schizophrenia and delusional disorders. We provide a more precise characterization of "logic" and, by extension, of "deficits in logical reasoning." A model is offered to categorize different forms of logical deficits. This model acknowledges not only problems with making inferences, which is how logic deficits are usually conceived, but also problems in the acquisition and evaluation of premises (i.e., filtering of "input"). Early (1940-1969) and modern (1970-present) literature on logical reasoning and schizophrenia is evaluated within the context of the presented model. We argue that, despite a substantial history of interest in the topic, research to date has been inconclusive on the fundamental question of whether patients with delusional ideation show abnormalities in logical reasoning. This may be due to heterogeneous definitions of "logic," variability in the composition of patient samples, and floor effects among the healthy controls. In spite of these difficulties, the available evidence suggests that deficits in logical reasoning are more likely to occur due to faulty assessment of premises than to a defect in the structure of inferences. Such deficits seem to be provoked (in healthy individuals) or exacerbated (in patients with schizophrenia) by emotional content. The hypothesis is offered that delusional ideation is primarily affect-driven, and that a mechanism present in healthy individuals when they are emotionally challenged may be inappropriately activated in patients who are delusional.

Cytokine expression, natural killer cell activation, and phenotypic changes in lymphoid cells from rhesus macaques during acute infection with pathogenic simian immunodeficiency virus.

We studied the innate and adaptive immune system of rhesus macaques infected with the virulent simian immunodeficiency virus isolate SIVmac251 by evaluating natural killer (NK) cell activity, cytokine levels in plasma, humoral and virological parameters, and changes in the activation markers CD25 (interleukin 2R ¿IL-2R alpha chain), CD69 (early activation marker), and CD154 (CD40 ligand) in lymphoid cells. We found that infection with SIVmac251 induced the sequential production of interferon-alpha/beta (IFN-alpha/beta), IL-18, and IL-12. IFN-gamma, IL-4, and granulocyte-macrophage colony-stimulating factor were undetected in plasma by the assays used. NK cell activity peaked at 1 to 2 weeks postinfection and paralleled changes in viral loads. Maximum expression of CD69 on CD3(-)CD16(+) lymphocytes correlated with NK cytotoxicity during this period. CD25 expression, which is associated with proliferation, was static or slightly down-regulated in CD4(+) T cells from both peripheral blood (PB) and lymph nodes (LN). CD69, which is normally present in LN CD4(+) T cells and absent in peripheral blood leukocyte (PBL) CD4(+) T cells, was down-regulated in LN CD4(+) T cells and up-regulated in PBL CD4(+) T cells immediately after infection. CD8(+) T cells increased CD69 but not CD25 expression, indicating the activation of this cellular subset in PB and LN. Finally, CD154 was transiently up-regulated in PBL CD4(+) T cells but not in LN CD4(+) T cells. Levels of antibodies to SIV Gag and Env did not correlate with the level of activation of CD154, a critical costimulatory molecule for T-cell-dependent immunity. In summary, we present the first documented evidence that the innate immune system of rhesus macaques recognizes SIV infection by sequential production of proinflammatory cytokines and transient activation of NK cytotoxic activity. Additionally, pathogenic SIV induces drastic changes in the level of activation markers on T cells from different anatomic compartments. These changes involve activation in the absence of proliferation, indicating that activation-induced cell death may cause some of the reported increase in lymphocyte turnover during SIV infection.

Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity.

Mutations in the gene encoding the amyloid protein precursor (APP) cause autosomal dominant Alzheimer's disease. Cleavage of APP by unidentified proteases, referred to as beta- and gamma-secretases, generates the amyloid beta-peptide, the main component of the amyloid plaques found in Alzheimer's disease patients. The disease-causing mutations flank the protease cleavage sites in APP and facilitate its cleavage. Here we identify a new membrane-bound aspartyl protease (Asp2) with beta-secretase activity. The Asp2 gene is expressed widely in brain and other tissues. Decreasing the expression of Asp2 in cells reduces amyloid beta-peptide production and blocks the accumulation of the carboxy-terminal APP fragment that is created by beta-secretase cleavage. Solubilized Asp2 protein cleaves a synthetic APP peptide substrate at the beta-secretase site, and the rate of cleavage is increased tenfold by a mutation associated with early-onset Alzheimer's disease in Sweden. Thus, Asp2 is a new protein target for drugs that are designed to block the production of amyloid beta-peptide peptide and the consequent formation of amyloid plaque in Alzheimer's disease.

[Eosinophilia and Strongyloides stercoralis infestation: case report] / Eosinofilia e infestazione da Strongyloides stercoralis: caso clinico.

Authors report about a case of Strongyloides stercoralis infestation. The patient, a 65-year old man, presented with a clinical history of eosinophilia but without symptomatology. Several stool specimen showed the presence of rhabditiform larvae of S. stercoralis and after therapy the patient had a normalization of the white blood ceIls count. The authors wish to point out the importance of the diagnosis because a change in immune status may convert a previously asymptomatic infection to hyperinfection.

Endocrine late effects in children who underwent bone marrow transplantation: review.

With the increasing use and success of BMT, larger numbers of children survive transplantation. Still, cancer treatment in children causes damage to the endocrine glands, often inducing growth deficiency, pubertal delay and thyroid dysfunction. This paper will deal with some of the most common endocrine disorders related to BMT in the pediatric population. Irradiation is the major contributor for growth impairment after BMT, acting through lesion to epiphyseal growth-plate, gonadal damage with delayed or precocious puberty, hypothyroidism, and growth hormone insufficiency. Gonadal dysfunction can be induced both by a direct injury to the gonads (irradiation, gonadotoxic agents) causing primary hypergonadotropic-hypogonadism, and with less frequency, by neuroendocrine injury to the hypothalamo-pituitary axis causing hypogonadotropic-hypogonadism. It seems that both doses of chemotherapy and of irradiation used by different regimens, fractionation of irradiation, and age at the time of BMT are the most important factors when we deal with toxic endocrine late-effects in long term survivors. In order to improve the quality of life of each single patient who receive BMT, and without inflicting the success-rate of this procedure, we recommend a life-long surveillance to prevent or to treat symptoms and disorders caused by hormone deficiencies, and we also advocate for a multidisciplinary team-approach that includes an endocrinologist consultant.

Poland sequence in two siblings suggesting an autosomal inheritance transmission.

We report on Poland sequence observed in two siblings (a girl and a boy) in the same family. This suggests an inheritance pattern consistent with an autosomal recessive or dominant trait transmission with reduced penetrance.

A consensus procedure for predicting the location of alpha-helical transmembrane segments in proteins.

To aid in the development of three-dimensional models of membrane-bound proteins, a consensus procedure for predicting alpha-helical transmembrane segments from amino acid sequence is presented. The algorithm combines the results of six individual prediction methods and some basic properties of membrane-spanning helices to obtain a final consensus prediction. Comparison with experiment and several other recently developed methods shows that the consensus procedure performs quite well in comparison to other recent methods. A FORTRAN program has been developed which takes an input file containing an amino acid sequence in one-letter code and outputs a list of the alpha-helical transmembrane segments predicted by the consensus algorithm.

An energy-based approach to packing the 7-helix bundle of bacteriorhodopsin.

Based on the heavy-atom coordinates determined by the electron microscopy for the seven main helical regions of bacteriorhodopsin with the all-trans retinal isomer, energy optimizations were carried out for helix bundles containing the all-trans retinal and 13-cis retinal chromophores, respectively. A combination of simulated annealing and energy minimization was utilized during the process of energy optimization. It was found that the 7-helix bundle containing the all-trans isomer is about 10 kcal/mol lower in conformational energy than that containing the 13-cis isomer. An energetic analysis indicates that such a difference in energy is consistent with the observation that absorption of a 570-nm proton is required for the conversion of a bacteriorhodopsin from its all-trans to 13-cis form. It was also found that the above conversion process is accompanied by a significant conformational perturbation around the chromophore, as reflected by the fact that the beta-ionone ring of retinal moves about 5.6 A along the direction perpendicular to the membrane plane. This is consistent with the observation by Fodor et al. (Fodor, S.P.A., Ames, J.B., Gebhard, R., van der Berg, E.M.M., Stoeckenius, W., Lugtenburg, J., & Mathies, R.A., 1988, Biochemistry 27, 7097-7101). Furthermore, it is interesting to observe that although the retinal chromophore undergoes a significant change in its spatial position, the orientation of its transition dipole changes only slightly, in accord with experimental observations. In other words, even though orientation of the retinal transition dipole is very restricted, there is sufficient room, and degrees of freedom, for the retinal chromophore to readjust its position considerably. This finding provides new insight into the subtle change of the retinal microenvironment, which may be important for revealing the proton-pumping mechanism of bacteriorhodopsin. The importance of electrostatic and nonbonded interactions in stabilizing the 7-helix bundle structure has also been analyzed. Electrostatic interactions favor an antiparallel arrangement among adjacent helices. Nonbonded interactions, however, drive most of the closely packed helices into an arrangement in which the packing angles lie around -160 degrees, a value very near the -154 degrees value computed earlier as the most favorable packing arrangement of two poly(Ala) alpha-helices (Chou, K.-C., Némethy, G., & Scheraga, H.A., 1983, J. Phys. Chem. 87, 2869-2881). The structural features of the 7-helix bundle and their relationship to those found in typical 4-helix bundle proteins are also discussed.(ABSTRACT TRUNCATED AT 400 WORDS)