Interaction between cytochalasin B-treated malarial parasites and erythrocytes. Attachment and junction formation.

We have previously demonstrated that invasion of erythrocytes (RBCs) by malaria merozoites follows a sequence: recognition and attachment in an apical orientation associated with widespread deformation of the RBC, junction formation, movement of the junction around the merozoite that brings the merozoite into the invaginated RBC membrane, and sealing of the membrane. In the present paper, we describe a method for blocking invasion at an early stage in the sequence. Cytochalasin-treated merozoites attach specifically to host RBCs, most frequently by the apical region that contains specialized organelles (rhoptries) associated with invasion. The parasite then forms a junction between the apical region and the RBC. Cytochalasin blocks movement of this junction, a later step in invasion. Cytochalasin-treated (Plasmodium knowlesi) merozoites attach to Duffy-negative human RBCs, although these RBCs are resistant to invasion by the parasite. The attachment with these RBCs, however, differs from susceptible RBCs in that there is no junction formation. Therefore the Duffy associated antigen appears to be involved in junction formation, not initial attachment.

Determinants on surface proteins of Plasmodium knowlesi merozoites common to Plasmodium falciparum schizonts.

In this report and (R. Schmidt-Ullrich, L. H. Miller, and D. F. H. Wallach. Manuscript in preparation.), we have demonstrated that malaria proteins on the surface of merozoites and infected erythrocytes cross-react between at least two primate malarias, Plasmodium knowlesi and P. falciparum. Sera from five Gambian adults who were highly immune to P. falciparum were used as a reagent to study the cross-reactivity between P. falciparum schizonts and surface proteins on P. knowlesi merozoites. Although the sera bound to the surface of viable, intact P. knowlesi merozoites, the sera did not block invasion of rhesus erythrocytes. 125I-lactoperoxidase-labeled surface proteins on merozoites formed complexes with the antibody. All major protein bands seen in the electrophoresis of the original Triton extract were bound by the immune sera. Because Gambians have never been exposed to P. knowlesi malaria, the antibodies that reacted with P. knowlesi merozoites must be directed against antigens of another parasite such as P. falciparum. We tested this hypothesis by competition for antibody in a Gambian serum between Triton-extracted antigens from P. falciparum schizont-infected erythrocytes and from surface-labeled P. knowlesi merozoites. P. falciparum inhibited the reaction, thus indicating cross-reaction between antigens in P. falciparum schizonts and P. knowlesi merozoites.

Visualization of specific B and T lymphocyte interactions in the lymph node.

Early events in the humoral immune response were visualized in lymph nodes by simultaneous tracking of antigen-specific CD4 T and B cells after immunization. The T cells were initially activated in the T cell areas when the B cells were still randomly dispersed in the B cell-rich follicles. Both populations then migrated to the edges of the follicles and interacted there, resulting in CD154-dependent B cell proliferation and germinal center formation. These results provide visual documentation of cognate T-B cell interactions and localize them to the follicular border.

NeuroCave: A web-based immersive visualization platform for exploring connectome datasets.

We introduce NeuroCave, a novel immersive visualization system that facilitates the visual inspection of structural and functional connectome datasets. The representation of the human connectome as a graph enables neuroscientists to apply network-theoretic approaches in order to explore its complex characteristics. With NeuroCave, brain researchers can interact with the connectome-either in a standard desktop environment or while wearing portable virtual reality headsets (such as Oculus Rift, Samsung Gear, or Google Daydream VR platforms)-in any coordinate system or topological space, as well as cluster brain regions into different modules on-demand. Furthermore, a default side-by-side layout enables simultaneous, synchronized manipulation in 3D, utilizing modern GPU hardware architecture, and facilitates comparison tasks across different subjects or diagnostic groups or longitudinally within the same subject. Visual clutter is mitigated using a state-of-the-art edge bundling technique and through an interactive layout strategy, while modular structure is optimally positioned in 3D exploiting mathematical properties of platonic solids. NeuroCave provides new functionality to support a range of analysis tasks not available in other visualization software platforms.

Molecules involved in T-cell costimulation.

Maximal expression of the interleukin-2 gene in T cells depends on biochemical signals in addition to those transduced by the T cell antigen receptor. Recent work indicates that the T-cell specific molecule CD28 transduces a 'costimulatory' signal when it binds its ligand, the B7 molecule, on the surface of an antigen-presenting cell. Results from experiments performed during the past year have raised the exciting possibility that immune responses can be either inhibited or augmented by manipulation of the CD28-B7 interaction.

Personality disorders in adolescence and risk of major mental disorders and suicidality during adulthood.

BACKGROUND: A community-based longitudinal study was conducted to investigate whether personality disorders (PDs) during adolescence increase the risk for Axis I psychiatric disorders and suicidality during early adulthood. METHOD: Psychosocial and psychiatric interviews were administered to a representative community sample of 717 youths and their mothers from 2 counties in the state of New York in 1975, 1983, 1985-1986, and 1991-1993. Anxiety, disruptive, eating, mood, personality, and substance use disorders and suicidal ideation and behavior were assessed in 1983 and 1985-1986, when the participants were adolescents, and in 1991-1993, when they were young adults. RESULTS: Adolescents with PDs were more than twice as likely as those without PDs to have anxiety, disruptive, mood, and substance use disorders during early adulthood. These associations remained statistically significant after co-occurring Axis I disorders during adolescence were controlled statistically. Cluster A, B, and C PDs and DSM-IV Appendix B PDs during adolescence were all associated with elevated risk for Axis I disorders during early adulthood after co-occurring Axis I and Axis II disorders during adolescence were controlled statistically. Cluster C PDs during adolescence were associated with elevated risk for suicidal ideation or behavior during early adulthood after co-occurring psychiatric disorders and suicidality during adolescence were controlled statistically. CONCLUSIONS: Adolescents in the community with personality disorders are at elevated risk for major mental disorders and suicidal ideation or behavior during early adulthood. This increase in risk is not accounted for by co-occurring Axis I disorders or suicidality during adolescence.

Childhood depression and adult personality disorder: alternative pathways of continuity.

BACKGROUND: This study extends previous findings of the risks posed by childhood major depressive disorder and other psychopathological features for later personality disorder (PD) in a random sample of 551 youths. METHODS: Self-reports and mother reports were used to evaluate DSM-III-R (Axes I and II) psychiatric disorders at mean ages of 12.7, 15.2, and 21.1 years. Logistic regression was used to examine the independent effects of major depressive disorder in childhood or adolescence on 10 PDs in young adulthood. RESULTS: Odds of dependent, antisocial, passive-aggressive, and histrionic PDs increased by more than 13, 10, 7, and 3 times, respectively, given prior major depressive disorder. Those effects were independent of age, sex, disadvantaged socioeconomic status, a history of child maltreatment, nonintact family status, parental conflict, preexisting PD in adolescence, and other childhood or adolescent Axis I psychopathological features, including disruptive and anxiety disorders. In addition, odds of schizoid and narcissistic PD increased by almost 6 times and odds of antisocial PD increased by almost 5 times given a prior disruptive disorder, and odds of paranoid PD increased by 4 times given a prior anxiety disorder. CONCLUSION: Personality disorders may represent alternative pathways of continuity for major depressive disorder and other Axis I disorders across the child-adult transition.

Association of maladaptive parental behavior with psychiatric disorder among parents and their offspring.

BACKGROUND: A longitudinal study was conducted to investigate the role of maladaptive parental behavior in the association between parent and offspring psychiatric disorder. METHODS: Psychosocial and psychiatric interviews were administered to a representative community sample of 593 biological parents and their offspring from 2 counties in the state of New York in 1975, 1983, 1985 to 1986, and 1991 to 1993. In 1975, the offspring were a mean age of 6 years. Maladaptive parental behavior was assessed in 1975, 1983, and 1985 to 1986. Parent and offspring psychiatric symptoms were assessed in 1983, 1985 to 1986, and 1991 to 1993. RESULTS: Maladaptive parental behavior substantially mediated a significant association between parental and offspring psychiatric symptoms. Parents with psychiatric disorders had higher levels of maladaptive behavior in the household than did parents without psychiatric disorders. Maladaptive parental behavior, in turn, was associated with increased offspring risk for psychiatric disorders during adolescence and early adulthood. Most of the youths that experienced high levels of maladaptive parental behavior during childhood had psychiatric disorders during adolescence or early adulthood, whether or not their parents had psychiatric disorders. In contrast, the offspring of parents with psychiatric disorders were not at increased risk for psychiatric disorders unless there was a history of maladaptive parental behavior. CONCLUSIONS: Maladaptive parental behavior is associated with increased risk for the development of psychiatric disorders among the offspring of parents with and without psychiatric disorders. Maladaptive parental behavior appears to be an important mediator of the association between parental and offspring psychiatric symptoms.

Childhood maltreatment increases risk for personality disorders during early adulthood.

BACKGROUND: Data from a community-based longitudinal study were used to investigate whether childhood abuse and neglect increases risk for personality disorders (PDs) during early adulthood. METHODS: Psychosocial and psychiatric interviews were administered to a representative community sample of 639 youths and their mothers from 2 counties in the state of New York in 1975, 1983, 1985 to 1986, and 1991 to 1993. Evidence of childhood physical abuse, sexual abuse, and neglect was obtained from New York State records and from offspring self-reports in 1991 to 1993 when they were young adults. Offspring PDs were assessed in 1991 to 1993. RESULTS: Persons with documented childhood abuse or neglect were more than 4 times as likely as those who were not abused or neglected to be diagnosed with PDs during early adulthood after age, parental education, and parental psychiatric disorders were controlled statistically. Childhood physical abuse, sexual abuse, and neglect were each associated with elevated PD symptom levels during early adulthood after other types of childhood maltreatment were controlled statistically. Of the 12 categories of DSM-IV PD symptoms, 10 were associated with childhood abuse or neglect. Different types of childhood maltreatment were associated with symptoms of specific PDs during early adulthood. CONCLUSIONS: Persons in the community who have experienced childhood abuse or neglect are considerably more likely than those who were not abused or neglected to have PDs and elevated PD symptom levels during early adulthood. Childhood abuse and neglect may contribute to the onset of some PDs.

Personality disorders predict onset of Axis I disorders and impaired functioning among homosexual men with and at risk of HIV infection.

BACKGROUND: A longitudinal study was conducted to investigate whether personality disorders (PDs) increase risk for the development of future Axis I disorders and serious functional impairment among human immunodeficiency virus (HIV)-seropositive and HIV-seronegative homosexual men. METHOD: Baseline assessments of PDs, Axis I disorders and symptoms, and Global Assessments of Functioning were conducted with a community sample of 107 (66 HIV-positive and 41 HIV-negative) homosexual men participating in a longitudinal study with semiannual interviews over 3 years. RESULTS: Logistic regression analysis indicated that PDs predicted onset of subsequent Axis I disorders after controlling for both HIV status and lifetime Axis I history (adjusted odds ratio, 4.31; P=.01; 95% confidence interval, 1.39 to 13.32). Of the 21 participants with PDs, 16 (76%) were subsequently diagnosed with Axis I disorders on at least one occasion. By contrast, only 36 (42%) of the 86 participants without PDs were subsequently diagnosed with Axis I disorders. Further, 33% of the participants with PDs, in comparison with only 8% of those without PDs, were assigned Global Assessments of Functioning scores of 50 or lower, indicating serious impairment during the postbaseline study period (adjusted odds ratio, 5.70; P<.005; 95% confidence interval, 1.66 to 19.53). CONCLUSION: Personality disorders may contribute to increased risk for onset of Axis I disorders and serious impairment among homosexual men regardless of HIV serologic status.

Co-stimulatory functions of antigen-presenting cells.

Antigen-presenting cells, in addition to presenting processed antigen, provide co-stimulatory signals that are necessary for stimulating maximal lymphokine production by CD4+ T cells. For interleukin 2 (IL-2)-producing CD4+ T cells, the B7 molecule provides an important co-stimulatory signal through interaction with its ligand on the T-cell surface, CD28. Populations of antigen-presenting cells that express high levels of B7 (e.g., dendritic cells) are much more potent stimulators of T-cell activation than cells that fail to express B7 (e.g., resting B cells). An increase in B7 expression could therefore explain the increased accessory function gained by Langerhans cells as they leave the skin and migrate to the draining lymph node.

Hemodynamic and antihypertensive effects of captopril, an orally active angiotensin converting enzyme inhibitor.

Captopril inhibits angiotensin II formation and bradykinin degradation in vivo. Eleven patients with essential hypertension (EH) and four patients with renovascular hypertension (RVH) were treated with captopril for periods ranging from 3 days to 12 months. All patients had a diastolic blood pressure (DBP) over 95 mm Hg after receiving a placebo for 3 days. Captopril given in ascending doses (10-1000 mg/day) caused normalization of blood pressure in all but three patients, one with severe RVH whose pressure fell 11%, one patient with severe EH, whose pressure fell 27%, and one with EH whose blood pressure fell 8.5%. The average control DBP in patients with EH was 113.7 +/- 5.5 (SE) mm Hg and fell to 89.9 +/- 3.6 mm Hg (p less than 0.001), while DBP in patients with RVH fell from 110.7 +/- 7.6 mm Hg to 94.5 +/- 8.2 (p less than 0.005). All patients were studied in balance on a 100 mEq sodium (Na) diet. Plasma renin activity (PRA) versus 24-hour urinary Na excretion increased sevenfold during therapy while converting enzyme activity fell by about one half. The magnitude of the blood pressure response was not related to control PRA. Cardiac output was estimated by echocardiography during placebo administration and during maintenance therapy with captopril. A significant change was not observed. Total peripheral resistance fell an average of 18.9% (p less than 0.05) in 11 of the 13 patients in whom the measurement could be made. It is concluded that captopril effectively lowers blood pressure in patients with EH or RHV by reducing total peripheral resistance.

Associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood: a community-based longitudinal investigation.

OBJECTIVE: The study investigated cross-sectional and longitudinal associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood. METHOD: Psychiatric interviews were administered to a representative community sample of 717 youths and their mothers in 1983 (mean age of youths=14 years) and again in 1985-1986, and 1991-1993. RESULTS: A wide range of psychiatric disorders co-occurred with bipolar disorder during adolescence and early adulthood. Adolescent anxiety disorders were uniquely associated with increased risk for early adulthood bipolar disorder after adolescent bipolar disorder was accounted for. Manic symptoms during adolescence were associated with increased risk for anxiety and depressive disorders during early adulthood after adolescent anxiety and depressive disorders were accounted for. CONCLUSIONS: Adolescents with anxiety disorders may be at increased risk for bipolar disorder or clinically significant manic symptoms during early adulthood. Adolescents with manic symptoms may be at increased risk for anxiety and depressive disorders during early adulthood.

Axis I psychiatric symptoms associated with HIV infection and personality disorder.

OBJECTIVE: The prevalences of personality disorders among HIV-positive and HIV-negative homosexual men were compared, and the presence of personality disorders was related to axis I psychiatric disorders, psychiatric distress, and impaired functioning. METHOD: The subjects were 162 homosexual men who either were HIV seronegative (N = 52) or were seropositive and had absent to moderate physical symptoms (N = 110). Lifetime and current histories of DSM-III-R axis I disorders, current diagnoses of DSM-III-R personality disorders, and levels of anxiety, depression, hopelessness, and adaptive functioning were assessed. RESULTS: In both the seropositive and seronegative groups, 19% of the study participants were diagnosed with personality disorders. The seropositive participants with personality disorders reported higher levels of psychiatric symptoms and poorer functioning than all participants without personality disorders, and they were over six times as likely as the seronegative participants without personality disorders to have current axis I disorders. CONCLUSIONS: These findings indicate that HIV infection and personality disorders may interactively increase the likelihood of clinically significant psychiatric symptoms.

Influence of child and adolescent psychiatric disorders on young adult personality disorder.

OBJECTIVE: This study examines associations between childhood psychopathology and young adult personality disorder in a random sample of 551 youths, who were 9 to 16 years old at first assessment. METHOD: Subjects were evaluated for DSM-III-R psychiatric disorders. Information was obtained prospectively from youths and their mothers at three points over 10 years. The predictive effects of prior axis I disorders and adolescent axis II personality disorder clusters A, B, and C on young adult personality disorder were examined in logistic regression analyses. RESULTS: The odds of young adult personality disorder increased given an adolescent personality disorder in the same cluster. Prior disruptive disorders, anxiety disorders, and major depression all significantly increased the odds of young adult personality disorder independent of an adolescent personality disorder. In addition, comorbidity of axis I and axis II disorders heightened the odds of young adult personality disorder relative to the odds of a disorder on a single axis. CONCLUSIONS: Assessment of personality pathology before late adolescence may be warranted. Childhood or adolescent axis I disorders may set in motion a chain of maladaptive behaviors and environmental responses that foster more persistent psychopathology over time. Identification and treatment of childhood disorder may help to reduce that risk.

Adolescent personality disorders associated with violence and criminal behavior during adolescence and early adulthood.

OBJECTIVE: A community-based, longitudinal prospective study was conducted to investigate whether personality disorders during adolescence are associated with elevated risk for violent behavior during adolescence and early adulthood. METHOD: A community-based sample of 717 youths from upstate New York and their mothers were interviewed in 1983, 1985-1986, and 1991-1993. Axis I and II disorders were assessed in 1983 and 1985-1986. Antisocial personality disorder was not assessed because most participants were less than 18 years of age in 1983 and 1985-1986. Violent behavior was assessed in 1985-1986 and 1991-1993. RESULTS: Adolescents with a greater number of DSM-IV cluster A or cluster B personality disorder symptoms were more likely than other adolescents in the community to commit violent acts during adolescence and early adulthood, including arson, assault, breaking and entering, initiating physical fights, robbery, and threats to injure others. These associations remained significant after controlling for the youths' age and sex, for parental psychopathology and socioeconomic status, and for co-occurring psychiatric disorders during adolescence. Paranoid, narcissistic, and passive-aggressive personality disorder symptoms during adolescence were independently associated with risk for violent acts and criminal behavior during adolescence and early adulthood after the covariates were controlled. CONCLUSIONS: Cluster A and cluster B personality disorders and paranoid, narcissistic, and passive-aggressive personality disorder symptoms during adolescence may increase risk for violent behavior that persists into early adulthood.

Accessory cell-derived signals required for T cell activation.

Various populations of accessory cells differ in their abilities to function as effective antigen-presenting cells (APC) and stimulate CD4+ T cells to produce interleukin-2. Three important factors directly related to APC potency are the expression of class II major histocompatibility complex molecules and the ability to present peptide antigens to the T cell antigen receptor, the expression of costimulatory ligands which deliver important activation signals independent of T cell receptor occupancy and the expression of adhesion molecules which promote conjugate formation so that these activation signals can be effectively delivered to the T cells. The relative importance of these accessory cell functions in T cell activation will be discussed, with an emphasis on costimulation and the CD28/B7 receptor/ligand pair. The consequence of inadequate costimulation by an otherwise effective APC in inducing T cell anergy will also be discussed.

Malignant hypertension in blacks. Malignant intrarenal arterial disease as observed by light and electron microscopy.

Volhard and Fahr recognized that hypertensive intrarenal vascular disease could be divided into two groups corresponding to the clinical states of benign and malignant hypertension. Since that time, numerous papers on malignant hypertension, primarily dealing with European derived populations, have emphasized fibrinoid necrosis of small arteries and arterioles as the lesion of malignant hypertension, although some have also recognized a myxoid intimal lesion as characteristic. Today in the United States, however, a significant proportion of malignant hypertension occurs in blacks. In the present study, patients have lacked fibrinoid necrosis of arterioles and only rarely have had some atypical necrosis of small arteries. The prominent, but not pathognomonic, lesion in this series is a myxoid intimal thickening of small arteries consisting of smooth muscle cells, acid mucopolysaccharides, basement membrane-like materal, collagen, and other amorphous and unidentified material, probably plasma derived.

Outpatient frozen sections by telepathology in a Veterans Administration medical center.

A relatively simple telepathology system is described for evaluating the margins of excision of cutaneous basal and squamous carcinomas. The system uses a microscope with a built-in television camera, but no eyepieces. The image is projected onto an adjacent monitor and transmitted by T1 line at 768 Kbs to a remote, large screen monitor. The microscope is operated by the surgeon under the telephone direction of the pathologist at the remote site. In a series of 66 cases involving more than 400 individual tissue blocks, we have had only 2 cases with false-negative interpretations and 2 in which the block was not fully displayed on the frozen section. In 15 cases, 1 or more surgical margins were positive, and the surgeon proceeded to excise additional tissue. Our success is attributed to dedicated involvement by the surgeon, very high-quality frozen sections, and the experience of the pathologist.

True hermaphroditism with peripheral blood and gonadal karyotyping.

Eight documented cases of true hermaphroditism have been seen in the reproductive endocrine unit at the Medical College of Georgia since 1969. There was histologic evidence of both ovarian and testicular tissue in all cases. Seven patients had peripheral blood karyotypes: 6 had normal 46,XX peripheral blood karyotypes, and 1 patient had a normal 46,XY blood karyotype. Four of the 7 patients studied had chromosomal analysis of 1 or both gonads. Five gonads were karyotyped as 46,XX and 1 revealed a mosaic gonadal pattern of 46,XX/46,XY. The clinical features, anatomic findings, and cytogenetic studies of these patients are reviewed. Discordant findings in peripheral blood and gonadal chromosomes are discussed.