Low prevalence of HTLV-II in Mayan Indians in the Yucatan Peninsula, Mexico

Infection with HTLV-II is endemic in Amerindians, with prevalence ranging from 0.89% - 33%. To determine the prevalence of HTLV-II among indigenous Mayans in the Yucatan Peninsula of Mexico, 440 indigenous Mayans were recruited, all native to and residents of one of six Mayan communities in the Yucatan Peninsula, (Xohuayan n=144, Yaxachen n=101, Kanxoc n=84, Xocen n=40, Nabalan n=46 and X'calot n=25) between May, 1992 and June, 1993. All of the above are pre-Hispanic settlements located in tropical forest with no immigrations for over 50 years. Of the 440 indigenous Mayans, only one woman from the X'calot tribe (0.23%) was shown to be infected with HTLV-II. A high percentage of indeterminate results was found (22/439, 5%), three of which were accounted for by the husband and two children of the positive female case. PCR analysis followed by specific restriction digestion demonstrated the virus to be of the HTLV-IIb subtype, similar to that described in the Guaymi Indians from Panama. The presence of HTLV-II in the Mayan ethnos, and in other Amerindian populations supports the idea that HTLV-II is an ancestral virus in America and that it has been sustained in "closed" communities.     

Prognostic value of a hand symptom diagram in surgery for carpal tunnel syndrome

OBJECTIVE: To evaluate symptom patterns on a hand diagram as predictors of surgical outcome in carpal tunnel syndrome (CTS). METHODS: 202 patients with CTS enrolled in a prospective, community based cohort study in Maine completed a hand symptom diagram before surgery and at 6 month followup. They were asked to mark on the hand diagram the location of 3 symptoms: pain, numbness/tingling (NT), and "other" symptoms. The diagram was first divided into 6 regions following a standardized procedure. For the 6 regions, symptom patterns were identified separately for each of the 3 symptoms. Outcomes 6 months after surgery were expressed as the percentage of change on the Symptom Severity Scale and Function Status Scale of the Carpal Tunnel Syndrome Assessment Questionnaire, and the satisfaction with the results of the surgery. RESULTS: Several distinct symptom patterns were associated with the 3 principal outcomes in univariate and multivariate analysis. In linear regression models controlling for the baseline severity of symptoms and function, as well as other predictors, the hand symptom pattern variables accounted for 30, 14, and 24%, respectively, of the total explained variance in satisfaction, symptom severity, and functional status. Patients receiving Workers' Compensation (37% of the cohort) had more wrist pain and NT of the arm, and less pain involving the arm and upper palm. This group also had worse outcomes and were less satisfied with surgery. Drawing expansion was associated with a low score on the SF-36 mental health subscale. However, psychological impairment was not associated with a worse outcome. CONCLUSION: Symptom patterns identified preoperatively with a hand symptom diagram help to predict the outcome of carpal tunnel release.     

Management of chronic medical conditions in children and adolescents

The care of children and adolescents with chronic medical conditions is an area of great interest for primary care physicians. With longer lives and more "mainstreaming" of care, the primary care physician often finds an increased role in the management of children and adolescents with chronic conditions such as mental retardation, Down syndrome, and diabetes mellitus. This article discusses familiarity with the most common chronic conditions and common pitfalls of management.     

Neurodevelopmental consequences of early exposure to phencyclidine and related drugs

In the early development of the central nervous system, stimulation of N-methyl-D-aspartate (NMDA) receptors may be critical for neuronal cell survival and differentiation, as well as the establishment of neural networks resulting from "experience-dependent plasticity." The trophic influence of NMDA receptor stimulation may be present only during a certain critical period of development. There are, therefore, major concerns associated with the administration of noncompetitive NMDA receptor antagonists (such as MK-801 [dizocilpine]) as neuroprotective and anticonvulsant agents to pregnant women, neonates, infants, and young children. Several studies showing disruptive effects of noncompetitive NMDA receptor antagonists on normal neurobehavioral development are reviewed in this article. This research has important public health implications because phencyclidine (PCP), a noncompetitive NMDA receptor antagonist, is a frequently-abused drug that may disrupt brain development in utero when abused by pregnant women. The article also reviews studies of neonatal blockade of the NMDA receptor complex in animals; studies that may lead to useful models of human neurodevelopmental disorders. These models may even mimic the relevant neurodevelopmental aspects of at least some forms of schizophrenia, especially the early developmental disconnection of circuits between the hippocampus and frontal cortex.     

Detection of a conserved alpha-helix in the kinase-docking region of the aspartate receptor by cysteine and disulfide scanning

The transmembrane aspartate receptor of Escherichia coli and Salmonella typhimurium propagates extracellular signals to the cytoplasm, where its cytoplasmic domain regulates the histidine kinase, CheA. Different signaling states of the cytoplasmic domain modulate the kinase autophosphorylation rate over at least a 100-fold range. Biochemical and genetic studies have implicated a specific region of the cytoplasmic domain, termed the signaling subdomain, as the region that transmits regulation from the receptor to the kinase. Here cysteine and disulfide scanning are applied to the N-terminal half of the signaling subdomain to probe its secondary structure, solvent exposure, and protein-protein interactions. The chemical reactivities of the scanned cysteines exhibit the characteristic periodicity of an alpha-helix with distinct solvent-exposed and buried faces. This helix, termed alpha7, ranges approximately from residue 355 through 386. Activity measurements probing the effects of cysteine substitutions in vivo and in vitro reveal that both faces of helix alpha7 are critical for kinase activation, while the buried face is especially critical for kinase down-regulation. Disulfide scanning of the region suggests that helix alpha7 is not in direct contact with its symmetric partner (alpha7') from the other subunit; presently, the structural element that packs against the buried face of the helix remains unidentified. Finally, a novel approach termed "protein interactions by cysteine modification" indicates that the exposed C-terminal face of helix alpha7 provides an essential docking site for the kinase CheA or for the coupling protein CheW.     

Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5

Calnexin is a 90-kDa integral membrane protein of the endoplasmic reticulum (ER). Calnexin binds Ca2+ and may function as a chaperone in the transition of proteins from the ER to the outer cellular membrane. We have purified human calnexin in association with the human interferon-gamma receptor and cloned calnexin cDNA from placenta. Fragments of calnexin have been prepared as glutathione S-transferase fusion proteins and analyzed for their abilities to bind 45Ca2+ and ruthenium red. A subdomain containing four internal repeats binds Ca2+ with the highest affinity. This sequence is highly conserved when compared to calreticulin (a luminal ER protein), an Onchocerca surface antigen, and yeast and plant calnexin homologues. Consequently, this sequence represents a conserved motif for the high-affinity binding of Ca2+, which is clearly distinct from the "E-F hand" motif. An adjacent subdomain, also highly conserved and containing four internal repeats, fails to bind Ca2+. The carboxyl-terminal, cytosolic domain is highly charged and binds Ca2+ with moderate affinity, presumably by electrostatic interactions. The calnexin amino-terminal domain (residues 1-253) also binds Ca2+, in contrast to the amino-terminal domain of calreticulin, which is relatively less acidic. We have also determined the cDNA sequences of mouse and rat calnexins. Comparison of the known mammalian calnexin sequences reveals very high conservation of sequence identity (93-98%), suggesting that calnexin performs important cellular functions. The gene for human calnexin is located on the distal end of the long arm of human chromosome 5, at 5q35.     

Phenomenologic comparison of the idiopathic psychosis of schizophrenia and drug-induced cocaine and phencyclidine psychoses: a retrospective study

Both stimulant-induced and phencyclidine (PCP)-induced psychoses have been proposed as models of the idiopathic psychosis of schizopherenia. In this two-part study, the phenomenology of the psychosis associated with a period of cocaine intoxication was evaluated retrospectively in 34 male crack cocaine-dependent patients without concomitant psychiatric disorder and then was compared with the psychosis of 16 actively psychotic schizophrenic men (without a history of drug or alcohol abuse in the past year). Certain First Rank Schneiderian Symptoms (FRSS) were more commonly observed in the schizophrenic patients (e.g., thought broadcasting, thought withdrawal) than in the cocaine addicts. In the second part of this study, we retrospectively examined the cocaine and PCP experiences of an additional 22 cocaine addicts who had a past history of separate periods of cocaine and PCP use. Overall, the frequency of FRSS recalled during periods of cocaine and PCP intoxication was similar. However, the psychosis related to cocaine intoxication was more associated with an intense suspiciousness and paranoia related to a fear of being discovered or harmed while using cocaine. PCP-induced psychosis was less associated with suspiciousness and more associated with delusions of physical power, altered sensations, and unusual experiences [e.g., out of body experiences, experiencing religious figures or events directly (e.g., being with Noah at the time of the Arc)]. As elements of both cocaine and PCP psychosis can be found in schizophrenia, a model integrating the mechanisms of several psychotogenic drugs may be more informative. Such an integrative model might better capture the heterogeneity of psychotic symptoms that can be seen in schizophrenia. Furthermore, different pharmacologic interventions (e.g., "anti-stimulant" versus "anti-PCP") might address different aspects of the positive symptom picture in schizophrenia.     

The Gag domain of the Gag-Pol fusion protein directs incorporation into the L-A double-stranded RNA viral particles in Saccharomyces cerevisiae

The L-A double-stranded RNA virus of yeast encodes its major coat protein, Gag, and a Gag-Pol fusion protein made by a -1 ribosomal frameshift, a coding strategy used by many retroviruses. We find that cells expressing only Gag from one plasmid and only Gag-Pol (in frame) from a separate plasmid can support the propagation of M1 double-stranded RNA, encoding the killer toxin. We use this system to separately investigate the functions of Gag and the Gag part of Gag-Pol. L-A contains two fusion protein molecules per particle, and although N-terminal acetylation of Gag is essential for viral assembly, it is completely dispensable for function of Gag-Pol. In general, the requirements on Gag for viral assembly and propagation are more stringent than on the Gag part of Gag-Pol. Finally, we directly show that it is Gag that instructs the incorporation of Gag-Pol into the viral particles.