FOS is induced by singing in distinct neuronal populations in a motor network

The acute and subacute effects of intracerebroventricularly (ICV) administered nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) on locomotor activity were evaluated in awake adult rats. Immediately after ICV injection through an implanted cannula, locomotor activity was measured by a computerized system using infrared photocells, which allowed us to record locomotion, motility, and rearing simultaneously. A single dose of 5 microg mouse beta-NGF produced significant increases in horizontal ambulatory components of locomotor activity (locomotion and motility), but not vertical movement (rearing) 30-45 min after ICV administration. These increases lasted for at least 3-4 h. Systemic injection of 2.0 mg/kg mecamylamine, a central nicotinic receptor antagonist, inhibited the hyperactivity induced by NGF. Systemic injection of 0.5 mg/kg scopolamine, a muscarinic receptor antagonist, did not interfere with the NGF effects. Thus, while scopolamine induced marked increases in all three measures of behavior in both NGF and cytochrome-c-treated animals, locomotion and motility remained significantly higher in the NGF group. Immunohistochemistry demonstrated that NGF diffused readily from the ventricular space into brain parenchyma on the injected side and could be visualized 1 h after ICV injection. These results suggest that ICV administration of NGF increases locomotor activity by inducing acetylcholine release, and that nicotinic receptors are involved in the hyperactivity induced by NGF. ICV administration of 5 microg recombinant human BDNF had no significant effect on locomotor activity during the 0- to 4-h period after ICV injection. However, it produced significant decreases in locomotion, motility, and rearing 24-26 h later. Hence ICV administration of BDNF has entirely different effects on animal behavior from those evoked by NGF. While NGF elicits increases in ambulatory behavior within hours, BDNF causes delayed decreases in ambulatory behavior.     

Beta-1-integrin expression in adult acute lymphoblastic leukemia: possible relationship with the stem cell antigen CD34

In the hemopoietic system, interactions between stem cells and components of the bone marrow microenvironment play a pivotal role in blood cell proliferation and differentiation. Among the adhesion molecules, the integrins of the beta 1-subfamily are known to direct cell-cell and cell-matrix interactions and evidence has been provided that CD34-positive stem cells bind either to the bone marrow stroma or to the extracellular matrix proteins through the beta 1-integrins. It seems that changes in their expression pattern or signalling function are likely to reflect disturbances at the hemopoietic bone marrow microenvironmental level. Any alteration of their biological functions makes them attractive candidates for playing decisive roles in the leukemic processes. In this view, beta 1-integrins have been recognized to mediate those cellular interactions and migrations that are important in the biology of leukemia. In this paper we review some aspects of the role played by beta 1-integrins, especially VLA-4 and VLA-5, in adult acute lymphoblastic leukemia in relation with the expression rate of the stem cell antigen CD34.     

Influence of two weeks of non-weight bearing on rat soleus motoneurons and muscle fibers

OBJECTIVES: To analyse the ethical implications of informing patients about their do-not-resuscitate status (DNR). DESIGN: Questionnaire. SETTING: Nationwide, 6 months after the publication of guidelines on DNR in 1994. SUBJECTS: A 10% random sample of the members of the Swedish Cardiac Society. 104 physicians and 196 nurses. MAIN OUTCOME MEASURES: To what extent are patients, physicians and nurses involved in decisions about DNR, and how should the ethical conflict involved in informing patients about their DNR status be described and analysed? RESULTS: Of 73% responding, 84% of the physicians and 8% of the nurses had made a DNR decision. The decision was regarded as ethically right and well timed and it was discussed with 33% of the competent patients. Half of the respondents believed that DNR orders should be discussed with the competent patient. but still only one third of the patients are involved. The ethical conflict is analysed using the principles of autonomy and nonmaleficence as value premises. CONCLUSIONS: Many physicians are still reluctant to find out what the patient wants. Being ignorant they risk harming the patient. It is recommended that information about DNR status should be given incrementally and that the attitudes of the old and chronically ill in-hospital patients are studied. Do they want to be informed, and if so, how and when do they want it to be done?     

Cycloalkylpyranones and cycloalkyldihydropyrones as HIV protease inhibitors: exploring the impact of ring size on structure-activity relationships

Previously, 3-substituted cycloalkylpyranones, such as 2d, have proven to be effective inhibitors of HIV protease. In an initial series of 3-(1-phenylpropyl) derivatives with various cycloalkyl ring sizes, the cyclooctyl analog was the most potent. We became interested in exploring the influence of other structural changes, such as substitution on the phenyl ring and saturation of the 5,6-double bond, on the cycloalkyl ring size structure-activity relationship (SAR). Saturation of the 5,6-double bond in the pyrone ring significantly impacts the SAR, altering the optimal ring size from eight to six. Substitution of a sulfonamide at the meta position of the phenyl ring dramatically increases the potency of these inhibitors, but it does not change the optimal ring size in either the cycloalkylpyranone or the cycloalkyldihydropyrone series. This work has led to the identification of compounds with superb binding affinity for the HIV protease (Ki values in the 10-50 pM range). In addition, the cycloalkyldihydropyrones showed excellent antiviral activity in cell culture, with ED50 values as low as 1 microM.     

Distribution of HIV type 1 (HIV-1) in blood components: detection and significance of high levels of HIV-1 associated with platelets

BACKGROUND: Although inactivation of enveloped viruses transmitted by plasma derivatives has been successful, no methods for virus inactivation or removal have been established for platelet concentrates or red cell (RBC) components. Relatively little is known regarding the extent or significance of virus interactions with the cellular constituents in these components. STUDY DESIGN AND METHODS: Units of whole blood were collected from six HIV type 1 (HIV-1)-positive, asymptomatic individuals and separated into peripheral blood mononuclear cells (PBMNCs), cell-free plasma, white cell-reduced platelet concentrate, and white cell-reduced RBCs. DNA and RNA polymerase chain reaction and virus culture methods were used to study the compartmentalization of HIV-1 immediately after component preparation and after storage. RESULTS: As expected, HIV DNA and infectious virus were detected in fresh blood and in PBMNCs, and virion-associated RNA was detected in fresh plasma from all six donors. The levels of viral nucleic acids in these preparations remained relatively stable with 4 degrees C storage, whereas infectivity of PBMNCs was rapidly lost. Washed RBCs tested negative for HIV in all assays at all time points. Platelets retained high levels of HIV RNA (but not infectivity) after extensive washing, as well as after storage at 4 and 22 degrees C. High-level platelet-associated HIV-1 was also demonstrated in samples collected during early seroconversion. Periseroconversion and postseroconversion levels of platelet-associated HIV-1 correlated with the level of plasma viremia and with the rate of progression to AIDS. Cell-free virus from donor plasma and tissue culture fluid rapidly and firmly attached to platelets from noninfected donors. Infectivity of tissue culture virus bound to platelets was demonstrated in vitro. CONCLUSION: Significant levels of HIV-1 are associated with platelets during all stages of infection. Platelet-associated HIV could either mediate virus clearance or facilitate virus dissemination and expanded tropism. Finally, virus inactivation research must address virus associations with platelets.     

Effects of hypesthesia on oral behaviors of the orthognathic surgery patient

PURPOSE: The purpose of this study was to compare orthognathic surgery patients with and without significant hypesthesia with respect to perceived problems with specific oral behaviors. PATIENTS AND METHODS: Data from 116 patients 6 months after bilateral sagittal split osteotomy (BSSO) and mandibular advancement were analyzed. Tactile sensation in the right and left mental nerve areas was determined using monofilaments and brush strokes (von Frey hairs). The right infraorbital region was used as a control. A difference of 450 mg of force between the control and test sites was considered significant hypesthesia. Patients rated their level of subjective problems with swallowing liquids or solids, smiling, spitting, kissing, speaking, eating, and drooling on a scale from 1 (none to mild) to 7 (extreme). A value of 5 or greater was considered significant impairment. RESULTS: Hypesthesia was shown in 23 patients (19.8%) with the monofilaments and in 29 patients (25.0%) using brush stroke direction. In each of these two groups, a significant correlation was observed between hypesthesia and difficulty in chewing and kissing. No correlation was observed between any of the remaining seven oral behaviors and hypesthesia. CONCLUSION: These findings suggest that only certain oral behaviors are affected by hypesthesia of the mental nerve.     

The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.     

On the duality of the facial nerve ganglion

OBJECTIVES: Describe quantitatively the number of ganglion cells in the geniculate (G) and meatal (M) segments of the human facial nerve. STUDY DESIGN: One hundred human temporal bone specimens that were sectioned horizontally and stained with hematoxylin and eosin were selected from a temporal bone collection on the basis of minimal artifact and absence of pathology involving the facial nerve. METHODS: Cells with a nucleolus in all sections through the facial nerve were projected on tracing paper with a camera lucida and counted manually. A modified Abercrombie technique was employed to compute total cells in the G and M segments. RESULTS: Ages of patients ranged from 1 month to 92 years; the male-to-female ratio was 56:44. The total number of cells in individual temporal bones ranged from 589 to 4183 (mean, 2162 cells). The range of cells in the G ganglion was from 66 to 4017 (mean, 1713 cells); in the M ganglion the number ranged from 0 to 2764 (mean, 448 cells). There was no correlation of total ganglion cell number to age or sex. The majority of cells were found in the G ganglion in 88% of temporal bones. In 8% temporal bones the majority of cells were in the M ganglion and in 4% the M and G ganglions contained an equal number of cells. CONCLUSIONS: The facial nerve sensory ganglion consists of two components: G and M. The G ganglion outnumbers the M component in the majority of temporal bones (88%). The M ganglion was equal to or greater in number than the G ganglion in 12% of temporal bones.     

MR angiography of the head and neck

A review of the basic physics and techniques for acquiring and evaluating magnetic resonance angiograms is provided, including time-of-flight and phase contrast techniques. Magnetic resonance (MR) angiography is becoming a routine method of evaluating carotid bifurcation atherosclerotic disease in both a screening and diagnostic capacity. The expanding clinical utility of MR angiography in the detection of intracranial aneurysms, characterization of arteriovenous malformations, and evaluation of intracranial atherosclerotic disease are also reviewed. Furthermore, MR angiography allows for the noninvasive diagnosis of arterial dissection. Magnetic resonance venography also allows the confirmation of the previously elusive and likely underdiagnosed entity of cerebral venous thrombosis.     

Seroprevalence survey of Egyptian tourism workers for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum infections: association of hepatitis C virus infections with specific regions of Egypt

Blood samples from 740 Egyptian Nationals working in the tourism industry at two sites in the South Sinai governorate were screened for markers of infection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Treponema pallidum. Study subjects included 467 individuals from a rural seashore tourist village and 273 persons at two hotels in a well-established resort town. Subjects' ages ranged from 15 to 70 years; 99.3% were male. The prevalence of serologic markers for currently asymptomatic or past HBV infection alone was 20.7% (n = 153), of markers for past or chronic HCV infection alone was 7.4% (n = 55), and of markers for both HBV and HCV was 6.9% (n = 51). Of the 204 individuals positive for anti-HBV core antibody, 12 (5.9%) were also positive for hepatitis B surface antigen. Two individuals (0.3%) had a serologic market suggestive of an active syphilitic infection. No subject was found to be HIV-seropositive. History of prior injections and number of injections were associated with infection with HCV. Primary residence in the Nile delta and valley areas where schistosomiasis is highly endemic, was also a statistically significant risk factor for HCV, but not HBV infection.