Neurofilament proteins are synthesized in nerve endings from squid brain

It is generally believed that the proteins of the nerve endings are synthesized on perikaryal polysomes and are eventually delivered to the presynaptic domain by axoplasmic flow. At variance with this view, we have reported previously that a synaptosomal fraction from squid brain actively synthesizes proteins whose electrophoretic profile differs substantially from that of the proteins made in nerve cell bodies, axons, or glial cells, i.e., by the possible contaminants of the synaptosomal fraction. Using western analyses and immunoabsorption methods, we report now that (a) the translation products of the squid synaptosomal fraction include neurofilament (NF) proteins and (b) the electrophoretic pattern of the synaptosomal newly synthesized NF proteins is drastically different from that of the NF proteins synthesized by nerve cell bodies. The latter results exclude the possibility that NF proteins synthesized by the synaptosomal fraction originate in fragments of nerve cell bodies possibly contaminating the synaptosomal fraction. They rather indicate that in squid brain, nerve terminals synthesize NF proteins.     

The platysma myocutaneous flap. Indications and caveats

Arterial hypertension has been identified as a major secondary risk factor for diabetic retinopathy. However, the mechanisms by which hypertension worsens retinopathy are unknown. Inhibition of advanced glycation product formation prevents the development of experimental diabetic retinopathy in normotensive diabetic rats. In this study the effect of hypertension on the rate of diabetic retinopathy development and the formation of arteriolar thrombosis was evaluated. We also evaluated the effect of aminoguanidine, an inhibitor of advanced glycation and product formation on retinal pathology of diabetic hypertensive rats. After 26 weeks of diabetes, hypertension accelerated the development of retinopathy despite a lower mean blood glucose level than in the non-hypertensive group (diabetic spontaneous hypertensive rats (SHR) 16.00 +/- 6.83 mmol/l; diabetic normotensive Wistar Kyoto rats (WKY) 34.9 +/- 3.64 mmol/l; p < 0.0001). Diabetic SHR had nearly twice as many acellular capillaries as diabetic WKY (SHR diabetic: 91.9 +/- 7.5 acellular capillaries per mm2 of retinal area vs WKY diabetic: 53.7 +/- 8.5 acellular capillaries per mm2 of retinal area), and a 3.8-fold increase in the number of arteriolar microthromboses (SHR diabetic 23,504 +/- 5523 microns2 vs SHR non-diabetic 6228 +/- 2707 microns2). Aminoguanidine treatment of SHR diabetic rats reduced the number of acellular capillaries by 50%, and completely prevented both arteriolar deposition of PAS-positive material and abnormal microthrombus formation. These data suggest that hypertension-induced deposition of glycated proteins in the retinal vasculature plays a central role in the acceleration of diabetic retinopathy by hypertension.     

Effective peer responses to impaired nursing practice

Subplate neurons, the first neurons of the cerebral cortex to differentiate and mature, are thought to be essential for the formation of connections between thalamus and cortex, such as the system of ocular dominance columns within layer 4 of visual cortex. To learn more about the requirement for subplate neurons in the formation of thalamocortical connections, we have sought to identify the neurotransmitters and peptides expressed by the specific class of subplate neurons that sends axonal projections into the overlying visual cortex. To label retrogradely subplate neurons, fluorescent latex microspheres were injected into primary visual cortex of postnatal day 28 ferrets, just prior to the onset of ocular dominance column formation. Subsequently, neurons were immunostained with antibodies against glutamate, glutamic acid decarboxylase (GAD-67), parvalbumin, neuropeptide Y (NPY), somatostatin (SRIF), or nitric oxide synthase (NOS). Retrograde labeling results indicate that the majority of subplate neurons projecting into the cortical plate reside in the upper half of the subplate. Combined immunostaining and microsphere labeling reveal that about half of cortically projecting subplate neurons are glutamatergic; most microsphere-labeled subplate neurons do not stain for GAD-67, parvalbumin, NPY, SRIF, or NOS. These observations suggest that subplate neurons can provide a significant glutamatergic synaptic input to the cortical plate, including the neurons of layer 4. If so, excitation from the axons of subplate neurons may be required in addition to that from lateral geniculate nucleus neurons for the activity-dependent synaptic interactions that lead to the formation of ocular dominance columns during development.     

1-[Carbon-11]-glucose radiation dosimetry and distribution in human imaging studies

1-[Carbon-11]-D-glucose ([11C]-glucose) is an important imaging agent for PET studies that have been used to study the normal brain, encephalitis, epilepsy, manic-depressive disorder, schizophrenia and brain tumors. METHODS: Dosimetry estimates were calculated in subjects undergoing imaging studies to help define the radiation risk of [11C]-glucose PET imaging. Time-dependent radioactivity concentrations in normal tissues in 33 subjects after intravenous injection of [11C]-glucose were obtained by PET imaging. Radiation absorbed doses were calculated according to the procedures of the Medical Internal Radiation Dose (MIRD) committee along with the variation in dose based on the calculated standard deviation of activity distribution seen in the individual patients. RESULTS: Total body exposure was a median of 3.0 microGy/MBq in men and 3.8 microGy/MBq in women. The effective dose equivalent was 3.8 microGy/ MBq in men and 4.8 microGy/MBq in women. The critical organs were those that typically take up the most glucose (brain, heart wall and liver). CONCLUSION: The organ doses reported here are small and comparable to those associated with other commonly performed nuclear medicine tests and indicate that potential radiation risks associated with this radiotracer are within generally accepted limits.     

Issues and controversies in venous thromboembolism

The developmental expression of salivary glycoconjugates was investigated in the rat submandibular and sublingual glands by conventional and lectin histochemistry. By the time of the first differentiation of secretory structures, in spite of similar morphological features, a different histochemical reactivity was detected, accounting for a relevant content of neutral glycoconjugates in the submandibular gland and the occurrence of both neutral and acidic glycoconjugates in the sublingual one. The use of lectins allowed the main changes of secretory components to be noted around gestational day 18. DBA and WGA lectins seemed to act as pre- and post-natal development markers while Con A lectin was indicative of post-natal differentiation. Taken together, data from lectin histochemistry indicated the transitional occurrence of glycoconjugates, probably involved in temporally restricted functions, as well as the co-existence of different secretory components that might also reflect maturational changes of single products.     

Asymmetrical hemispheric activation and emotion: the effects of unilateral forced nostril breathing

Relative nostril efficiency is associated with greater activation of the hemisphere contralateral to the more efficient (dominant) nostril and with improved performance on cognitive tasks which reflect the functions of that hemisphere (see Shannahoff-Khalsa, 1993, for review). In this experiment we demonstrate a similar relationship between nasal efficiency and the emotional functions of the cerebral hemispheres. Following left nostril forced breathing through the dominant nostril, subjects report a more negative emotional state, score higher on the Spielberger State Anxiety Inventory, and tell stories about an ambiguous picture that are more negative in emotional tone. These results are similar to those found with unilateral muscle contractions and therefore support the hypothesis that unilateral contractions are effective because of contralateral hemispheric activation.     

Preparing tomorrow's health sciences librarians: feasibility and marketing studies

The University of North Carolina at Chapel Hill is devising and evaluating five curricular models designed to improve education for health sciences librarianship. These models fit into a continual learning process from the initial professional preparation to lifelong learning opportunities. Three of them enhance existing degree and certificate programs in the School of Information and Library Science (SILS) with a health sciences specialization, and two are new programs for working information professionals. The approaches involve partnerships among SILS, the Health Sciences Library, and the program in Medical Informatics. The planning process will study the feasibility of the proposed programs, test the marketability of the models to potential students and employers, and make recommendations about implementation.     

Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease

This study examines cerebrospinal fluid from patients with three neuropsychiatric diseases of childhood for the presence and levels of several cytokines relevant to cell-mediated (type 1) and humoral (type 2) immunity. The patient groups include childhood-onset schizophrenia (n = 22), obsessive-compulsive disorder (OCD) (n = 24), and attention deficit hyperactivity disorder (n = 42). The cytokines examined include IL-2, IFN-gamma, TNF-beta/LT, IL-4, IL-5, IL-10, and TNF-alpha. Patients with OCD had a preponderance of type 1 cytokines. IL-4 was detectable only in samples from patients with schizophrenia. IL-10 was rarely detected and never in patients with OCD. Few patients with schizophrenia had detectable amounts of IFN-gamma in CSFL. We conclude that there is a relative skewing of CSFL profiles toward type 1 cytokines in patients with OCD, whereas in schizophrenia the relative preponderance is toward type 2 mediators. Patients with attention deficit hyperactivity disorder exhibited profiles intermediate between OCD and schizophrenia. We infer that cell-mediated immunity may be involved in the etiopathogenesis of OCD, whereas a relative lack of cell-mediated immunity and involvement of humoral immunity may be present in schizophrenia. These data provide a rationale for immune-based strategies of study and therapeutics in childhood neuropsychiatric disease.     

Importance of MEK in neutrophil microbicidal responsiveness

Exposure of neutrophils to inflammatory stimuli such as the chemoattractant FMLP leads to activation of responses including cell motility, the oxidative burst, and secretion of proteolytic enzymes. A signaling cascade involving sequential activation of Raf-1, mitogen-activated protein kinase (MEK), and extracellular signal regulated kinase (ERK) is also rapidly activated after agonist exposure. The temporal relationship between these events suggests that the kinases may be involved in triggering the effector functions, but direct evidence of a causal relationship is lacking. To assess the role of the MEK/ERK pathway in the activation of neutrophil responses, we studied the effects of PD098059, a potent and selective inhibitor of MEK. Preincubation of human neutrophils with 50 microM PD098059 almost completely (>90%) inhibited the FMLP-induced activation of MEK-1 and MEK-2, the isoforms expressed by neutrophils. This dose of PD098059 virtually abrogated chemoattractant-induced tyrosine phosphorylation and activation of ERK-1 and ERK-2, implying that MEKs are the predominant upstream activators of these mitogen-activated protein kinases. Pretreatment of neutrophils with the MEK antagonist inhibited the oxidative burst substantially and phagocytosis only moderately. In addition, PD098059 antagonized the delay of apoptosis induced by exposure to granulocyte-macrophage CSF. However, the effects of PD098059 were selective, as it failed to inhibit other responses, including chemoattractant-induced exocytosis of primary and secondary granules, polymerization of F-actin, chemotaxis, or activation of phospholipase A2. We conclude that MEK and ERK contribute to the activation of the oxidative burst and phagocytosis, and participate in cytokine regulation of apoptosis.     

Swallow recovery in an oral cancer patient following surgery, radiotherapy, and hyperthermia

BACKGROUND: No study has examined the nature and extent of swallowing impairment in oral cancer patients following treatment with combined hyperthermia and interstitial radiotherapy. Few studies have examined the effects of voluntary swallow maneuvers (supersupraglottic and Mendelsohn) on pharyngeal phase swallowing in the oral cancer patient treated with surgery or radiotherapy. This study examined the effects of combined radiotherapeutic salvage treatments of hyperthermia and interstitial implantation and swallow recovery using swallow maneuvers in a surgically treated and irradiated oral cancer patient. METHODS: The patient under study, a 51-year-old man, underwent radiotherapy, according to Radiation Therapy Oncology Group (RTOG) protocol #8419, consisting of a combination of interstitial irradiation and hyperthermia to the base of tongue, for a recurrent squamous cell cancer. He underwent videofluorographic (VFG) examination of his swallowing, a modified barium swallow at three time points: 2 days following radiotherapy treatment (VFG1), 4 weeks later (VFG2), and 8 months later (VFG3). Temporal and biomechanical analyses of swallows were performed at each time point. RESULTS: Swallow maneuvers and time resulted in improved laryngeal elevation and laryngeal vestibule closure during the swallows on VFG2. Maximum upper esophageal sphincter (UES) opening width and duration were more normal. Fewer swallows were required for bolus clearance through the pharynx. Base of tongue tissue necrosis occurred as a complication of radiotherapy between VFG2 and VFG3, with resultant severe reduction in posterior movement of the tongue base, incomplete tongue base contact to the posterior pharyngeal wall, reduced laryngeal elevation, and incomplete laryngeal vestibule closure during swallowing at VFG3. UES opening became less normal and a greater number of swallows were required for bolus clearance through the pharynx. CONCLUSIONS: Combined interstitial irradiation and hyperthermia can cause oropharyngeal swallowing problems. Time and swallow therapy can improve these swallow disorders. Tongue base tissue necrosis can cause further swallow impairment, emphasizing the importance of the tongue base in normal deglutition. Further studies are needed to examine the impact of combined hyperthermia and interstitial implantation for treatment of tongue base tumors on swallow functioning in a larger group of patients.