The efficacy and safety of maprotiline (Ludiomil) was compared to imipramine in patients with manic-depressive illness, depressed type (DSM II 296.2). Three hundred forty-one patients from 16 ...different centers entered this four-week double-blind controlled trial, with 171 in the maprotiline and 170 in the imipramine group. Efficacy measurements included the Hamilton Depression Scale, the Self-Rating Depression Scale, and the Investigator's Overall Assessment of Effectiveness. Tolerability was monitored by collection of treatment-emergent signs and symptoms (TESS), blood pressure and pulse measurements, EKGs, and EEGs. Dosage was fixed for the first week at 50 mg t.i.d. and thereafter could be varied between 50 and 300 mg daily. Clinically and statistically significant reductions in symptomatology were noted in both drug groups for most efficacy parameters at each visit during therapy. Comparison between the drug groups revealed no difference in terms of the scales utilized. A trend toward fewer TESS in the maprotiline group was noted, especially for the side effects nausea, nervousness, and increased sweating.
Historically, military recruits have been at high risk of acquiring meningococcal disease. Beginning in the 1940s, the US military relied on mass treatment with sulfadiazine to control outbreaks in ...training camps. In the 1960s, a vaccine was developed in response to the emergence of sulfadiazine-resistant strains. Since 1971, all new recruits in the US military have been immunized against Neisseria meningitidis during their first days of service. Serogroups represented in vaccines given to service members have changed over time: the quadrivalent (A, C, Y, W135) vaccine has been given since 1982. In the US military, meningococcal disease rates decreased by ∼94% from 1964 to 1998. After initiating routine immunization in 1971, crude rates decreased sharply and have remained low; in addition, there have been few cases of disease caused by serogroups represented in contemporaneously administered vaccines. In the US military, immunizations have been effective for the prevention of disease caused by vaccine-homologous serogroups of N. meningitidis.
Complete 18S ribosomal RNA gene sequences were determined for 8 Eimeria species of chickens and for Eimeria bovis of cattle. Sequences were aligned with each other and with sequences from 2 ...Sarcocystis spp., Toxoplasma gondii, Neospora caninum, and 4 Cryptosporidium spp. Aligned sequences were analyzed by maximum parsimony to infer evolutionary relationships among the avian Eimeria species. Eimeria bovis was found to be the sister taxon to the 8 Eimeria species infecting chickens. Within the avian Eimeria species, E. necatrix and E. tenella were sister taxa; this clade attached basally to the other chicken coccidia. The remaining Eimeria spp. formed 3 clades that correlated with similarities based on oocyst size and shape. Eimeria mitis and Eimeria mivati (small, near spherical oocysts) formed the next most basal clade followed by a clade comprising Eimeria praecox, Eimeria maxima, and Eimeria brunetti (large, oval oocysts), which was the sister group to Eimeria acervulina (small, oval oocysts). The 4 clades of avian Eimeria species were strongly supported in a bootstrap analysis. Basal rooting of E. necatrix and E. tenella between E. bovis and the remaining Eimeria species and the apparent absence of coccidia that infect the ceca of jungle fowl all suggest that E. necatrix and E. tenella may have arisen from a host switch, perhaps from the North American turkey, Meleagris gallopavo.
Antibodies raised against an intracellular and
extracellular domain of the GH secretagogue receptor (GHS-R)
confirmed that its topological orientation in the lipid bilayer is as
predicted for G ...protein-coupled receptors with seven transmembrane
domains. A strategy for mapping the agonist-binding site of the human
GHS-R was conceived based on our understanding of ligand binding in
biogenic amine and peptide hormone G protein-coupled receptors. Using
site-directed mutagenesis and molecular modeling, we classified GHS
peptide and nonpeptide agonist binding in the context of its receptor
environment. All peptide and nonpeptide ligand classes shared a common
binding domain in transmembrane (TM) region 3 of the GHS-R. This
finding was based on TM-3 mutation E124Q, which eliminated the
counter-ion to the shared basic N+ group of all
GHSs and resulted in a nonfunctional receptor. Restoration of function
for the E124Q mutant was achieved by a complementary change in the
MK-0677 ligand through modification of its amine side-chain to the
corresponding alcohol. Contacts in other TM domains TM-2 (D99N), TM-5
(M213K, S117A), TM-6 (H280F), and extracellular loop 1 (C116A) of the
receptor revealed specificity for the different peptide, benzolactam,
and spiroindolane GHSs. GHS-R agonism, therefore, does not require
identical disposition of all agonist classes at the ligand-binding
site. Our results support the hypothesis that the ligand-binding pocket
in the GHS-R is spatially disposed similarly to the well characterized
catechol-binding site in theβ
2-adrenergic receptor.
A surface‐to‐tunnel seismic survey was conducted to estimate fracture intensity and distribution in the proposed nuclear waste repository area at Yucca Mountain, Nevada. A 5‐km‐long source line and a ...3‐km‐long receiver line were located on top of Yucca Mountain ridge and inside the Exploratory Study Facility (ESF) tunnel, respectively. Numerical modeling showed that the first arrival P waves are mainly propagated in the repository horizon at depth. Therefore two‐dimensional travel time inversions were performed after the actual source locations on the ridge were projected onto the layer of interest at depth. Static corrections were applied to absorb the scatter in the new source locations and to correct for variations in source and receiver coupling and travel time shifts. Zero‐offset amplitude variations of the first arrivals across the receiver line inside the tunnel showed strong correlation with the fracture density determined by measurements along the tunnel wall. Wave guidance by subhorizontal fractures is suggested as a possible source for this phenomenon. Tomographic inversion of the travel time data revealed a low‐velocity zone in the south central area of the repository horizon. Conversion of the velocity tomography results to fracture‐density tomograms showed good correlation with fracture intensity mapped along tunnel walls. The fractured zone extends over a large area in the southern region of the potential repository, in particular, southwest of the intensely fractured zone encountered in the ESF tunnel. The rock in the northern section of the repository appears more competent compared to the highly fractured areas in the south.
Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral ...hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R was shown, by immunocytochemistry, to be present in the human infundibular nucleus/median eminence, paraventricular nucleus, lateral hypothalamic area, and perifornical area, although in the latter two regions, only a few MCH1R-containing cells were found. In addition, MCH1R staining was found in nerve fibers in the periventricular nucleus, dorsomedial and ventromedial nucleus, suprachiasmatic nucleus, and tuberomammillary nucleus. A significant 1.6 times increase in the number of MCH1R cell body staining was found in the infundibular nucleus in postmortem brain material of cachectic patients, compared with matched controls, supporting a role for this receptor in energy homeostasis in the human.
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