Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus in vitro in the absence of glutamate excitation.

Glutamate and GABA are two major fast neurotransmitters (excitatory and inhibitory, respectively) in the CNS, including the hypothalamus. They play a key role in the control of excitation/inhibition balance and determine the activity and excitability of neurons in many neuronal circuits. Using neuronal cultures, whole-cell recording, Ca(2+) imaging, and Northern blots, we studied the compensatory regulation of neuronal activity during a prolonged decrease in glutamate excitation.

ENT experience in a family medicine clerkship: is there enough?

Background: Curriculum planning is an essential process at any institution of learning. Currently, at Indiana University, a 1-week required otorhinolaryngology clerkship is being considered for removal from the curriculum, and this exposure is planned for integration into other primary care clerkships. A data collection system for patient encounters was created to obtain objective quantitative data about ear, nose, and throat conditions in the family medicine clerkship.

Gender and preceptors' feedback to students.

To determine whether evaluation comments differed based on preceptors' and students' genders, preceptors' evaluations of medical students were analyzed. Preceptors tended to comment on the same themes in the same proportions, regardless of gender. However, women preceptors commented about "Personality/Maturity" and "Personality/Character" more frequently for men students than they did for women students.

Novel class of thiourea compounds that inhibit herpes simplex virus type 1 DNA cleavage and encapsidation: resistance maps to the UL6 gene.

In our search for novel inhibitors of herpes simplex virus type 1 (HSV-1), a new class of thiourea inhibitors was discovered. N-(4-[3-(5-Chloro-2,4-dimethoxyphenyl)-thioureido]-phenyl)-acetamide and its 2-fluoro-benzamide derivative inhibited HSV-1 replication. HSV-2, human cytomegalovirus, and varicella-zoster virus were inhibited to a lesser extent.

Identification of a novel gene cluster encoding staphylococcal exotoxin-like proteins: characterization of the prototypic gene and its protein product, SET1.

We report the discovery of a novel genetic locus within Staphylococcus aureus that encodes a cluster of at least five exotoxin-like proteins. Designated the staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading frames have between 38 and 53% homology to each other. All five proteins contain consensus sequences that are found in staphylococcal and streptococcal exotoxins and toxic shock syndrome toxin 1 (TSST-1).

Steric hindrance regulation of the Pseudomonas aeruginosa amidase operon.

Expression of the amidase operon of Pseudomonas aeruginosa is controlled by AmiC, the ligand sensor and negative regulator, and AmiR the transcription antitermination factor activator. We have titrated out AmiC repression activity in vivo by increased AmiR production in trans and shown AmiC regulation of the antitermination activity of AmiR by a steric hindrance mechanism. In the presence of the co-repressor butyramide we have isolated a stable AmiC.

Structural adaptation to selective pressure for altered ligand specificity in the Pseudomonas aeruginosa amide receptor, amiC.

The AmiC protein in Pseudomonas aeruginosa is the negative regulator and ligand receptor for an amide-inducible aliphatic amidase operon. In the wild-type PAC1 strain, amidase expression is induced by acetamide or lactamide, but not by butyramide. A mutant strain of P.

Leiomyosarcoma of the larynx: diagnosis aided by advances in immunohistochemical staining.

We present only the 12th reported case of a laryngeal leiomyosarcoma. This tumor was diagnosed with the aid of the newer immunohistochemical stains on archival paraffin-embedded tissue. The diagnosis and management of these tumors is based largely on the patterns seen in the small number of earlier reported cases of head and neck leiomyosarcomas and laryngeal sarcomas.

HSP70 expression is increased during the day in a diurnal animal, the golden-mantled ground squirrel Spermophilus lateralis.

Heat shock protein 70 (HSP70) gene expression was studied in a seasonal hibernator, the diurnal ground squirrel, Spermophilus lateralis. RNA transcripts of 2.7 and 2.

Crystal structure and induction mechanism of AmiC-AmiR: a ligand-regulated transcription antitermination complex.

Inducible expression of the aliphatic amidase operon in Pseudomonas aeruginosa is controlled by an antitermination mechanism which allows production of the full-length transcript only in the presence of small-molecule inducers, such as acetamide. Ligand-regulated antitermination is provided by AmiC, the ligand-sensitive negative regulator, and AmiR, the RNA-binding positive regulator. Under non-inducing or repressing growth conditions, AmiC and AmiR form a complex in which the activity of AmiR is silenced.

Gene expression in the brain across the hibernation cycle.

The purpose of this study was to characterize changes in gene expression in the brain of a seasonal hibernator, the golden-mantled ground squirrel, Spermophilus lateralis, during the hibernation season. Very little information is available on molecular changes that correlate with hibernation state, and what has been done focused mainly on seasonal changes in peripheral tissues. We produced over 4000 reverse transcription-PCR products from euthermic and hibernating brain and compared them using differential display.

Developmental changes in nicotinic receptor mRNAs and responses to nicotine in the suprachiasmatic nucleus and other brain regions.

Our previous studies demonstrated that nicotine induces c-fos expression in the suprachiasmatic nucleus (SCN) of the rat during a narrow developmental window occurring in the perinatal period. We have extended these observations by showing that c-fos cannot be induced in the adult SCN by nicotine even during the subjective night, when phase shifts do occur. In contrast to the SCN, significant induction of c-fos and NGFI-A was observed in the medial habenula and paraventricular nucleus at all circadian times.

Amphotropic murine leukemia virus entry is determined by specific combinations of residues from receptor loops 2 and 4.

Pit2 is the human receptor for amphotropic murine leukemia virus (A-MuLV); the related human protein Pit1 does not support A-MuLV entry. Interestingly, chimeric proteins in which either the N-terminal or the C-terminal part of Pit2 was replaced by the Pit1 sequence all retained A-MuLV receptor function. A possible interpretation of these observations is that Pit1 harbors sequences which can specify A-MuLV receptor function when presented in a protein context other than Pit1, e.

Inhibition of influenza A virus replication by compounds interfering with the fusogenic function of the viral hemagglutinin.

Several compounds that specifically inhibited replication of the H1 and H2 subtypes of influenza virus type A were identified by screening a chemical library for antiviral activity. In single-cycle infections, the compounds inhibited virus-specific protein synthesis when added before or immediately after infection but were ineffective when added 30 min later, suggesting that an uncoating step was blocked. Sequencing of hemagglutinin (HA) genes of several independent mutant viruses resistant to the compounds revealed single amino acid changes that clustered in the stem region of the HA trimer in and near the HA2 fusion peptide.

Characterization of the circadian system of NGFI-A and NGFI-A/NGFI-B deficient mice.

The genes NGFI-A (also known as EGR-1, zif/268, and Krox-24) and NGFI-B (nur/77) have previously been shown to be induced in the SCN of rats and hamsters by photic stimulation during the subjective night. The purpose of this study is to determine whether these genes are also induced in the SCN of mice and, if so, to characterize the circadian system of animals in which either NGFI-A or both NGFI-A and NGFI-B were eliminated by homologous recombination. In wildtype mice, NGFI-A mRNA was found to be induced in the SCN as in other rodent species.

Nicotine and nicotinic receptors in the circadian system.

Considerable data support a role for cholinergic influences on the circadian system. The extent to which these influences are mediated by nicotinic acetylcholine receptors (nAChRs) has been controversial, as have the specific actions of nicotine and acetylcholine in the suprachiasmatic nucleus (SCN) of the hypothalamus. In this article we review the existing literature and present new data supporting an important role for nAChRs in both the developing and adult SCN.

CL387626 exhibits marked and unusual antiviral activity against respiratory syncytial virus in tissue culture and in cotton rats.

CL387626 (4,4'-Bis[4,6-di[3-aminophenyl-N,N-bis(2-carbamoylethyl)-sulfon ilimino]-1,3,5-triazine-2-ylamino-bi-phenyl-2,2'-disulfonic acid, disodium salt), a compound synthesized by Wyeth-Ayerst Research Laboratories, was tested for its cytotoxicity and antiviral activity against respiratory syncytial virus (RSV) in tissue culture and in cotton rats. The median cell inhibitory (IC50) and median efficacious (EC50) concentrations of CL387626 against RSV in proliferating HEp2 or Vero tissue culture cells were determined to be 375 and 0.25 microg/ml, respectively, giving the compound an apparent selective index (S.

Tracking the contribution of a family medicine clerkship to the clinical curriculum.

Background And Objectives: Medical educators are working to articulate the objectives and measure the outcomes of medical education. In clinical training, faculty need methods to identify both the principal educational contributions of individual clerkships and how prior experiences influence student learning.

Methods: We analyzed students' perceived acquisition of clinical knowledge and skills on a 4-week, community-based family medicine clerkship.

Single amino acid insertion in loop 4 confers amphotropic murine leukemia virus receptor function upon murine Pit1.

Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch of amino acids named region A was identified in Pit1 (residues 550 to 558 in loop 4) as critical for GALV and FeLV-B receptor function.

Keratin subsets and monoclonal antibody HBME-1 in chordoma: immunohistochemical differential diagnosis between tumors simulating chordoma.

Thirty-five chordomas and more than 100 other tumors that have to be considered in the differential diagnosis, were immunohistochemically analyzed using a panel of antibodies including those to subsets of keratins (K), HBME-1, a monoclonal antibody recognizing an unknown antigen on mesothelial cells, and neuroendocrine markers. The patterns of immunoreactivities in chordoma were compared with those in renal cell carcinoma, colorectal mucinous adenocarcinoma, pituitary adenoma, skeletal chondrosarcoma, and extraskeletal myxoid chondrosarcoma (ESMC). Chordomas were consistently positive for keratin cocktail AE1/AE3, and for the individual keratins K8 and K19, and nearly always positive for K5, but they showed negative or only sporadic reactivity for K7 and K20.

Distal fibular notch: a frequent manifestation of the rheumatoid ankle.

Objective: To describe the distal fibular notch, an infrequently described manifestation of rheumatoid arthritis, and to speculate on its etiology through gross dissection, histologic correlation and MR imaging.

Design And Patients: One hundred and twenty-one conventional ankle radiographs were obtained and reviewed in 76 patients with clinically diagnosed rheumatoid arthritis. Additional imaging of three ankles was obtained utilizing CT and MR imaging.

Fungal phosphate transporter serves as a receptor backbone for gibbon ape leukemia virus.

Pit1, the receptor for gibbon ape leukemia virus (GALV), is proposed to be an integral membrane protein with five extracellular loops. Chimeras made between Pit1 homologs differing in permissivity for infection and between Pit1 and the related protein Pit2 have shown that the fourth extracellular loop plays a critical role in infection. However, further elucidation of the roles of the extracellular loops in infection is hampered by the high level of sequence similarity among these proteins.

Rheumatoid nodules: MR/pathological correlation.

Purpose: To demonstrate the signal characteristics of subcutaneous rheumatoid nodules in correlation to their histopathologic features.

Method: The magnetic resonance imaging (MRI) features of biopsy proven subcutaneous rheumatoid nodules are described in five patients with rheumatoid arthritis established by classic criteria.

Results: Two morphologic appearances of rheumatoid nodules were observed on MRI: one predominantly cystic, with enhancing peripheral component; and a second type which is predominantly solid, with uniform enhancement following gadolinium injection.

Daily variation of CNS gene expression in nocturnal vs. diurnal rodents and in the developing rat brain.

Expression of c-fos has been shown to vary throughout the brain over the course of the 24-h day. The magnitude of these changes appear to be similar in a light:dark (LD) cycle or in constant dark (DD). To further examine whether the diurnal and circadian changes in c-fos and other immediate-early gene (IEG) expression in brain are related to waking behaviors such as locomotor activity, we conducted three experiments using Northern analysis.