Regulation of PHO4 nuclear localization by the PHO80-PHO85 cyclin-CDK complex.

PHO4, a transcription factor required for induction of the PHO5 gene in response to phosphate starvation, is phosphorylated by the PHO80-PHO85 cyclin-CDK (cyclin-dependent kinase) complex when yeast are grown in phosphate-rich medium. PHO4 was shown to be concentrated in the nucleus when yeast were starved for phosphate and was predominantly cytoplasmic when yeast were grown in phosphate-rich medium. The sites of phosphorylation on PHO4 were identified, and phosphorylation was shown to be required for full repression of PHO5 transcription when yeast were grown in high phosphate.

Molecular analysis of neurotransmitter transport into secretory vesicles.

Molecular cloning of the transport proteins involved in packaging monoamines and ACh into secretory vesicles has implicated their activity in neural degeneration as well as signaling. Future studies will explore further the mechanism of active transport, its regulation, and the membrane trafficking of the proteins with the long-term goal of understanding how the regulation of transmitter release and, in particular, quantal size influences information processing and behavior. In addition, the bioenergetics of vesicular GABA and glutamate transport suggests that the proteins responsible for these activities may belong to a distinct gene family.

Fine-needle aspiration biopsy of the liver: diagnostic problems.

FNA of the liver is a diagnostic test that can be used to identify the vast majority of neoplasms of a primary or metastatic nature. Well-prepared FNA samples, in conjunction with cell button preparations, and correlation with the clinical history are necessary for optimal results. Even with the best of samples, however, well-differentiated hepatocellular neoplasms, both benign and malignant, and rare lesions still can remain difficult to diagnose by FNA.

Fine-needle aspiration of lymph nodes: use of flow cytometry immunophenotyping.

Fine-needle aspiration of lymph nodes can be used successfully in the clinical work-up of lymphadenopathy. The procedure has some limitations, some of which can be overcome by using such ancillary studies as flow cytometry or immunophenotyping. The authors discuss the use of these techniques in establishing definitive diagnosis of the most common and well-recognized lymphadenopathies.

Self determinant selection and acquisition of the autoimmune T cell repertoire.

Autologous proteins are continuously processed and presented in the form of peptides associated with self major histocompatibility (MHC) molecules at the surface of antigen-presenting cells for interaction with autoreactive T cells. During thymic selection, the presentation of self peptides is an essential element in the establishment of the T cell repertoire. Developing T cells which recognize self peptide/self MHC complexes with sufficient affinity are clonally deleted.

Simultaneous diffusion and metabolism of betamethasone 17-valerate in the living skin equivalent.

Simultaneous diffusion and metabolism of betamethasone 17-valerate was studied using betamethasone 17-valerate, betamethasone 21-valerate, and betamethasone as permeants. These corticosteroids were suspended in silicone adhesive and applied to an artificial living skin equivalent (LSE) for 72 h. When betamethasone was applied, no metabolites were detected in the receptor medium.

Osteoarthritis. A continuing challenge.

Osteoarthritis is a disorder of cartilage that affects almost 85% of the population by age 75. A lack of rigorous clinical and radiographic criteria for defining the disorder makes precise determination of its prevalence impossible. The process of wear and tear explains many manifestations of osteoarthritis, but it does not account for some of the clinical findings or the biochemical changes in osteoarthritic cartilage.

Amino acid substitutions in the structured domains of histones H3 and H4 partially relieve the requirement of the yeast SWI/SNF complex for transcription.

Transcription of many yeast genes requires the SWI/SNF regulatory complex. Prior studies show that reduced transcription of the HO gene in swi and snf mutants is partially relieved by mutations in the SIN1 and SIN2 genes. Here we show that SIN2 is identical to HHT1, one of the two genes coding for histone H3, and that mutations in either can result in a Sin- phenotype.

Transport of histamine by vesicular monoamine transporter-2.

Histamine mediates signalling by a wide range of neural and non-neural cells including mast cells. Like other biogenic amines, histamine is released from specialized secretory vesicles and requires transport from the cytoplasm into these vesicles. Of the two vesicular monoamine transporters, histamine potently inhibits 3H-serotonin transport by one (VMAT2) but not the other (VMAT1).

Congenital heart disease in adults.

Patients reaching adulthood with unoperated and operated congenital heart disease require attention to issues of exercise, antibiotic prophylaxis, contraception, and pregnancy. A careful clinical history is important to establish the degree of a person's disability, if any, and the symptoms responsible for the disability, whether due to heart failure, cyanosis, or both. The findings of a physical examination and a noninvasive evaluation, including electrocardiogram, chest x-ray film, and echocardiography, are often sufficient to establish a diagnosis and to assess the adequacy of a previous operation.

Neuroendocrine disorders of the gut.

The regulation of gastrointestinal function is known to involve elements of the enteric nervous system. Processes such as secretion, motility, blood flow, and immune function are all influenced by a complex network of neurons whose cell bodies lie in the gut. These neurons use a wide spectrum of substances as neurotransmitters, although the majority use peptides once thought to function only as gut hormones.

Using prediction models and cost-effectiveness analysis to improve clinical decisions: emergency department patients with acute chest pain.

Prediction models and cost-effectiveness analysis are two of the methodologies included in the broad definition of outcomes research. These methodologies are designed to improve physicians' abilities to identify clinical risks and to choose appropriate management strategies based on these risks. For the evaluation and management of patients with acute chest pain, prediction models have markedly improved our ability to estimate risk, and cost-effectiveness analyses have helped guide the development of new paradigms and the incorporation of new technologies.

Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy.

Nitric oxide (NO) is synthesized in skeletal muscle by neuronal-type NO synthase (nNOS), which is localized to sarcolemma of fast-twitch fibers. Synthesis of NO in active muscle opposes contractile force. We show that nNOS partitions with skeletal muscle membranes owing to association of nNOS with dystrophin, the protein mutated in Duchenne muscular dystrophy (DMD).

Common clinical presentations of occupational respiratory disorders.

Occupational lung disorders can mimic other respiratory diseases. Recurrent upper respiratory irritation, bronchitis, flu-like syndromes, adult-onset asthma and interstitial lung disease can be caused by dust, gases and fumes. The diagnosis of a work-related respiratory disorder requires a high index of suspicion and a thorough occupational history.

Ion channel forming colicins.

Entry of proteins into membranes and transmembrane ion channel formation are two fundamental aspects of membrane biology. The ion channel forming colicins beautifully exemplify both properties. Recent results delineate the structure of a whole colicin; coupled with new biophysical studies, a mechanism for insertion is proposed.

Alfentanil slightly increases the sweating threshold and markedly reduces the vasoconstriction and shivering thresholds.

Background: Hypothermia is common in surgical patients and victims of major trauma; it also results from environmental exposure and drug abuse. In most cases, hypothermia results largely from drug-induced inhibition of normal thermoregulatory control. Although opioids are given to a variety of patients, the thermoregulatory effects of opioids in humans remain unknown.

Screening for cancer. Useful despite its limitations.

Effective primary prevention strategies are currently available for only a limited number of types of malignant neoplasms. In the meantime, the most effective intervention for cancer control is screening for the early detection of cancer in otherwise asymptomatic persons. Screening is probably most useful for cancers wherein the stage at diagnosis is clearly related to curability.

Lipoma arborescens of the shoulder: magnetic resonance imaging findings.

Lipoma arborescens is a rare intra-articular lesion that typically affects the knee. This condition represents villous lipomatous proliferation of the synovial membrane. The magnetic resonance imaging findings are diagnostic and include a frond-like, fatty synovial mass and associated joint effusion.

Characterization of spontaneous excitatory synaptic currents in salamander retinal ganglion cells.

1. Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded under voltage-clamp conditions. Consistent with activation of non-NMDA-type glutamate receptors, the sEPSCs reversed at potentials above 0 mV, were blocked by 1 microM CNQX and prolonged by 2 mM aniracetam.

Tumor angiogenesis correlates with lymph node metastases in invasive bladder cancer.

Neovascularization of tumor tissue (tumor angiogenesis) is considered essential for tumor growth, proliferation and eventually metastasis. Microvessel density or count, a measure of tumor angiogenesis, correlates with clinical outcome in skin, breast, lung and prostate carcinomas. To determine whether an association of tumor angiogenesis and nodal metastasis exists in invasive bladder cancer, microvessel counts in 41 primary invasive stages (T2 to 4,NX,M0) bladder cancers were assessed.

Cost and quality of life: thrombolysis and primary angioplasty.

In an era of limited health care resources, analyses of the cost-effectiveness of cardiac interventions are becoming increasingly important. By generally accepted cost-effectiveness methodologies, the incremental cost for thrombolysis with streptokinase in patients with acute myocardial infarction ranges from approximately $3,500 to approximately $21,000/year of life saved. The estimated incremental cost-effectiveness of tissue-type plasminogen activator (t-PA) compared with streptokinase ranges from approximately $16,000 to $60,000/year of life saved.

Enigmas in sarcoidosis.

Sarcoidosis is a multisystem granulomatous disorder of unknown cause that presents most frequently in young adults with bilateral hilar adenopathy, pulmonary infiltrates, and skin or eye lesions. The multisystem clinical manifestations of this disease are a diagnostic challenge to all physicians. Although the clinical and pathologic characteristics of sarcoidosis are well described, the decision to treat and the optimal therapy are less well defined.

Plantaris muscle injury: evaluation with MR imaging.

Purpose: To determine the MR imaging appearance of injury to the plantaris muscle.

Materials And Methods: Fifteen patients with sports-related injuries to the lower leg underwent magnetic resonance (MR) imaging with T1- and T2-weighted, gradient-echo T2*-weighted, short inversion time inversion-recovery, and fast spin-echo sequences. The plantaris muscle and tendon, as well as the surrounding structures, were retrospectively examined for abnormalities.

Thermoregulatory vasoconstriction impairs active core cooling.

Background: Many clinicians now consider hypothermia indicated during neurosurgery. Active cooling often will be required to reach target temperatures < 34 degrees C sufficiently rapidly and nearly always will be required if the target temperature is 32 degrees C. However, the efficacy even of active cooling might be impaired by thermoregulatory vasoconstriction, which reduces cutaneous heat loss and constrains metabolic heat to the core thermal compartment.