Vesicular neurotransmitter transport and the presynaptic regulation of quantal size.

Specific transport activities package classical neurotransmitters into secretory vesicles for release by regulated exocytosis, but the proteins responsible for the vesicular transport of neurotransmitters are still being identified. One family of proteins includes vesicular transporters for monoamines and acetylcholine. Genetic manipulation in cells and in mice now shows that changes in the expression of these proteins can alter the amount of neurotransmitter stored per synaptic vesicle, the amount released and behavior.

Molecular mechanisms of hepatic fibrosis and principles of therapy.

Tremendous insights into the understanding of hepatic fibrosis have taken place over the past ten years. Foremost among these is the recognition that hepatic stellate cells (formerly known as lipocytes, Ito cells, or fat-storing cells) play a central role based on their ability to undergo activation following liver injury of any cause. Stellate cell activation is a broad phenotypic response, characterized by distinct functional changes in proliferation, contractility, fibrogenesis, cytokine secretion, and matrix degradation.

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).

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.

Headache.

Headache-prone patients have many highly effective therapeutic options open to them. Used only at the time of headache, sumatriptan succinate by mouth or injection and dihydroergotamine nasal spray are novel choices now or soon to be available. The original migraine therapy, ergotamine, is highly effective in its rectal suppository formulation, when used at a subnauseating dosage.

Selective targeting of the immune response in autoimmune demyelination.

Recent developments in molecular and cellular immunology have led to the formulation of refined models that describe how tolerance to self-antigens is broken and autoimmunity develops. This knowledge can now be used to develop alternative approaches to conventional immunosuppression for the treatment of autoimmune demyelinating disorders. The ideal therapy would reverse established disease or prevent further progression by selectively eliminating the aggressive effector molecules or cells while leaving the immune system virtually intact.

Neurotrophic factors and neurologic disease.

Discovered only 40 years ago, nerve growth factor is the prototypic neurotrophic factor. By binding to specific receptors on certain neurons in the peripheral nervous system and brain, nerve growth factor acts to enhance their survival, differentiation, and maintenance. In recent years, many additional neurotrophic factors have been discovered; some are structurally related to nerve growth factor while others are distinct from it.

Chloride currents in freshly isolated rat retinal pigment epithelial cells.

Cells of the retinal pigment epithelium (RPE) were isolated from neonatal rats. The perforated-patch clamp technique, using amphotericin-B, revealed a chloride current, which was detected as a 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)-sensitive component. A variety of chloride-channel inhibitors, other than DIDS, also blocked the chloride current, including 9-anthracenecarboxylic acid (9-AC), niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and N-phenylanthranilic acid (DPC).

Case-mix adjustment using objective measures of severity: the case for laboratory data.

Objective: We evaluate the use of routinely gathered laboratory data to subclassify surgical and nonsurgical major diagnostic categories into groups homogeneous with respect to length of stay (LOS).

Data Sources And Study Setting: The source of data is the Combined Patient Experience database (COPE), created by merging data from computerized sources at the University of California San Francisco (UCSF) Medical Center and Stanford University Medical Center for a total sample size of 73,117 patient admissions.

Study Design: The study is cross-sectional and retrospective.

Voltage-operated calcium channels in fresh and cultured rat retinal pigment epithelial cells.

Purpose: There is little known about the membrane properties of retinal pigment epithelial (RPE) cells with respect to calcium. The authors attempted to characterize membrane calcium channels from solitary fresh and cultured RPE cells from normal and dystrophic rat retinas.

Methods: RPE cells were enzymatically dissociated from eyes of neonatal rats of several strains, including dystrophic RCS strains.

Ethical considerations in prenatal diagnosis.

Prenatal diagnostic testing raises a number of important ethical issues, some related to diagnostic testing in general and others related to the special circumstances of pregnancy. These issues are most effectively addressed in the context of a broader understanding of the goals of prenatal diagnosis. Our dual obligations--to the pregnant woman and to the fetus--have an important influence on the goals of testing.

Prenatal diagnosis of inherited metabolic diseases.

Advances in the prenatal diagnosis of inherited metabolic disease have provided new reproductive options to at-risk couples. These advances have occurred in both sampling techniques and methods of analysis. In this review we present an overview of the currently available prenatal diagnostic approaches for the diagnosis of metabolic disease in a fetus.

Scarless skin wound repair in the fetus.

The ability of a fetus to heal without scar formation depends on its gestational age at the time of injury and the size of the wound defect. In general, linear incisions heal without scar until late in gestation whereas excisional wounds heal with scar at an earlier gestational age. The profiles of fetal proteoglycans, collagens, and growth factors are different from those in adult wounds.

Fetal surgery.

While most prenatally diagnosed malformations are best managed by appropriate medical and surgical therapy after birth, a few may require or benefit from correction before birth. Extensive experimental work in animals and innovative technologic developments have made fetal surgery a viable approach to perinatal care. Managing preterm labor continues to be a vexing problem.

Prenatal diagnosis using fetal cells from the maternal circulation.

All current methods of fetal karyotyping are invasive and carry a definite, albeit small, procedure-related risk. Because of this and testing costs, only women older than 35 years who have a greater risk for fetal aneuploidy are currently offered prenatal testing. But this detects only 20% to 25% of fetuses with Down syndrome.

Preimplantation diagnosis.

Preimplantation embryonic biopsy and analysis offer couples at increased risk of having offspring affected with a genetic disorder the possibility of an early prenatal diagnosis. For many couples, this approach would avoid the issue of the selective termination of affected fetuses. Substantial advances have been made in the area of preimplantation diagnosis, but the possible difficulties with this approach cannot be ignored.

Cardiac ultrasonography in structural abnormalities and arrhythmias. Recognition and treatment.

Fetal cardiac ultrasonography has become an important tool in the evaluation of fetuses at risk for cardiac anomalies. It can both guide prenatal treatment and assist the management and timing of delivery. We recommend that a fetal echocardiogram be done when there is a family history of congenital heart disease; maternal disease that may affect the fetus; a history of maternal drug use, either therapeutic or illegal; evidence of other fetal abnormalities; or evidence of fetal hydrops.

Current issues concerning the epidemiology of acquired immunodeficiency syndrome and human immunodeficiency virus.

This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H.

Comparison of four objective methods of monitoring digital venous congestion.

This study sought to determine which of the four most commonly used objective monitoring modalities--pulse oximetry, laser Doppler flowmetry, skin surface temperature measurement, and skin surface fluorescence--is best able to detect early digital venous congestion. Digital venous congestion was induced in 12 hands by inflating a digital cuff to 5 mm Hg above the resting diastolic pressure. The cuff remained inflated for 1 hour while monitoring was done at 10-minute intervals.

Multiple modes of engrailed regulation in the progression towards cell fate determination.

The engrailed gene product of Drosophila specifies the fate of a subset of cells in each segment. Our studies of engrailed regulation suggest that fate determination is an elaborate, multistep process. At the time in embryogenesis when the engrailed-dependent cell fate is probably determined, four modes of control act in an overlapping progression to govern engrailed expression.

The Allen's test: analysis of four methods.

Forty nonrandomly selected hands were studied with use of four types of Allen's test: (1) the digital systolic blood pressure method, (2) the subjective method, (3) the pulse oximeter method, and (4) the laser Doppler flowmetry method. The digital systolic blood pressure method, regarded as the standard, indicated abnormal pressure in three hands. Laser Doppler flowmetry gave the same results as those obtained by the digital systolic pressure method and, in addition, was easier to perform.

Treatment of comminuted femoral subtrochanteric fractures using the Russell-Taylor reconstruction intramedullary nail.

Seven patients with comminuted subtrochanteric fractures of the femur were treated with Russell-Taylor reconstruction intramedullary nails. Six of the seven fractures were AO/ASIF Type C and had resulted from high-energy trauma. The average time to clinical union was 10.