Introns and gene evolution

In one scenario of gene evolution, exon shuffling has a fundamental role in increasing gene diversity. As DNA sequences accumulate in the databases, the picture of the intron/exon structures of genes becomes more and more clear. We discuss in this review some features of this picture that suggest that introns have been present since the early stages of evolution, and that exon shuffling was a fundamental process in the construction of ancient as well as modern genes.     

Linitis Plastica of the Esophagus

A 62-yr-old woman was evaluated for a 2-wk history of regurgitation and weight loss. Radiologic studies demonstrated a stenotic region in the distal third of the esophagus. Multiple endoscopic biopsies were nondiagnostic. Esophagectomy and esophagogastrostomy revealed a diffusely infiltrating adenocarcinoma ("linitis plastica") of the distal esophagus, sparing the gastroesophageal junction and stomach. Despite the absence of metastatic disease at laparotomy, the patient developed metastases unresponsive to chemotherapy. The pathologic, radiographic, and endoscopic findings are consistent with primary linitis plastica of the esophagus.     

Preventing percutaneous absorption of industrial chemicals: the "skin" denotation

Percutaneous absorption has received comparatively little attention in occupational health, although this route of entry has repeatedly caused occupation-related intoxications. In practice, the evaluation of skin penetration rates is far from simple. Much evidence has been obtained from studies of chemicals used for cosmetics and topical therapeutics, but the information available on compounds encountered in occupational health is limited. The data obtained from experimental studies have confirmed that the concentration, type of vehicle, skin area, skin condition, and extent of occlusion are important factors in determining the degree of percutaneous absorption, but no general model has been developed. Also, too little is known about the basic chemical properties governing the rate of penetration. Thus, prediction is difficult and bound to be rather inaccurate. Current preventive practice follows the procedure used by ACGIH and is mainly based on a "skin" denotation in official listings of chemicals to which exposure limits have been allocated. The number of substances and groups of chemicals which have received skin denotation in 17 selected countries varies between 24 and 179 and a total of 275 are listed as a skin hazard in one or more countries; ACGIH lists 143. Thus, the denotation practice varies. As an unfortunate result of these discrepancies and the dichotomy of skin denotation, the absence of skin denotation may erroneously indicate that efforts to protect the skin are unnecessary. Thus, an evaluation of skin penetration potentials should be incorporated in occupational health practice as a supplement to the official denotations.     

Local circuits and ocular dominance columns in monkey striate cortex

The relationships between ocular dominance columns and intrinsic cortical circuitry were examined in brain slices prepared from the striate cortex of macaques. Ocular dominance columns in layer 4C beta were visualized in vitro following anterograde transport of rhodamine injected into the lateral geniculate nucleus in vivo. The axonal and dendritic arborizations of individual layer 4C beta cells were revealed by intracellular fluorescent dye injections. Both qualitative observations and quantitative analysis showed that the dendrites of cells close to borders remained preferentially, although not absolutely, in the "home" column (the column containing the cell body). Thus, the segregated pattern of afferent input appears to have considerable influence on the pattern of dendritic arbors. Similarly, while axon collaterals within layer 4C beta could cross into the adjacent column, their limited lateral spread produced arbors that remained primarily within the home column. The terminal arbors of collaterals that travelled from layer 4C beta to layer 3 had a larger lateral spread, and the termination pattern appeared to be independent of column borders. Thus, our observations indicate that, while the course of many layer 4C beta dendrites appears to be guided by columnar boundaries as defined by geniculate afferents, there exist morphological substrates for intercolumnar interactions even between 4C beta cells. Intercolumnar interactions are seen more commonly in layer 3, however, where larger, denser axon arbors originating from 4C beta cells can freely cross ocular dominance column boundaries.     

The Role of Horizontal Connections in Generating Long Receptive Fields in the Cat Visual Cortex

The cells in the primary visual cortex possess numerous functional properties that are more complex and varied than those seen in the cortical input. These properties result from the network of intrinsic cortical connections running across the cortical layers and between cortical columns. In the current study we relate the long receptive fields that are characteristic of layer 6 cells to the input that these cells receive from layer 5. The axons of layer 5 pyramidal cells project over long distances within layer 6, enabling layer 6 cells to collect input from regions of cortex representing large parts of the visual field. When layer 5 was locally inactivated by injection of the inhibitory transmitter GABA, layer 6 cells lost sensitivity over the portion of their receptive fields corresponding to the inactivated region of layer 5. This suggests that the extensive convergence in the projection from layer 5 to layer 6 is responsible for generating the long receptive fields characteristic of the layer 6 cells.     

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be oxidized only after an initial oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me₂) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me₂) which cannot be oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-¹⁴C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid >16-iodo-3-R,S-methyl palmitic acid>16-iodo-2-R,S-methyl palmitic acid>16-iodo-2,2-dimethyl palmitic acid>16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethylbranched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[¹²⁵I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1-¹⁴C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched-palmitic acids were found in hepatocyte or secred phospholipids as compared with palmitic acid. This metabolic fate of methyl-branched iodo palmitic acids argues against their utilization as imaging probes to monitor in vivo the synthesis and the secretion of triglycerides by the liver.     

An anatomic and functional classification for the diagnosis and treatment of inguinal hernia

A simple classification of inguinal hernias is presented which can be valuable to surgeons as a (1) blueprint for dissecting the canal, (2) means for choosing the most appropriate operative procedure, (3) means for evaluating and correlating the prognosis of postoperative symptoms, time of convalescence, and degree of disability, and (4) method of identifying and communicating the exact anatomic derangement found so that accurate and consistent follow-up studies and statistics can be prepared. Diligent follow-up is essential for verifying the true results of hernia surgery techniques. Such follow-up requires that the surgeon be dedicated to examining his patients for many years, as well as to understanding, recording, and referencing the exact anatomic and functional defects found and the repairs used to correct them. Only with these factors identified and recorded can there be a basis for meaningful reporting and valuable conclusions. The classification of inguinal hernias presented here is intended to provide surgeons an opportunity to better evaluate their own methods and to more clearly communicate results with colleagues. As Oliver Wendell Holmes once said, "Many times ideas grow better when they are transplanted from one mind to another."     

Communication skills training with alcoholics for improving performance of two of the alcoholics anonymous recovery steps

Thousands of men and women have begun their recovery from alcoholism through the support of Alcoholics Anonymous (AA). AA recognizes its social support role in defining itself as a "fellowship," but it also sees itself as offering a program of recovery. This program is comprised of the well-known "12-Step" method, which has been adapted by a variety of self-help groups. The purpose of the present study was to determine whether performance of two of these steps, Steps 4 and 5, could be facilitated by teaching communication skills specifically designed to improve their performance. Hospitalized alcoholics were assigned to communication-skills training, discussion and assessment-only groups, and their pre- and posttreatment performance on videotaped role-plays of Steps 4 and 5 was assessed. Subjects in the communication-skills training group were found to improve significantly on internal versus external focus, personal responsibility taking, congruent affect and composite skill variables compared to the discussion and assessment-only groups. These results suggest that, among treatment programs that utilize AA's recovery program, the behavioral skills inherent in completing Steps 4 and 5 need to be taught. Merely discussing or alluding to the steps, as is often-times done in group therapy of "step-study" sessions, is unlikely to have any effect on alcoholics' abilities to "work the steps."     

In vitro studies on the effect of delaminated a-C:H film fragments on bone marrow cell cultures

Amorphous hydrogenated carbon (a-C:H) films have many outstanding properties required for a protective coating material on load bearing medical implants. Recently, titanium doped a-C:H films have been evaluated regarding their effects on bone marrow cell cultures. But many materials that are well-tolerated in bulk form are able to induce toxic reaction if present particulate form. In order to further assess biocompatibility aspects of these two coatings, film delamination has been mimicked in exposure to fluids. In the present study, particles from a-C:H, a-C:H/Ti and a-C:H-a-C:H/Ti bilayer films were added to bone marrow cell cultures in vitro. The results showed that plain a-C:H and to a certain extent a-CH/Ti particles were inert. Both kinds of particles did not significantly stimulate the osteoclast-related enzyme tartrate resistant acid phosphatase (TRAP). A slight increase in cell proliferation and total culture TRAP was found in cultures treated by a-C:H-a-C:H/Ti bilayer films. Latter effect can probably be traced back by the relative high percentage of small particles of a size of around 2 microm. However, if corrected by the cell number also no differences between particle-treated and untreated control cultures could be found, indicating the absence of a toxic effect from delaminated a-C:H coatings.