Evolutionary exploitation of design options by the first animals with hard skeletons.

The set of viable design elements available for animals to use in building skeletons has been fully exploited. Analysis of animal skeletons in relation to the multivariate, theoretical "Skeleton Space" has shown that a large proportion of these options are used in each phylum. Here, we show that structural elements deployed in the skeletons of Burgess Shale animals (Middle Cambrian) incorporate 146 of 182 character pairs defined in this morphospace. Within 15 million years of the appearance of crown groups of phyla with substantial hard parts, at least 80 percent of skeletal design elements recognized among living and extinct marine metazoans were exploited.

Utilization of an 86 bp exon generates a novel adducin isoform (beta 4) lacking the MARCKS homology domain.

A novel isoform of beta-adducin has been amplified and characterized from a human bone marrow cDNA library (GenBank #U43959). This isoform arises from the insertion of an 86 bp alternatively spliced and previously unrecognized exon (now termed exon 15) within codon 581 of the human red blood cell beta-adducin sequence. This results in an insertion of 28 novel amino acids. The remainder of the red cell beta-adducin mRNA is then translated in a different reading frame, adding an additional 35 novel amino acids prior to the stop codon. This new isoform, thus, replaces beta 1-adducin sequence after residue 580 with a total of 63 new amino acids. Sequences from genomic clones of the human beta-adducin gene show that this alternate exon is flanked by splice consensus sequences and is appropriately located in the genomic map between exons encoding up-stream and down-stream sequences, thus defining a new exon. The COOH-terminus of this new isoform, which we designate beta 4, lacks a 22 amino acid lysine-rich sequence common to both the human red cell alpha- and beta-adducin subunits and homologous to a highly conserved region in MARCKS, a filamentous actin-cross linking protein regulated by protein kinase C and calcium/calmodulin. beta 4-adducin preserves a previously identified calmodulin binding domain. PCR analysis indicates that this new beta-adducin isoform is expressed in fetal brain and liver, bone marrow, and NT-2 (neuroepithelial) cells, but is not detected in several other tissues. We anticipate that this new beta 4 isoform of beta-adducin will display unique and tissue-specific functional properties.

Stomatin.

Stomatin is a 31-kDa integral membrane protein, named after the rare human haemolytic anaemia hereditary stomatocytosis. In some cases of this anaemia, in which the red cells leak sodium and potassium ions, this protein is absent from the membrane, immediately suggesting that it has a role in the regulation of ion transport. The protein has a single hydrophobic domain, presumed to be membrane-associated, is phosphorylated, and is widely distributed in animal tissues. Mutations of a homologue in sensory nerve cells of the nematode Caenorhabditis elegans disrupt a neuronal transduction mechanism, in which mechanosensory information is relayed to an ion channel, whose opening initiates an action potential. It could be that this protein is a molecular link in a genetic stretch-sensitive system. Abnormalities of red cell ion transport are well known in human hypertension, but the molecular basis has never been elucidated: this protein and its functional associates, operating in a stretch- or pressure-sensitive complex, might be important.

Continuities between psychiatric disorders in adolescents and personality disorders in young adults.

OBJECTIVE: Personality disorders are a major mental health problem, but little information about their etiology and natural history is available. This study examined continuities between axis I disorders in adolescents and personality disorders in young adults. METHOD: The authors interviewed 145 young adults (mean age, 19.6 years) who had been diagnosed with a variety of DSM-III emotional and disruptive disorders during adolescence (mean age, 13.7 years). The Personality Disorder Examination was used to establish whether the subjects currently suffered from personality disorders. RESULTS: Subjects who had had disruptive disorders during adolescence showed high rates of all types of personality disorders (40% had a personality disorder at follow-up), while subjects who had had emotional disorders had a lower rate of personality disorders (12%). Men were more likely to have cluster A personality disorders, and women were more likely to have cluster C personality disorders. Disruptive diagnoses were associated with cluster B personality disorders, but emotional disorders did not show an association with cluster C personality disorders. Oppositional disorder did not increase the likelihood of passive-aggressive personality disorder. There was an association between attention deficit disorder with hyperactivity and borderline personality disorder. CONCLUSIONS: The rate of personality disorders was lower among young adults who had had emotional disorders during adolescence than among those who had had disruptive disorders, suggesting either that treatment for emotional disorders is more effective or that the personality psychopathology in these adolescents is not as severe as that in adolescents with disruptive disorders.

DSM-III axis IV revisited.

Clinicians have traditionally inquired about stressful life events preceding the onset of a psychiatric disorder. Axis IV of DSM-III attempted to improve on this by suggesting that a wide range of events be considered and that the information obtained be integrated into a global rating of severity. After reviewing recent evidence, the authors suggest that this process might result in ratings with lower reliability than expected. They also discuss some of the methodological difficulties in this field and explore directions for further research.

Effect of dimethyl adipimidate on K+ transport and shape change in red blood cells from sickle cell patients.

Dimethyl adipimidate (DMA) reduces K+ loss from, and dehydration of, red cells containing haemoglobin S (HbS cells). Three membrane transporters may contribute to these processes: the deoxygenation-induced cation-selective channel (Psickle), the Ca2+-activated K+ channel (or Gardos channel) and the K+-CI- cotransporter (KCC). We show that DMA inhibited all three pathways in deoxygenated HbS cells. The Gardos channel could be activated following Ca2+ loading. Considerable KCC activity was present in oxygenated HbS cells, showing a selective action of DMA on the transporter in deoxygenated cells. Inhibition of sickling correlated strongly with that of Psickle and moderately with that of KCC activity. We conclude that DMA does not inhibit the K+ pathways directly, but acts mainly by preventing HbS polymerisation and sickling. These findings are relevant to the development of novel chemotherapeutic agents for amelioration of sickle cell disease.

The human erythrocyte Cl-dependent Na-K cotransport system as a possible model for studying the action of loop diuretics.

1 The recent demonstration of the chloride-dependence of the red cell Na-K cotransport system suggests an analogy between this process and the active Cl- absorption in the ascending loop of Henle, which is the target transport system for loop diuretics. 2 Using red cell K influx, four known loop diuretics, six experimental frusemide analogues, two thiazides, two K-retaining diuretics and one organomercurial were compared for inhibitory potency on the red cell Na-K cotransport system. 3 Except for mersalyl, whose exact mode of action in the kidney is still in doubt, the inhibition of the red cell system by various loop diuretics was consistent with both published whole body diuretic data and isolated perfused tubule studies, while the system did not respond to the thiazides or the K-retaining diuretics. 4 It is concluded that the human red cell Na-K cotransport system is a possible valid model process on which to study the activity of loop diuretics.

Influence of vein-patch angioplasty on carotid endarterectomy healing.

We studied the influence of venous patching on the patency, endothelial regeneration, and wall healing of endarterectomized carotid arteries in a canine model. Thirteen dogs underwent bilateral common carotid endarterectomies (intimectomy and partial media excision). In each dog, one artery was closed by continuous suture and the contralateral artery was closed by external jugular vein-patch angioplasty; arteries were excised at two postoperative intervals (two to three and four to five weeks) for light, scanning, and transmission electron microscopy. The patency of arteries closed primarily (9/13 [69%]) was not significantly different compared with arteries closed with venous patches (12/13 [92%]). By scanning electron microscopy, regeneration of the endothelial monolayer occurred by migration from the endarterectomy end points and suture lines. Despite survival of the vein-patch endothelium, the rate and pattern of reendothelialization was not altered by venous patching. In both patched and unpatched vessels, endothelial regeneration was incomplete at two to three weeks and completed by four to five weeks. The histologic characteristics of the endarterectomized arterial wall after operation were also not influenced by the closure technique. In contrast with the healing artery wall, vein-patch walls did not develop a thickened intima. Although venous patching does not influence early patency, endothelial regeneration, or wall healing after endarterectomy, vein-patch angioplasty does increase vessel diameter and prevents the development of circumferential intimal thickening, attributes that are beneficial in minimizing restenosis.

Extraction of depression scores in adolescents from a general-purpose behaviour checklist.

Using a clinical sample of adolescents (n = 207), an attempt was made to find whether a multi-purpose, multi-informant instrument which measures a number of symptom domains, such as the Child Behavior Checklist (CBCL)/Youth Self-Report (YSR), could be used to extract Children's Depression Inventory (CDI) scores. Using item analysis procedures, a cluster of 15 items was selected from the YSR, which yielded a correlation of 0.74 with the CDI. The internalising scale of the YSR also correlated highly (0.73) with the CDI score. The corresponding CBCL items and scales showed poor capacity in predicting CDI scores.

Dehydrated hereditary stomatocytosis with transient perinatal ascites.

The case is reported of a mother and baby with dehydrated hereditary stomatocytosis and perinatal ascites, an autosomal dominant condition not previously reported in Britain. Recognition is important for the management of pregnancy and for avoidance of splenectomy which, if performed, can predispose the patient to fatal thromboembolic events.

The curious genomic path from leaky red cell to nephrotic kidney.

The human red cell has proved to be an invaluable model cell for the study of many aspects of membrane structure and function. It has a series of transport pathways which mediate the movements of the univalent cations Na and K, which are either identical or similar to systems in other human tissues, including the human kidney. The balance between the energy-consuming NaK pump and a 'passive leak' component maintains a net deficit of cations within the cell, which defends the cell volume against osmotic swelling. There exist a series of dominantly inherited human red cell conditions, gathered under the generic title 'hereditary stomatocytoses', in which the so-called 'passive leak' to Na and K is pathologically increased. In the more severe variants this compromises the integrity of the cell and the patients suffer haemolytic anaemia. Some less severe variants present with pseudohyperkalaemia caused by loss of K from red cells on storage of blood at room temperature. The most severe variants show a deficiency in a widely distributed 'raft' protein known as stomatin. The stomatin protein is homologous to the 'podocin' protein, the gene for which is mutated in a recessively inherited form of nephrotic syndrome. Among other possible functions, both proteins could be involved in the trafficking of membrane proteins to and from the plasma membrane.

Pseudohyperkalaemia and pseudomacrocytosis caused by inherited red-cell disorders of the 'hereditary stomatocytosis' group.

Unusual dominantly inherited conditions of the red cell, collected under the generic title 'hereditary stomatocytosis and allied disorders', exist, in which the red cell 'leaks' the univalent cations sodium (Na+) and potassium (K+). In some kindreds with these disorders, bizarre temperature effects can occur that have profound effects on the way in which the cells behave when removed from the body and cooled to either room or refrigerator temperatures. In some types, the cells lose K+ at room temperature, giving rise to pseudohyperkalaemia; in others, this occurs in concert with swelling of the red cell and pseudomacrocytosis. In some of these conditions, a red-cell abnormality is clearly demonstrated by the presence of haemolytic anaemia; however, routine haematology can be virtually normal in the milder versions. All are inherited as dominants, although new mutations can be seen.

Patellofemoral rehabilitation.

We have presented a brief overview of therapeutic exercise and patellofemoral biomechanics and their relation to a rehabilitation program of the nonoperative patient with patellofemoral dysfunction. This was followed by a specific protocol for extensor mechanism reconstruction, which can in part be applied to the nonoperative patient with a more vigorous lifestyle. Self-discipline and perseverance on the part of the patient are the only factors that cannot be controlled; yet, without these, no surgical procedure or rehabilitation program will ever succeed.

Serum potassium, hydrogen ion and magnesium: neuromuscular regulation by variation of cation concentration in the extracellular fluid?

It is a common clinical observation that changes in serum [K] are frequently associated with changes in serum [H] and/or [Mg]. Thus, hypokalaemia and alkalosis are associated, as are hyperkalaemia and acidosis, and hypokalaemia and hypomagnesaemia. Most investigators would accept that these ions have important roles in the maintenance of neuromuscular excitability. Extracellular potassium exerts its effect by defining the potassium gradient across the cell membrane and therefore the membrane potential in the resting state; magnesium and hydrogen ion 'screen' negative charges on the surface of nerve cells, modulating the local transmembrane potential gradient, to which the voltage-sensitive channels governing the initiation of the action potential respond. It is pointed out here that the changes in ionic concentration observed in pathophysiology are not incompatible with the idea that the associated changes reflect regulatory events in the extracellular fluid designed to preserve excitability.

Evaluation of a program of university placement for spinal cord injured rehabilitation clients in Louisiana.

The Louisiana State Department of Social Services, Rehabilitation Services (LRS) offers a program of financial support for spinal cord injured persons to attend college. We evaluated this program's effectiveness and attempted to identify factors that may predict student success. We examined the LRS case records of all students with documented SCI who had enrolled in the LRS college program before 1988. We compared the proportion of LRS clients who graduated with the proportion of general population students attending the same schools. We measured the association between graduation and factors that may help predict success. Of the 51 LRS clients studied, 25 (49%) graduated from baccalaureate institutions within 6 years. Of Louisiana students-at-large who attended the colleges that housed LRS students, 36% of those graduated within 6 years. The best predictor of success was the American College Test score. All students with a score of 17 or more graduated. A larger proportion of LRS-sponsored students graduated than did students from the general population.

High school football-related cervical spinal cord injuries in Louisiana: the athlete's perspective.

Louisiana has one of the highest rates in the nation of cervical spinal cord injuries to high school football players. When the national rate of these injuries is applied to the number of high school participants in Louisiana, we would expect there to be only one catastrophic neck injury every 14 years. Louisiana, however, has averaged 2.3 spinal cord injuries per year for the past seven football seasons. Players who use the top of their helmets to tackle, block, or strike opponents are at greatest risk for these injuries. This study was undertaken to describe the safe tackling knowledge, attitudes, and practices of Louisiana high school football players. We surveyed 596 players from 16 Louisiana high schools. When asked if it was within the rules to tackle anyone by using the top of their helmet, 29% incorrectly answered "yes". Similarly, when asked if they had ever tackled anyone using the top of their helmet, 33% reported that they had. Twenty-eight percent said that they had been taught to use this unsafe method. Of these, 83% said that their coach taught them this dangerous and illegal method. Using the helmet as a battering ram must be discouraged. Education for officials, coaches, and players is needed to improve recognition of improper tackling. Proper training in tackling and blocking is an important means of minimizing the possibility of catastrophic injury.