Genetic interactions of Hox genes in limb development: learning from compound mutants

Some investigators have noted an increased incidence of suicidal ideation and attempts in individuals with panic attacks. The direct temporal relationship between the panic state and suicidal thoughts and behaviors has not been well elucidated however. Furthermore, although aggressive behavior is often manifested in individuals with suicidal behavior, the relationship between aggression and panic has received little attention. The aim of this study was to assess the frequency and type of reported suicidal and aggressive ideation and behaviors that occur during the panic state in patients with panic disorder. In order to evaluate the contribution of depression, individuals with pure (i.e. uncomplicated) panic disorder were compared with individuals who had comorbid panic and major depression. Nineteen patients with a diagnosis of pure panic disorder and 28 patients with comorbid panic plus major depression were included in the study. All patients were given the Panic, Suicide and Aggression Scale (PSAS), a questionnaire specifically designed to assess reported suicidal and aggressive thoughts and behaviors that occur during panic attacks. Other scales given to all patients included overall measures of impulsivity, suicide risk and violence risk. Patients with pure panic disorder reported high rates of suicidal and aggressive ideation and behavior during panic. The presence of comorbid depression resulted in a doubling of the rate of reported panic-associated suicidal ideation, property destruction and assaults, and a five-fold increase in the rate of homicidal ideation. The rate of reported suicide attempts was equal in the pure panic and comorbid group. There were also high correlations in all panic patients between measures of panic-associated suicide and aggression with the psychometric measures of impulsivity, suicide risk and violence risk.     

Variable phenotype of familial adenomatous polyposis in pedigrees with 3'' mutation in the APC gene

Traumatic rupture of the corpus cavernosum is relatively frequent in the authors' experience. Based on the study of a series of 80 cases and a review of the literature, the authors analyse the diagnostic and therapeutic aspects and outcome of this disease. The patients in this series had a mean age of 30 years. Meticulous and intimate clinical interview demonstrated that the commonest mechanism is forced manipulation of the erect penis (68%). Clinical examination localized the site of the fracture (proximal: 57%, distal 43%). The fracture was unilateral (78 cases), rarely bilateral (2 cases) and associated with complete rupture of the urethra (1 case). Treatment was surgical in 79 patients. A distal semicircumferential incision was used in the case of bilateral rupture, distal rupture and associated urethral lesion (34 cases). A favourable course was observed in 86% of cases. However, 9 postoperative complications (12.5%) were observed (6 cases of fibrous plaques, 3 cases of chordee of the penis), due either to the extent of the haematoma or to the delay in treatment. Traumatic rupture of the corpus cavernosum is a disease of young adults, which requires early surgical treatment with an approach adapted to the type of lesions.     

Cryoablation: a novel approach to neurolysis of the ganglion impar

BACKGROUND: The main goal in the surgical repair of total anomalous pulmonary venous drainage is to reestablish a wide patent connection between the common pulmonary vein and the left atrium. Several techniques have been proposed for achieving this objective, each of which has advantages and disadvantages. The superior approach between the superior vena cava and the ascending aorta was introduced in 1976 for the repair of supracardiac forms of total anomalous pulmonary venous drainage, but it often provides a less than optimum exposure, particularly in tiny infants. We proposed a modification of this approach that includes division of the ascending aorta and offers excellent exposure. METHODS: Seventeen patients (15 neonates and 2 infants) with supracardiac total anomalous pulmonary venous drainage (n = 13) or mixed forms of total anomalous pulmonary venous drainage (n = 4) underwent surgical repair with the use of the modified superior approach. Circulatory arrest was not required in 10 patients and the mean cross-clamp time was 32.5 +/- 13.8 minutes. RESULTS: There was 1 postoperative death resulting from intractable pulmonary hypertension in a compromised infant who was referred to our unit receiving extracorporeal membrane oxygenation. One patient with common hypoplasia underwent reoperation twice at 2 months and then 3 months after the first procedure. All the other patients had a smooth postoperative course, and midterm evaluation showed a widely patent anastomosis between the common vein and the left atrium. CONCLUSIONS: The modified superior approach for the repair of supracardiac total anomalous pulmonary venous drainage can be useful to enhance exposure during surgical repair and may contribute to improved patient outcome.     

Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation

Protease nexin-1 (PN-1), a member of the serpin superfamily, controls the activity of extracellular serine proteases and is expressed in the brain. Mutant mice overexpressing PN-1 in brain under the control of the Thy-1 promoter (Thy 1/PN-1) or lacking PN-1 (PN-1-/-) were found to develop epileptic activity in vivo and in vitro. Theta burst-induced long-term potentiation (LTP) and NMDA receptor-mediated synaptic transmission in the CA1 field of hippocampal slices were augmented in Thy 1/PN-1 mice and reduced in PN-1-/- mice. Compensatory changes in GABA-mediated inhibition in Thy 1/PN-1 mice suggest that altered brain PN-1 levels lead to an imbalance between excitatory and inhibitory synaptic transmission.     

Non-covalent complexes between DNA-binding drugs and double-stranded deoxyoligonucleotides: a study by ionspray mass spectrometry

The non-covalent complexes between some DNA-binding drugs and duplex oligodeoxynucleotides were studied by ionspray mass spectrometry, with the aim of evaluating the suitability of this technique to screen rapidly a series of drugs exerting their activity through non-covalent binding to specific base sequences of DNA. Two classes of drugs were considered, distamycins (which show affinity for the minor groove of DNA) and anthracyclines (which interact through intercalation between bases). For the former, d(CGCGAATTCGCG)2 was chosen as the model oligodeoxynucleotide. Following optimization of sample preparation and instrumental conditions, the complexes of different distamycins were observed; depending on the ligand considered, 1:1 or 2:1 complexes were formed preferentially. A semi-quantitative evaluation of the relative affinities was made by measuring the ratio of the complexes signals to those of the duplex, and also by competitive binding with equimolar amounts of distamycin. For anthracyclines, the daunorubicin-d(CGATCG)2 complex was chosen as the model for a preliminary mass spectrometric study; however, the signals of the duplex and the complex were very low compared with the monomer signal. Since the complex was known to be stable in solution, this was ascribed to gas-phase instability, probably caused by electrostatic repulsion between negatively charged phosphate groups.     

A comparison of speaking and mute individuals with autism and autistic-like conditions on the Autism Behavior Checklist

The item, total, and subscale scores on the Autism Behavior Checklist (ABC) were compared for 155 mute and 335 speaking individuals with autism spectrum disorders. Although no significant difference was observed between the groups on the ABC total score, the mute group demonstrated significantly more pathology on 21 of 57 items and 3 of 5 subscales. The speaking group obtained significantly higher scores on only 8 items and 1 subscale (Language). The appropriateness of providing greater pathology scores on expressive language items to speaking, rather than to mute, individuals is called into question. The authors speculate whether the expressive language items are weighted too heavily, in regard both to the Language subscale and to the ABC total score. If the expressive language items were removed, the mute group would have significantly higher ABC total scores and therefore a greater degree of autism severity.     

Uptake of long chain fatty acids by human placental choriocarcinoma (BeWo) cells: role of plasma membrane fatty acid-binding protein

In order to understand the mechanisms by which fatty acids are taken up by the placenta, the uptake of oleic, linoleic, arachidonic, and docosahexaenoic acids by cultured human placental choriocarcinoma (BeWo) cells was examined. Fatty acid uptake by BeWo cells was temperature-dependent and exhibited saturable kinetics. Oleic acid was taken up least and docosahexaenoic acid most by these cells. Moreover, competitive studies of fatty acid uptake by BeWo cells also indicated preferential uptake compared with oleic acid in the order of docosahexaenoic acid, arachidonic acid, and linoleic acid. Western blot analysis demonstrated that BeWo cells express a protein immunoreactive with antibodies to the human placental plasma membrane fatty acid-binding protein (p-FABPpm). Furthermore, pre-treatment of BeWo cells with these antibodies inhibited most of the uptake of docosahexaenoic (64%) and arachidonic acids (68%) whereas oleic acid uptake was inhibited only 32% compared with the controls treated with preimmune serum. These results clearly demonstrate that the pFABPpm may be involved in the preferential uptake of essential fatty acids (EFA) and their long chain polyunsaturated fatty acids (LCPUFA) by these cells. Studies on the distribution of radiolabeled fatty acids in the cellular lipids of BeWo cells showed that docosahexaenoic acid was incorporated mainly in the triacylglycerol fraction, followed by the phospholipid fraction, whereas for arachidonic acid the reverse was true. The preferential incorporation of docosahexaenoic acid into triacylglycerol suggests that triacylglycerol may play an important role in the placental transport of docosahexaenoic acid to the fetal circulation. Together these results demonstrate the preferential uptake of EFA/LCPUFA by BeWo cells that is most probably mediated via the pFABPpm. We thus propose that the p-FABPpm may be involved in the sequestration of maternal plasma LCPUFA by the placenta.     

Gastrointestinal autonomic nerve tumor (plexosarcoma): report of a case with fine needle aspiration biopsy and histologic, immunocytochemical and ultrastructural study

BACKGROUND: Gastrointestinal stromal tumors (GISTs) encompass a large group of mesenchymal neoplasms that display common cytologic spindle-shaped morphology on light microscopy. Immunocytochemical and ultrastructural studies can demonstrate several patterns of differentiation. CASE: A 70-year-old male presented with two intraabdominal small bowel masses. The cytopathologic features of a fine needle aspiration biopsy (FNAB) included plump spindle cells in densely populated aggregates or in a fasciculated pattern, without significant pleomorphism. An epithelioid component in a lobular arrangement with abundant, eosinophilic cytoplasm was also noted. The nuclei were vesicular, with a very evident, eosinophilic nucleolus and finely distributed chromatin. Groups of loosely cohesive cells with slender, dendritic-like cytoplasm were evident. Immunocytochemical study of the embedded, fine needle aspirated fragments of the neoplasm demonstrated immunoreactivity for vimentin and neuron-specific enolase. Cytokeratin immunoreactivity or muscular, vascular, neuroendocrine or nerve sheath differentiation failed to be demonstrated. The cytologic and immunocytochemical findings correlated well with the histologic features of the neoplasm. The morphologic diagnosis was confirmed by ultrastructural study. CONCLUSION: FNAB and immunocytochemistry can be valuable in making the correct diagnosis between gastrointestinal stromal tumors.     

Deuterium kinetic isotope effects and the mechanism of the bacterial luciferase reaction

A combined experimental and theoretical investigation of the deuterium isotope effects on the bacterial luciferase reaction is described. The experimental studies focus on determining if the unusual aldehydic deuterium isotope effect of approximately 1.5 observed in these reactions is an intrinsic isotope effect resulting from a single rate-limiting step or is a composite of multiple rate-limiting steps. The isotope effect observed is not significantly affected by variation in the aldehyde chain length, changes in the pH over a range of 6-9, use of alphaC106A and alphaC106S site-directed mutants, or chloride substitution at the 8-position of the reduced flavin, though the isotope effect is decreased when the 8-methoxy-substituted flavin is used as a substrate. From these observations it is concluded that the aldehydic isotope effect arises from the change in rate of a single kinetic step. A stopped-flow kinetic analysis of the microscopic rate constants for the reactions of 1-[1H]decanal and 1-[2H]decanal in the bacterial luciferase reaction was carried out, and aldehyde hydration isotope effects were determined. From the results it is estimated that the aldehydic deuterium isotope effect is approximately 1.9 after formation of an intermediate flavin C4a-hydroperoxy hemiacetal. Ab initio calculations were used to examine the transformation of the aldehyde into a carboxylic acid and to predict isotope effects for possible mechanisms. These calculations indicate that the mechanism involving rate-limiting electron transfer from the flavin C4a-hydroxide to an intermediate dioxirane is consistent with the enigmatic aldehydic isotope effect and that the intermediacy of a dioxirane is energetically plausible.