In vivo aortic muscle cell growth kinetics. Differences between thoracic and abdominal segments after intimal injury in the rabbit

Focal proliferation of smooth muscle cell (SMC) is an integral part of atherosclerotic plaque formation: characterization of regional variation in SMC growth kinetics is therefore important to the understanding of atherogenesis. SMC growth kinetics of rabbit abdominal and thoracic segments were compared. Rabbit aortas were denuded of endothelium and the animals killed after 3H-thymidine and Evans blue injections at 0 to 48 days after denudation. Incorporation of 3H-thymidine into both aortic segments peaked at 48 hours; no detectable incorporation occurred in the first 24 hours. Abdominal segment DNA specific activity (SA, dpm/micrograms DNA) and total kinetic activity (TKA, dpm/0.1 mm internal elastic lamina) at 48 hours were significantly greater than values for the thoracic aorta. Abdominal SA and TKA curves decreased exponentially after the 48-hour peak and parallel thoracic levels after day 7. SA and TKA values for each segment reflected the subsequent SMC intimal growth rates as measured morphometrically. Therefore, both segments share similar growth kinetic characteristics; however, the abdominal response to initimal injury is greater than the thoracic and leads to greater myointimal proliferation. The difference in response to injury in the two segments suggests regional variation in SMC's which are phenotypically similar.     

Verapamil-induced "primary" polydipsia

An 11-month-old male infant with recurrent supraventricular tachycardia (SVT) was treated with oral verapamil. Shortly thereafter he developed marked changes in behavior including lethargy, intensely increased thirst and urination, and irritability when denied fluids. "Primary" polydipsia was diagnosed following an evaluation which showed no evidence of adrenal insufficiency, diabetes insipidus, diabetes mellitus, hypercalcemia, hyperosmolality, or renal disease. The symptoms resolved 1 week after verapamil was discontinued.     

Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin

Two randomized, double-blind clinical trials in dogs with spontaneous appendicular osteosarcoma treated with combination chemoimmunotherapy are reported. In both trials, dogs without overt metastasis underwent complete amputation of the affected limb. In trial 1, 40 dogs were treated with cisplatin chemotherapy [(CDDP), 70 mg/m2 i.v. every 28 days x 4]. Following CDDP, dogs without evidence of overt metastasis (n = 25) were randomized to receive liposome-encapsulated muramyl tripeptide phosphatidylethanolamine ](L-MTP-PE), 2 mg/m2 i.v.) or placebo liposomes (lipid equivalent) twice weekly for 8 weeks. Of 14 dogs in the placebo group, 13 (93%) died of metastasis; the median survival time was 9.8 months. Of 11 dogs in the L-MTP-PE group, 8 (73%) developed metastasis; the median survival time was 14.4 months, which was significantly longer than that of the placebo group (P < 0.01). In trial 2, 64 dogs received CDDP (70 mg/m2 i.v. every 21 days x 4) and were randomized to concurrently receive L-MTP-PE (2 mg/m2 i.v.) twice or once weekly, or placebo liposomes once weekly for 8 weeks. Median survival times were 10.3, 10.5, and 7.6 months, respectively. There were no significant differences among the three treatment groups in trial 2. Survival times for dogs receiving L-MTP-PE in trial 1 were significantly longer than those for dogs in trial 2 that received four doses of CDDP concurrently with twice weekly L-MTP-PE (P < 0. 04). The results of the first trial confirm our previous observation that L-MTP-PE has antimetastatic activity in dogs with osteosarcoma when given following amputation. The results of the second trial demonstrate that there is no survival advantage of administering L-MTP-PE concurrently with CDDP.     

Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal

Campomelic dysplasia (CD) is a skeletal malformation syndrome frequently accompanied by 46,XY sex reversal. A mutation-screening strategy using SSCP was employed to identify mutations in SOX9, the chromosome 17q24 gene responsible for CD and autosomal sex reversal in man. We have screened seven CD patients with no cytologically detectable chromosomal aberrations and two CD patients with chromosome 17 rearrangements for mutations in the entire open reading frame of SOX9. Five different mutations have been identified in six CD patients: two missense mutations in the SOX9 putative DNA binding domain (high mobility group, or HMG, box); three frameshift mutations and a splice-acceptor mutation. An identical frameshift mutation is found in two unrelated 46,XY patients, one exhibiting a male phenotype and the other displaying a female phenotype (XY sex reversal). All mutations found affect a single allele, which is consistent with a dominant mode of inheritance. No mutations were found in the SOX9 open reading frame of two patients with chromosome 17q rearrangements, suggesting that the translocations affect SOX9 expression. These findings are consistent with the hypothesis that CD results from haploinsufficiency of SOX9.     

Physiological actions of the neuropeptide Antho-RNamide on antagonistic muscle systems in sea anemones

Several studies have reported that the bulk aluminum (Al) concentration is increased in the brain in Alzheimer disease (AD), while other studies have failed to demonstrate an increase. Most of these investigations have had one or more methodological deficiencies, including lack of adequate neuropathological assessment; failure to age-match the control samples; small sample sizes, lacking statistical power; and geographical heterogeneity in the AD and control populations. The present population-based study of 92 clinically and histopathologically diagnosed AD patients and normal elderly nursing home residents was designed to avoid these potential biases. When a subsample of AD cases with the most severe brain pathology was compared with controls having no or minimal pathology, no statistically significant differences were found in the bulk aluminum concentration measured by graphite furnace atomic absorption spectrometry in frontal cortex (1.8 +/- 0.7 vs. 1.7 +/- 0.7 micrograms/g dry wt), temporal cortex (1.4 +/- 0.3 vs. 1.5 +/- 0.5 micrograms/g dry wt), liver (2.0 +/- 1.3 vs. 2.0 +/- 1.2 micrograms/g dry wt), or head of femur (2.4 +/- 1.6 vs. 2.2 +/- 1.0 micrograms/g ash wt). Within the whole series of 92 cases, there was no difference in the bulk aluminum concentration of the frontal cortex between individuals diagnosed as definite, probable, and possible cases of AD using the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. The density of senile plaques and neurofibrillary tangles in frontal and temporal cortex showed no correlation with the bulk aluminum concentration. Logistic regression analyses, which controlled for age and sex, did not influence outcome for any of the comparisons. The data show conclusively that in AD, bulk aluminum concentration is not increased in two cortical brain regions that are selectively vulnerable to the neuropathological changes associated with this disorder.     

Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase

The interaction of the Fyn SH3 domain with the p85 subunit of PI3-kinase is investigated using structural detail and thermodynamic data. The solution structure complex of the SH3 domain with a proline-rich peptide mimic of the binding site on the p85 subunit is described. This indicates that the peptide binds as a poly(L-proline) type II helix. Circular dichroism spectroscopic studies reveal that in the unbound state the peptide exhibits no structure. Thermodynamic data for the binding of this peptide to the SH3 domain suggest that the weak binding (approximately 31 microM) of this interaction is, in part, due to the entropically unfavorable effect of helix formation (delta S0 = -78 J.mol-1.K-1). Binding of the SH3 domain to the intact p85 subunit (minus its own SH3 domain) is tighter, and the entropic and enthalpic contributions are very different from those given by the peptide interaction (delta S0 = +252 J.mol-1.K-1; delta H0 = +44 kJ.mol-1). From these dramatically different thermodynamic measurements we are able to conclude that the interaction of the proline-rich peptide does not effectively mimic the interaction of the intact p85 subunit with the SH3 domain and suggest that other interactions could be important.     

Metastatic papillary thyroid carcinoma presenting as a typical branchial cyst

Two cases of papillary thryoid carcinoma presenting as a cystic lateral neck mass are reported. This tumour characteristically presents in patients under 40-years-old and in the presence of an occult primary tumour may mimic a branchial cyst. In such cases simple aspiration of the cyst will produce a chocolate-brown serous fluid which excludes the diagnosis of a branchial cyst and is characteristic of papillary thyroid carcinoma. Cytological examination of the fluid has a high degree of sensitivity and specificity in the diagnosis of thyroid malignancy and should avoid delay in diagnosis and unnecessary surgical exploration prior to definitive treatment.     

Aggressive boys' hostile perceptual and response biases: the role of attention and impulsivity

The present study addressed whether (1) aggressive boys show hostile biases or general deficits in social perception, (2) aggressive boys' social perceptual difficulties also characterize isolate and isolate-aggressive children, (3) aggressive, isolate, and isolate-aggressive boys' social perceptual difficulties are attributable to inattention and impulsivity, and (4) aggressive and nonaggressive boys differ in the links between social perception and proposed behavioral responses. Aggressive boys demonstrated hostile biases, but not general deficits, in intention-cue detection relative to average-status boys. Isolate-aggressive boys resembled aggressive boys in social perception, whereas isolate boys showed mild deficits relative to average-status boys. Although isolates' general deficits were predominantly accounted for by inattention and impulsivity, aggressives' and isolate-aggressives' hostile biases remained after these problems were statistically controlled. The aggressive groups proposed aggressive responses much more frequently than the nonaggressive groups following intentions perceived as nonhostile. Measures corresponding to several stages of Dodge's social information processing model discriminated the aggressive from nonaggressive groups, thus providing support for this model.     

Video-assisted thoracoscopic placement of paravertebral catheters: a technique for postoperative analgesia for bilateral thoracoscopic surgery

Paravertebral catheters were placed bilaterally through a Tuohy needle under direct video control in a patient undergoing video-assisted thoracoscopic (VAT) surgery for recurrent, bilateral pneumothoraces. Postoperative analgesia was produced by infusing bupivacaine through the catheters. This provided good analgesia. VAT placement of paravertebral catheters is easily accomplished and may be a part of the surgical procedure.