Role for M5 muscarinic acetylcholine receptors in cocaine addiction

Muscarinic cholinergic receptors of the M5 subtype are expressed by dopamine-containing neurons of the ventral tegmentum. These M5 receptors modulate the activity of midbrain dopaminergic neurons, which play an important role in mediating reinforcing properties of abused psychostimulants like cocaine. The potential role of M5 receptors in the reinforcing effects of cocaine was investigated using M5 receptor-deficient mice in a model of acute cocaine self-administration. The M5-deficient mice self-administered cocaine at a significantly lower rate than wild-type controls. In the conditioned place preference procedure, a classic test for evaluating the rewarding properties of drugs, M5-deficient mice spent significantly less time in the cocaine-paired compartment than control mice. Moreover, the severity of the cocaine withdrawal syndrome (withdrawal-associated anxiety measured in the elevated plus-maze) was significantly attenuated in mice lacking the M5 receptor. These results demonstrate that M5 receptors play an important role in mediating both cocaine-associated reinforcement and withdrawal.     

Aplasia of zygomatic arch and dislocation of temporomandibular joint capsule in Treacher-Collins syndrome: three-dimensional reconstruction of computed tomographic scans

Seven patients with Treacher-Collins syndrome were studied. All of patients were children or teenagers. Helical CT scanner (Toshiba) was used to reconstruct zygomatic arch and temporomandibular joint capsule on lateral aspect of temporal bone in five patients of microtia and atresia of both ears and two patients of narrow ear canals of both ears without microtia.Three-dimensional reconstructions of computed tomography on lateral aspect of temporal bone demonstrated various congenital abnormality including aplasia of zygomatic arch in seven patients and dislocation of temporomandibular joint capsule in seven patients.     

Increased sensitivity to cytosine arabinoside in human leukemia by c-raf-1 antisense oligonucleotides

c-raf-1, a cytoplasmic serine/threonine protein kinase, plays an important role in mitogen- and damage-responsive cellular signal transduction pathways. Expression of c-raf-1 modifies cell growth, proliferation and survival. Although expression of c-raf-1 has been studied in several tumors, the role of c-raf-1 in leukemia is so far unclear. We examined the expression of c-raf-1 in the human leukemia cell lines U937 and K562, and in a cytosine arabinoside (Ara-C)-resistant cell line (K562AC) derived from K562. Expression of c-raf-1 was increased in U937 and in Ara-C-resistant K562AC cells compared with the parental cells. We then investigated whether inhibition of c-raf-1 expression by antisense oligonucleotides increases the sensitivity to Ara-C in U937 and K562AC cells. Antisense oligonucleotides for c-raf-1 inhibited expression of c-raf-1 mRNA, but did not affect cell growth and increased sensitivity to Ara-C but not to other drugs such as adriamycin, VP-16 or vincristine. These results suggest that c-raf-1 is one of the factors involved in Ara-C resistance in leukemia and lend weight to the case for development of anti-cancer therapeutics involving oncogene-targeted antisense oligonucleotides.     

Behavioral outcome including attention deficit hyperactivity disorder/hyperactivity disorder and minor neurological signs in perinatal high-risk newborns at 4−6 years of age with relation to risk factors

BACKGROUND: Diagnostic problems with the criteria of attention deficit hyperactivity disorder (ADHD) in the Diagnostic Statistical Manual, 4th edn, have been identified. The aim of this study was to clarify whether the minor neurological signs test (MNT) the authors had previously reported was a predictor for the criteria of ADHD or hyperactivity disorder (HD) in perinatal risk children at 4-6 years of age and what kind of risk factors related to MNT. METHODS: A total of 136 children discharged from neonatal intensive care units were examined at the age of 4-6 years by a developmental neuropediatrician using both MNT and diagnostic criteria of DSM-IV ADHD/ICD-10 (International Classification of Diseases, 10th edn) HD. SPSS base and professional were used for statistical analysis. RESULTS: On comparison of diagnostic criteria between ADHD (11.0%) and HD (27.5%), the incidence in the same subjects showed significant difference. MNT scores showed significant correlation with criteria of ADHD (P < 0.01) and HD (P < 0.05). Diagnostic validity of MNT for predicting ADHD was demonstrated with 78% sensitivity and 79% specificity. High positive rates on MNT did not show a significant difference between the very low birthweight (VLBW) and non-low birthweight (NLBW) groups. Behavioral outcome with relation to risk factors were analyzed using multiple regression analysis. Apgar 5 in the NLBW group and toxemia of pregnancy and small for gestational age (SGA) in VLBW group were highly correlated with behavioral outcome. CONCLUSIONS: Minor neurological signs test score was a significant predictor for criteria of ADHD and HD. High incidences of positive MNT were suspected in not only VLBW children but also NLBW children and Apgar 5 in NLBW children and toxemia of pregnancy and SGA in VLBW children influenced behavioral outcome.     

A case of pulmonary artery bypass surgery for a patient with isolated Takayasu pulmonary arteritis and a review of the literature.

A 45-year-old female was presented with progressive dyspnea and bilateral leg edema. Pulmonary angiography revealed total occlusion of the right pulmonary artery and significant stenosis of the left pulmonary artery. The inferior lobar artery as well as the segmental arteries were well patent. No pathology was detected elsewhere at the aorta and its branches. The diagnosis of chronic pulmonary arterial occlusion by isolated Takayasu arteritis was made because of the characteristic pattern of angiographic findings and the presence of unusual shunt formation from the coronary artery to the peripheral portion of the pulmonary artery, as well as a characteristic presentation of HLA typing in blood analysis, which strongly suggested the diagnosis of Takayasu arteritis. To restore the pulmonary blood flow, we employed reconstructive surgery by means of bypass procedure, using PTFE graft. Postoperatively there was marked improvement in cardiopulmonary function and the quality of life of the patient. The graft was proved to be patent at long-term follow-up study. An extremely rare case of chronic occlusive pulmonary arteritis, which was surgically treated by means of bypass procedure, is reported herein, and a brief review of previous reports on this subject was attempted.     

Angle between the common and internal carotid arteries detected by ultrasound is related to intima-media thickness among those with atherosclerotic disease

Objectives

Although carotid artery structural variations have been detected by ultrasound, their clinical significance is not fully understood. The objective of this study was to determine whether the angle between the common carotid artery (CCA) and the internal carotid artery (ICA), designated angle α, an ultrasound-detectable carotid artery structural variation, is related to carotid artery intima-media thickness (IMT), a surrogate marker for carotid atherosclerosis.

Methods

As a cross-sectional study, we measured angle α in routine carotid artery ultrasounds from 176 subjects (130 men) with atherosclerotic disease/risk factors that attended Kouseiren Hospital in Kagoshima City, Japan between August 2007 and April 2009. We evaluated the correlation between the angle α and CCA- or ICA-IMT.

Results

Angle α was weakly correlated with age but significantly correlated with ICA-IMT. The correlation was stronger in subjects with an ICA-IMT ≥ 0.5 mm than in those with an ICA-IMT < 0.5 mm (Right side r = 0.475 vs. 0.246, Left side r = 0.498 vs. 0.301, respectively). Upon multivariate logistic regression analysis, angle α and serum low-density lipoprotein cholesterol were independent explanatory variables for ICA-IMT.

Conclusion

Angle α is related to ICA-IMT in subjects with atherosclerotic disease or risk factors in this study.

Electronic supplementary material

The online version of this article (doi:10.1007/s12199-015-0453-7) contains supplementary material, which is available to authorized users.     

Negative scotopic ERG and photopic ERG ON response impairment in a patient with normal dark adaptation

Purpose To present ocular findings in a patient who showed negative scotopic electroretinogram (ERG) and reduced ON response, but normal dark adaptation.Case An 18-year-old Japanese male patient who complained of severe asthenopia. His corrected visual acuities were 1.2 in both eyes. His fundi were normal. He had normal contrast sensitivity and normal dark adaptation.Methods The patients underwent ERG (including the standard protocol and photopic long flash recordings).Results The amplitudes of the rod ERG b-wave were reduced. The scotopic standard combined ERG response showed negative configuration. The photopic response to long flash revealed the reduced b-wave (ON response), while the amplitude of the first peak of the d-wave (OFF response) was within the normal range.Conclusions Postsynaptic abnormalities in both the rod and cone ON-pathways, which are often found in patients with night blindness, were suggested in the ERG findings, but the dark adaptation of our patient was normal. Neuromuscular evaluation of the patient and ophthalmological evaluation, including ERG, of his parents were normal. To our knowledge, the ophthalmological and electrophysiological findings of our patient cannot be attributed to any known clinical entity.     

Bone status assessment in preterm and term infants by dual-energy X-ray absorptiometry

We assessed the bone status of preterm and term infants by measuring their bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Thirty neonates weighing 699–3590 g were selected as subjects. Infants with multiple anomalies or severe chronic lung disease were excluded. Using the corrected term age (35–48 weeks), we measured their lumbar spinal BMD (L1–L4) by DXA. Alkaline phosphatase (ALP) and skeletal alkaline phosphatase (B-ALP) were measured at the same time. In addition, we compared the BMD values with growth parameters and chemical markers. The term BMD correlated significantly with the birth weight (r = .90), height (r = .85), and gestational age (r = .76). The birth weight correlated more closely with the BMD than with the weight at the time of BMD measurement. The B-ALP level showed an inverse correlation with BMD (r = −0.41). The preterm infants apparently acquired lower BMDs during intrauterine life. The inverse correlation of B-ALP with BMD may be found only in the neonatal period. The BMD measured by DXA and the B-ALP level are very useful parameters for assessing bone status in infants, including extremely low birth weight infants. Received: Aug. 21, 1997 / Accepted: Nov. 6, 1997     

Neonatal effects of the delivery interval during cesarean section under spinal anesthesia

The relationships between I-DI (induction to delivery interval) or U-DI (uterine incision to delivery interval) and fetal acid-base status or neonatal clinical condition were studied in 60 healthy parturients undergoing elective cesarean section under spinal anesthesia. The patients were divided into groups, i.e. group A (U-DI less than 90 sec, I-DI greater than 14 min, 18 cases), group B (U-DI less than 90 sec, I-DI greater than 14 min, 12 cases), group C (U-DI greater than 90 sec, I-DI less than 14 min, 15 cases) and group D (U-DI greater than 90 sec, I-DI greater than 14 min, 15 cases). Acid-base values for maternal arterial (MA), umbilical venous (UV) and umbilical arterial blood (UA), and acid-base gradients for (MA-UV) and (UV-UA) in each group were all in the normal range and revealed no significant differences among 4 groups, though U-DI was correlated with UVPCO2, UAPCO2, and (UV-UA) base deficit (r = 0.322, 0.266, -0.256: p less than 0.05). Acid-base states in cases of long and excessively long U-DI (greater than 90 sec and greater than 150 sec, respectively) were more acidotic than those of short U-DI groups (less than 90 sec). Both 1 and 5 minute Apgar scores were 8 or more in all neonates. There was no correlation between I-DI and fetal acid-base values or neonatal clinical conditions. It is conceivable that gentle and careful manipulations of the uterus and fetus rather than shortening of U-DI might be important in preventing against fetal or neonatal depression during cesarean section under spinal block.