Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study.

Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in various brain functions. They also are thought to play an important role in nicotine addiction of smokers. Chronic (-)-nicotine, a nAChR agonist, treatment in mice and rats elicits a dose-dependent increase in nAChRs in the brain. Upregulation of nAChRs in postmortem human brains of smokers has also been reported. However, changes in nAChRs after cigarette smoking cessation in humans are poorly understood. The aim of this study was to detect the dynamic changes of nAChRs after smoking and smoking cessation in the brains of living subjects. METHODS: We performed 5-(123)I-iodo-A-85380 ((123)I-5IA) SPECT on nonsmokers and smokers (n = 16) who had quit smoking for 4 h, 10 d, and 21 d and calculated and compared distribution volumes (Vt) of (123)I-5IA. RESULTS: The binding potential of nAChRs (Vt of (123)I-5IA) in the brains of smokers decreased by 33.5% +/- 10.5% after 4 h of smoking cessation, increased by 25.7% +/- 9.2% after 10 d of smoking cessation, and decreased to the level of nonsmokers after 21 d of smoking cessation. CONCLUSION: Because the upregulation of the nAChRs of the smokers after chronic exposure of the nicotine was downregulated to the nonsmokers' level by around 21 d after smoking cessation, the upregulation is a temporary effect. The decrease in nicotinic receptors to nonsmoker levels may be the breaking point during the nicotine withdrawal period.     

Surgical repair of pulmonary arterial sling associated with tetralogy of fallot

Pulmonary artery sling associated with tetralogy of Fallot was successfully repaired in 2 patients. In 1 patient, extensive reconstruction was needed for severe hypoplasia in the left pulmonary artery, followed by definitive repair. In the other patient, surgical repair was achieved in a single-stage fashion.     

Regression of an Aggressive Abdominal Desmoid Tumor in a Patient with Familial Adenomatous Polyposis by Hyperthermoradiotherapy

A case of huge desmoid tumor successfully treated by hyperthermoradiotherapy is described. A 23-year-old man with familial adenomatous polyposis was operated upon for a desmoid tumor in the mesenterium involving the right kidney and small intestine in 1988. In 1990, the tumor recurred and could not be resected because of the involvement of the vena cava. The tumor grew larger and larger, and occupied two-thirds of the right lower quadrant. Several therapies using sulindac, tamoxifen, prednisolone, indomethacin, luteinizing hormone-releasing hormone analogue, and ascorbate were all ineffective. Finally, the combination of radiation and hyper-thermia was used over a 6-month period. At the end of the hyperthermoradiotherapy, the tumor in the abdominal wail was markedly reduced in size, and the protruded abdominal wall became flat. To our best knowledge, this is the first report of the successful treatment of a huge desmoid tumor by hyperthermoradiotherapy.     

Antispasm therapy using combination of midazolam and propofol for severe tetanus]

A 68-year-old healthy woman without any evidence of recent wound, developed nuchal pain, difficulty in swallowing and trisumus in 10 days. Because of respiratory failure due to generalized muscle spasm, she was intubated and required mechanical ventilation. Midazolam was administered as an antispastic therapy followed by human tetanus immune globulin and tetanus toxoid. Propofol was added on 9 days after intubation, since muscle spasm such as opisthotonus or respiratory spasm did not improve under midazolam and intermittent administration of vecuronium. Thereafter, her muscle spasm and hypertensive response were well controlled. The authors suggested that a combined use of midazolam and propofol was an optional antispastic therapy in patients with severe tetanus.     

The prenatal age critical for the development of the pontosubicular necrosis

Pontosubicular neuronal necrosis is characterized by neuronal karyorrhexis, showing a peculiar distribution. In infants delivered at more than 29 gestational weeks (GW), neuronal karyorrhexis is restricted to the pons and subiculum, while in very premature infants (delivered at less than 28 GW), neurons in other brain regions, such as the inferior olivary nucleus, cerebellum, basal ganglia, thalamus and cerebral cortex, are also involved. Thus, karyorrhexis is more widely distributed in the more immature brain, implicating neuronal maturation as one of the pathogenetic factors relevant to this type of neuronal cell death.     

Paramedian thalamic and midbrain infarcts associated with palilalia

A patient with paramedian thalamic and midbrain infarcts developed palilalia.     

The map kinase ERK regulates renal activity of cyclin-dependent kinase 2 in experimental glomerulonephritis.

BACKGROUND: In vitro, the extracellular signal-regulated kinase (ERK) is an intracellular convergence point of multiple stimuli, which affect the cell cycle. However, the role of ERK in cell cycle regulation in vivo is unknown. METHODS: To address this issue, ERK activity was blocked both in vitro in mesangial cells (MC) and in vivo in experimental glomerulonephritis (GN) by a pharmacological inhibitor (U0126) of the ERK-activating kinase. RESULTS: In stimulated MC, inhibition of ERK reduced cyclin-dependent kinase 2 (CDK2) phosphorylation, CDK2 activity and cyclin E/A expression, whereas downregulation of CDK inhibitor p27(Kip1) expression was inhibited. In vivo, U0126 was given to rats in the acute phase of anti-Thy 1.1 GN. We previously showed that glomerular cell proliferation was reduced by 67% upon treatment with the inhibitor compared to nephritic controls. Now, we detected a significant increase in renal CDK2-activity/phosphorylation in the nephritic controls, that was significantly and dose-dependently reduced by ERK inhibition. CDK2 activation was accompanied by an increase in renal expression of cyclins E/A and the enhanced binding of these cyclins to CDK2 in the nephritic controls. These changes were blunted by U0126 treatment. Finally, we noted an increased expression and CDK2-binding of p27(KIP1) protein in the nephritic controls which was decreased in U0126 treated rats. CONCLUSIONS: Our observations provide the first evidence that ERK is an intracellular regulator of renal CDK2 activity in vivo in a glomerulonephritis model.     

Association of AKT1 with schizophrenia confirmed in a Japanese population.

BACKGROUND: Abnormality of the V-akt murine thymoma viral oncogene homologue 1 (AKT1) may be a predisposing factor in schizophrenia. Recent evidence supporting this hypothesis showed decreased AKT1 protein levels in patients with schizophrenia and significant association of AKT1 haplotypes according to the transmission disequilibrium test. METHODS: We provide the first replication of this evidence using a relatively large case-control sample (507 Japanese schizophrenia and 437 control subjects). We genotyped five single nucleotide polymorphisms (SNPs) from the original study and one additional SNP. RESULTS: We found a positive association with an SNP (SNP5) different from the original study's findings (SNP3) and also significance in the haplotypes constructed from the combination of SNP5. Linkage disequilibrium around SNP5 was complex and may produce this positive association. CONCLUSIONS: Our study provides support for the theory that AKT1 is a susceptibility gene for Japanese schizophrenia. Fine linkage disequilibrium mapping is required for a conclusive result.     

Increased alveolar fluid clearance following thoracotomy: Report of a case and results of an analysis

Alveolar fluid clearance was studied in the resected lung of a 58-year-old man who had undergone exploratory thoracotomy 9 days earlier. An isosmolar albumin solution was instilled into the distal air spaces, and the albumin and electrolyte concentrations were measured over 4h. Alveolar sodium and fluid clearance had increased by nearly 200% from the control values in the resected lungs of patients without prior thoracotomy (n=5), and histological examination showed that the number of alveolar type II epithelial cells was markedly elevated. These results suggest that an increase in the number of alveolar type II cells may accelerate alveolar fluid clearance under certain clinical conditions.