NAD(P)H: quinone oxidoreductase (NQO1) gene polymorphism and schizophrenia.

NAD(P)H: quinone oxidoreductase (NQO1), an obligate two-electron reductase of quinones, prevents their participation in redox cycling and subsequent generation of reactive oxygen species (ROS). Reduced or negative activity of NQO1 would lead to an excess of neurotoxic compounds of cathecolamine o-quinones and ROS. Recently, there has been increasing evidence that catecholamine o-quinones and ROS might contribute to the development of schizophrenia.

A perspective on molecular genetic studies of tardive dyskinesia: one clue for individualized antipsychotic drug therapy.

Interindividual genetic profile differences related to antipsychotic drug therapy may be determined based on molecular genetic studies of the pathogenesis of schizophrenia and studies of antipsychotic drug responses (therapeutic as well as adverse responses). In the present article, we review molecular genetic studies of tardive dyskinesia (TD), which is a representative adverse response to antipsychotic drugs. Such studies have been performed to explore the gene-associated pharmacokinetic and pharmacodynamic processes of antipsychotic drugs.

Oxidative damage of rat cerebral cortex and hippocampus, and changes in antioxidative defense systems caused by hyperoxia.

In order to elucidate the oxidative damage in rat brain caused by oxidative stress, regional changes in the levels of lipid peroxidation products and antioxidative defense systems in cerebral cortex and hippocampus, and in their synapses, which modulate learning and memory functions in the brain, were studied. When rats were subjected to hyperoxia as an oxidative stress, thiobarbituric acid reactive substance (TBARS) in the regions studied increased more than in normal rats by approximately 35%. The values in oxygen-unexposed vitamin E-deficient rats were also higher than in normal rats.

Genetic approaches to polydipsia in schizophrenia: a preliminary report of a family study and an association study of an angiotensin-converting enzyme gene polymorphism.

The pathophysiology of polydipsia in patients with schizophrenia is inadequately understood. This study aims to investigate the genetic influence on polydipsia in schizophrenia, and is comprised of a family study and an association study. First, we screened in-patients in 14 psychiatric hospitals and found a total of 36 pairs of a proband and his/her first-degree relative, both of whom were diagnosed with schizophrenia.

Different glial reactions to hippocampal stab wounds in young adult and aged rats.

Brain injury induces reactive gliosis. To examine the activation of glial cells after brain injury in young versus aged rats, we used a brain stab-wound model and examined the expression of cells positive for ED1 (ED1(+)) and glial fibrillary acidic protein (GFAP(+)) in the hippocampus in young-mature (3 months) and aged (25 months) Wistar rats at various times following hippocampal stab injury. ED1(+) cells appeared more frequently in the aged rats than in the young-mature rats under control conditions, whereas the number of GFAP(+) cells was not different between two groups.

Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia.

Nitric oxide (NO) has been identified as a widespread and multifunctional biological messenger molecule in the central nervous system (CNS), with possible roles in neurotransmission, neurosecretion, synaptic plasticity, and tissue injury in many neurological disorders, including schizophrenia. Neuronal NO is widely produced in the brain from L-arginine catalyzed by neuronal NO synthase (NOS1). We therefore hypothesized that the NOS1 gene may play a role in the pathophysiology of schizophrenia.

[An epidemic of rotavirus infection in a nursing home for the elderly in Japan].

An outbreak of diarrheal disease in a Japanese home for aged is reported. Out of 202 residents, 47 cases complained of diarrhea (23.3%) during a month.

Genetic association analysis of 5-HT(6) receptor gene polymorphism (267C/T) with tardive dyskinesia.

Possible involvement of serotonergic (5-hydroxytryptamine: 5-HT) receptors in the pathophysiology of tardive dyskinesia (TD) has been suggested. In the present study, the relationship between the 5-HT(6) receptor gene (HTR6) polymorphisms and TD was studied in 173 Japanese patients with schizophrenia. The 267C/T allele of HTR6 was genotyped using PCR amplification followed by endonuclease digestion.

Analysis of association between the Gln192Arg polymorphism of the paraoxonase gene and schizophrenia in humans.

An increasing amount of evidence suggests a possible implication of oxidative stress in the pathophysiology of schizophrenia. Oxidized low-density lipoproteins (oxLDL) have been reported to be capable of eliciting neurocytotoxicity. On the other hand, paraoxonase (PON1), an arylesterase, plays a role in protection against oxidative modifications of LDL and is considered to be one of the antioxidant enzymes.

Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems.

To elucidate the influence of oxidative stress on the brain functions during aging, the cognitive performance ability of rats was assessed by using the water-maze test as an oxidative stress before and after hyperoxia. Young rats showed significantly greater learning ability than both old rats and vitamin-E-deficient rats. Although the memory functions of all rats were Impaired after oxidative stress, the memory retention of young rats was greater than those of other groups.

Association between three functional polymorphisms of dopamine D2 receptor gene and tardive dyskinesia in schizophrenia.

The dopamine D2 receptor (DRD2) gene is considered one of the candidate genes contributing to the development of tardive dyskinesia (TD). In the present study, we investigated the genetic association between three functional polymorphisms (Ser311Cys, -141C Ins/Del and TaqI A) in the DRD2 gene and TD (200 patients with schizophrenia: 44 with TD and 156 without TD). No significant difference in the allelic and genotypic distribution between patients with TD and those without TD was observed.

[Tumor markers in lung cancer].

Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA), and pro-gastrin-releasing peptide (proGRP) can be used as tumor markers for lung cancer. CEA is sensitive for adenocarcinoma, SCC and CYFRA for squamous cell carcinoma, and NSE and proGRP for small cell carcinoma. A tumor marker is generally used as a marker to monitor the clinical course.

Retrospective study of hyponatremia in gastric cancer patients treated with a combination chemotherapy of 5-fluorouracil and cisplatin: a possible warning sign of severe hematological toxicities?

Background: Some anti-neoplastic agents induce hyponatremia. The relationship between hyponatremia and other toxicities in gastric cancer patients treated with 5-fluorouracil and cisplatin (FP) was investigated retrospectively to clarify its clinical significance.

Methods: The subjects were 50 advanced gastric cancer patients treated with FP.

A phase I/II trial of cisplatin, docetaxel and ifosfamide in advanced or recurrent non-small cell lung cancer.

This trial was initiated to evaluate the toxicity and activity of combination chemotherapy employing cisplatin (CDDP), docetaxel (DCT) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), and to determine the maximum tolerated dose (MTD) of IFX. Chemotherapy-naive patients with advanced or recurrent NSCLC received 60 mg/m(2) DCT followed after a 3-h interval by 60 mg/m(2) CDDP on chemotherapy day 1, and IFX at an escalating dose with mesna protection on days 2-4. The chemotherapy was repeated every 3 weeks.

Novel polymorphism in the 5'-upstream region of the human 5-HT6 receptor gene and schizophrenia.

The localization of 5-hydroxytryptamine6 (5-HT6) receptor in the limbic and cortical regions, and the high affinity of atypical antipsychotic drugs such as clozapine for the receptor, suggest the possible involvement of the receptor in the pathogenesis of schizophrenia. In this study, we searched systematically for polymorphisms in the 5'-upstream region of the human 5-HT6 receptor gene. We identified a trinucleotide repeat polymorphism, (GCC)2/3, at a nucleotide position between -1093 and -1085 bp upstream from the translation start site.

Phase I and pharmacological study of paclitaxel given over 3 h with cisplatin for advanced non-small cell lung cancer.

Background: To establish the toxicities and maximum tolerated dose of paclitaxel given over 3 h in combination with cisplatin, to determine the pharmacokinetic profiles of these two drugs and to observe their antitumor activity, we conducted a combination phase I study in non-small cell lung cancer.

Methods: Patients received paclitaxel doses of 150-210 mg/m2 given over 3 h and cisplatin doses of 60-80 mg/m2 as a 1 h infusion 2 h after the end of the paclitaxel infusion.

Results: A total of 25 patients with previously untreated non-small cell lung cancer were enrolled.

Polymorphisms of tryptophan hydroxylase gene and the symptomatology of schizophrenia: an association study.

Serotonergic neurotransmission may be involved in the etiology of schizophrenia. We systematically searched for human tryptophan hydroxylase (TPH) coding polymorphisms, and detected a novel pentanucleotide repeat deletion polymorphism (GTTTT)4/5 in TPH intron 1b. We also confirmed A779C intron 7.

Association analysis between two functional dopamine D2 receptor gene polymorphisms and schizophrenia.

The dopamine D2 receptor (DRD2) gene has been listed as one of the candidate genes for susceptibility to schizophrenia. To date, a significant association between schizophrenia and two functional DRD2 gene polymorphisms, Ser311Cys and -141C Ins/Del, in Japanese samples, has been reported by Arinami et al. [1994: Lancet 343:703-704; 1997: Hum Mol Genet 6:577-582].

Phase I study of a weekly infusion of irinotecan hydrochloride (CPT-11) and a 14-day continuous infusion of etoposide in patients with lung cancer: JCOG trial 9408.

Background: The aim was to determine the maximum tolerated dose (MTD) and recommended dose of irinotecan hydrochloride (CPT-11) in combination with a 14-day continuous infusion of etoposide in patients with refractory advanced lung cancer (LC), especially small cell lung cancer (SCLC).

Methods: Etoposide was administered continuously at 25 mg/m2/day for 14 days. The initial dose of CPT-11 was 40 mg/m2 given as a 90 min intravenous infusion on days 1, 8 and 15 and the dose escalation of CPT-11 was planned in increments of 20 mg/m2 until severe or life-threatening toxic effects were observed.

Clara cell secretory protein (CC16) gene polymorphism and schizophrenia in humans.

An increasing amount of evidence suggests that the pathophysiology of schizophrenia is associated with activation of the inflammatory response system, as indicated by lower serum concentrations of Clara cell secretory protein (CC16), an endogenous anti-inflammatory protein in patients with schizophrenia. In the present study, we investigated the genetic association between a functional polymorphism (A38G) in human CC16 gene and schizophrenia (248 Japanese schizophrenic patients and 206 healthy controls). No significant positive association between the CC16 gene polymorphism and schizophrenia was observed.

The metabolism of plasma glucose and catecholamines in Alzheimer's disease.

Several lines of evidence suggest that the cholinergic system in the hippocampus plays a pivotal roll in regulating the peripheral metabolism of glucose and catecholamines. The injection of cholinergic stimulators including neostigmine, the acetylcholine esterase inhibitor, into the third ventricle or the hippocampus induces the elevation of glucose or catecholamines in plasma in rats. Under stress conditions, release of acetylcholine in the hippocampus increases, which coincides with the elevation of plasma glucose and catecholamines.