[Comparison of clinical characteristics of dependence on nicotine, alcohol, stimulants, organic solvents, and tranquilizers].
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Biomedical subjects
Publications and source records attributed to S Ushijima.
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A study was performed to evaluate the significance of aberrations of the newly identified DNA demethylase, MBD2, in human carcinogenesis. Levels of expression of DNA demethylase mRNA were examined by reverse transcription followed by real-time quantitative detection of the PCR products in 32 samples of colorectal cancer tissue, 24 stomach cancers, and the corresponding noncancerous mucosae. DNA demethylase mRNA levels normalized with glyceraldehydephosphate dehydrogenase (GAPDH) mRNA were reduced in 31 (97%) of the 32 colorectal cancers and in 22 (92%) of the 24 stomach cancers when compared with the levels in the corresponding noncancerous mucosae. The average levels of DNA demethylase mRNA expression normalized with GAPDH mRNA in each of the colorectal (0.81 +/- 0.55) and stomach (2.88 +/- 0.23) cancers were significantly lower than in the noncancerous mucosae (1.90 +/- 0.16 and 5.11 +/- 0.34, respectively, p < 0.0001). There was no significant association between the DNA demethylase mRNA level and malignant potential in both colorectal and stomach cancers. These data suggest that reduced expression of DNA demethylase may play a role at a certain step of multistage carcinogenesis. Reduction of DNA demethylase mRNA expression may be, if anything, one of the early events of carcinogenesis, but may not participate in the malignant progression of tumors.
To examine the significance of aberrant DNA methylation in hepatocarcinogenesis, the DNA methylation status at the D17S5 locus and mRNA expression of a candidate tumor suppressor gene, HIC-1 (hypermethylated-in-cancer), which was identified at the D17S5 locus, in primary hepatocellular carcinomas (HCCs) and their corresponding noncancerous liver tissues were assessed. DNA hypermethylation at the D17S5 locus was detected in 44% of the noncancerous liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, but was not observed in noncancerous liver tissues showing no remarkable histological findings. The incidence of DNA hypermethylation at this locus was significantly higher in HCCs (90%) than noncancerous liver tissues (P <.001). Loss of heterozygosity at the D17S5 locus, which was preceded by DNA hypermethylation at the same locus, was detected in 54% of HCCs. The HIC-1 mRNA expression level of noncancerous liver tissues showing chronic hepatitis or cirrhosis was significantly lower than that of noncancerous liver tissues showing no remarkable histological findings (P <.01), and that of HCCs was even lower than that of noncancerous liver tissues (P <.05). Poorly differentiated HCCs showed lower expression levels than well- to moderately differentiated HCCs. Mutation of the p53 gene may be involved in HIC-1 inactivation. Moreover, wild-type p53 did not overcome DNA hypermethylation at the D17S5 locus to activate HIC-1 in HCCs. These data suggest that aberrant DNA methylation at this locus and reduced HIC-1 mRNA expression participate in hepatocarcinogenesis during both early developmental stages and malignant progression of HCCs.
The attitudes of Japanese psychiatrists toward their patients who suffer from schizophrenia were investigated. We were concerned specifically with whether the psychiatrists inform their patients of the suspected diagnosis. We discuss how the term 'schizophrenia' may influence a psychiatrist's decision to inform his patients of the diagnosis. A self-reported questionnaire was distributed to 150 executive board members of the Japanese Society of Psychiatry and Neurology and analysis of the data obtained from 110 respondents was carried out. The results showed that the concepts that psychiatrists use when they give a diagnosis of schizophrenia vary considerably. Fifty-nine per cent of the respondents informed their patients of a diagnosis of schizophrenia on a case-by-case basis, while 37% informed only the patients' families. A tree analysis showed that the most important predictors for informing the patients of the diagnosis were assumptions about the public image of schizophrenia and a negative impression of the term schizophrenia, translated as 'Seishin Bunretsu Byou' in Japanese. The results revealed that the Japanese term for schizophrenia influences a psychiatrist's decision to inform patients of the diagnosis and that, by changing the term to a less stigmatized one, the disclosure of information about schizophrenia to patients would be promoted.
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The aim of this study was to elucidate the significance of aberrant DNA methylation in gastric carcinogenesis. The DNA methylation status at the D17S5 locus, at which a candidate tumor suppressor gene, HIC-1, was identified, of gastric cancers and non-cancerous gastric mucosae from 42 gastric cancer patients was examined by Southern blotting using a methylation-sensitive restriction enzyme. DNA hypermethylation was observed in 15, 13, 25 and 45% of the tissues showing no remarkable histological findings, chronic gastritis without intestinal metaplasia, intestinal metaplasia and gastric cancer, respectively. The incidence of DNA hypermethylation was significantly higher in gastric cancers than in non-cancerous gastric mucosae (P < 0.05). DNA hypermethylation was often accompanied by allelic loss at the same locus in gastric cancers. DNA hypermethylation at the D17S5 locus, which was even detected in precancerous conditions, including intestinal metaplasia, may play a role in gastric carcinogenesis.
Patients with small-cell lung cancer who survive more than 2 years have a significantly increased risk (relative risk of 3.6) of developing a second primary tumour. The cessation of cigarette smoking after successful therapy is associated with a significantly decreased risk of a second primary tumour.
The clinical data of 86 cases of primary circadian rhythm sleep disorder (primary CRSD) were retrospectively examined and compared to 40 cases of secondary circadian rhythm sleep disorder (secondary CRSD), who had presented with some kind of psychiatric or medical disorder, and had exhibited sleep-wake rhythm disorders that were judged to be secondary CRSD based on sleep logs. The comparison of cases found that: (i) the mean age at first presentation to the clinic was significantly younger for primary CRSD compared to secondary CRSD; (ii) more secondary CRSD cases were unemployed than were Primary CRSD cases; (iii) more cases in the secondary CRSD group had a clear trigger for sleep-wake rhythm disorder onset than cases in the primary CRSD group; and (iv) the types of sleep-wake rhythm disorders in the primary CRSD group consisted of delayed sleep phase syndrome (DSPS), 72 (83.7%), non-24 pattern, 11 (12.8%), and irregular, 3 (3.5%). In the secondary CRSD group there were 25 (62.5%) cases of DSPS pattern, 1 (2.5%) of non-24 pattern and 14 (35.0%) with irregular pattern. The 56 (65.1%) cases with primary CRSD showed good response to vitamin B12 and bright light therapy; however, 28 (70.0%) cases with secondary CRSD did not respond to such therapies.
The author will describe the changing trend of psychotherapy since the 1960s. The main theme in the 1960s was to establish psychotherapy for schizophrenics, although the school of Morita therapy had been continuing to treat the neurotic patients, particularly obsessional areas of neuroses. When social therapy came to dominate the clinical situation of schizophrenia in the course of time, the dynamic psychotherapists turned their attention to borderline patients. It was during this time that the borderline patients had been becoming the main theme in the clinical practices and the new theories and techniques had been successively imported. This situation is continuing even now. The rapid change of family structure had changed the personality structures and had given rise to the necessity for the family therapy. It is also emphasized that the new personality with ego splitting, who were likely to involve many people in the course of psychotherapy, has been asking us not only for individual psychotherapy but also a team approach.
PURPOSE: To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. RESULTS: All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression. CONCLUSION: A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.
The desynchronaization between sleep-wakefulness rhythm and other biological rhythms such as rectal temperature rhythm and melatonin rhythm is the most unique characteristics for human circadian rhythms. Based on the findings of desynchronaization, a multi-oscillator hypothesis has been advanced for the human circadian clock. Three kind of the hypotheses such as Wever, Kronauer and two-process model were introduced in this article. According to the multi-oscillator hypothesis, one clock regulates rectal temperature and melatonin rhythm and another clock regulates sleep-wake rhythm. There are a few differences between the two different kind of circadian rhythms. For example, the oscillator mechanism which regulates the rectal temperature and the melatonin rhythm are reseted directly by the bright light, but the sleep-wake rhythm is entrained by the bright light through an internal coupling to the former mechanism. And it is also recognized that the length and the structure of sleep are depended strongly on the phase of biological clock which regulates the rectal temperature rhythm.
Our study was designed to clarify the significance of silencing the E-cadherin gene, which is located on 16q22.1, due to CpG methylation during hepatocarcinogenesis. The CpG methylation status of primary hepatocellular carcinomas (HCCs) and corresponding liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, were assessed by digesting DNA with methylation-sensitive and non-sensitive restriction enzymes. CpG methylation around the promoter region of the E-cadherin gene was detected in 46% of liver tissues showing chronic hepatitis or cirrhosis and 67% of HCCs examined. Immunohistochemical examination revealed reduced E-cadherin expression in 59% of HCCs examined. CpG methylation around the promoter region correlated significantly with reduced E-cadherin expression in HCCs (p < 0.05). CpG methylation around the promoter region, which increases during the progression from a precancerous condition to HCC, may participate in hepatocarcinogenesis through reduction of E-cadherin expression, resulting in loss of intercellular adhesiveness and destruction of tissue morphology.
The efficacy of lithium carbonate in the first reported case of a female with mild mental disability who engaged in public and compulsive masturbation is described. The patient was born in 1975, and was 19 years old at first admission. A diagnosis of schizophrenia was initially suspected, therefore the patient was given medication including pimozide, haloperidol, carbamazepine, diazepam and levomepromazine. These medications, however, did not control the symptoms, and the patient showed several side effects, such as incontinence. Only lithium carbonate was efficacious among the medications administered; the patient's abnormal sexual behavior was significantly reduced and no conspicuous side effects were recognized. The mechanisms of lithium carbonate in controlling abnormal sexual behavior are discussed.
Distigmine is widely used for the treatment of dysuria, which is caused by various types of psychotropic medications. Distigmine, however, is also known to induce adverse cholinergic effects, such as diarrhea and salivation, with a decreased level of serum cholinesterase. We evaluated the possibility of using serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as specific clinical markers for the adverse cholinergic effects of distigmine. Of the twelve patients treated with distigmine for dysuria caused by psychotropic drugs six patients presented both adverse cholinergic effects and decreased levels of serum AChE and BChE. The other six presented neither of these changes. This study suggests that the values of serum AChE and BChE may be useful markers for the manifestation of adverse cholinergic effects caused by distigmine.
We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of 'receiver operator characteristics' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.
Despite recent advances in control of acute emesis following cisplatin-based chemotherapy regimens, delayed emesis remains a significant cause of treatment-related morbidity and factors associated with delayed emesis have not yet been evaluated. A prospective randomised trial was conducted to compare the efficacy and toxicity of granisetron, dexamethasone plus prochlorperazine with granisetron alone in controlling cisplatin-induced delayed emesis and to identify the important factors that influence its occurrence and severity. Seventy cisplatin-naive patients with inoperable solid tumors participated in the trial. Patients who received 80 mg m-2 or 100 mg m-2 of cisplatin were randomly assigned to receive either granisetron 40 micrograms kg-1 intravenously (i.v.) on day 1, dexamethasone 20 mg i.v. on days 2 and 3 and prochlorperazine 5 mg orally thrice daily on days 1-5 or granisetron 40 micrograms kg-1 i.v. on day 1 alone. There was no difference in their acute antiemetic efficacy. A combination regimen was more effective than granisetron alone in preventing delayed symptoms, with superior rates of complete plus major responses of 77% vs 51% (P = 0.0460). Treatment arm was the only determinant factor for the occurrence of delayed emesis (P = 0.0101).
In order to clarify the significance of DNA methylation in both earlier and later stages of hepatocarcinogenesis, the DNA methylation state on chromosome 16, on which loss of heterozygosity (LOH) has frequently been detected in human hepatocellular carcinomas (HCCs), was examined. DNA from primary HCCs and tissues showing chronic hepatitis and liver cirrhosis, which are considered to be precancerous conditions, was analyzed by digestion with methylation-sensitive and non-sensitive restriction enzymes. DNA hypermethylation at the D16S32, tyrosine aminotransferase (TAT) and D16S7 loci and hypomethylation at the D16S4 locus were detected in 18%, 58%, 20% and 48% of examined HCCs, respectively. Aberrant DNA methylation occurred more frequently in advanced HCCs than in early HCCs. Moreover, DNA hypermethylation at the D16S32, TAT and D16S7 loci was frequently observed in chronic hepatitis and liver cirrhosis. The incidence of DNA hypermethylation was higher than that of LOH (42% at the TAT locus). These data suggest that DNA hypermethylation might predispose the locus to allelic loss. Aberrant DNA methylation is a significant change which may participate in the early developmental stages of HCCs.
In the present study, 126 alcoholics aged 60 years or older were compared with 104 alcoholics aged 35-45 years. No dementia was found in the younger group, whereas 62.7% of the aged patients had dementia; the dementia being irreversible in 32.9% of such patients. Cases of so-called alcohol dementia excluding organic brain diseases accounted for 42.1%. The percentage of aged alcoholics having dementia increased with age, being far beyond the frequency of senile dementia in the general aged. Among various physical complications, hepatic injury and myocardiopathy were more frequent in the aged alcoholics than in general aged people, suggesting that hypertension, myocardiopathy and hepatic injury underlie the manifestation of dementia. There was no case of dementia attributable to the direct effect of alcohol distinctly exceeding the effects of various physical factors. Problem behaviors characteristic of the aged group included 'being soaked in drink' and being inebriated, showing no correlation with the presence or absence of dementia. There was no significant difference in frequency of delirium between the aged group and the younger group. However, in aged alcoholics delirium tended to continue for a longer period during abstinence and was more likely to occur even during non-abstinence. A similar trend was found in aged alcoholics with dementia compared with those without dementia.