Detection of circulating tumor cells in patients with pancreatic cancer: a preliminary result

Background/Purpose

It has been reported that circulating tumor cells (CTCs) can be used to predict survival in metastatic breast cancer. In this preliminary study, we examined the level of CTCs in pancreatic cancer (PC) patients to elucidate whether we could predict survival in PC.

Methods

The eligible subjects, at Tokyo Medical University Hospital, were 26 patients with PC, 11 with chronic pancreatitis, and 10 healthy volunteers. Three PC patients underwent surgery, 18 patients (who were stage IV) were treated with gemcitabine (GEM), and 5 patients received best supportive care (BSC).

Results

The CTC count was 1/7.5 ml blood or higher (defined as positive) in 11 of the 26 patients (42%; mean, 16.9/7.5 ml blood; range, 1-105/7.5 ml blood). Gemcitabine was administered to 6 of the 11 CTC-positive patients (3.8 courses on average). The treatment was continued for more than three courses in 2 patients, in both of whom the CTC count was only 1/7.5 ml blood. Operation was performed in 1 of the 11 CTC-positive patients. The remaining 4 patients of the 11 CTC-positive patients received only BSC. CTC was negative in 15 patients with PC (stage II, 1; stage III, 1; stage IVa, 7; and stage IVb, 6) and in the subjects with benign conditions. The median survival times (MSTs) of the CTC-positive and-negative patients were 110.5 and 375.8 days (P < 0.001). When the analysis was limited to the 14 stage-IVb patients, the MSTs of the CTC-positive and-negative patients were 52.5 and 308.3 days (P < 0.01).

Conclusions

The present study demonstrated that the detection of CTCs in peripheral blood may be useful to predict prognosis in patients with PC.     

Psychiatric and cognitive profile in Anderson-Fabry patients: a preliminary study

Anderson-Fabry disease (AFD) is an X-linked inherited lysosomal storage disorder disease caused by a deficiency in the activity of the α-galactosidase enzyme. We investigated neuropsychological and psychiatric function in AFD patients. We studied 16 AFD patients, aged 7 to 61 years. Intelligence, language, vision-spatial abilities, memory, sensorimotor abilities, and attention and executive functions were tested with a computerized test battery as well as standard paper and pencil tests. The results were compared to known age-based norms. In addition, all patients were screened for lifelong DSM-IV Axis-I and Axis-II psychiatric diagnoses, and 4 were interviewed by a psychiatrist. Performance on most cognitive measures was within average range. All measures of information processing speed were significantly reduced, as were some measures of executive functions. Ten out of 16 patients met DSM-IV criteria for Axis I or Axis II diagnoses at some point in their lives. This preliminary study delineates a psychiatric and cognitive phenotype in AFD patients and contributes to the growing field of characterizing behavioral phenotypes of patients with genetic diseases. We suggest that psychiatric and neuro-psychological evaluation be included in the patient's evaluation.     

Intraarticular lymphoscintigraphy of the human knee joint: a preliminary study

Intraarticular (knee) lymphoscintigraphy using 99mTc-nanocoll was performed in five patients with chronic synovitis. Scintigrams from the anterior and lateral view of the knee and of the iliac region were taken 1, 2, 4, and 22 hours after injection. The inguinal and iliac lymph nodes uniformly visualized in about 2 hours. Based on radioactivity in regional lymph nodes measured at prescribed time intervals, we were able to quantify lymph drainage from the knee joint. Lymphoscintigraphy is without complication and discomfort and is potentially useful to study synovial fluid reabsorption in joint diseases.     

Detection of valvular insufficiency by a platinum electrode technic: A preliminary study

Hydrogen- and ascorbic acid-sensitive platinum electrodes have been applied through a catheter technic for the detection of tricuspid, aortic, pulmonary and mitral valvular insufficiency in the experimental laboratory.Miniaturization of these catheters might add a valuable technic for the evaluation of clinical valvular heart disease and for the quantitative determination of the amount of valvular regurgitation.     

Urinary excretion of retinol in patients with multiple myeloma: a preliminary study

Urinary excretion of vitamin A was studied in patients with multiple myeloma (MM). Eight of the 12 patients studied excreted retinol in urine; only one of them had elevated serum creatinine (115-150 micromol/L). There was a highly significant correlation between urinary retinol and serum creatinine (P < 0.0004). Urinary retinol correlated also with urine protein (P < 0.0001) and albumin (P = 0.001), but not with urinary immunoglobulin light chains. Urinary retinol excretion may be an early manifestation of renal dysfunction in MM patients. The effect of urinary retinol excretion on vitamin A homeostasis in MM deserves further study.     

Graves病患者甲状腺细胞凋亡的初步研究

目的　研究Graves病 (GD)甲状腺细胞凋亡和凋亡相关蛋白Fas、可溶性Fas(sFas)及Fas配基 (Fas L)的表达特征 ,探讨Fas介导的细胞凋亡与GD发病机制之间的内在联系。方法甲状腺组织取自 7例GD手术患者和 3例意外死亡健康个体 ,采用原代甲状腺细胞 (TEC)培养技术、流式细胞术、ELISA及半定量RT PCR法检测TEC凋亡率及Fas、sFas和Fas L的表达情况。结果(1)GDTEC凋亡率为 (3.42± 0 .81) %,明显高于正常对照 (P <0 .0 1)。 (2 )GDTECFas表达率为 (8.3± 1.7) %,与正常对照相比差异无显著性。 (3)GDTEC培养上清液中sFas含量明显高于正常对照(P <0 .0 1)。 (4 )正常及GDTEC均表达Fas及sFasmRNA ,而Fas LmRNA仅在GDTEC表达。与正常对照相比 ,GDTECFasmRNA差异无显著性 ,sFasmRNA含量则明显升高 (P <0 .0 1)。结论GD患者甲状腺细胞存在细胞凋亡和Fas系统的异常表达 ,提示Fas介导的细胞凋亡参与GD的发病过程 ,sFas产生增加可能与甲状腺细胞增殖有关。     

The association of HTR3A mRNA expression and craving in Han Chinese alcohol-dependent patients: a preliminary study

ABSTRACT

Background: 5-Hydroxytryptamine (5-HT) 3 receptor plays a crucial role in craving of alcohol dependence. Recent evidence shows that chronic alcohol exposure causes changes in gene expression and induces behavioral changes. However, the relationship between gene expression of 5-HT3 receptor and craving in alcohol-dependent patients is not fully understood. Objectives: The aim of this preliminary study was to investigate the relationship between gene expression of the 5-HT3 receptor and craving in alcohol-dependent patients and the epigenetic mechanism. Methods: We recruited 50 male Han Chinese alcohol-dependent patients and 46 male Han Chinese healthy controls. We investigated the changes of HTR3A mRNA, which encodes the 5-HT3 receptor A subunit, and H3K9 acetylation in HTR3A promoter region. Obsessive Compulsive Drinking Scale (OCDS) was used to assess the craving of alcohol-dependent patients relative to controls. Results: HTR3A mRNA expression levels and acetylation levels of H3K9 in the HTR3A promoter region were significantly higher in the alcohol-dependent patients. HTR3A mRNA expression levels were positively correlated with OCDS scores. Moreover, HTR3A mRNA expression levels were positively correlated with acetylation levels of H3K9 in HTR3A promoter region. Conclusion: The current findings suggest that HTR3A mRNA expression levels were positively correlated with craving in Han Chinese alcohol-dependent patients. The regulation of H3K9 histone acetylation in HTR3A promoter region may offer a target for the treatment of alcohol dependence.     

The thyroid hormone derivative 3-iodothyronamine increases food intake in rodents

Background:  The thyroid hormone derivative 3-iodothyronamine (T₁AM), an endogenous biogenic amine, is a potent agonist of the G protein–coupled trace amine-associated receptor 1 (TAAR1). T₁AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis.
Aim:  The aim of this study was to determine the effects of T₁AM on food intake in rodents.
Methods:  We determined the effect of (i) intraperitoneal (i.p.) administration of T₁AM on food intake, oxygen consumption (VO₂) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T₁AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T₁AM in male rats; and (iv) direct injection of T₁AM into the arcuate nucleus (ARC) of male rats on food intake.
Results:  (i) T₁AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO₂ or locomotor activity. (ii) ICV administration of T₁AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T₁AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T₁AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake.
Conclusion:  These data suggest that T₁AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.     

Increased cervical dysplasia in intravenous cyclophosphamide-treated patients with SLE: a preliminary study

To determine if intravenous cyclophosphamide (IV-C) causes an excess of cervical dysplasia and/or cancer in systemic lupus erythematosus (SLE) patients, a retrospective review was conducted. Patients with SLE who received IV-C between 1988-98 (study group) were compared with a group of SLE patients who had not received IV-C (control group). Of the 79 IV-C-treated SLE patients identified, we excluded 18 because of absence of pertinent data. We found 10 cases of cervical dysplasia in the remaining 61 patients, compared to 2 in 49 non-exposed patients (P<0.04). Comparison of the two groups revealed no difference in: mean years of disease duration, months of follow-up and age. The non-exposed patients were more likely to be on estrogen and hydroxychloroquine but less often on steroids and azathioprine. The study group with and without dysplasia were assessed; we found no difference in the mean, or total IV-C dose, smoking and estrogen use. There was a significant decrease in time to dysplasia in those, given IV-C, with previous dysplasia compared to those without. These preliminary data suggests that IV-C causes an increased number of abnormal Papanicolaou (Pap) smears in SLE patients, particularly those with previous dysplasia.     

Therapy with statins in patients with refractory rheumatic diseases: a preliminary study

We have explored the therapeutic potential of statins in patients with different inflammatory rheumatic diseases refractory to conventional therapy. We found that simvastatin (80mg o.d. for eight days) induced a rapid and significant reduction in proteinuria levels in three systemic lupus erythematosus (SLE) patients. A similar kind of therapy had a marked beneficial effect in a patient with Wegener's granulomatosis and a patient with erythema nodosum. On the other hand, five patients with rheumatoid arthritis (RA) who received atorvastatin for eight days (20mg/day) showed reduction in C-reactive protein levels and a clinical improvement that was classified as an ACR20 response. Prior to the administration of statins, all these patients had received aggressive conventional therapy with no satisfactory response. A significant reduction in spontaneous apoptosis of peripheral blood lymphocytes and expression of CD69 and HLA-DR was observed in SLE patients after simvastatin therapy. These results prompted us to perform a pilot short-time comparative (simvastatin versus chloroquine) open clinical trial in 15 patients with RA who were receiving methotrexate as a single disease modifying antirheumatic drug with no satisfactory response. Most patients (9/10) who received simvastatin (40mg/day) showed an ACR50 or better response after eight weeks, whereas such a response was not observed in any patient (0/5) treated with chloroquine. Our preliminary results indicate that statins may be an important therapeutic tool for the treatment of inflammatory rheumatic diseases.     

Bacteriological study of trophic ulcers in leprosy patients (a preliminary study)

Swabs from trophic ulcers from 108 cases were studied by culture. 37 cases yielded single organism (Ps. aeruginosa, 18, Proteus species 11, Staph. pyogenes 4, Others 4). 71 cases yielded mixed growth with two or more organisms. Ps. aeruginosa, Proteus species and Diphtheroids were the predominant organisms in these cultures. Ps. aeruginosa was sensitive to Gentamycin (96.6%), Streptomycin (62.7%) and Chloramphenicol (33.9%). Other organisms although comparatively more sensitive showed a similar pattern.     

重组多肽酶联免疫吸附法检测抗Scl-70抗体的初步应用

目的制备人Scl-70抗原207～765位氨基酸片段融合蛋白作为自身抗原,探讨ELISA检测抗Scl-70抗体的敏感性和特异性。方法构建编码Scl-70抗原第207至第765位氨基酸片段的重组体,在宿主菌E.coliBL21（DE3）中表达融合蛋白,经Ni^2＋-NTA亲和层析纯化后,免疫印迹法鉴定抗原性,ELISA检测北京协和医院免疫科血清库中系统性硬化（SSc）及部分其他结缔组织病患者血清抗Scl-70抗体。结果重组融合蛋白在宿主菌中获得可溶性表达,免疫印迹法鉴定表明其能与标准抗Scl-70抗体阳性血清反应,而与正常血清、其他抗血清无反应。在36份SSc患者血清中,天然抗原免疫双扩散（DID）法共检出的6份阳性血清用重组多肽ELISA检测有5份呈阳性,30份经天然抗原DID法检测为阴性的血清用重组多肽ELISA检测有3份呈阳性;20份其他结缔组织病患者血清用重组多肽ELISA检测均为阴性。结论重组的207—765位氨基酸片段是Scl-70抗原的主要抗原表位区域,以重组多肽为基质ELISA检测抗Scl-70抗体的敏感性较高,为进一步研究抗体水平与临床病情变化的相关性奠定了基础。     

Detection of Mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a preliminary report

We have searched for Mycobacterium leprae DNA for 36kDa protein in urine using a M. leprae specific PCR technique. A limited number of 16 patients (of which 11 belonged to lepromatous leprosy and five to tuberculoid leprosy) and eight healthy individuals were included for the present study. The number of urine samples positive by PCR were 36.4% (4/11) in lepromatous patients and 40% (2/5) in tuberculoid patients. None of the samples from healthy individuals was positive. To our knowledge, the results indicate, for the first time, the presence of M. leprae DNA in urine from leprosy patients. Another important finding obtained out of the study is that amongst treated patients 66.6% (4/6) were positive whereas amongst untreated only 20% (2/10) were positive. From the present indicative data it appears that treatment improves the PCR results with urine as a sample. Thus, the approach could prove to be useful for monitoring the treatment response of individual patients and needs to be further evaluated with a large number of patients.     

Detection of early atherosclerotic lesions in the carotid artery: Experimental and preliminary human data

There is a strong need to directly image, noninvasively, atheromatous lesions for early lesion detection, serial assessment of the presence and extent of disease, and treatment monitoring of atherosclerosis. The aim of this study was to investigate the value of polyclonal¹¹¹Inhuman IgG (¹¹¹In-HIG) in human carotid artery disease. A comparative study between¹¹¹In-HIG and¹²⁵I-LDL uptake in atheromatous lesions was also performed in 12 cholesterol-fed New Zealand white rabbits. Ultrasonographic and scintigraphic findings in 58 patients were compared. HIG was labeled with 500 µCi¹¹¹Indium by the diethyleneaminepentaacetic anhydride (DTPA). After injection of 10 µCi¹²⁵I-LDL, the respective entry into aortic segments was evaluated in the animals.¹¹¹In-HIG accumulation was higher in reendothelialized areas, foam cells, at the edge of lesions, and in hyperlipidemic rabbits. Ultrasound examinations of the carotid arterial wall showed wall thickening in 45 patients and plaques in 44 patients. Scintigraphic imaging of the identical area provided increased uptake in 40 patients and no abnormal uptake of¹¹¹In-HIG in 18 patients. There was, however, no significant correlation between the radiotracer retention and the ultrasonographic findings or laboratory and clinical parameters. The data provide evidence that the two imaging techniques for early atherosclerotic lesions are visualizing different aspects of atherogenesis: the functional (HIG) on the one side, and the morphological (ultrasonography) on the other side.