The sympathetic skin response (SSR) is considered as one of the indexes of autonomic nervous system functions, especially related with the sudomotor function of unmyelinated sympathetic fibers. SSRs are recorded as the potentials with biphasic or multiphasic waveforms by conventional electromyography. SSRs are evaluated by measuring latency (time from the stimulus to the onset), amplitude, and area (the space under the curve of the waveform). Although dysautonomia is a feature of chronic obstructive pulmonary disease (COPD), as demonstrated by acetylcholine sweat-spot test, there are no data concerning SSR in COPD patients. In this study, we electrophysiologically investigated the sudomotor function of the sympathetic nervous system in patients with COPD. SSRs were recorded in 30 patients with COPD and 21 healthy volunteers. Normal responses were obtained from all subjects in the control group. No response was observed in three patients with COPD. The mean latency, amplitude and area values of the potentials recorded of the remaining 27 patients were compared to the control. The mean latency was longer (p < 0.01) and the mean amplitude and area values were lower (p = 0.012, p = 0.021, respectively) in the patients compared to the control. We also demonstrated significant correlations between the latency, amplitude, or area values of the SSR and two parameters of pulmonary function tests forced expiratory volume one second/forced vital capacity (FEV1/FVC) and FEV1/FVC %. In conclusion, SSR is impaired in patients with COPD, which indicates the dysfunction of the sympathetic nervous system. Furthermore, the degree of impairment in SSR may reflect the severity of airway obstruction in patients with COPD.
Free oxygen radicals and lipid peroxidation are responsible for adriamycin-induced cardiotoxicity. Amifostine is a scavenger of free radicals and may function as a selective cytoprotective agent. The aim of this study was to investigate the effects of amifostine on adriamycin-induced lipid peroxidation and the levels of protective enzymes in the heart. Male Wistar rats were randomly allocated to three groups: pretreated, untreated, and control (n = 10 in each group). Rats were pretreated with an intraperitoneal injection of amifostine (200 mg/kg) 30 min before the injection of adriamycin. The pretreated rats were given an intraperitoneal injection of adriamycin (10 mg/kg) and were sacrificed after 72 h. Likewise, rats received intraperitoneal injection of adriamycin (untreated) or saline (control). The hearts were removed for the analyses of malondialdehyde (MDA), reduced glutathione (GSH) and catalase. MDA levels were increased (p < 0.005) in the heart tissues of untreated rats compared to control, while GSH and catalase levels were decreased (p < 0.05 and p < 0.001, respectively) in untreated animals. In amifostine-preatreated group, MDA levels were lower (p < 0.01), and GSH and catalase levels were higher (p < 0.05 for both) than the untreated group. GSH levels were even higher in the amifostine-pretreated group compared to control (p < 0.01), although catalase levels were significantly lower in the pretreated group (p < 0.05). These results indicate that amifostine decreases adriamycin-induced lipid peroxidation and increases the levels of the protective enzymes in the heart tissue. Therefore, amifostine may ameliorate the adriamycin-induced acute cardiotoxicity.
Of a number of DNA marker typing techniques for personal identification in the field of forensic medicine, polymorphic short tandem repeat (STR) typing is currently the most frequently used technique. However, the multiplex STR method is time consuming. In contrast, single nucleotide polymorphism (SNP) detection methods are relatively rapid and amenable to high throughput. The discrimination power of each SNP is inferior to that of an STR, but a combination of many SNPs could realize a high discriminating power. In this regard, 16 highly informative SNP markers were selected in the introns of genes whose alleles had a proportion of 0.4-0.6 in the Japanese SNP database. The 16 SNPs were sequentially detected within 40 min using the hybridization probe assay on the LightCycler system. The allele and genotype frequencies of these SNPs were determined in a group comprising 64 unrelated Japanese subjects. Based on the frequency data of this group, the combined matching probability, defined as the estimated probability that two unrelated individuals selected at random would possess identical multilocus genotypes, was calculated with the 16 SNPs in the Japanese population and was found to be 2.025 × 10−7. This system is an effective tool in the forensic medicine to obtain information on personal identification.
Pulse wave velocity (PWV) is a well-known indicator of arterial stiffness and a marker of the presence of vascular lesions. Cardiovascular mortality in Russia has become the highest in the world. The Japanese are enjoying long lives, and the mortality caused by cardiovascular diseases has thus far remained at lower levels than that in Russia. In this study, we focused on brachial-ankle pulse wave velocity (baPWV) obtained from normal human subjects in Russia as well as in Japan, and compared their respective cardiovascular risks. We evaluated baPWV in 337 Japanese and 138 Russian healthy subjects. The baPWV was recorded using a PWV diagnosis device. BaPWV was measured between 2 locations of the arterial tree. The baPWV in the Russian group was significantly higher than that obtained in the Japanese of two groups categorized by age (40-59 years and 60- years). Further, body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure in the Russian group were significantly higher than those obtained in Japanese in three age groups (under 39 years, 40-59 years, and 60- years). Moreover, the baPWV indicated a positive correlation with age, BMI and SBP in both Japanese and Russians, although the increasing trend of the baPWV against age of the Russian group had a larger value than that of the Japanese. Therefore, we suggest that arterial stiffness might be promoted earlier in the Russian group, which might be the main cause of the increased cardiovascular risk in Russia.
Many patients with biliary atresia (BA) have impaired metabolism of copper (Cu) and zinc (Zn) because of the obstruction of bile ducts. An excessive Cu accumulation is cytotoxic and results in fibrosis in hepatic tissues. Since Zn works antagonistically to Cu, lower Zn concentrations may deteriorate liver damage. In the 1980's, we performed a series of surgeries on BA patients for the construction and alteration of the bile flow route, which is the major excretion route for Cu. We obtained liver and serum samples at each surgery, and measured Cu and Zn concentrations by inductively coupled plasma atomic emission spectrometry. Hepatic Cu concentration decreased with the improvement of cholestasis after the establishment of bile excretion. Conversely, when cholestasis persisted or recurred, increases in hepatic and serum Cu concentrations were noted. Hepatic Zn concentration was lower than previously reported normal values. High hepatic and serum Cu concentrations due to persistent or recurrent cholestasis and low hepatic Zn concentration may deteriorate hepatic fibrosis and liver cirrhosis.
Congenital bilateral absence of the vas deferens (CBAVD) is characterized by azoospermia and male infertility. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with cystic fibrosis (CF), the most common autosomal recessive disorder in Caucasians. Recent publications on CBAVD raised the question whether CFTR gene mutations are responsible for CBAVD occurrence or not. This study was conducted to explore the role of CFTR gene mutations in the occurrence of CBAVD-dependent male infertility. Forty-four chromosomes of 22 CBAVD patients from Austrian ancestry were studied. For detection of the most common mutation ΔF508, a deletion of phenylalanine at the 508th position of mature CFTR chloride channel protein, the 10th exon of the gene was screened by heteroduplex analysis. In order to identify non-ΔF508 mutations, we also analyzed the entire coding regions, exon/intron boundaries of 27 exons and the 5'- and 3'-untranslated regions of the gene by denaturing gradient gel electrophoresis (DGGE) after polymerase chain reaction. All exons showing different banding patterns on the DGGE gels were sequenced to define existing DNA sequence variations. Among the analyzed 44 chromosomes of 22 patients, disease producing mutations were found in 31.8% (14/44). The most common mutation was ΔF508 with a frequency of 43% (6/14), followed by R117H with 29% (4/14). Our results indicate that CFTR gene mutations are common but not the only reason for the occurrence of CBAVD-dependent male infertility. We recommend screening of the CFTR gene in these patients.
Helicobacter pylori (H. pylori) is causally related to chronic active gastritis, peptic ulcer disease, primary low-grade B-cell gastric lymphoma, and is also a risk factor for gastric cancer. In addition, a high seroprevalence of H. pylori has been found in many extragastrointestinal disorders, including active bronchiectasis and chronic obstructive pulmonary disease (COPD). It appears that H. pylori has a close relationship with respiratory diseases, but data in the literature on the relationship between H. pylori infection and asthma are poor. We therefore investigated the relationship between them. In this study we evaluated 46 patients with mild asthma, 48 age- and sex-matched patients with peptic ulcer and 48 healthy control subjects. All enrolled subjects underwent a serologic test for H. pylori IgG and cytotoxin-associated gene-A (CagA) by enzyme-linked immunosorbent assay (ELISA). There was no significant difference in both anti-H. pylori IgG seropositivity (p = 0.6580) and anti-H. pylori-CagA IgG seropositivity (p = 0.7183) between the asthmatic and control subjects. In contrast, both anti-H. pylori IgG seropositivity and anti-H. pylori-CagA IgG seropositivity were significantly higher in peptic ulcer patients than these in asthmatic patients (p < 0.01). Despite the sero-epidemiological association of H. pylori infection with many inflammatory conditions, our data show no significant association between mild asthma and H. pylori infection.
In the lung, anti-inflammatory actions of glucocorticoids would be determined by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), the microsomal enzyme responsible for the breakdown of bio-active glucocorticoids. However, regulation of 11β-HSD2 under inflammatory conditions such as acute lung injury is not well understood. In the present study, we examined whether inflammatory substances would influence the activity and mRNA expression of 11β-HSD2 in the lung. In a human bronchial epithelial cell line BEAS-2B, endotoxin inhibited 11β-HSD2 enzyme activity in a dose-dependent manner over 48 h with a significant decrease in the mRNA expression. Likewise, tumor necrosis factor (TNF)-α inhibited both activity and mRNA expression of 11β-HSD2. The TNF-α-dependent decrease in the enzyme activity was completely blocked by anti-TNF-α antibody, while antibody alone showed no significant influence on the enzyme activity. An nitric oxide donor (NO) sodium nitropusside or a cGMP analog 8-br-cGMP caused moderate but significant decreases in both activity and mRNA expression of 11β-HSD2. Importantly, treatment of rats with endotoxin significantly decreased both activity and mRNA expression of 11β-HSD2 in the lung tissue. We conclude that lung inflammation reduces local glucocorticoid breakdown and augments glucocorticoid action in the lung by down-regulating 11β-HSD2 via multiple mechanisms.
In patients receiving hemodialysis, exercise capacity is extremely limited. Although vasodilation is one of the key phenomena for blood perfusion into working skeletal muscles during exercise, it is not clear whether the vasodilator capacity is increased after physical training in this population. We attempted to clarify whether handgrip exercise training increases forearm vasodilator responses to arterial occlusion, and to determine the relationship between muscle contraction function and the vasodilator responses in patients receiving hemodialysis. Eight patients and 7 age-matched healthy controls were tested. The patients participated in handgrip training four times a week for 6 weeks. Before and after the training the maximum muscle strength and endurance were measured with a handgrip dynamometer, and the forearm vasodilator responses to 3-minute arterial occlusion were measured by the near infrared spectroscopy technique. Maximum strength and endurance were significantly lower in the patients than in the controls. Maximum strength (from 183 ± 84 to 228 ± 92 Newtons, p < 0.05) and endurance (from 19 ± 6 to 31 ± 8 sec, p < 0.05) were both increased after the training in the patients. Vasodilator responses estimated by the ratio of the maximum value of oxyhemoglobin after relief of arterial occlusion to its minimum value before the relief were significantly smaller in the patients compared with those in the controls (132 ± 20 vs 161 ± 27%, p < 0.05). In contrast to the findings in muscle function, the decreased vasodilator responses were not improved after the training (141 ± 17%). Additionally, no improvement in the vasodilator responses was observed in the parameters estimated by oxygen saturation. These data suggest that exercise capacity increased by physical training is produced by the functional improvement of skeletal muscles per se, but not by alterations in blood perfusion for oxygenation of the muscles in patients receiving hemodialysis.
Esophageal cancer is the 6th most common cancer in the world, and genetic factors (p53 mutations) in addition to the environmental factors (food, nutrition, smoking, drinking, etc.) are involved in its development. In this study, the association between the both factors, environmental risk factors for esophageal cancer and p53 mutations, in tumor tissues was investigated in 77 patients living in a high-incidence area and 50 patients living in a low-incidence area in Hebei Province, China. Among these patients, p53 mutations were observed in about 50%, without regional differences in the respective frequencies. G : C > A : T (G to A or C to T) transition mutations were the major type of mutations observed in patients in the high-incidence area (19 patients, 50%), whereas G : C > A : T transitions and insertions were observed with equal frequency (8 patients, 33.3%) in the low-incidence area. As for the association with environmental factors, p53 mutations occurred with higher frequency in patients with a daily intake of spicy foods and in those who used unboiled well water in the low-incidence area. Logistic regression analysis showed no association between food intakes and p53 mutations in high- and low-incidence areas. Thus, higher frequency of spicy food intake and use of unboiled well water may be risk factors of esophageal cancer via p53 mutations in China.
Informal care by family members still plays an important role in home care after acute stroke. This study determined the clinical and demographic factors, such as family structure, that predict discharge to home and length of hospital stay (LOS) after acute stroke hospitalization. We reviewed the sex, age, family structure before stroke, type of stroke, size of the lesion, activities of daily living (ADL) function at discharge, discharge destination, and LOS of stroke patients (114 cerebral infarctions and 44 intracerebral hemorrhages) admitted to a neurosurgical hospital. Patients with cerebral infarction were older than those with intracerebral hemorrhage (median 75 vs 66 years). Ninety-eight were discharged to home (62%). In the logistic regression analysis, low ADL function, medium or large infarction, and intracerebral hemorrhage (vs lacunar infarction) were significantly associated with discharge to a destination other than home. Of the patients discharged home, low ADL function was strongly associated with LOS in the multiple regression analysis. In addition, living with a spouse only had the opposite effect on LOS in men and women (p = 0.050 and 0.071, respectively). LOS tended to be shorter for men with a wife, but longer for women with a husband. The structure and gender roles in a stroke patient's household may need further attention for the efficient use of hospital resources.
Uniparental disomy (UPD) is the inheritance of a chromosome pair from one parent and is increasingly recognized as a cause of abnormal phenotypes either due to imprinted genes or, in the case of isodisomy, to homozygosity of recessive alleles. Maternal uniparental disomy for chromosome 14 (matUPD) may cause a characteristic phenotype including precocious puberty. Central precocious puberty (CPP) was diagnosed in a 6-year-old girl with some dysmorphic features, truncal obesity, small hands, and small feet. Cytogenetic analysis of her peripheral blood demonstrated chromosomal rearrangement: Robertsonian translocation 45, XX, der(13;14)(q10;q10). MatUPD(14) was demonstrated in the patient by haplotype analysis of chromosome 14, showing that the CPP is one of the features caused by matUPD(14). The CPP was successfully treated with higher dosage of long-acting gonadotropin releasing hormone (GnRH) analogue, Leuprolide®, 90 μg/kg/month. This is the first report that describes GnRH analogue treatment for CPP associated with matUPD(14), suggesting that the GnRH analogue treatment is appropriate even for such a specific type of CPP.