Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological analysis.

Esophageal squamous cell cancer (ESCC) is a high-grade carcinoma that is treated with multidisciplinary approaches, including chemoradiotherapy (CRT) followed by surgery. Despite some success with these therapies, overall survival remains poor. In order to investigate a newer CRT regimen, we designed a comparative study to evaluate preoperative CRT using docetaxel (DOC) or 5-Fluorouracil and cisplatin (FU+CDDP [FP] therapy) for treatment of resectable ESCC. In a retrospective review of patients with resectable, locally advanced ESCC, 95 patients received preoperative CRT between 2001 and 2007. CRT was administered using either FP (n = 40) or DOC (n = 55). Pathological response and clinical outcomes were compared between the two groups. Hazard ratios and time-to-event analyses were used to assess outcomes; the ratios were controlled by multivariate logistic regression analysis of potential prognostic factors, and survival was presented with Kaplan-Meier curves. In the FP group, a significant curative effect was observed on the basis of pathological examination of postoperative lesions. However, the DOC group presented a significantly better prognosis on the basis of cumulative survival rates. Logistic regression analysis revealed that the presence of five or more lymph node metastases was an independent predictor of reduced survival. Patients with lymph node metastasis exhibited a better prognosis in the DOC group than those in the FP group. Preoperative CRT for locally advanced esophageal cancer using DOC results in similar or better long-term outcomes compared with FP-based CRT. Therefore, CRT using DOC is a promising therapy option for esophageal cancer.

Serum high-molecular weight adiponectin is related to early postprandial glycemic increases and gastric emptying in patients with type 2 diabetes mellitus.

BACKGROUND: Postprandial hyperglycemia and hyperlipidemia are frequently associated with type 2 diabetes mellitus. The aim of the present study is to investigate the clinical determinants of postprandial glycemia and lipemia, especially serum high-molecular weight adiponectin. METHODS: Twenty-seven diabetic patients treated with diet alone and 13 healthy volunteers took liquid test meal containing 53 g carbohydrate and 47 g lipid, dosed with nonradioactive isotope (13)C-acetate. Venous blood and breath samples were obtained for 180 min after the meal. Gastric emptying was evaluated by peak excretion time of (13)CO(2) in the breath samples. Delayed gastric emptying was defined as peak excretion time > 2.5 h (mean + 2 SD in the healthy volunteers). RESULTS: Diabetic patients showed delayed insulin secretion, postprandial hyperglycemia and hyperlipidemia compared with control. Postprandial glycemic increases significantly correlated with enhanced gastric emptying. Serum high-molecular weight adiponectin correlated with postprandial glycemic increases at 30 and 60 min after meal (r = 0.42, p < 0.05; r = 0.37, p < 0.05, respectively). Serum high-molecular weight adiponectin also correlated with gastric emptying (versus peak excretion time r = - 0.58, p < 0.05). In addition, diabetic patients with delayed gastric emptying showed the suppressed postprandial glycemia with lower serum high-molecular weight adiponectin than those with normal gastric emptying. On the other hand, postprandial increases in serum triglyceride were not related to serum high-molecular weight adiponectin or gastric emptying, but significantly related to liver function test (serum transaminases) and body mass index. CONCLUSIONS: Early postprandial glycemic increases were related to elevated serum high-molecular weight adiponectin, which might be associated with enhanced gastric emptying.

Altered postural regulation of foot skin oxygenation and blood flow in patients with type 2 diabetes mellitus.

AIMS: Although skin oxygenation is an important factor in the development and healing of foot ulcers, its regulation was not fully understood. We studied changes in foot skin oxygenation and blood flow during postural changes in patients with type 2 diabetes mellitus. METHODS: Skin oxygenation was measured using transcutaneous oxygen pressure (TcPO(2)) and skin blood flow by laser Doppler flowmetry in 40 patients with type 2 diabetes mellitus without evidence of peripheral arterial disease and 13 healthy control subjects. RESULTS: TcPO(2) in the supine position was significantly lower in patients with type 2 diabetes mellitus compared with control, although skin blood flow was not different. In the sitting position, TcPO(2) significantly increased in control and diabetic patients. The postural change-related increase in TcPO(2) was significantly enhanced in diabetic patients. On the other hand, skin blood blow significantly decreased in the sitting position from the supine position in control subjects but remained stable in diabetic patients. Orthostatic drop in systolic blood pressure correlated negatively with TcPO(2) in the supine position while correlated positively with %change in TcPO(2) and blood flow by postural changes. CONCLUSIONS: The present study demonstrated the dissociated regulation of skin oxygenation and blood flow in response to leg dependency. Impaired postural vasoconstriction was associated with altered regulation of skin oxygenation probably due to sympathetic vascular dysfunction in diabetic patients.

Crystallization and preliminary X-ray analysis of gamma-glutamyltranspeptidase from Escherichia coli K-12.

gamma-Glutamyltranspeptidase (EC 2.3.2.2) from Escherichia coli K-12 has been purified and crystallized by means of vapor diffusion in hanging drops. Two kinds of crystals on cell dimensions were found for X-ray diffraction analysis, one from ammonium sulfate and the other from polyethylene glycol 6000 as precipitants. The crystals of the orthorhombic form grown in the presence of 15% polyethylene glycol and 20 mM sodium acetate buffer were chosen for further analysis. The crystals belonged to space group P2(1)2(1)2(1), with cell dimensions of a = 128.1, b = 129.9 and c = 79.2 A, and two molecules constitute an asymmetric unit. These crystals diffracted to 2.0 A resolution and were suitable for X-ray crystallographic studies.

The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia.

BACKGROUND: The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS: Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS: Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS: The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.

Magnetic resonance imaging study of the cavum septi pellucidi in patients with schizophrenia.

OBJECTIVE: High-resolution magnetic resonance imaging was used to evaluate the prevalence of the cavum septi pellucidi (CSP) in 79 normal subjects and 86 patients with schizophrenia. METHOD: The CSP was assessed by counting the number of consecutive coronal 1-mm slices containing the CSP. A CSP equal to or greater than 6 mm in length was defined as large. RESULTS: The CSP was found in 74.4% of the patients and 74.7% of the normal subjects, a nonsignificant difference. No difference between groups was found in the prevalence of a large CSP. CONCLUSIONS: The findings support the idea that a small CSP is a normal anatomical variant. More cases of a large CSP are needed to elucidate the implications of this abnormality in schizophrenia.

Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment.

OBJECTIVE: The goal of this study was to evaluate the effects of the addition of tandospirone, a serotonin-1A (5-HT(1A)) agonist, to ongoing treatment with typical antipsychotic drugs, on two cognitive domains that are relevant to functional outcome in patients with schizophrenia. METHOD: Twenty-six patients with schizophrenia who were receiving stable doses of typical antipsychotics were randomly assigned to adjunctive treatment with 30 mg/day of tandospirone or placebo for 6 weeks. Executive function and verbal memory as well as psychopathology were assessed at baseline and after 6 weeks. RESULTS: Both cognitive measures improved significantly in the patients who received tandospirone; subjects who did not receive tandospirone showed no change. There was no significant change in psychopathology ratings in either group. CONCLUSIONS: The results suggest the usefulness of 5-HT(1A) agonists for enhancing some types of cognitive performance and possibly social and work function in patients with schizophrenia.

Subunit association of gamma-glutamyltranspeptidase of Escherichia coli K-12.

gamma-Glutamyltranspeptidase [EC 2.3.2.2] of Escherichia coli K-12 consists of one large subunit and one small subunit, which can be separated from each other by high-performance liquid chromatography. Using ion spray mass spectrometry, the masses of the large and the small subunit were determined to be 39,207 and 20,015, respectively. The large subunit exhibited no gamma-glutamyltranspeptidase activity and the small subunit had little enzymatic activity, but a mixture of the two subunits showed partial recovery of the enzymatic activity. The results of native-polyacrylamide gel electrophoresis suggested that they could partially recombine, and that the recombined dimer exhibited enzymatic activity. The gene of gamma-glutamyltranspeptidase encoded a signal peptide, and the large and small subunits in a single open reading frame in that order. Two kinds of plasmid were constructed encoding the signal peptide and either the large or the small subunit. A gamma-glutamyltranspeptidase-less mutant of E. coli K-12 was transformed with each plasmid or with both of them. The strain harboring the plasmid encoding each subunit produced a small amount of the corresponding subunit protein in the periplasmic space but exhibited no enzymatic activity. The strain transformed with both plasmids together exhibited the enzymatic activity, but its specific activity was approximately 3% of that of a strain harboring a plasmid encoding the intact structural gene. These results indicate that a portion of the separated large and small subunits can be reconstituted in vitro and exhibit the enzymatic activity, and that the expressed large and small subunits independently are able to associate in vivo and be folded into an active structure, though the specific activity of the associated subunits was much lower than that of native enzyme. This suggests that the synthesis of gamma-glutamyltranspeptidase in a single precursor polypeptide and subsequent processing are more effective to construct the intact structure of gamma-glutamyltranspeptidase than the association of the separated large and small subunits.

Neural correlates of memory organization deficits in schizophrenia. A single photon emission computed tomography study with 99mTc-ethyl-cysteinate dimer during a verbal learning task.

Regional cerebral blood flow (rCBF) during a verbal learning task was measured using 99mTc-ethyl-cysteinate dimer and single photon emission computed tomography in 10 patients with schizophrenia and nine normal controls. Verbal repetition was used as a control task. The schizophrenic patients showed failure to spontaneously utilize implicit category information to learn the word lists. In the normal controls, rCBF in the left inferior frontal and left anterior cingulate regions was significantly increased during the verbal learning task, compared with the verbal repetition task. In contrast, there was no significant frontal lobe activation by the verbal learning in the schizophrenic patients. The patients had lower rCBF during the verbal learning task than the controls in the bilateral inferior frontal, left anterior cingulate, right superior frontal, and bilateral middle frontal regions. Activation in the left inferior frontal region was significantly positively correlated with categorical clustering in the task in the controls, but no such correlation was found in the patients. These results indicate that memory organization deficits in schizophrenia may be related to dysfunction in the prefrontal areas, especially in the left inferior frontal region.

Usefulness of blood parameters, especially viscosity, for the diagnosis and elucidation of pathogenic mechanisms of the hand-arm vibration syndrome.

In the present study it was found that, in vibrating-tool operators with Raynaud's phenomenon, whole blood viscosity was significantly higher than in operators without Raynaud's phenomenon at shear rates from 230 to 11.5 s-1. In addition rats were experimentally exposed to local vibration (60 Hz, 5 g) on their hind limbs for 4 h/d for 30 or 90 d. In the case of 30-d exposure, the small arteries in the exposed site did not change. However, after exposure for 90 d, disruption of the internal elastic lamina was observed in the small arteries. The disruption was followed by focal cell proliferation with regenerative formation of collagen and elastic fibers. The fibro-cellular thickening of the intima was further augmented, and, in addition, a complete stenosis of the small lumen of the small artery was observed. Medial thickness did not show significant differences between the control and exposed groups for either exposure duration. The whole blood viscosity was significantly increased by the 90-d but not by the 30-d exposure. These results suggest that there are some relationships between the increase in whole blood viscosity and the intimal thickening of some small arteries in the exposed site.

Statistical parametric mapping in brain single photon computed emission tomography after carbon monoxide intoxication.

The purpose of this retrospective study was to assess regional cerebral blood flow in patients after carbon monoxide intoxication by using brain single photon emission computed tomography and statistical parametric mapping. Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms after carbon monoxide intoxication were studied with brain single photon emission tomography imaging with 99mTc-hexamethyl-propyleneamine oxime. Forty-four control subjects were also studied. We used the adjusted regional cerebral blood flow images in relative flow distribution (normalization of global cerebral blood flow for each subject to 50 ml x 100 g(-1) x min(-1) with proportional scaling) to compare these groups with statistical parametric mapping. Using this technique, significantly decreased regional cerebral blood flow was noted extensively in the bilateral frontal lobes as well as the bilateral insula and a part of the right temporal lobe in the patients with delayed neuropsychiatric sequelae as compared with normal volunteers (P< 0.005). In the patients with no neuropsychiatric symptoms, significantly decreased regional blood flow in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased regional cerebral blood flow in the right frontal lobe and insula in the patients with delayed neuropsychiatric sequelae as compared to those with no neuropsychiatric sequelae. It is concluded that statistical parametric mapping is a useful technique for highlighting differences in regional cerebral blood flow in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced blood flow noted in this investigation supports the contention that the decrease following carbon monoxide intoxication may be prolonged and further worsen in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.

Residual pesticides and their toxicity to freshwater shrimp in the littoral and pelagic zones of Lake Kasumigaura, Japan.

Pesticide residues in water and their toxicity to the freshwater shrimp (Paratya compressa improvisa) were studied in a river mouth in Takahamairi Bay, Lake Kasumigaura, from April to July in 1987. Concentrations of fenthion, diazinon and fenobucarb in water of the littoral zone were lower than that in the pelagic zone. The maximum concentration of fenthion, diazinon, iprobenfos and simetryn in water were 1.9, 0.8, 6.5, and 1.1 micrograms 1(-1), respectively. The 4-day mortality of the freshwater shrimp increased in lake water at Takahamairi Bay, reaching 50% at maximum in May. The mortality was probably due to residual insectside fenthion.

[Peripheral circulatory responses to sustained handgrip in workers using vibrating tools].

In order to study the effects of static force such as a handgrip in detail, the peripheral circulatory function and the autonomic nervous function of workers who used chain-saws were examined in a handgrip test at 30% of maximum voluntary contraction (30% MVC). Workers using chain-saws were divided into three groups: group A without any symptoms, group B with numbness and/or pain but without Raynaud's phenomenon and group C with Raynaud's phenomenon. The results obtained were as follows: 1. The finger blood flow (FBF) of all groups significantly decreased during the handgrip and significantly increased after the end of the handgrip as compared with the initial value. There was a tendency for the FBF decrease of group C to be less than that of group A. 2. The mean value of both maximum FBF decrease and maximum FBF increase during handgrip tests fell in alphabetical order (A, B, C). The maximum FBF increase of group C was significantly less than that of group A. 3. The finger skin temperature (FST) of each group significantly fell during the handgrip but there was no significant difference among the three groups. FST returned to the level of the initial value one minute after the end of the handgrip, and significantly rose two minutes and three minutes after the end of the handgrip as compared with the initial value. 4. Both the systolic blood pressure and the diastolic blood pressure of all groups significantly rose during the handgrip but there was no significant difference among the three groups. Concerning the maximum rise of diastolic blood pressure, which is an indicator of autonomic nervous function, there was no significant difference among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of whole-body vibration exposure on DOPAC and VIP-like immunoreactivity in the rat brain].

In order to clarify the involvement of cerebral 3,4-dihydroxyphenylacetic acid (DOPAC) and vasoactive intestinal polypeptide (VIP) in whole-body vibration stress, DOPAC and VIP-like immunoreactivity (VIP-LI) in various discrete brain regions of rats exposed to whole-body vibration (4G, 20 Hz, 90 min) were assayed. The results showed that the whole-body vibration increased the DOPAC level in the frontal cortex and nucleus accumbens, but did not induce a concurrent change of VIP-LI in these regions. VIP-LI was significantly increased in the amygdala, and decreased in the hippocampus, accompanied by no significant change of DOPAC. These results show that whole-body vibration affects cerebral VIP neuron systems in addition to its nonspecific action, i.e. the activation of mesofrontal and mesoaccumbens dopamine neuron systems. It is assumed that the amygdalofugal VIP neuronal system is involved in the regulation of hypothalamic and pituitary hormone secretions, and that VIP in the hippocampus plays a part in modulating the blood circulation in the cortex in whole-body vibration stress.

[Thyroid scintigraphy in patients with thyroid tumors using 99mTc-hexakis 2-methoxy isobutyl isonitrile].

Early and delayed thyroid scintigraphy with 99mTc-hexakis 2-methoxy isobutyl isonitrile (99mTc-MIBI) was performed in 18 patients with thyroid tumor, including 8 with papillary carcinoma, 1 each with follicular carcinoma, anaplastic carcinoma, and malignant lymphoma, and 7 with thyroid adenoma. Scintigrams obtained were compared with those taken with other radionuclides. In all 11 patients with malignant tumors, increased 99mTc-MIBI uptake was noted in the tumors on early images, although anaplastic carcinoma and malignant lymphoma had mild uptake. On delayed images, 99mTc-MIBI washout was noted in 45.4% (5/11). In one patient with extensive cervical lymph node metastasis, 99mTc-MIBI concentration was evident in the metastatic foci. In the 4 where, the thyroid adenoma consisted mainly of cystic degeneration, a focal defect was noted, but two of the three patients whose thyroid adenoma consisted mainly of a solid component had an intense tracer uptake in the tumors on early and delayed images. In conclusion, there were increased 99mTc-MIBI accumulations in all of the 14 solid thyroid tumors. The quality of 99mTc-MIBI scintigraphic images of thyroid tumors was equal or slightly superior to that taken with 201Tl scintigraphy. 99mTc-MIBI thyroid scintigraphy may be useful in detecting a solid thyroid tumor and its metastasis, although it cannot be used to differentiate between benign and malignant tumors.

[Experimental studies on the development of acute gastric lesions induced by vibration stress in rats and its pathogenetic mechanisms].

To clarify the pathogenetic mechanisms in acute gastric lesions induced by vibration (VIB), the effects of VIB (3.0 G, 10 Hz, 90 min) on changes in gastric mucosal blood flow (GMBF), plasma corticosterone (COR) and catecholamines (CA) as well as ulcer formation were compared with those of forced water immersion stress (FWI). While the VIB increased the GMBF during the exposure, the FWI decreased it during and after the stress. No difference in the severity of ulcer formation between the VIB groups was seen. Although both VIB and FWI increased the COR and CA, the degree of increased in the COR by the VIB tended to be less than that by the FWI. The truncal vagotomy inhibited the reduction of the GMBF and ulcer formation by the FWI, but promoted the reduction of the GMBF by the VIB. These results suggest that ulceration induced by VIB is caused primarily by its direct, mechanical and specific actions and not through the central nerve system.