Diet restriction impairs extracellular signal-regulated kinase activation of peritoneal exudative cells after N-formyl-methionyl-leucyl-phenylalanine stimulation in a murine peritonitis model

BACKGROUND: Phosphorylation of extracellular signal-regulated kinase (ERK) enhances various inflammatory responses in immune cells. It is unknown whether dysfunction of immune cells during malnutrition is attributed to derangement of ERK activation. METHODS: Male Institute of Cancer Research (ICR) mice received chow (146 g/kg per day, ad libitum or 36.5 g/kg per day, diet-restricted) for 7 days. Mice (n = 55) were given 6.5 mg/kg of an ERK inhibitor (PD98059) or vehicle intraperitoneally (IP), at 2 hours before cecal ligation and puncture (CLP). Survival was observed up to 60 hours. Detection of phosphorylated ERK (pERK) in the peritoneal exudative cells (PECs) was done as follows. In a separate study, PECs were harvested by peritoneal lavage 2 hours after an IP injection of 1% glycogen. PECs were incubated with or without 100 nmol/L N-formyl-methionyl-leucyl-phenylalanine (fMLP) for 1 minute. PEC ERK activation was detected with Western blot analysis (n = 38), by densitometric quantification, and with a laser scanning cytometer (LSC; n = 13). Subpopulations of PECs were determined by Wright-Giemsa staining. Unstimulated pERK expression was normalized to 100% for Western blot analysis. RESULTS: Diet restriction reduced survival after CLP compared with the ad libitum mice. ERK inhibition showed no effect on survival in diet-restricted mice but reduced survival in ad libitum mice. There were no differences in subpopulations of PECs 2 hours after glycogen injection between the groups. Western blot analysis revealed that fMLP stimulation significantly increased the phosphorylation of ERK1/2 in PECs from the ad libitum group (ERK1, 199 +/- 41%; ERK2, 211 +/- 49%; p < .03) but not in those from diet-restricted mice (ERK1, 98 +/- 10%; ERK2, 91 +/- 9%). Mean fluorescence intensity (MFI) of pERK in PECs obtained by LSC was significantly elevated after fMLP in the ad libitum group (from 19.4 +/- 1.5 MFI to 22.4 +/- 1.2 MFI; p < .05) but did not change in the diet-restricted group (from 19.4 +/- 1.8 MFI to 19.1 +/- 1.5 MFI). CONCLUSIONS: ERK activation is essential for survival in this murine sepsis model. Impaired ERK activation of PECs may, at least in part, impair host defense during malnutrition.     

Multi-center study for the evaluation of clinical usefulness of attenuation and scatter correction on 201Tl myocardial SPECT

The aim of this study was to evaluate the clinical usefulness of attenuation and scatter correction (AC, SC) on a 201Tl myocardial single-photon emission computed tomography (201Tl SPECT) as a multi-center trial. With a dual-detecter and a triple-detector SPECT systems with a 99mTc transmission source, simultaneous transmission/emission tomography (TCT/ECT) was performed on 38 patients with angiographically coronary heart disease (CHD) and 26 patients without evidence of CHD. Stress and delayed attenuation and scatter corrected images (SAC) and uncorrected images (NC) were reconstructed. On NC images of normal cases, influence of attenuation was greater in male than female. In comparison of 201Tl distribution between male and female, significant decrease in 201Tl activity was observed in the inferoposterior wall in male and that was observed in the anterobasal wall of the left myocardium in female. Such a difference in 201Tl distribution between male and female disappeared on SAC images. On the diagnostic performance for the identification of CHD, SAC images demonstrated improved specificity and accuracy values in the right coronary arterial territory (RCA) with visual analysis statistically. Sensitivity value in the RCA was also improved, but it was not statistically significant. Sensitivity value in the left circumflex arterial territory (LCX) increased without decrease in specificity value on SAC images. In the left anterior descending arterial territory (LAD), sensitivity value increased on SAC images. Although specificity value decreased on SAC images in LAD territory, it was not statistically significant. The difference in 201Tl distribution between male and female is improved in normal cases by attenuation and scatter correction on 201Tl myocardial SPECT. Diagnostic performance of CHD is also improved by attenuation and scatter correction, especially in territories of which specificity in assessing the absence of disease have been suboptimal. In conclusion, attenuation and scatter correction on 201Tl myocardial SPECT is considered to be clinically useful.     

Evaluation of 18F-FDG PET in acute ischemic stroke: assessment of hyper accumulation around the lesion

PURPOSE: Although pathophysiology of cerebrovascular disease has been reported previously, few clinical studies of glucose metabolism in acute stroke have been published. Purpose of this study is to evaluate glucose metabolism in acute stroke patients by 18F-FDG PET. SUBJECTS AND METHODS: Twenty-four patients with acute ischemic stroke were involved in this study. All subjects underwent MRI (conventional T1- and T2-weighted images, diffusion-weighted imaging, and MR angiography), CT and 18F-FDG PET. 18F-FDG PET was performed within 1 to 7 days after the first episode. 18F-FDG PET images were visually evaluated as well as MRI and CT images. RESULTS: Four patients out of 24 showed no abnormal 18F-FDG accumulation, while MRI demonstrated abnormal signal area and abnormal vascular findings that suggested acute stroke. Decreased 18F-FDG accumulation corresponding with abnormal signal area on MR images was noted in 20 cases. In 7 cases among these 20 with decreased 18F-FDG, hyper accumulation of 18F-FDG was recognized around the decreased accumulation area. CONCLUSION: Increased 18F-FDG accumulation (increased glucose metabolization) around the lesion may be due to: 1) acceleration of anaerobic glycolysis, 2) activated repair process of damaged brain tissue, i.e., phagocytosis and gliosis, and 3) neuronal excitation by excito-toxic amino acids which can be released after ischemia.     

Oxidized low-density lipoprotein associates strongly with carboxy-terminal domain of tissue factor pathway inhibitor and reduces the catalytic activity of the protein

Tissue factor pathway inhibitor (TFPI) is a physiological protease inhibitor of the extrinsic blood coagulation pathway. Previously we have shown that TFPI associates quite rapidly with oxidized low-density lipoprotein (ox-LDL), with a reduction of the inhibitory activity on factor X activation. In the present study, it was found, by means of agarose gel electrophoresis, that the pre-incubation of full-length rTFPI with heparin or the carboxy (C)-terminal part (peptide 240-265) of TFPI prevented the association with ox-LDL in a dose-dependent manner. When rTFPI lacking the C-terminal basic part of the molecule (rTFPI-C) was mixed with ox-LDL, only a small amount of rTFPI-C was shifted to the position of ox-LDL on electrophoresis. Further, ox-LDL did not reduce the activity of rTFPI-C. These results indicate that the C-terminal domain of TFPI molecule plays a predominant role in the binding to ox-LDL and the binding through the C-terminal part is essential for the ox-LDL-dependent reduction of the anticoagulant activity of TFPI.     

Late onset ataxia phenotype in dentatorubro-pallidoluysian atrophy (DRPLA)

We clinically and genetically studied three patients in a family with dentatorubro-pallidoluysian atrophy (DRPLA). The proband patient had 58/24 CAG repeat alleles of the DRPLA gene (normal ≤ 34 repeats). Cerebellar ataxia first developed in the 6–7^th decades and was the predominant feature for more than 10 years in all three, after which two of them manifested dementia and choreiform movements in the advanced stage. Atrophy of the cerebellum and brain stem an CT or MRI had suggested dominant spinocerebellar ataxia as a diagnosis in their ataxia-predominant stage, with a diagnosis of DRPLA being impossible based on the clinical findings alone. Our experience implies that DRPLA must be taken into account in the differential diagnosis of late onset ataxic disorders, since it can easily be overlooked. Received: 2 April 2001, Received in revised form: 23 July 2001, Accepted: 21 August 2001     

Clinical manifestations of 25 patients with prostatic-type polyps in the prostatic urethra

To clarify the clinical manifestations of prostatic-type polyps (PP) in the prostatic urethra, a sample of 25 patients with PP who presented themselves to our hospital with hematuria or hematospermia was reviewed with respect to their symptoms and endoscopic findings. Recurrence of the conditions was also investigated. The patients were 26 to 68 years old, with a mean age of 48.5 years. Sixteen patients (64%) had hematuria and 8 (32%) had hematospermia. A bloody urethral discharge was observed in 6 patients (24%). Analysis of the character of the hematuria showed that total hematuria occurred in 44% of the patients. In 38% of the patients with hematospermia there was the additional symptom of post-ejaculatory hematuria. PP developed beside the verumontanum in 18 patients (72%), on the posterior urethral wall lateral to the verumontanum in 4 patients (16%), and on the verumontanum in 7 patients (28%). The prognosis could be investigated only in 22 (88%) of the 25 patients. Two patients (9%) experienced reccurrence during the follow-up period (1 to 5.8 years, mean: 3.7 years). Consequently, special attention should be paid to the possibility of PP in the prostatic urethra, particularly the verumontanum and nearby area, during endoscopic examination, when diagnosing patients with hematuria, hematospermia or with bloody urethral discharge.     

Sequential changes of various parameters of arterial blood samples

BACKGROUND: Since the values of various parameters in arterial blood samples changes with time, they should be measured without delay. There are some situations, however, where it is quite difficult to carry out the measurement immediately. In this study, we aim to obtain a series of parameters by which we can estimate true values from stale blood samples. METHODS: Arterial blood gases (PaCO2, PaO2, pH), electrolytes, blood sugar and lactate were measured at 0 min, 30 min, 60 min after collecting the samples. Cytometry was done at 0 min. We calculated proton ion concentration ([H+]) and oxygen content (CaO2). Relationships between the change of various parameters in arterial blood samples and the numbers of red blood cell (RBC), white blood cell (WBC) and platelet were analyzed using multiple regression analysis. RESULT: The values of PaCO2, lactate and [H+] increased, and those of PaO2, blood sugar and CaO2 decreased with time. Electrolytes changed little. There were significant relationships between the number of RBC and the change of blood sugar, and between the number of WBC and the change of CaO2 value. CONCLUSION: From these result, we found a series of expression by which we can estimate appropriate values from stale blood samples.     

Cavernous hemangioma in the anterior mediastinum; report of a case

A rare case of mediastinal hemangioma was reported in this article. A 63 years old male was pointed out an abnormal shadow in the chest CT scan though he had no symptoms. It showed a well-defined round mass with low density in the anterior mediastinum. MRI (T2 weight) showed the lesion as a high intensity tumor. We diagnosed it thymoma and planned the surgical treatment. The tumor was resected completely through median partial sternotomy. The tumor was 2 cm in diameter. Histological examination revealed it cavernous hemangioma, and neither coagulations nor phleboliths were identified in vessels of the tumor.     

WHO classification in thymoma

WHO classification of thymic epithelial tumors have been shown to reflect their oncological behaviors, and type A, AB and B1 tumors have better prognosis than type B2 and B3 tumors, suggesting the significance of this classification in the clinical practice of thymomas. Type B tumors are more invasive than type A and AB tumors. Type B1 and B2 tumors are frequently associated with myasthenia gravis while type A and AB tumors are not. The findings of computed tomography (CT) imaging revealed that type A and AB tumors tend to be round and have the smooth surface while type B1, B2 and B3 tumors are often flat and have irregular surface. Type AB, B1 and B2 tumors possess a significant number of CD4+CD8+ double positive T cells in the tumor. These observations are supposed to be useful for preoperative evaluation of WHO classification of thymomas, and to help the clinicians decide application of preoperative therapy and the method of surgical resection including endoscopic surgery.     

Evaluation of the management of blunt renal trauma and indication for surgery

OBJECTIVES: Appropriate management of renal trauma is still controversial. Many of the patients have minor injuries and conservative treatment can achieve excellent outcomes without any complications. For major injuries of deep lacerations or ruptures, we have been performing early surgical treatment to salvage the kidney in the selected cases after the precise evaluation of the injury. To obtain the optimal management options, we evaluated the clinical results of our procedures. PATIENTS AND METHODS: We conducted a retrospective study, which included 106 cases of blunt renal trauma with evident etiology over the past 22 years and 9 months. The severity of the injury was evaluated mainly by CT scanning. The indication of renal exploration included persistent renal bleeding, large hematoma around the kidney, dislocated fragments, nonviable tissue, massive urinary extravasation and vascular injury. With the patients who required an operation, we first controlled the bleeding by clamping the hilar vessels. Then, the final decision whether to repair or remove the kidney was made based on the direct inspection of the injured kidney after the complete removal of the hematoma. The severity of renal trauma was classified by the classifications found in The Organ Injury Committee of the American Association for the Surgery of Trauma. RESULTS: Sixty-three patients were managed conservatively without any interventions, while 22 surgical repairs and 21 nephrectomies were performed. Of the 63 patients, 35 patients (81.4%) were operated on within 2 days after the injury. Judging from systolic blood pressure, red cell count, blood loss during surgery and transfusion requirements, surgically treated patients were more severely injured than conservatively treated patients. And nephrectomized patients than surgically repaired patients. All the surgically repaired cases were confirmed to have preserved renal functions postoperatively. In all of the 50 patients with Grade I injuries, conservative treatment was successful. Eight out of the 19 Grade II and III cases, who were indicated for kidney exploration because of multiple lacerations or considerable bleeding, were also successfully repaired. Localized hematoma with no urine leakage, even when it was large, settled spontaneously without complication. For the 37 Grade IV and V injuries, including 4 cases with hilar injuries, we implemented conservative procedures on 2 patients, surgical repair on 14 patients and nephrectomy on 21 patients. In the conservatively treated cases, one deep laceration with relatively large, but localized, hematoma, and minimal urine extravasation healed spontaneously. Atrophy of the segment and hypertension developed in the other ruptured kidney with dislocated fragments, large hematoma and urine leakage. This kidney, which also required later surgical exploration, did have good parenchymal blood flow. Hilar injury cases were all resulted in nephrectomy. CONCLUSION: In most of our cases the indication for surgical exploration or nephrectomy based on our criteria seemed to be properly decided. Several cases, though, might have received overtreatment. Recent advances in evaluations and strategies of renal trauma have decreased the need for surgical exploration. This may have overreached the indication for conservative management. Severely injured kidneys may be managed conservatively because in most cases bleeding settles after the full formation of large hematoma within the Gerota's fascia. In such cases, though, no one can predict whether the injury will heal spontaneously or not, and, moreover, whether a complication will develop or not. We think that the optimal management of the patient requires an accurate evaluation of the injured kidney. Therefore the indication for surgical exploration should be made based on the degree of the injury.