Detection of amyloid plaques in mouse models of Alzheimer's disease by magnetic resonance imaging.

We performed three-dimensional, high-resolution magnetic resonance imaging (MRI) of fixed mouse brains to determine whether MRI can detect amyloid plaques in transgenic mouse models of Alzheimer's disease. Plaque-like structures in the cortex and hippocampus could be clearly identified in T2-weighted images with an image resolution of 46 microm x 72 microm x 72 microm. The locations of plaques were confirmed in coregistration studies comparing MR images with Congo red-stained histological results. This technique is quantitative, less labor-intensive compared to histology, and is free from artifacts related to sectioning process (deformation and missing tissues). It enabled us to study the distribution of plaques in the entire brain in 3D. The results of this study suggest that this method may be useful for assessing treatment efficacy in mouse models of Alzheimer's disease (AD).     

Pulse-spray pharmacomechanical thrombolysis for proximal deep vein thrombosis.

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and feasibility of pulse-spray pharmacomechanical thrombolysis to treat proximal deep vein thrombosis (DVT) in conjunction with the placement of a non-permanent IVC filter. METHODS: We studied 31 consecutive patients with acute proximal DVT defined as the inferior vena cava (IVC), iliac vein and/or femoral vein, who were diagnosed using duplex ultrasonography and/or contrast venography. All were treated with pulse-spray urokinase. Early success was assessed by comparing the pre- and post-treatment venographic severity score. Non-permanent IVC filters were used to reduce the risk of pulmonary thromboembolism. RESULTS: The average total urokinase dose was 1.71 million IU (range: 0.72-3.6 million IU) and the average duration of therapy was 2.4 days. The average percentage of thrombus lysed was 85% (range: 22-100%). A large thrombus trapped by the filter was detected using cavography before extraction of the filter in one patient. There was no major treatment-related adverse event. CONCLUSION: The combination of pulse-spray pharmacomechanical thrombolysis and the prophylactic use of a non-permanent IVC filter was a safe and effective approach for treating acute proximal DVT.     

Effects of angiotensin II type 1 receptor antagonist on pressor responses to pulsatile compression of the rostral ventrolateral medulla in rats.

The rostral ventrolateral medulla (RVLM) is known to be a major center regulating sympathetic and cardiovascular activities. A possible association between neurovascular compression of the RVLM and essential hypertension has been indicated. The present study was performed to determine the role of angiotensin II (AngII) in the pressor and sympathetic responses to pulsatile compression of the RVLM. To determine the role of glutamate and AngII in the RVLM, L-glutamate (Glu) 2 nmol or AngII 100 pmol was injected into the RVLM with or without RVLM pretreatment of kynurenate (Glu receptor antagonist) 3nmol, candesartan (AngII type 1 (AT1) receptor antagonist) 2 nmol, or PD123319 (AngII type 2 (AT2) receptor antagonist) 1 nmol in anesthetized Wistar rats. In addition, to determine the role of glutamate and AngII in the pressor and sympathetic effects to the RVLM compression, kynurenate, candesartan, or PD123319 was locally injected before pulsatile compression of the RVLM. Finally, to determine the effects of peripherally administered AngII antagonists in these pressor and sympathetic excitatory responses, candesartan 0.25 micromol or PD123319 0.05 micromol was intravenously injected before pulsatile compression of the RVLM. Glu injected into the RVLM significantly increased mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SNA), and these effects were reduced by RVLM pretreatment with kynurenate, but were unaffected by candesartan or PD123319. AngII injected into the RVLM and pulsatile compression of the RVLM also increased MAP and SNA. However, in contrast with Glu injections, these effects were reduced by RVLM pretreatment with candesartan or kynurenate, but were unaffected by PD123319. Pressor and sympathetic excitatory responses to RVLM compression were reduced by intravenous pretreatment with candesartan but not with PD123319. These results indicate that, upon pulsatile compression of the RVLM, AngII may activate RVLM neurons via AT1 receptors and stimulate Glu release to thereby elicit sympathetic activation and pressor effects. Candesartan may exert its hypotensive effect at least in part by affecting the RVLM neurons to reduce sympathetic outflow induced by pulsatile compression of the RVLM.     

Therapeutic Effect of Ansamitocin Targeted to Tumor by a Bispecific Monoclonal Antibody

We have constructed a murine hybrid hybridoma that secretes a bispecific monoclonal antibody (mAb) by fusing a hybridoma secreting an anti-ansamitocins mAb with a hybridoma secreting an anti-human transferrin receptor (TfR) mAb that binds to human A431 epidermoid carcinoma cells. The bispecific mAb, reactive to both ansamitocins and TfR, was purified by a combination of hydrophobic column chromatography and hydroxyapatite high-performance liquid chromatography, and evaluated in in vivo experiments using human tumor cell-implanted nude mice. Ansamitocin P-3 targeted through one of the antigen combining sites of the bispecific mAb was potentially more effective in suppressing the growth of established A431 tumor xenografts implanted on nude mice than unconjugated ansamitocin P-3 or the immunoconjugate of ansamitocin P-3 and monospecific anti-ansamitocins antibody, and the targeted ansamitocin P-3 finally eradicated the tumor mass. The bispecific mAb also played an important role in reducing such undesirable side-effects of ansamitocin P-3 as the loss of body weight, the damage to liver functions and the decrease in the number of white blood cells.     

Spontaneous rupture of the urinary bladder

A case of non-traumatic rupture of the urinary bladder is reported. The patient, a 52-year-old woman, was admitted to our clinic with the chief complaints of dysuria and gross hematuria after hemorrhoidectomy. Ultrasonography and CT scan showed a huge mass in Retzius' cavity. Then, rupture of the bladder was diagnosed through subsequent cystoscopy and cystography. During surgery, we recognized a large defect in the anterior wall of the urinary bladder associated with reddish-yellow fluid in the pelvic cavity. Histological findings showed no malignant change in the bladder. Various factors were suspected to be related to this spontaneous rupture of the urinary bladder.     

Assessment of regional and transmural myocardial perfusion by means of intraoperative myocardial contrast echocardiography during coronary artery bypass grafting.

By using intraoperative myocardial contrast echocardiography, we assessed regional myocardial perfusion and transmural blood flow distribution immediately after myocardial revascularization. A total of 62 revascularized myocardial areas were studied in 31 patients undergoing coronary artery bypass grafting. The revascularized areas were divided into three different areas: S area, supplied by significantly stenosed coronary arteries (43 areas); C area, supplied by coronary collateral situation associated with totally occluded coronary arteries (12 areas); MI area, preexisting transmural myocardial infarction (7 areas). Myocardial contrast echocardiography was obtained by direct injection of 2 ml of sonicated 5% human albumin into the saphenous vein grafts at rest and during atrial pacing. Each area was divided into two layers of endocardial and epicardial halves, and myocardial enhancement of peak intensity was measured for each half and endocardial/epicardial gray level ratio was calculated: (1) The peak intensity of myocardial enhancement in S area and C area was significantly higher than that in MI area at rest as well as during pacing after myocardial revascularization. There was no significant difference in the peak intensity between S area and C area both at rest and during pacing. In S area the peak intensity significantly increased during pacing (p < 0.01), whereas it did not change in C area and MI area. (2) S area demonstrated no significant change in endocardial/epicardial intensity ratio during pacing. In contrast, the ratio in C area significantly decreased during pacing. (3) In S area with preoperative percent increase of segmental wall thickening lower than 25%, there was a significant correlation (r = 0.84, p < 0.001) between the peak intensity of myocardial enhancement and the postoperative changes of percent increase of segmental wall thickening in the revascularized areas. Thus, immediately after myocardial revascularization, intraoperative myocardial contrast echocardiography could provide a quantitative assessment of regional myocardial perfusion as well as blood flow distribution in the areas with myocardial infarction and with coronary collateral situation and in the areas supplied by stenosed coronary arteries.     

Smoking and Obesity in Relation to the Etiology and Disease Progression of Prostate Cancer in Japan

Background:
Various risk factors have been investigated concerning the etiology of prostate carcinoma, but many questions about the significance of the risk factors remain unanswered. To evaluate the relationship between smoking and obesity in prostate cancer, a case-control study was performed.
Methods:
Between 1986 and 1995, 329 patients with untreated prostate cancer and 188 patients with benign prostate hyperplasia (control patients) were evaluated according to their smoking habits and the degree of obesity. Also, the progression of prostate cancer in relationship to smoking and obesity was examined.
Results:
Smoking and obesity were not risk factors for the development of prostate cancer (odds ratio, 0.986, 0.836; 95% confidence interval, 0.69-1.41, 0.57-1.24, respectively). Nor were smoking or obesity a risk factor for survival in stage D2 patients, however, in stage B1-D1 patients, obese men had a tendency for disease progression.
Conclusion:
This study demonstrated that neither smoking nor obesity increase the risk of developing prostate cancer, or the risk of disease progression in prostate cancer patients. However, obese men have a tendency for progression of stage B1-D1 prostate cancer although further studies are necessary to confirm this finding.     

Localized malignant peritoneal mesothelioma containing rhabdoid cells

A case Is presented of localized malignant peritoneal mesothelioma appearing as a liver neoplasm. The patient underwent tumor resection but developed a recurrent growth and died 10 months after the Initial surgery. The primary tumor showed sarcomatous features with rhabdoid cells. Examination revealed the presence of hyaluronic acid, co-Immunoreactivlty for cytokeratln epithelial membrane antigen and vlmentln, cellular contacts with small desmosomes, and intracytoplasmic lumina. These findings supported the mesothelial nature of this tumor. The recurrent tumor was composed of predominantly tubulopaplllary proliferation. It was concluded that the present tumor was a localized malignant mesothelioma of a blphasic type showing a predominantly sarcomatous component in the primary tumor.     

Benign schwannoma of the breast: Report of a case

We report herein the case of a 62-year-old woman who presented to our hospital for investigation of occasional pain in her left breast. Although there was no mass palpable in her left breast, mammography and ultrasonography revealed a round tumor in the upper outer quadrant of the right breast. Although the mammography findings indicated that the tumor was benign, the possibility of a malignant neoplasm could not be ruled out by the ultrasonographic images. A final diagnosis of schwannoma was established by histopathological examination of the excised mass.