Antiactin-targeted immunoliposomes ameliorate tissue plasminogen activator-induced hemorrhage after focal embolic stroke.

Thrombolytic stroke therapy with tissue plasminogen activator (tPA) is limited by serious risks of intracerebral hemorrhage. In this study, the authors show that a novel antiactin-targeted immunoliposome significantly reduced tPA-induced hemorrhage in an established rat model of embolic focal stroke. Spontaneously hypertensive rats were subjected to focal ischemia using homologous blood clot emboli. Delayed administration of tPA (10 mg/kg, 6 hours after ischemia) induced intracerebral hemorrhage at 24 hours. In control rats treated with tPA plus vehicle, hemorrhage volumes were 9.0 +/- 2.4 uL (n = 7). In rats treated with tPA plus antiactin immunoliposomes, hemorrhage volumes were significantly reduced to 4.8 +/- 2.7 uL (n = 8, P < 0.05). No significant effects were seen when rats were treated with tPA plus a nontargeted liposome (7.8 +/- 2.1 uL, n = 9). Fluorescent immunohistochemistry showed that rhodamine-labeled targeted liposomes colocalized with vascular structures in ischemic brain that stained positive for endothelial barrier antigen, a marker of cerebral endothelial cells. These data suggest that immunoliposomes may ameliorate vascular membrane damage and reduce hemorrhagic transformation after thrombolytic therapy in cerebral ischemia.     

Biological markers for Alzheimer disease]

The development of diagnostic markers for earlier and more reliable diagnosis of Alzheimer disease (AD) is essential, particularly because therapeutic medication is available for AD. Cerebrospinal fluid (CSF) is a useful source of diagnostic information. Previously we found the increase of total tau protein in CSF in normal pressure hydrocephalus patients, and others reported the increase also in corticobasal degeneration and frontotemporal dementia. To differentiate the AD from other diseases, further approach was employed and oxidized protein in CSF was investigated. Heat stable fractions of CSF were analyzed on the content of carbonyl residues, which are derivatives of protein oxidization. The result suggests that protein oxidation is highly involved in AD and that this method might be useful to differentiate AD from other neurological disease.     

Infarct prediction and treatment assessment with MRI-based algorithms in experimental stroke models.

There is increasing interest in using algorithms combining multiple magnetic resonance imaging (MRI) modalities to predict tissue infarction in acute human stroke. We developed and tested a voxel-based generalized linear model (GLM) algorithm to predict tissue infarction in an animal stroke model in order to directly compare predicted outcome with the tissue's histologic outcome, and to evaluate the potential for assessing therapeutic efficacy using these multiparametric algorithms. With acute MRI acquired after unilateral embolic stroke in rats (n=8), a GLM was developed and used to predict infarction on a voxel-wise basis for saline (n=6) and recombinant tissue plasminogen activator (rt-PA) treatment (n=7) arms of a trial of delayed thrombolytic therapy in rats. Pretreatment predicted outcome compared with post-treatment histology was highly accurate in saline-treated rats (0.92+/-0.05). Accuracy was significantly reduced (P=0.04) in rt-PA-treated animals (0.86+/-0.08), although no significant difference was detected when comparing histologic lesion volumes. Animals that reperfused had significantly lower (P<0.01) GLM-predicted infarction risk (0.73+/-0.03) than nonreperfused animals (0.81+/-0.05), possibly reflecting less severe initial ischemic injury and therefore tissue likely more amenable to therapy. Our results show that acute MRI-based algorithms can predict tissue infarction with high accuracy in animals not receiving thrombolytic therapy. Furthermore, alterations in disease progression due to treatment were more sensitively monitored with our voxel-based analysis techniques than with volumetric approaches. Our study shows that predictive algorithms are promising metrics for diagnosis, prognosis and therapeutic evaluation after acute stroke that can translate readily from preclinical to clinical settings.     

Osteosarcoma of the proximal fibula. An analysis of 13 cases in the northern Japan

Osteosarcoma is the most common form of malignant bone tumor that occurs during childhood and adolescence. The proximal fibula is a relatively rare site for osteosarcoma. We reviewed 305 cases of osteosarcoma registered at the Tohoku Musculoskeletal Tumor Society (TMTS) between 1975 and 1999. Thirteen patients (4.3%) had their osteosarcomas localized in the proximal fibula. Conventional fibroblastic osteosarcoma accounted for 46% of the cases in this series. Limb-sparing surgery was performed in all 13 patients during initial surgery, and the peroneal nerve was preserved in 4 cases. These 4 cases developed local recurrences, but additional wide excision or radiation had a beneficial effect on the recurrences. In our series, the patients showed a 5-year survival rate 76 per cent. The postoperative function of the knee remained good despite various reattachment procedures of lateral co-lateral ligament. As well as resection of the proximal fibula, our results indicate that osteosarcoma of the proximal fibula has a good prognosis for cases who undergo adequate initial surgery.     

Biomedical knowledge navigation by literature clustering

There is an urgent need for a system that facilitates surveys by biomedical researchers and the subsequent formulation of hypotheses based on the knowledge stored in literature. One approach is to cluster papers discussing a topic of interest and reveal its sub-topics that allow researchers to acquire an overview of the topic. We developed such a system called McSyBi. It accepts a set of citation data retrieved with PubMed and hierarchically and non-hierarchically clusters them based on the titles and the abstracts using statistical and natural language processing methods. A novel point is that McSyBi allows its users to change the clustering by entering a MeSH term or UMLS Semantic Type, and therefore they can see a set of citation data from multiple aspects. We evaluated McSyBi quantitatively and qualitatively: clustering of 27 sets of citation data (40643 different papers) and scrutiny of several resultant clusters. While non-hierarchical clustering provides us with an overview of the target topic, hierarchical clustering allows us to see more details and relationships among citation data. McSyBi is freely available at http://textlens.hgc.jp/McSyBi/.     

Intra-articular synovial lipoma of the knee joint (located in the lateral recess): a case report and review of the literature

This report describes a rare intra-articular synovial lipoma of the knee joint which developed in a 66-year-old female. The patient suffered from sudden knee pain and a catching or slight interruption of normal motion of the left knee and then noticed the tumor. The tumor was located in the lateral recess of the knee joint and showed a signal intensity similar to subcutaneous fat on T1 and T2()-weighted magnetic resonance images. The arthroscopy revealed a smooth, globular, yellowish, encapsulated tumor extending into the lateral recess from the surface of the lateral condyle and the tumor was totally excised under arthroscopic guidance. Histologic examination of the specimen revealed a tumor composed of mature adipose cells covered by a thin fibrous layer of varying thickness and normal synovial lining cells. The diagnosis was intra-articular synovial lipoma. Intra-articular synovial lipomas should be distinguished from other similar lipomatoid conditions such as Hoffa disease and villous lipomatous proliferation of the synovial membrane (lipoma arborescens). Intra-articular synovial lipoma should be considered in the differential diagnoses when examining a patient with sudden knee pain, and a catching or locking knee.     

Mild hypothermia prolongs the survival time during uncontrolled hemorrhagic shock in rats

OBJECTIVE: To test our hypothesis that during lethal uncontrolled hemorrhagic shock (UHS) in rats, mild hypothermia of either 36 or 34 degrees C would prolong the survival time in comparison with normotherma of 38 degrees C. METHODS: Twenty-four rats were lightly anesthetized with halothane and maintained spontaneous breathing. UHS was induced by blood withdrawal of 2.5 ml/100 g over 15 min, followed by 75% tail amputation. Immediately after the tail cut, the rats were randomly divided into three groups (eight rats for each); normothermic Group 1 (control, rectal temperature 38 degrees C), and mild hypothermic Groups 2 (36 degrees C) and 3 (34 degrees C). Hypothermia was induced and maintained by body surface cooling. The rats were then observed without fluid resuscitation until their death (apnea and no pulse) or for a period of 240 min maximum. RESULTS: The rectal temperature was cooled down to 36 and 34 degrees C in 5 and 10 min, respectively. The mean survival time, which was 76+/-26 min in the control group (38 degrees C), was nearly doubled by mild hypothermia, 178+/-65 min for Group 2 (36 degrees C) (P<0.01 vs. control) and 144+/-54 min for Group 3 (34 degrees C) (P<0.05 vs. control) (no significant difference between Group 2 and 3). Additional blood losses from tail stumps were not significantly different among the three groups. CONCLUSION: Mild hypothermia of either 36 or 34 degrees C prolongs the survival time during lethal UHS in rats.     

Recovery from a psychotropic drug overdose tends to depend on the time from ingestion to arrival, the Glasgow Coma Scale, and a sign of circulatory insufficiency on arrival

Purpose

The aim of this study was to investigate which factors on arrival correlate with the duration of unconsciousness induced by a psychotropic drug overdose.

Basic Procedure

Patients were 175 consecutive intubated patients unconscious due to psychotropic drug overdose. They were divided into 2 groups, an “early” group in which the patients were extubated within 2 days from hospitalization, and a “delayed” group who were not extubated within 2 days.

Main Findings

Glasgow Coma Scale (P = .001) scores in the early group were higher than those in the delayed group. The estimated time from ingestion to admission (P < .0001), creatine kinase level (P < .01), number of cases demonstrating shock (P < .05), shock index (P < .0001), and heart rate (P = .001) in the early group were smaller than those in the delayed group. Two subjects in the delayed group died of pneumonia and pulmonary embolism.

Principal Conclusions

Delayed arrival from ingestion, a low level of unconsciousness, and a sign of circulatory insufficiency in a patient with a psychotropic drug overdose were risk factors of a delayed recovery and death.     

Three‐dimensional structure of seminiferous tubules in the adult mouse

Seminiferous tubules develop from sex cords, which are embryonic structures with simple C‐shaped arches. Histologically, the epithelium of adult mouse seminiferous tubules has been divided into 12 stages based on the associations of spermatogenic cells in four cycles of spermatogenesis. However, the gross characteristics of the seminiferous tubules themselves, including their number, length, run, and mutual relationships remain largely unknown. In the present study, we analyzed all seminiferous tubules in a single adult mouse testis with high resolution using serial paraffin sections and high‐perfomance three‐dimensional reconstruction software. There were 11 seminiferous tubules with an average length of 140 mm. Each tubule ran along circular paths within the testis while making convolutions with cranial and caudal hairpin turns. The cranial turns of all tubules were in contact with the tunica albuginea, whereas the caudal turns were not, resulting in funnel‐shaped networks of these tubules with tapered caudal portions. The caudally located networks surrounded the preceding cranially located networks from the bottom and outside, similar to stacked paper cups. Five out of the 11 seminiferous tubules were continuous from one end to the other both connected with the rete testis (10 connection points). Nine branching points, one blind end, and 18 more connection points with the rete testis were detected in the remaining six seminiferous tubules, making the paths of these tubules complicated to various degrees. The present study revealed that the 3D structures of seminiferous tubules were highly regular as a whole in the adult mouse testis.