Early CT signs in patients with acute middle cerebral artery occlusion: incidence of contrast staining and haemorrhagic transformations after intra-arterial reperfusion therapy.

AIM: To investigate how often early computed tomography (CT) signs are associated with blood-brain barrier (BBB) disruption and result in haemorrhagic transformations. MATERIALS AND METHODS: Serial CT findings were prospectively evaluated in 61 patients with acute middle cerebral artery (MCA) occlusion who underwent initial CT examination within 3h of stroke onset and who were treated with intra-arterial reperfusion therapy within 6h of stroke onset. Obscuration of the margin of the lentiform nucleus and loss of the insular ribbon were evaluated as early CT signs in the deep MCA territories. Cortical effacement was also evaluated. BBB disruption was defined as contrast medium staining in post-therapeutic CT just after reperfusion therapy. The relationship between pre-therapeutic early CT signs and post-therapeutic contrast staining or haemorrhagic transformations was investigated. RESULTS: The frequency of early CT signs in the deep MCA territories was significantly higher than that of cortical effacement (68.9 versus 27.9%). There were significant correlations between pre-therapeutic early CT signs and post-therapeutic contrast staining in both the deep and superficial MCA territories. Compared with early CT signs in the deep MCA territories, cortical effacement had a significantly higher incidence of post-therapeutic contrast staining (54.8 versus 82.4%). Although not statistically significant, cortical effacement tended to develop into haemorrhagic transformations. There was no correlation between early CT signs in the deep MCA territories and haemorrhagic transformations. CONCLUSION: Cortical effacement may be an advanced CT sign with BBB disruption and potential risk for haemorrhagic transformations. The presence of early CT signs in the deep MCA territories may not be a contraindication of reperfusion therapy.

Tenascin-C regulates proliferation and migration of cultured astrocytes in a scratch wound assay.

Tenascin-C (TNC), an extracellular matrix glycoprotein, is involved in tissue morphogenesis like embryogenesis, wound healing or tumorigenesis. Astrocytes are known to play major roles in wound healing in the CNS. To elucidate the roles of TNC in wound closure by astrocytes, we have examined the morphological changes of cultured astrocytes in a scratch wound assay and measured the content of soluble TNC released into the medium. We have also localized the expression of TNC mRNA, TNC, glial fibrillary acidic protein (GFAP), vimentin and integrin beta1. After wounding, glial cells rapidly released the largest TNC isoform and proliferated in the border zones. Subsequently, they became polarized with unidirectional processes and finally migrated toward the denuded area. The proliferating border zone cells and pre-migratory cells intensely expressed TNC mRNA, TNC-, vimentin-, GFAP- and integrin beta1-like immunoreactivity, while the migratory cells showed generally reduced expression except the front. Exogenous TNC enhanced cell proliferation and migration, while functional blocking with anti-TNC or anti-integrin beta1 antibody reduced both of them. These results suggest that mechanical injury induces boundary astrocytes to produce and release TNC that promotes cell proliferation and migration via integrin beta1 in an autocrine/paracrine fashion.

Spontaneous regeneration of the corticospinal tract after transection in young rats: a key role of reactive astrocytes in making favorable and unfavorable conditions for regeneration.

We demonstrated the occurrence of marked regeneration of the corticospinal tract (CST) after a single transection and failure of regeneration after a repeated transection in young rats. To provide convincing evidence for the complete transection and regeneration we used retrograde neuronal double labeling. Double-labeled neurons that took up the first tracer from the transection site and the second tracer from the injection site caudal to the transection site were observed in the sensorimotor cortex. The anterograde tracing method revealed various patterns of regeneration. In the most successful cases the vast majority of regenerated fibers descended in the normal tract and terminated normally whereas a trace amount of fibers coursed aberrantly. In the less successful cases fibers descended partly normally and partly aberrantly or totally aberrantly. To clarify the role of astrocytes in determining the success or failure of regeneration we compared expression of glial fibrillary acidic protein (GFAP), vimentin and neurofilament (NF) immunoreactivity (IR) in the lesion between single and repeated transections. In either transection, astrocytes disappeared from the CST near the lesion site as early as 3 h after lesioning. However, by 24 h after a single transection, immature astrocytes coexpressing GFAP- and vimentin-IR appeared in the former astrocyte-free area and NF-positive axons crossed the lesion. By contrast, after a repeated transection the astrocyte-free area spread and NF-positive axons never crossed the lesion. It appears likely that the major sign, and possibly cause of failure of regeneration is the prolonged disappearance of astrocytes in the lesioned tract area.

Parenchymal hyperdensity on computed tomography after intra-arterial reperfusion therapy for acute middle cerebral artery occlusion: incidence and clinical significance.

BACKGROUND AND PURPOSE: The purpose of the present study was to assess the incidence and clinical significance of the intraparenchymal hyperdense areas on the posttherapeutic CT scan just after intra-arterial reperfusion therapy. METHODS: Seventy-seven patients with acute middle cerebral artery occlusion were studied prospectively with post-therapeutic CT. Hyperdense areas were classified into three groups: those in the lentiform nucleus, insular cortex and cerebral cortex. We investigated the incidence of hyperdense areas and hemorrhagic transformations and assessed whether location of hyperdense areas may play a role in the incidence of hemorrhagic transformations. We also evaluated correlation between early CT signs and hyperdense areas. RESULTS: Forty-five hyperdense areas were seen in 37 of the 77 patients (48.1%): 19 of the 45 (42.2%) were confirmed to be hematomas themselves, 6 (13.4%) showed later conversion to petechial hemorrhages, and 20 (44.4%) showed rapid disappearance without hemorrhagic transformations. Eleven of the 37 patients (29.7%) had neurological worsening due to massive hematoma (symptomatic hemorrhage), whereas none of the 40 patients without hyperdense areas had symptomatic hemorrhage. The incidence of hemorrhage among hyperdense areas was significantly lower in the insular cortex than in the other 2 regions (P<0.01). On the other hand, hyperdense areas in the lentiform nucleus had a significantly higher incidence of neurological worsening (P<0.05). There was a significant correlation between early CT signs and hyperdense areas (P<0.0001). CONCLUSIONS: The presence of hyperdense areas was a significant risk factor for severe hemorrhagic transformations, although only 29.7% of patients with hyperdense areas had symptomatic hemorrhage. On the contrary, the absence of hyperdense areas was a reliable negative predictor for symptomatic hemorrhage.

Serial changes in signal intensities of the adjacent discs on T2-weighted sagittal images after surgical treatment of cervical spondylosis: anterior interbody fusion versus expansive laminoplasty.

BACKGROUND: There have been many reports about newly developed degenerative changes in the adjacent segments after anterior interbody fusion. It is a controversial issue whether the adjacent-segment disease in patients treated by anterior interbody fusion is the result of progressive cervical spondylosis at the adjacent levels or is caused by the arthrodesis. The aim of this study is to clarify the difference in postoperative effect on the adjacent segments between anterior interbody fusion and expansive laminoplasty. METHOD: This study included 14 patients who underwent pre- and postoperative MR images at 6 and 12 months. Seven patients underwent cervical interbody fusion and the other 7 patients underwent expansive laminoplasty. Disc degeneration was evaluated semiquantitatively by calculating the degenerative index (DI) that is a ratio of the intensity in the disc to that in the upper cervical cord. FINDINGS: In the anterior interbody fusion group, the adjacent disc intensities decreased within 12 months (F = 20.42; P < 0.01). The pre-operative mean DI was 0.59 +/- 0.16. The post-operative mean DIs were 0.56 +/- 0.16 at 6 months and 0.47 +/- 0.16 at 12 months. In the expansive laminoplasty group, the signal intensities of both the adjacent discs and the discs within the range of laminoplasty had no serial changes during the same period (F = 2.67; P = 0.09 and F = 0.15; P = 0.87 respectively). INTERPRETATION: Anterior interbody fusion had a significant influence on the adjacent discs even as soon as 12 months after surgery, but laminoplasty had no influence on them during the same period.

Calcium phosphate crystal-associated proteins: alpha-2-HS-glycoprotein, prothrombin fragment 1 and osteopontin.

To study the inhibitory effects of calcium phosphate-associated proteins on calcium oxalate crystallization and urinary concentrations of proteins in people who form stones and healthy controls. From 60 L of urine from healthy men, calcium phosphate-associated proteins (alpha-2-HS-glycoprotein, prothrombin fragment 1 and osteopontin) were obtained. The effects of the proteins on calcium oxalate (CaOx) crystallization were studied with a mixed suspension mixed product removal system. To examine urinary concentrations of the proteins, urine samples were collected from 17 healthy subjects and 15 stone formers and analyzed using anion-exchange chromatography and an enzyme immunoassay. Prothrombin fragment 1 (PTF1) and osteopontin (OPN) had strong inhibitory effects on CaOx crystallization, while alpha-2-HS-glycoprotein had a mild inhibitory effect. Urinary concentrations of PTF1 and OPN were lower in stone formers than in healthy controls. Low urinary concentrations of PTF1 and OPN might be one of the reasons for stone formation.

Correlation of early CT signs in the deep middle cerebral artery territories with angiographically confirmed site of arterial occlusion.

BACKGROUND AND PURPOSE: Early CT signs in the deep middle cerebral artery (MCA) territories have been reported to be seen at the initial period of ischemia. We attempted to investigate the incidence of parenchymal hypodensity within 3 hours after ischemic onset among patients with angiographically proved embolic MCA occlusion and to assess the correlation of subtle hypodensity in the deep MCA territories with involvement of the lenticulostriate arteries in the presence of ischemia. METHODS: Fifty CT images obtained within 3 hours after onset of embolic MCA occlusion were retrospectively reviewed by three neurosurgeons who were aware of clinical features. Early CT signs in the deep MCA territories were divided into three grades according to their anatomic location: grade I, normal basal ganglia with hypodensity localized to the insula; grade II, partial obscuration of the posterolateral part of the putamen; and grade III, hypodensity of the entire lentiform nucleus. A grade I CT sign was considered to be a negative finding for lenticulostriate artery involvement, whereas grade II and III CT signs were considered to be positive findings. Site of occlusion and involvement of the lenticulostriate arteries were confirmed by angiography. RESULTS: Thirty-eight (76%) of 50 patients had early CT signs in the deep MCA territories. Sensitivity and specificity of a grade I CT sign indicating absence of lenticulostriate artery involvement in ischemia were 65% and 87%, respectively. On the other hand, sensitivity and specificity of grade II and grade III CT signs for presence of lenticulostriate artery involvement in ischemia were 77% and 100%, respectively. Grade II CT signs resulted from various sites of occlusion, whereas grade III was unequivocally predictive of proximal occlusion to all of the lenticulostriate arteries. CONCLUSION: Involvement of the lenticulostriate arteries may be presumed by precise evaluation of subtle, CT-revealed hypodensity in the deep MCA territories, even within 3 hours of ischemic onset.

Radiographic and scintigraphic courses of union in cervical interbody fusion: hydroxyapatite grafts versus iliac bone autografts.

UNLABELLED: This study investigated the radiographic and scintigraphic courses of union in cervical interbody fusion using hydroxyapatite (HA) grafts or iliac bone autografts. METHODS: Twelve patients underwent both serial plain radiography and bone scintigraphy during the 12 mo after surgery. Serial plain radiographs were obtained every month until the end of the study period. Bone scintigrams with 99mTc-hydroxymethylene diphosphonate (HMDP) were obtained at 2 wk and at 1, 2, 3, and 6 mo. Uptake of 99mTc-HMDP in the graft was expressed as a ratio of the counts in the graft to those in the axis. RESULTS: In the HA graft group, the plain radiographs of all patients showed a radiolucent stripe that disappeared 7.3 +/- 1.5 (mean +/- SD) months after surgery. In the autograft group, a radiolucent stripe around the graft was not seen for any patient, and union was confirmed by follow-up radiographs within 6 mo after surgery. The serial changes in the 99mTc-HMDP uptake ratio showed no difference between the 2 groups. The 99mTc-HMDP uptake ratio peaked 1 mo after surgery and decreased rapidly to a plateau within 2 mo. CONCLUSION: In the HA graft group, despite the presence of a radiolucent stripe around the graft for more than 6 mo, the scintigraphic course of union was not different from that in the autograft group. The likelihood is that the presence of a radiolucent stripe around the HA graft in the early months after surgery is not always a sign of pseudoarthrosis.

Inhibitory effect of calcium phosphate-associated proteins on calcium oxalate crystallization: alpha2-HS-glycoprotein, prothrombin-F1 and osteopontin.

OBJECTIVE: To analyse urinary calcium phosphate- associated proteins and assess their inhibitory effects on calcium oxalate crystallization. Materials and methods Urine samples were collected over 24 h from five healthy men and calcium phosphate crystallization induced with NaOH solution. The bound proteins were separated on a cellulose column. To examine the effect of urinary calcium phosphate-associated proteins on calcium oxalate crystallization, 60 L of urine was collected from the healthy men. The effect of the separated fractions was studied in a mixed suspension/mixed product removal system. RESULTS: The separated proteins were identified as alpha2-HS-glycoprotein, prothrombin fragment 1 and osteopontin. Prothrombin fragment 1 and osteopontin strongly inhibited the growth of calcium oxalate crystals in artificial urine. CONCLUSION: alpha2-HS-glycoprotein, prothrombin fragment 1 and osteopontin selectively bound with calcium phosphate crystals in urine. Prothrombin fragment 1 and osteopontin in urine may strongly influence stone formation.

Angiographic cerebral circulation time before and after endovascular therapy for symptomatic vasospasm.

AIM: To investigate the correlation between angiographic cerebral circulation time (CCT) and cerebral blood flow (CBF) evaluated by single photon emission computed tomography (SPECT) before and after endovascular treatment for symptomatic vasospasm. MATERIALS AND METHODS: Seven patients with unilateral vasospasm as demonstrated by catheter angiography who underwent pre- and post-treatment SPECT were selected. All patients had angiographic vasospasm of unilateral middle cerebral artery (MCA). Eight vessels in seven patients underwent intra-arterial papaverine infusion and three vessels underwent percutaneous transluminal angioplasty. Angiographic CCT was defined as the interval from the first image in which contrast medium was visible at the origin of MCA to its disappearance from the cortical arteries in the MCA territory. In SPECT studies, the ischaemic degree in MCA territory was analysed by side to side comparison with calculating the asymmetry index (AI). RESULTS: The pre-treatment mean CCT was 4.1 +/- 0.8 s. The mean CCT immediately after treatment was 2.7 +/- 0.5 s. In the control subjects (n = 15) with unruptured aneurysm, mean CCT was 3.5 +/- 0.2 s. The pre-treatment mean CCT was significantly prolonged compared with that in the control subjects (P = 0.02). The post-treatment mean CCT was significantly shortened compared with that in the control subjects (P = 0.001). The pre-treatment mean AI was 71.2 +/- 7.4%, and that immediately after treatment was 90.5 +/- 3.6%. AI increased in all territories treated with endovascular treatment; the mean change was 19.3%. Angiographic CCT was closely correlated with AI in both pre- (r = - 0.95) and post-treatment (r = - 0.79). CONCLUSION: Measurement of CCT is useful in evaluating cerebral haemodynamics of endovascular treatments in patients with cerebral vasospasm.

Thresholds of ischemia salvageable with intravenous tissue plasminogen activator therapy: evaluation with cerebral blood flow single-photon emission computed tomographic measurements.

OBJECTIVE: This study investigated the cerebral blood flow (CBF) thresholds of ischemic cortices that were salvageable with intravenous tissue plasminogen activator (t-PA) infusion therapy. METHODS: We retrospectively reviewed data for 20 patients who were treated with intravenous low-dose (7.2 mg) native t-PA infusion therapy for distal embolic occlusions of middle cerebral artery divisions or branches, without early computed tomographic ischemic changes. All patients underwent pretreatment single-photon emission computed tomographic CBF measurements using (99m)Tc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethylester. Intravenous t-PA infusion was initiated within 6 hours (average, 3 h) after symptom onset for 14 patients and 6 to 14 hours (average, 8.8 h) after the last time the patient was noted to be in normal condition for the other 6 patients. Pretreatment single-photon emission computed tomographic and 3-month post-treatment computed tomographic scans were compared using computerized coregistration. Ischemic cortices in single-photon emission computed tomographic scans were divided into areas of reversible and irreversible ischemia. The degree of hypoperfusion was analyzed with an asymmetry index (AI). The AI was calculated as C(a)/C(b) x 100%, where C(a) represents the mean reconstructed counts for the ipsilateral ischemic area and C(b) represents the mean reconstructed counts for the corresponding contralateral area. RESULTS: Partial recanalization, with clinical improvement, at 60 minutes was confirmed by angiography for 14 of the 20 patients (70%). Seventeen of the 20 patients (85%) exhibited major neurological improvements (defined as decreases in National Institutes of Health Stroke Scale scores of > or =4 points) at 24 hours, suggesting that recanalization occurred within 24 hours for almost all patients. AIs for the 25 irreversible lesions ranged from 15.0 to 53.4% (37.3 +/- 11.6%), whereas AIs for the 38 reversible lesions ranged from 45.0 to 83.1% (69.3 +/- 8.6%). There was a significant difference in the AIs for these two groups (P < 0.0001). The ischemia in tissue with AIs of more than 53.4% was reversible. In contrast, ischemic tissue with AIs of less than 45.0% could not escape cerebral infarction with our treatment. The ischemia in tissue with AIs between 45.0 and 53.4% was reversible in some patients and irreversible in others. CONCLUSION: To save ischemic tissue with our intravenous t-PA infusion therapy, residual CBF should be at least 45% of the contralateral presumed normal CBF value. CBF thresholds for ischemia that would be surely salvageable with our intravenous t-PA infusion therapy might be approximately 50 to 55% of the contralateral presumed normal CBF values.

[An investigation of serum soluble interferon receptor levels in patients with renal cell carcinoma].

OBJECTIVE: Serum soluble interferon alpha/beta receptor (s-IFN-receptor) levels were determined in renal cell carcinoma (RCC) patients to study the clinical significance of the measurement. SUBJECTS AND METHODS: S-IFN-receptor levels were measured in RCC patients (n = 27) and healthy volunteers (n = 22) by enzyme immunoassay technique. RESULTS: Significantly higher serum s-IFN-receptor levels were observed in RCC patients compared with the healthy volunteers (p < 0.003). The high s-IFN receptor levels in the patients suggested seriousness and mal-prognosis of this disease. The 4-years survival rate of the higher level group (with the mean value of 2.7 +/- 1.7 ng/ml or more) was 53.3%, while the lower level group's rate was 78.7% (Statistical analysis result by Logrank (Mantel-Cox) test; p = 0.4289). CONCLUSION: Further study in more subjects is required to determine the feasibility of the s-IFN receptor levels as a prognosis marker, since correlation between the prognosis and s-IFN receptor level was not clarified by this study result.

A combination of wrapping and clipping using a collagen-impregnated dacron fabric (Hemashield).

BACKGROUND: We describe techniques combining wrapping and clipping using a collagen-impregnated Dacron knitted fabric (Hemashield) for accidental arterial perforations and broad-based aneurysms. The results of these techniques in seven patients are presented. METHODS: Clip-reinforced wrapping was performed to obtain hemostasis in two patients with arterial perforations and in a patient with a ruptured broad-based aneurysm in the internal carotid artery. Clipping of the broad neck of the aneurysm and wrapping with Hemashield (wrap-clipping) was performed in four patients with unruptured aneurysms (one internal carotid artery, two middle cerebral artery, one basilar artery). RESULTS: In the three patients treated with clip-reinforced wrapping, complete hemostasis was obtained just after clip application. In the patient with a ruptured broad-based aneurysm, postoperative angiography demonstrated that the dome of the aneurysm was well compressed. In the four patients treated with wrap-clipping, postoperative angiography revealed successful clipping of the broad neck of the aneurysm. CONCLUSION: In this early experience, there were no problems in the use of Hemashield for clip-reinforced wrapping or wrap-clipping.

Intravenous low-dose native tissue plasminogen activator for distal embolism in the middle cerebral artery divisions or branches: a pilot study.

OBJECTIVE: We prospectively evaluated the safety and efficacy of an intravenous infusion of low-dose native tissue plasminogen activator for distal embolisms in the middle cerebral artery divisions or branches. METHODS: Twenty patients were selected according to the following computed tomographic and angiographic criteria and treated with intravenous infusion of 7.2 mg of tisokinase: 1) no early ischemic changes on the initial computed tomographic scan, and 2) embolic occlusion of the middle cerebral artery divisions or branches without the involvement of the lenticulostriate arteries. For comparison, the records of 12 patients from previous years who met the above inclusion criteria but underwent no thrombolytic therapy were reviewed retrospectively. The degree of neurological recovery was assessed using the National Institutes of Health Stroke Scale at 24 hours after admission. Major neurological improvement was defined as a decrease in the stroke score by 4 points or more. RESULTS: There was no significant difference in stroke scores at the time of admission between the treatment group (mean +/- standard deviation, 12.8 +/- 2.8) and the untreated group (14.0 +/- 2.4). In the treatment group, major neurological improvement was seen in 17 (85%) of 20 patients, whereas in the untreated group only 5 (41.7%) of 12 patients showed major neurological improvement (P < 0.05). The mean score at 24 hours in the treatment group (3.6 +/- 3.5) was significantly lower than that in the untreated group (9.4 +/- 7.3) (P < 0.05). There was no hemorrhagic complication with neurological exacerbation in the treatment group. CONCLUSION: Even with delayed initiation (>3 h after symptom onset), intravenous infusion of low-dose tisokinase may be safe and effective for small distal emboli in the middle cerebral artery divisions or branches, when early ischemic changes on computed tomographic scans and involvement of the lenticulostriate arteries are absent.

Calcium phosphate crystal-associated proteins: alpha2-HS-glycoprotein, prothrombin F1, and osteopontin.

PURPOSE: To elucidate the process of urinary stone formation, many urinary constituents have been examined as inhibitors or promoters. MATERIALS AND METHODS: We analyzed specific binding proteins of calcium phosphate (CaP) crystals generated in human urine and found that the separated proteins were alpha2-HS-glycoprotein, prothrombin fragment 1 (PTF1), and osteopontin (OPN). We also studied their inhibitory effects on calcium oxalate crystallization and the quantitative differences in urinary excretion of the proteins in healthy individuals and stone formers. RESULTS: Both PTF1 and OPN had strong inhibitory effects on growth of calcium oxalate crystals. No differences in alpha2-HS-glycoprotein were found between healthy subjects and stone formers. Urinary concentrations of PTF1 and OPN were lower in stone formers than in healthy controls. No differences in these proteins were seen between single and recurrent stone formers. CONCLUSION: Low urinary concentrations of PTF1 and OPN might be one reason for stone formation.

Poststenotic signal attenuation on 3D phase-contrast MR angiography: a useful finding in haemodynamically significant carotid artery stenosis.

We performed blinded visual evaluation of MR angiography (MRA) films in 44 patients with unilateral carotid artery stenosis to determine whether a flow gap and poststenotic signal attenuation on 3D-PC MRA were useful signs of severe carotid artery stenosis. Although nine patients with a flow gap alone had various degrees of stenosis ranging from 22.2 to 77.3% without any decrease in regional cerebral blood flow (rCBF), 13 patients with both a flow gap and poststenotic signal attenuation had severe stenoses of 80% or more, with a definite decrease in baseline rCBF. The presence of both a flow gap and poststenotic signal attenuation on 3D-PC MRA appeared to be a reliable marker of severe carotid artery stenosis with a decrease in rCBF.

Reversibility of ischemia evaluated by ischemic duration and residual cerebral blood flow.

SUMMARY: We first investigated the time course of CBF thresholds of ischemic cortices by a retrospective review of 19 patients with MCA occlusion who had clearly defined ischemic duration from onset to angiographic complete recanalization. Secondly, CBF thresholds of ischemic cortices salvageable with intravenous low dose native t- PA infusion therapy (7.2 mg of tisokinase) were examined by a retrospective review of 20 patients with distal embolic occlusions of MCA divisions or branches. All patients underwent pretreatment CBF measurement by SPECT using 99mTc-ECD. Pretreatment SPECT and 3 months post-treatment CT images were compared using computerized coregistration. The degree of hypoperfusion was analyzed by an asymmetry index (AI), which was a count-density ratio for the ischemic lesion to the contralateral corresponding area. Ischemic cortices on SPECT were divided into reversible and irreversible lesions. Judging from the regression lines with 95% confidence interval between the ischemic duration and AI, the infarcted CBF thresholds at 3 and 6 hours after onset may be about 30 and 50% of contralateral presumed normal CBF, respectively. On the other hand, to save the ischemic tissue with our intravenous t-PA infusion therapy, residual CBF might be needed at least 45% of contralateral presumed normal CBF. It is likely that CBF threshold of ischemia surely salvageable with our intravenous t-PA infusion therapy may be approximately 50-55% of contralateral presumed normal CBF.

Analysis of urinary concentrations of calcium phosphate crystal-associated proteins: alpha2-HS-glycoprotein, prothrombin F1, and osteopontin.

It has been reported that prothrombin F1 and osteopontin (OPN) have strong inhibitory effects on calcium oxalate crystallization and are produced in stone-forming kidneys in animal models. It is important to evaluate urinary concentrations of these proteins for patients with renal stones and healthy control subjects. Urinary macromolecules were collected from nine healthy individuals, nine stone-formers, and five patients with primary hyperparathyroidism (HPT). Each 50-mg aliquot of urinary macromolecules was mixed with calcium phosphate solution, and calcium phosphate crystal-precipitated proteins (alpha2-HS-glycoprotein, prothrombin F1, and OPN) were obtained. The proteins were analyzed by anion-exchange chromatography. Furthermore, OPN levels in whole urine from 18 healthy individuals, 31 stone-formers, and two patients with HPT were measured using a new enzyme immunoassay system. The elution peaks for prothrombin and OPN were significantly smaller for the stone-formers and patients with HPT, compared with the healthy control subjects. Urinary concentrations of OPN assessed using the enzyme-linked immunosorbant assay were significantly lower for stone-formers. Lower urinary excretion of prothrombin F1 and OPN by stone-formers might be one of the reasons for stone formation.

Simultaneous up-regulation of urokinase-type plasminogen activator (uPA) and uPA receptor by hepatocyte growth factor/scatter factor in human glioma cells.

Several lines of evidence indicate that hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, may play an important role in progression of human glioma. In this study, effects of HGF/SF on urokinase- type plasminogen activator (uPA)-mediated proteolysis network were examined in c-Met-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of uPA proteins accompanying increased transcription of uPA mRNA in a dose dependent fashion. The levels of uPA receptor (uPAR) mRNAs were also elevated simultaneously upon HGF/SF stimulation, and the cell-surface associated uPA activity was also elevated by the treatment. Since concomitant expression of HGF and its receptor c-Met are frequently observed in malignant gliomas, these results suggest that HGF/SF participates in invasive process of malignant glioma cells not only by its motility-stimulating activity but also through enhanced degradation of the extracellular matrix induced by autocrine activation of uPA proteolysis network.

Expression of heat shock proteins in developing and degenerating rat testes.

In the testis, several types of heat shock proteins (HSPs) have been identified and characterized, although the cellular basis of the HSPs remains elusive. In the present study, alterations in the cellular localization of HSPs, including HSP 25, 60, 70, and 90, were studied during the developing and degenerating periods in the rat testis using immunohistochemistry and Western blotting. HSP25 was expressed in neither germ cells nor somatic cells on all days examined. In contrast, HSP 60 was expressed in Leydig cells during neonatal and prepuberty periods, and only in spermatogonia and primary spermatocytes after puberty. HSPs 70 and 90 were expressed in germ cells, Sertoli cells, and Leydig cells during neonatal and early developing testes, and in spermatocytes and round spermatids after puberty. Besides, there was faint expression of HSP 90 protein in spermatogonia in this period. In the degenerative condition, all HSP proteins were markedly expressed in germ cells after surgery. It would appear that HSPs play roles in unique homeostasis in testes.