Absence of the Anterior Communicating Artery on Selective MRA is Associated with New Ischemic Lesions on MRI after Carotid Revascularization.

BACKGROUND AND PURPOSE: ICA-selective MRA using a pencil beam presaturation pulse can accurately visualize anterior communicating artery flow. We evaluated the impact of anterior communicating artery flow on the perioperative hemodynamic status and new ischemic lesions after carotid revascularization. MATERIALS AND METHODS: Eighty-three patients with carotid artery stenosis were included. We assessed anterior communicating artery flow using ICA-selective MRA. The preoperative hemodynamic status was measured using SPECT. We also measured the change in regional cerebral oxygen saturation after temporary ICA occlusion. New ischemic lesions were evaluated by DWI on the day after treatment. RESULTS: Anterior communicating artery flow was detected in 61 patients, but it was not detected in 22 patients. Preoperative cerebrovascular reactivity was significantly higher in patients with (versus without) anterior communicating artery flow with a mean peak systolic velocity of ≥200 cm/s (39.6% [SD, 23.8%] versus 25.2% [SD, 16.4%]; P = .030). The decrease in mean regional cerebral oxygen saturation was significantly greater in patients without (versus with) anterior communicating artery flow (8.5% [SD, 5.6%] versus 3.7% [SD, 3.8%]; P = .002). New ischemic lesions after the procedure were observed in 23 patients. The multivariate logistic regression analysis revealed that anterior communicating artery flow (OR, 0.07; 95% CI, 0.012-0.45; P = .005) was associated with new ischemic lesions. CONCLUSIONS: The absence of anterior communicating artery flow influenced the perioperative hemodynamic status in patients with carotid stenosis and was associated with an increased incidence of new ischemic lesions after carotid revascularization.

Bone-destructive osseous arteriovenous fistula at the jugular bulb mimicking a glomus jugular tumor.

BACKGROUND: Some reports have described intraosseous arteriovenous fistulas showing osteolytic changes, but an osseous arteriovenous fistula (AVF) at the jugular bulb showing extensive bone destruction is a very rare disease. CASE DESCRIPTION: A 60-year-old man presented with pulsatile tinnitus and right facial nerve palsy. Radiological imaging showed a large homogenously enhanced osteolytic lesion at the right jugular foramen. A cerebral angiogram showed a high-flow vascular lesion of the jugular bulb associated with retrograde sinus reflux, resulting in venous congestion of the deep venous system. These findings led us to misdiagnose this lesion as a glomus jugular tumor. However, combined arterial and venous angiography after transarterial embolization revealed the precise angioarchitecture, and we finally diagnosed this lesion as a high-flow osseous AVF at the jugular bulb. We performed transvenous embolization using a triple catheter technique. The lesion was successfully obliterated, and the 6-months angiogram showed no recurrence. CONCLUSION: A rare case of high flow osseous AVF at the jugular bulb associated with osteolytic changes in the surrounding bony structure is reported. Although many hypervascular lesions at the jugular bulb are glomus tumors, bone destructive osseous AVF at the jugular bulb should be considered.

DWI for Monitoring the Acute Response of Malignant Gliomas to Photodynamic Therapy.

BACKGROUND AND PURPOSE: Photodynamic therapy is a novel treatment that provides effective local control, but little is known about photodynamic therapy-induced changes on MR imaging. The aim of this study was to assess the utility of DWI and ADC in monitoring the response of malignant gliomas to photodynamic therapy. MATERIALS AND METHODS: Time-dependent changes in DWI and ADC values after photodynamic therapy were analyzed in a group that received photodynamic therapy in comparison with a group that did not. RESULTS: Twenty-four patients were enrolled (photodynamic therapy, n = 14; non-photodynamic therapy, n = 10). In all patients who received photodynamic therapy, linear high signals on DWI in the irradiated area were detected adjacent to the resection cavity and were 5-7 mm in depth from 1 day posttreatment and disappeared in about 30 days without any neurologic deterioration. The non-photodynamic therapy group did not show this change. The photodynamic therapy group had significantly lower ADC values from 1 day posttreatment (P < .001), which increased steadily and disappeared by 30 days. There was no decline or time-dependent change in ADC values in the non-photodynamic therapy group. CONCLUSIONS: The acute response of malignant gliomas to photodynamic therapy was detected as linear high signals on DWI and as a decrease in ADC values. These findings were asymptomatic and transient. Although the photodynamic therapy-induced acute response on MR imaging disappeared after approximately 30 days, it may be helpful for confirming the photodynamic therapy-irradiated area.

Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas.

AIMS: Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. METHODS: We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation. RESULTS: The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265. CONCLUSIONS: The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.

Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway.

CD44 is a widely distributed cell surface adhesion molecule and is implicated in diverse biological processes. However, the nature of intracellular signaling triggered by CD44 remains to be elucidated. Here, we show that CD44 undergoes sequential proteolytic cleavage in the ectodomain and intracellular domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. Consequently, CD44ICD acts as a signal transduction molecule, where it translocates to the nucleus and activates transcription mediated through the 12-O-tetradecanoylphorbol 13-acetate-responsive element, which is found in numerous genes involved in diverse cellular processes. Expression of an uncleavable CD44 mutant as well as metalloprotease inhibitor treatment blocks CD44-mediated transcriptional activation. In search of the underlying mechanism, we have found that CD44ICD potentiates transactivation mediated by the transcriptional coactivator CBP/p300. Furthermore, we show that cells expressing CD44ICD produce high levels of CD44 messenger RNA, suggesting that the CD44 gene is one of the potential targets for transcriptional activation by CD44ICD. These observations establish a novel CD44 signaling pathway and shed new light on the functional link between proteolytic processing of an adhesion molecule at the cell surface and transcriptional activation in the nucleus.

[Efficacy of cibenzoline for chest oppression and ventricular arrhythmia during effort and alcohol consumption in a patient with hypertrophic obstructive cardiomyopathy: a case report].

A 67-year-old man presented with chest oppression and palpitation during effort and alcohol consumption. Echocardiography demonstrated asymmetric septal hypertrophy and systolic anterior motion of the anterior mitral leaflet with a pressure gradient of 80 mmHg across the left ventricular outflow tract (LVOT), leading to the diagnosis of hypertrophic obstructive cardiomyopathy. During the treadmill exercise test, blood pressure decreased with electrocardiographic ST-segment depression and subsequent frequent premature ventricular contractions. Holter-electrocardiographic monitoring also showed ST-segment depression with premature ventricular contractions during effort and alcohol consumption. Coronary angiography showed no abnormalities and cardiac catheterization at baseline showed a systolic pressure gradient of only 2 mmHg across the LVOT. However, the gradient increased to 33 mmHg after premature ventricular contraction, 27 mmHg at Valsalva maneuver and 75 mmHg with dobutamine infusion (5 micrograms/kg/min) and disappeared with 70 mg of intravenous cibenzoline. Medication with cibenzoline (300 mg/day) for one month reduced the LVOT gradient at rest to 53 mmHg and strikingly improved symptoms and exercise tolerance and also suppressed premature ventricular contractions during exercise and alcohol consumption. We conclude that cibenzoline was effective for reduction of LVOT gradient both at rest and during exercise and alcohol consumption.

[Spontaneous resolution of the unruptured dissecting aneurysms of bilateral vertebral arteries with conservative treatment: analysis of the transient enlargement of aneurysmal dilatation].

A case of unruptured dissecting aneurysms of bilateral vertebral arteries was reported. A 47-year-old man was admitted to our hospital with right Wallenberg's syndrome. On the tenth hospital day, angiography revealed a pearl and string sign in the right vertebral artery and aneurysmal dilatation in the left vertebral artery. On the 38th hospital day, the pearl and string sign in the right vertebral artery was improved, but the aneurysmal dilatation in the left vertebral artery had enlarged. On the 222nd hospital day, angiography showed a spontaneous resolution of the aneurysmal dilatation in the left vertebral artery. He suffered no recurrence and returned to his previous life style. Because aneurysmal dilatation may be resolved spontaneously, especially in the chronic stage, surgery should not be undertaken lightly.

Thrombocytopenia induced by Jui, a traditional Chinese herbal medicine.

Jui is a traditional Chinese herbal medicine. The causal relation between the drug and thrombocytopenia was proved by a rechallenge test.

Knocking Detection of a Gasoline Engine by Utilizing an Optical Fiber with Specific Refractive-index Composition.

Abnormal combustion of a gasoline engine is often accompanied by a sharp metallic noise called knocking. A recently proposed method of in-cylinder pressure measurement is applied to detect the knocking, where the bending power loss of a single-mode fiber with specific refractive-index composition is utilized. The high-frequency response of a prototype sensor is obtained with a small structure to utilize the bending mechanism that is installed into an engine head gasket. Knocking signals are detected in a wide range of trace- to heavy-knock conditions.

The heterogeneous interaction of substoichiometric TNP-ATP and F1-ATPase from Escherichia coli.

The interactions of substoichiometric TNP-ATP and F1-ATPase from Escherichia coli (EF1) were examined and compared with those in the case of mitochondrial F1-ATPase (MF1) and F1-ATPase from thermophilic Bacillus PS3 (TF1). EF1 hydrolyzed substoichiometric TNP-ATP faster than TF1 or MF1, although some 20% of the TNP-ATP remained unhydrolyzed even in the presence of excess chase ATP. The affinity of the catalytic site of EF1 for the product, TNP-ADP, was weaker than that of TF1 or MF1, and the TNP-ADP was readily released upon addition of excess ATP. The amplitude of the difference absorption spectrum induced by binding of TNP-AT(D)P to EF1 was smaller than that of MF1 or TF1 under similar experimental conditions. When an excess amount of TNP-ATP was added to EF1 and the change of the difference spectrum was measured, the shape of the difference spectrum of the ATP-replaceable fraction was very similar to that in the case of binding of TNP-ATP to the isolated beta subunit of TF1, indicating that the rapidly replaceable fraction of bound TNP-ATP was actually at the catalytic site and most of the non-replaceable portion was bound at noncatalytic sites. Weaker affinity of the catalytic site for TNP-ATP may account for the heterogeneous binding and hydrolysis under the conditions described in this paper.

Multiplex in-cylinder pressure measurement utilizing an optical fiber with specific refractive-index composition.

An approach to multiplex in-cylinder pressure measurement that utilizes a single-mode optical fiber with specific refractive-index composition has been proposed. The sensing fiber has been designed to show a certain amount of optical power loss with a small change in the fiber-local-bend radius. Along with pressure-transferring diaphragms the sensing fiber was embedded into the head gasket of a four-cylinder gasoline engine. The internal-pressure change in each combustion chamber was detected on the basis of bending power loss in the fiber. Combustion pressure peaks for each cylinder were clearly observed.

Analysis of time-dependent change of Escherichia coli F1-ATPase activity and its relationship with apparent negative cooperativity.

Except for the case of gradual activation of EF1 (F1-ATPase from Escherichia coli) caused by the dissociation of the epsilon subunit [Laget, P. P. and Smith, J. B. (1979) Arch. Biochem. Biophys. 197, 83-89], EF1 has long been thought not to show a time-dependent change in activity [Senior, A.E. et al. (1992) Arch. Biochem. Biophys. 297, 340-344]. Here, we report the time-dependent inactivation and activation of EF1, which are apparently similar to those of mitochondrial F1-ATPases [Vasilyeva, E.A. et al. (1982) Biochem. J. 202, 15-23]. Analysis of these changes as a function of ATP concentrations in relation to negative cooperativity revealed that the initial inactivation phase was attributable to the decrease in the Vmax associated with the low Km (around 10 microM), and the following activation, probably due to the dissociation of the epsilon subunit, corresponded to the increase in the Vmax associated with the high Km (in the order of 100 microM). Thus, the time-dependent change in EF1 activity is closely related to the apparent negative cooperativity (multiple Km values) of ATP hydrolysis.

Catalytic cooperativity of beef heart mitochondrial F1-ATPase revealed by using 2',3'-O-(2,4,6-trinitrophenyl)-ATP as a substrate; an indication of mutually activating catalytic sites.

The interaction of 2',3'-O-(2,4,6-trinitrophenyl)ATP (TNP-ATP) with bovine mitochondrial F1-ATPase (MF1) was examined under substoichiometric and stoichiometric conditions to investigate the relationship between the amount of bound TNP-AT(D)P and extent of inhibition on steady state ATP hydrolysis. The hydrolysis of bound TNP-ATP under substoichiometric condition proceeded slowly, with a first order rate constant of 0.014 s-1. However, hydrolysis was greatly accelerated by addition of excess ATP. The hydrolyzed product, TNP-ADP, did not dissociate from the enzyme even after the addition of excess ATP. These properties were the same for both native and nucleotide depleted enzyme. The difference spectrum induced by binding TNP-ATP to MF1 had a distinct peak at 410 nm and a deep trough at 395 nm, which were similar to those induced when TNP-ATP bound to the isolated beta subunit of the thermophilic F1-ATPase. The magnitude of difference spectra as a function of TNP-ATP concentration suggested the presence of at least two types of binding sites on the MF1 molecule. The first site, where substoichiometric TNP-ATP was hydrolyzed, had a very high affinity for TNP-ATP. TNP-AT(D)P bound to this site did not dissociate even in the presence of excess ATP. TNP-AT(D)P bound to the second site dissociated slowly when excess ATP was added. The steady state ATPase activity at 100 microM ATP was linearly suppressed as pre-loaded TNP-ATP increased. The binding of 2 mol of TNP-ATP per mol of MF1 was required to abolish ATPase activity. A model which assumes mutually-activating two catalytic sites is presented to explain these results.

[Combination chemotherapy using cyclophosphamide, adriamycin, and cisplatin in recurrent or advanced endometrial cancer--a preliminary report].

Four patients with recurrent or advanced endometrial cancer have undergone combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP). All drugs were administered by I.V. on day 1 in the following doses: Cyclophosphamide 500 mg/m2, Adriamycin 50 mg/m2 and Cisplatin 50 mg/m2. The treatment was repeated every 4 weeks and continued as long as there was disease progression. Two complete clinical responses and two partial responses were achieved. Based on these good results, we have initiated post-operative prophylactic chemotherapy using CAP in high risk patients. Adverse effects including myelo-suppression, nausea, and vomiting, and alopecia were seen in almost all patients. In no case, however, did any patient experience life-threatening toxicity. Based on our experience, CAP therapy appears tolerable when used per our schedule.

[A primary malignant lymphoma of the vulva--a case report].

Malignant lymphoma is a rare entity in the neoplasms of the female genital tract, and thus a case of malignant lymphoma of the vulva is reported in this paper. On admission, the patient, a 37-year-old, Japanese female, had complained of vulvar swelling and pain that had persisted for one month. Stage IV tumors were noted in the vulva and bladder and a histological diagnosis indicated non-Hodgkin's lymphoma with diffuse, large cell and B cell types, according to the classification of the Lymphoma Study Group. The patient thus was treated with CH* OP therapy, which consisted of Cyclophosphamide, Aclarubicin Vincristine (Oncovin), and Prednine , and given brain irradiation. Unfortunately her condition has rapidly deteriorated during the 5 months since her admission.

[Statistics on the diagnosis and treatment of infertile patients--psychologic examination and analysis of the questionnaire].

Authors present the statistics of the diagnosis and treatment of infertile patients who visited the outpatient clinic of the Department of Obstetrics and Gynecology, School of Medicine, University of Occupational and Environmental Health, Japan throughout 1985. The number of primary infertility (78) was greater than that of secondary infertility (63). The average age and the duration of infertility were 30.5 y. old/3.86 y. (primary) and 31.6 y. old/3.59 y. (secondary), respectively. The most frequent cause of infertility was ovarian-endocrine factor both in primary and secondary infertilities. The second cause was the male factor in primary infertility in spite of the idiopathic factor in secondary infertility. Tubal disorder as a cause was relatively few in both infertilities. So-called open laparoscopy was performed on 11 patients, with little hope of cure. In eight of these patients, disorders of tubal patency and endometriosis, which were not found by hysterosalpingography and hydrotubation before laparoscopy, were discovered for the first time. In twenty pregnancies at the day of statistics, the number of secondary infertility (13) was greater than that of primary infertility (7). All pregnant cases were under 35 years of age and under 5-year of infertility duration at the initial visit to our outpatient clinic. The number 1 cause of infertility was ovarian-endocrine factor. In eight pregnant cases, hysterosalpingography was performed in the same or one cycle before the pregnant cycle. According to the summation of the questionnaire of 65 infertile patients, most of infertile patients were affirmative to in-vitro-fertilization and embryo transfer. Depressive and neurotic tendencies were not remarkable at that time by Self-Rating-Depression Scale (SDS) and Cornell Medical Index (CMI) in 42 infertile patients.