Estimation of regional cerebral blood flow using N-isopropyl-p-123I iodoamphetamine acquisition data from the lungs and brain. An improved non-invasive technique.

AIM: Previously, we devised a method for estimating123I labeled N-isopropyl-p-iodoamphetamine (123I IMP) arterial blood activity at 10 minutes after intravenous injection of 123I IMP (Ca10) without any blood sampling using 123I IMP autoradiography (ARG) acquisition data, and verified its usefulness for quantification of regional cerebral blood flow (rCBF). In this study, we attempted to develop an improved noninvasive method for estimating rCBF. PATIENTS, METHODS: 123I IMP studies with 23 patients and 15O-H2O positron emission tomography (PET) ARG studies with 20 patients were evaluated. Multiple regression analysis was used to estimate an integral of the arterial blood counts during the time after injection of 123I (∫Ca) using parameters from the time series of the lung counts and brain counts as the explanatory variables and the fraction [brain single-photon emission computed tomography (SPECT) average count / the mean of rCBFs (mean CBF) measured by 15O-H2O PET ARG method] as the objective variable. RESULTS: The regression equation was as follows: Estimated ∫Ca = (7.09×10⁻³ · Cb12) - (1.57×10⁻4 · CbpreSPECT) + (9.48×10⁻5 · CbpostSPECT) + (1.35×10⁻4 · L15) - (6.95×10⁻4 · L33) + (7.61×10⁻4 · L81) - (0.417), where Cb12: brain count at 12 minutes, Cbpre-SPECT: brain count before SPECT, Cbpost-SPECT: brain count after SPECT, L15, L33, and L81: lung count at 15, 33, and 81 seconds, respectively. The mean CBF values (ml/min/100g) calculated using the estimated ∫Ca values more closely correlated with those measured by 15O-H2O PET ARG method (r = 0.833, p < 0.01) than those obtained by our previous method (r = 0.590, p < 0.01). CONCLUSION: The rCBFs obtained by this method approximated more accurately to the values measured by 15O-H2O PET ARG method than those obtained by our previous method.

Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas.

Spindle cell sarcomas consist of tumors with different biological features, of which distant metastasis is the most ominous sign for a poor prognosis. However, metastasis is difficult to predict on the basis of current histopathological analyses. We have identified actin filament-associated protein 1-like 1 (AFAP1L1) as a candidate for a metastasis-predicting marker from the gene expression profiles of 65 spindle cell sarcomas. A multivariate analysis determined that AFAP1L1 was an independent factor for predicting the occurrence of distant metastasis (P=0.0001), which was further confirmed in another set of 41 tumors by a quantitative mRNA expression analysis. Immunohistochemical staining using paraffin-embedded tumor tissues revealed that the metastasis-free rate was significantly better in tumors negative for AFAP1L1 (P=0.0093 by log-rank test). Knocking down the AFAP1L1 gene in sarcoma cells resulted in inhibition of the cell invasion, and forced expression of AFAP1L1 in immortalized human mesenchymal stem cells induced anchorage-independent growth and increased cell invasiveness with high activity levels of matrix metallopeptidase. Furthermore, tumor growth in vivo was accelerated in AFAP1L1-transduced sarcoma cell lines. These results suggest that AFAP1L1 has a role in the progression of spindle cell sarcomas and is a prognostic biomarker.

Reproductive responses of invasive and native predatory lady beetles (Coleoptera: Coccinellidae) to varying prey availability.

As adults, many predatory insects must adjust to a constantly changing prey environment while balancing between survival and reproduction. Two laboratory experiments were conducted to compare reproductive responses of females of two species of lady beetles, invasive Coccinella septempunctata L. and native C. transversoguttata richardsoni (Brown), in Utah alfalfa fields to varying availability of prey. When both lady beetles were placed immediately on experimental diets after being collected from the field (first experiment) and when they were provided excess prey for 14 d before being placed on experimental diets (second experiment), C. septempunctata produced more but individually smaller eggs than C. transversoguttata. Overall, however, in both experiments, C. septempunctata and C. transversoguttata responded similarly when they consumed pea aphids in varying amounts, by laying fewer and less viable eggs when fewer prey were consumed. In particular, the experiments provided no evidence that C. septempunctata converts pea aphids into eggs at a relatively higher rate than C. transversoguttata under limited prey availability. However, C. septempunctata had greater ability than C. transversoguttata to maintain body weight, even as they were producing eggs at low rates. This suggests that low aphid availability is less stressful for C. septempunctata, perhaps because it has more physiological ability than C. transversoguttata to assimilate pea aphid nutrients at low aphid availability. Such ability might contribute to the numerical dominance of the introduced C. septempunctata in alfalfa fields, which have supported low numbers of aphids in recent years.

Crescentic glomerulonephritis associated with totally implantable central venous catheter-related Staphylococcus epidermidis infection.

A 59-year-old woman was admitted to our hospital for treatment of acute renal insufficiency. She had been under home intravenous hyperalimentation therapy through a totally implantable central venous catheter for 2 years because of post-radiation enteritis. Clinical examination on admission revealed severe renal insufficiency complicated with hypocomplementemia, marked proteinuria and hematuria. Chest roentgenography demonstrated moderate pulmonary congestion. Hemodialysis was initiated and her pulmonary congestion improved. On the 14th and 21st hospital day, blood culture revealed Staphylococcus epidermidis colonization. Cefazolin was administered and C-reactive protein decreased, however, renal insufficiency and hypocomplementemia did not improve. To investigate the genesis of renal insufficiency, renal biopsy was performed. Light microscopic findings of the kidney revealed severe crescentic glomerulonephritis complicated with moderate tubulointerstitial damage. Immunofluorescence-microscopic findings of the kidney revealed positive IgG, IgM, C3 deposition along the capillary lumen. From these laboratory findings and the clinical course, we diagnosed her renal disease as crescentic glomerulonephritis induced by catheter-related bloodstream infection, and the central venous catheter was removed. After removal, urinary output and hypocomplementemia remarkably improved, however, unfortunately, her renal dysfunction did not improve and maintenance hemodialysis needed to be continued. Although her renal disease was not caused by ventriculo-atrial shunt but by central venous catheter-related bloodstream infection, we supposed that the pathogenesis was a closely similar entity to shunt nephritis.

Brain lesions in the course of generalised tetanus.

A 47-year-old woman developed left hemiparesis primarily affecting the lower limbs during the course of severe generalised tetanus. MRI on the 82nd hospital day revealed cortical and subcortical lesions predominantly in the right frontal and parietal lobes in addition to marked brain atrophy. Three months later, the enhancing lesions were still present on follow up MRI. We postulate that structures above brainstem may be involved in severe generalised tetanus.

Effect of tactile interference stimulation of the ear in human primary somatosensory cortex: a magnetoencephalographic study.

OBJECTIVE: To confirm the somatotopic representation of the ear in the primary somatosensory cortex (SI), we studied the tactile interference effects on somatosensory evoked magnetic fields (SEFs) following stimulation of the ear (Helix, Lobulus and Tragus). METHODS: We applied tactile interference stimulation to the neck or face area continuously and concurrently while a time-locked electrical stimulation was applied to the ear. If the amplitude would be reduced by the interference, this would indicate that the cortical representation for both the time-locked electrical stimulation and the continuous interference stimulation overlapped. A two or 3-source model, Source 1 in the neck area of SI, Source 2 in the face area of SI, and Source 3 in the secondary somatosensory cortex (SII), was found to be the most appropriate by brain electric source analysis (BESA). RESULTS: Amplitudes of Sources 1 and 2 in most interference conditions were decreased. Source 1 following stimulation of all 3 sites was significantly reduced when the interference was applied to the neck area. Source 2 following stimulation of all 3 sites was significantly reduced when the interference was applied to the face area. CONCLUSIONS: These findings showed that the interference effect was found in both the neck and face areas of SI following the ear stimulation. SIGNIFICANCE: The representation of the ear in SI might be located in both the neck and face areas.

Interaction of thyroid-stimulating antibody with Graves' thyroid-stimulating hormone-binding antibody.

OBJECTIVE: Evidence of anti-thyroid-stimulating hormone (TSH) antibody in Graves' serum has been reported. We found that extremely high Graves' anti-TSH antibodies neutralized other Graves' thyroid-stimulating antibody (TSAb) activity. METHOD: TSAb-IgG was affinity-purified by Sepharose-bound Graves' anti-TSH antibody (extremely high). RESULT: The thyroid-stimulating activity in affinity-purified TSAb-IgG increased about 4-5 times compared to that before purification. TSH-binding inhibitory immunoglobulin (TBII) activity in affinity-purified TSAb-IgG also increased using TSH receptor-coated tube assay. A similar increase of thyroid-stimulating activity accompanied with TBII activity was also observed in affinity-purified TSAb-IgG-F(ab')(2). CONCLUSION: This suggests the possibility that either TSAb may be an anti-idiotypic antibody against anti-TSH antibody or anti-TSH antibody may be an anti-idiotypic antibody against anti-TSH receptor antibody.

Functional magnetic resonance imaging evidence for a representation of the ear in human primary somatosensory cortex: comparison with magnetoencephalography study.

Our previous study (T. Nihashi et al., 2001, Neuro- Image 13: 295-304), using magnetoencephalography (MEG), revealed somatotopy of the ear in the human primary somatosensory cortex (SI); that is, the signals following stimulation of the ear reach both the neck and face areas of the SI. However, since this was the first report on somatotopy of the ear in humans, we performed an fMRI activation study to confirm the somatotopic representation, and compared the electrical activity by MEG and the cerebral blood flow change by fMRI. We studied eight healthy subjects using 3-T MRI. We stimulated three parts of the left ear: the helix, the lobulus, and the tragus. First, we identified the location of the ear area in the SI based on our previous MEG study, in which equivalent current dipoles (ECDs) were located in the neck and/or face areas of the SI. Then, we determined the search volume as a sphere with a 15-mm radius, which was placed in the neck and/or face area. We analyzed whether or not fMRI activation occurred inside such spheres. Stimulation of the helix activated the neck area of the SI in four of eight subjects, and both the neck and face areas in two. No activation was observed in two subjects. Stimulation of the lobulus activated the neck area in one subject, the face area in two, both in four, and neither in one. Stimulation of the tragus activated the face in four, both in three, and neither in one. These fMRI findings confirm the result of MEG that the representation of the ear in the SI is separated into neck and face areas.

Effect of early induction of hypothermia on severe head injury.

Although therapeutic hypothermia for patients with head injury has improved the outcome, the results in the most severe cases (GCS 3-6) have not been satisfactory so far. We induced hypothermia in head injury patients within 3 hours after the trauma, and compared the outcome of the treatment without hypothermia. Fourteen patients with GCS less than 6 were entered into this study (age range 13 to 58, mean 27.0 years). Seven of them were treated by hypothermia and 6 by the conventional method. The patients undergoing hypothermia were cooled to 34 degrees C within 3 hours after injury, kept at 32-34 degrees C for 48 hours, and then rewarmed. The outcome was evaluated at 6 months post-trauma, and the results were compared in the two groups. Therapeutic hypothermia dramatically suppressed brain swelling on CT in 3 of 7 patients. Four patients including these 3 showed a favorable outcome (good or moderate disability) and 3 died in the hypothermia group. In the conventional treatment group, only 1 patient was moderately disabled and 6 exhibited an unfavorable outcome (severely disabled, vegetative, or death). Early induction of hypothermia can improve the outcome in patients with severe head injury by reducing the severe brain swelling.

MRI of cortical dysplasia--correlation with pathological findings.

Cortical dysplasia (CD) is the most epileptogenic structural lesion associated with epilepsy and patients with intractable seizures caused by this condition are good surgical candidates. MRI plays an important role in detecting the abnormalities of CD. We clarified the MRI characteristics of CD by comparing imaging and histological findings in 20 patients with intractable seizures who underwent surgical resection. There were 12 males and eight females, mean age at operation was 15 years. MRI was performed at 1.5 tesla; T1-weighted, T2- and proton density-weighted spin-echo and fluid-attenuated inversion-recovery (FLAIR) images were obtained. The lesions were in the frontal lobe in nine cases, temporal in two, occipital in another two, insular in one and multilobar in six. Blurring of the grey/white matter junction was seen in all patients, and T2 prolongation in white matter and/or at the grey/white matter junction in 19. Abnormal signal intensity was more frequent in the white matter or at the grey/white matter junction than in the grey matter. FLAIR images made this abnormal high signal easier to appreciate, and we thought them very useful in this context. In areas of T2 prolongation, we saw dysplastic neurones and/or balloon cells, dysmyelination, and ectopic neuronal clustering histologically; glial proliferation played an important role in prolonging T2.

Intratumoral microinfusion of nimustine (ACNU) for recurrent glioma.

We investigated stereotactic intratumoral microinfusion of nimustine (ACNU) in recurrent brain tumors. Eligibility required histologic confirmation of glioma recurrence despite standard radiotherapy and chemotherapy as well as enhancement of the recurrence with gadolinium on magnetic resonance imaging (MRI). A total intratumoral dose of 10 mg of ACNU was administered continuously with a microinfusion pump over an average of 13h. Fifteen infusions were given in nine patients. All patients completed the treatment safely. On MRI, necrotic changes surrounded the infusion area in all patients, and tumor progression was inhibited or performance score was improved in seven of nine patients. No symptomatic systemic toxicity was evident, although one patient developed permanent left oculomotor palsy locally after treatment of a left medial temporal tumor. It is concluded that direct microinfusion of ACNU into recurrent gliomas can induce tumor necrosis and inhibit tumor growth.

[Inflammatory pseudotumor of the kidney: report of a case].

We report a case of inflammatory pseudotumor of the kidney. A 73-year-old man presenting with general malaise and minimal grade fever visited a medical department in our hospital. Computerized tomography incidentally revealed a tumor, 3.5 cm in diameter, in the lower pole of the left kidney, and he was referred to our outpatient department. Selective left renal arteriography disclosed an avascular mass on the affected site. Left radical nephrectomy was performed under the diagnosis of avascular renal cell carcinoma. Histological examination demonstrated a tumor composed of spindle-shaped fibroblastic cells infiltrated by variable numbers of plasma cells, small lymphocytes and histiocytes. The pathologic diagnosis was renal inflammatory pseudotumor. Fourteen previously reported cases of this tumor have reviewed in the literature.

Expression and distribution of beta amyloid precursor protein and beta amyloid peptide in reactive astrocytes after transient middle cerebral artery occlusion.

BACKGROUND: In the brains of Alzheimer's disease patients, beta amyloid protein is the major component of senile plaque. In ischemic stress, beta amyloid precursor protein (APP) and beta amyloid peptide are reported to be upregulated. METHOD: Using Male Wistar-ST rats, expression and distribution of APP and beta amyloid peptide were examined immunohistochemically after transient ischemia induced by a 2-h middle cerebral artery occlusion (MCAO). After reperfusion for 3, 7, 14, 30 and 60 days, brains were removed and immunostaining was performed. FINDINGS: The reactive astrocytes with APP were observed in the periphery of infarct from 3 days to 60 days post-occlusion. The immunoreactivity of beta amyloid peptide was also localized in the reactive astrocytes in the peripheral zone of infarct at 7, 14, and 30 days post-occlusion. However, beta amyloid expression was not identified at 3 days or 60 days post MCAO. Transient ischemia temporarily induced beta amyloid peptide expression in reactive astrocytes, but this expression peaked at 30 days and disappeared at 60 days. INTERPRETATION: These findings suggested that beta amyloid peptide was derived from the processing of APP produced in the same reactive astrocytes and the production of the peptide stopped within 60 days after the ischemic stress.

Vasodilatory effect of basic fibroblast growth factor in isolated rat cerebral arterioles: mechanisms involving nitric oxide and membrane hyperpolarization.

Basic fibroblast growth factor (bFGF), a potent mitogen, acutely dilates cerebral blood vessels and may be effective in reducing cerebral infarction. However, the vasodilatory mechanism, which may involve nitric oxide (NO), is not completely understood. This study investigated whether membrane hyperpolarization is also involved in this mechanism. Membrane potential (MP) of smooth muscle cells and vessel diameter of isolated intracerebral arterioles were simultaneously measured following extraluminal application of bFGF in rats. The involvement of NO and adenosine triphosphate-sensitive potassium (KATP) channels in bFGF-induced vasodilation and membrane hyperpolarization was evaluated using specific inhibitors, NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) and glibenclamide (GB, 10(-5) M), respectively. The resting MP was recorded at a mean value of -31.9 +/- 4.5 mV. bFGF (1 to 1000 ng/ml) produced significant vasodilation and hyperpolarization. Treatment with L-NMMA caused vasoconstriction and significantly attenuated bFGF-induced vasodilation without affecting membrane hyperpolarization. In the presence of GB, the membrane potential was significantly depolarized but the vessel diameter was only marginally reduced, so bFGF-induced membrane hyperpolarization was inhibited while arteriolar dilation was attenuated. These results suggest that bFGF-induced vasodilation is mediated by a mechanism involving both NO and membrane hyperpolarization, and that membrane hyperpolarization is caused by the activation of KATP channels.

[Predictive value of prostate specific antigen density in the detection of prostate cancer in patients with elevated prostate specific antigen levels and normal digital rectal findings or stage A prostate cancer].

We compared the usefulness of PSA and PSA density (PSAD) in diagnosing prostate cancer in 102 men who had a PSA value higher than 4.0 ng/ml and normal digital rectal examination and who had undergone transrectal ultrasonography-guided systematic sextant biopsies of the prostate between August 1996 and October 1999. In addition, for a group of 53 patients who underwent retropubic simple prostatectomy, PSA, PSAD and PSA transition zone (PSA-TZ) examination results for those with stage A prostate cancer were compared with the results for those with benign prostatic hyperplasia (BPH). Of the former 102 men, 20 (19.6%) had prostate cancer. There was no significant difference in mean PSA level between patients with negative and those with positive biopsy results (mean 9.3 and 11.8, respectively, p = 0.295), but the mean PSAD of patients with positive biopsy results was significantly higher than that of those with negative results (mean 0.55 and 0.29, respectively, p = 0.0007). Of the 53 men who underwent retropubic simple prostatectomy, 10 (18.9%) were diagnosed with stage A prostate cancer. There was no significant difference in mean PSA, PSAD and PSA-TZ examination results between patients with BPH and those with stage A prostate cancer. For all 102 patients and for 71 patients with PSA levels of 4.1-10.0 ng/ml, a PSAD cutoff value of 0.1 reduced the number of biopsies 15.7% (16 of 102 cases), and 22.5% (16 of 71 cases), respectively. These results suggest that by measurement of PSAD some patients with benign disease could be spared a biopsy which would have been performed based on PSA results alone.

[Seminal vesicle cyst with ipsilateral renal agenesis: a case report].

A 26-year-old man was referred to our hospital for further evaluation of a cystic lesion in the pelvis. He was completely asymptomatic, although he experienced gross hematuria 10 months before his visit. Drip infusion pyelography (DIP) and abdominal computerized tomography (CT) showed a cystic structure behind the bladder and absence of the left kidney. Transrectal ultrasonography (TRUS) suggested left ejaculatory duct obstruction and seminal vesicle deformity. On cystoscopy a large bulging mass under the left side of the bladder was seen. The left half of the trigone and left ureteral orifice were absent. Vasovesiculography demonstrated dilated and tortuous left seminal vesicle. Three days after this procedure, the patient suffered left epididymitis. It did not respond rapidly to antibiotic therapy, so percutaneous drainage of the cyst was performed. He has been completely free of symptoms and no seminal vesicle cysts have been detected on TRUS at five months follow-up.

Efficacy of adjuvant therapy with procarbazine, MCNU, and vincristine for oligodendroglial tumors.

An adjuvant chemotherapy regimen consisting of procarbazine, MCNU, and vincristine (PMV) was evaluated for the treatment of malignant oligodendroglial tumors. Ten patients with histologically proven oligodendroglial tumors were treated with PMV therapy and the effectiveness was assessed using magnetic resonance imaging. Four patients with primary tumors underwent PMV after radiation therapy, and six patients with recurrent tumors were treated using PMV only. Tumor response was defined as radiological evidence of mass size change after completion of three courses of PMV. Complete or partial responses (more than 50% reduction in tumor mass) were noted in six patients, and tumor growth stabilized in four patients. In particular, inhibition of tumor growth using PMV was achieved in three patients with recurrent oligodendroglial tumors, despite the initial response after chemoradiation therapy (interferon-beta, MCNU, radiation) or nitrosourea chemotherapy (ACNU, MCNU). This PMV regimen (a modified PCV regimen using drugs available in Japan) is effective for treating malignant oligodendroglial tumors despite recurrence after other initial treatment procedures.

Sensitive assay to detect thyroid stimulating antibody (TSAb) in the presence of thyroid stimulation blocking antibody (TSBAb) in serum.

The detection of thyroid stimulating antibody (TSAb) activity in the presence of thyroid stimulation blocking antibody (TSBAb) in Graves' serum is difficult because TSBAb blocks TSAb activity. We recently demonstrated that polyethylene glycol (PEG) augments TSAb activity in porcine thyroid cells (PTC) assay. This PEG-induced augmentation makes it possible to develop a sensitive assay to detect TSAb in the presence of TSBAb. We studied the effects of PEG on TSAb- and TSBAb-activities in PTC using 4 different preparations of the samples; (1) crude IgG using PEG 22.5% precipitated fraction (PF) from Graves' serum (0.2 ml), (2) crude IgG using PEG 12.5% PF, (3) serum (50 microl), and (4) serum (50 microl) in the presence of 5% PEG (final). When the effects of PEG on TSAb activity using crude IgG were examined, PEG 22.5% PF showed significantly higher TSAb activity than PEG 12.5% PF as reported previously. The augmentative effect of PEG on TSAb activity was also observed by the addition of 5% PEG to serum. We also demonstrated that PEG augmented TSAb-activities even in TSBAb-positive serum by two methods (crude IgG using PEG 22.5% PF and the addition of 5% PEG to serum). TSBAb activities were expressed by two calculation methods (A= [1 - (a - b)/(c - d) x 100] and B = [1 - (a - d)/(c - d) x 100], where a is cAMP produced in the presence of bTSH and patient's IgG, b is cAMP produced in the presence of patient's IgG, c is cAMP produced in the presence of bTSH and normal IgG, and d is cAMP produced in the presence of normal IgG). In the presence of TSAb, the values of A method were always higher than those of B method, since TSAb stimulated cAMP synthesis. We have developed two sensitive methods to detect TSAb even in the presence of TSBAb in serum using PEG; 1) incubation of crude IgG using PEG 22.5% PF from serum (0.2 ml), and 2) co-incubation of 5 % PEG with test serum (50 microl).