Simulation of the capacity and precision of working memory in the hypodopaminergic state: Relevance to schizophrenia.

Working memory (WM) impairment has received attention as a behavioral characteristic of schizophrenia. Neurobiological studies have led to the hypothesis that a deficit in dopamine transmission through D1 receptors in the prefrontal cortex (PFC) is associated with WM impairment in schizophrenia. However, empirical approaches that aim to clarify the nature of the impairment and its underlying mechanism are difficult to enact, especially in unmedicated patients. By contrast, computational approaches using biologically plausible models have formed a powerful theoretical framework for the study of WM impairment in schizophrenia. This article attempts to directly connect neurobiological findings to the neuropsychological behaviors present in patients with schizophrenia. Using a biologically plausible prefrontal cortical circuit model, we simulated sustained activity during a simultaneous, multi-target WM task. We subsequently analyzed how dopaminergic modulation via D1 receptor activation alters the capacity and precision of WM and investigated the underlying mechanism. Hypodopaminergic modulation resulted in imprecision and a reduced capacity in WM primarily due to decreased N-methyl-d-aspartate (NMDA) conductance. Increasing NMDA conductance ameliorated both impairments. These results account for the mechanism that underlies WM impairments in schizophrenia and provide a theoretical basis for combination therapy with antipsychotic drugs and drugs that enhance NMDA receptor function, which is expected to be effective for the treatment of WM impairments in these patients.

Incrustation and uptake of skeletal imaging agent in transitional cell carcinoma.

We present a case of transitional cell carcinoma of the bladder visualized by 99mTc-HMDP bone scintigraphy and suggest possible uptake mechanisms. Pelvic CT demonstrated a sessile bladder tumor with punctate and curvilinear calcifications on the surface areas (incrustation). Technetium-99m-HMDP bone scintigraphy demonstrated intense uptake corresponding to the site of the bladder tumor. Chemisorption of urinary 99mTc-HMDP, rather than of blood-born 99mTc-HMDP, may have occurred at the tumor surface.

Comparison of fluorine-18-FDG PET and thallium-201 SPECT in evaluation of lung cancer.

UNLABELLED: We compared the diagnostic value of [18F]2-fluoro-2-deoxy-D-glucose (FDG) PET imaging and 201Tl SPECT imaging in the detection of primary lung cancer and mediastinal lymph node metastases. METHODS: Thirty-three patients with histologically-proven primary lung cancer were examined with both FDG PET and TI SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the tumor-to-nontumor activity ratio (T-to-N ratio) was calculated. RESULTS: Although both techniques delineated focal lesions with an increase in tracer accumulation in 28 patients, PET identified three additional patients in whom Tl SPECT images did not visualize any lesions on both early and delayed scans. In the detection of lung cancer of less than 2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than did Tl SPECT early scan (one of seven, 14.3%) and delayed scan (four of seven, 57.1%). Neither technique visualized any lesions in two patients who had bronchioloalveolar carcinoma. The T-to-N ratio was significantly higher with FDG PET (10.39 +/- 6.63) than it was with Tl SPECT (early scan, 2.37 +/- 0.86; delayed scan, 3.01 +/- 1.01) (p < 0.0001), whereas there was significant positive correlation between the FDG T-to-N ratio and the thallium T-to-N ratio (p < 0.01). Twenty-two patients had thoracotomies. Regarding the staging of mediastinal nodes, FDG PET detected mediastinal lymph node metastasis that was negative on Tl SPECT, whereas both techniques excluded tumor involvement in enlarged node at CT. CONCLUSION: Both techniques have clinical value for the noninvasive detection of primary lung cancer that is 2 cm or greater in diameter. However, if a PET camera is available, FDG PET is considered the method of choice for the evaluation of patients with suspected primary lung cancer that is less than 2 cm in diameter.

Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma.

UNLABELLED: The goals of our study were to establish PET accuracy with 18F-fluorodeoxyglucose (FDG) in finding localized formations of bronchioloalveolar lung carcinoma (BAC) and to investigate the correlation between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung. MATERIALS: Twenty-nine patients with 30 adenocarcinomas of the lung (7 bronchioloalveolar lung carcinomas, 9 well differentiated, 2 well-moderately differentiated, 11 moderately differentiated and 1 poorly differentiated) were studied. All patients underwent thoracotomies within 4 wk after the FDG PET study. For qualitative analysis, the degree of FDG activity in the tumors was visually scored using a five-point grading system: 0 = same to background activity, 1 = less than mediastinal blood-pool activity, 2 = same to mediastinal blood-pool activity, 3 = slightly greater than mediastinal blood-pool activity and 4 = substantially greater than mediastinal blood-pool activity. Foci of activity with Grades 2-4 were considered tumors. For semiquantitative analysis, standardized uptake values (SUV) were calculated. RESULTS: In 7 BACs, 4 lesions (57%) showed negative results on FDG PET, while in 23 non-BACs, only 1 lesion (4%), which was a well-differentiated adenocarcinoma showed a negative result. BACs' mean visual score (1.43 +/- 1.27) was significantly lower than that of non-BACs (3.17 +/- 1.03) (p = 0.001). The BACs' mean SUV (1.36 +/- 0.821) was significantly lower than that of well-differentiated adenocarcinomas (2.92 +/- 1.28) (p = 0.014); the mean SUV of well-differentiated adenocarcinomas was significantly lower than that of moderately differentiated adenocarcinomas (4.63 +/- 1.86) (p = 0.031). No significant differences were apparent in average size among these three histologic types. CONCLUSION: A correlation was observed between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung. FDG PET may show negative results for BAC.

Intraocular lesions in patients with systemic disease: findings on MR imaging.

Twenty-one intraocular lesions associated with various systemic diseases in 15 patients were studied by MR imaging. The disorders included diabetes mellitus, cardiovascular disease, Behçet disease, sarcoidosis, and ankylosing spondylitis. MR was performed on a 0.5-T system using a surface-coil technique. Ophthalmoscopic visualization of the fundus was precluded by the presence of opaque media in all cases. MR was found to be effective in demonstrating intraocular bleeding, vitreous opacity, detached lesions of the posterior pole, and eyeball deformity. Surface-coil MR is a useful adjunct in the evaluation of the eyes affected by systemic diseases, especially in patients with opaque media.

MR sialography in patients with Sjögren syndrome.

PURPOSE: The purpose of this study was to evaluate the effectiveness of MR sialography of the parotid gland ducts in the diagnosis and staging of Sjögren syndrome. METHODS: MR imaging was performed on a 1.5-T unit with a neck phased-array coil. MR sialographic source images were obtained using a heavily T2-weighted fast spin-echo sequence with spectral fat suppression. All images were analyzed on the basis of maximum intensity projection reconstruction. Five healthy control subjects and 51 patients with definite Sjögren syndrome (43 with primary disease and eight with secondary disease) were examined with MR sialography. A labial gland biopsy was performed in all patients and histopathologic grading was done by means of focal scores. The findings of MR sialography were compared with the results of labial gland biopsy to determine the effectiveness of the technique in the diagnosis and staging of Sjögren syndrome. RESULTS: In all five control subjects, the main duct and the primary branching ducts of the parotid glands were clearly visible on MR sialographic images. In patients with Sjögren syndrome, a punctate, globular, cavitary, or destructive appearance was well seen within the parotid glands. Findings obtained at MR sialography correlated well with the results of labial gland biopsy. CONCLUSION: MR sialography has the potential to produce diagnostic findings in the parotid gland ducts of patients with Sjögren syndrome. Our results suggest that this method will augment and possibly replace X-ray sialography.

Gallium-67-citrate scintigraphy of primary renal lymphoma.

We present a case of primary renal lymphoma, which is a rare entity and poses diagnostic challenge. Ultrasound and CT scan demonstrated a nonspecific solid tumor in the left kidney. 67Ga-citrate scintigraphy demonstrated an intense uptake in the tumor, which led to a correct diagnosis, so that we could spare unnecessary laparotomy and possible nephrectomy.

Single photon emission CT images in a case of intraventricular neurocytoma.

Although Tc-99m HMPAO uptakes in various brain tumors have been reported, SPECT images of neurocytoma have not been described. The authors report a patient with intraventricular neurocytoma (IN) who demonstrated significant uptake of Tc-99m HMPAO and Tl-201 Cl before brain biopsy. Residual tumor after biopsy showed significant uptake of I-123 IMP on early SPECT images, but this uptake was decreased on delayed images. The three radionuclides seem to have different uptake mechanisms.

SA96: an immunopharmacological profile in vitro.

We have screened from various thiol compounds SA96 (2-mercapto-2-methylpropanolyl-L-cysteine) as a stimulant of LPS-induced proliferative response of murine lymphocytes, and the immunopharmacological profile of this compound was studied in vitro. SA96, only at 10(-3) M concentration, caused 3H-thymidine (3H-TdR)uptake in the presence of foetal calf serum (FCS). The effects of SA96 on the proliferative response to mitogens were biphasic. The uptake 3H-TdR induced by Con A or LPS was suppressed in a dose-dependent manner below 10(-4) M, but was enhanced at 10(-3) M in the case of LPS. The response to Con A was recovered from the suppression at 10(-3) M, but did not exceed the control level. Some experiments suggested that cysteine moiety might importantly contribute to the proliferative response caused by SA96. SA96 enhanced the PFC response to SRBC in vitro at 10(-5) approximately 10(-4) M (nonmitogenic doses), but markedly inhibited the elevated response in the presence of 2-mercaptoethanol (2-ME). On the other hand, PFC response to DNP-Ficoll )a T-independent antigen) was augmented by SA96 irrespective of the presence of 2-ME. These findings suggest that SA96, a thiol compound, may be useful as an immunomodulator like levamisole.

Determination of C-reactive protein in serum and plasma from healthy dogs and dogs with pneumonia by ELISA and slide reversed passive latex agglutination test.

The concentrations of C-reactive protein (CRP) in serum from dogs diagnosed as normal by clinical, haematological, and biochemical examination were determined by enzyme-linked immunosorbent assay (ELISA) and slide reversed passive latex agglutination (RPLA), using IgG antibody isolated from rabbit anti-canine CRP serum. The mean value of CRP in 66 normal dogs kept in private households was 8.4 +/- 4.9 micrograms/ml by ELISA and 8.5 +/- 6.3 micrograms/ml by RPLA. Thus, no significant difference was demonstrated between the values obtained by ELISA and RPLA. No significant age and sex-related differences were found in the CRP values. The mean concentration of CRP in 84 6-month-old Beagle dogs kept in kennels by breeders was 6.2 +/- 3.9 micrograms/ml by ELISA and 8.0 +/- 4.0 micrograms/ml by RPLA. Again no significant difference was found. The CRP values determined by ELISA and RPLA were closely correlated (r = 0.913). The serum and plasma concentrations of CRP measured by RPLA were also closely correlated (r = 0.994). This indicates that plasma can be used as well as serum to determine CRP concentrations by RPLA.

Quantitative capillary reversed passive latex agglutination test for C-reactive protein (CRP) in the dog.

A capillary reversed passive latex agglutination test (capillary RPLA) was developed which allows quantification of serum C-reactive protein (CRP) within approximately 15 min. The logarithmic regression line (calibration curve) obtained after measuring each CRP concentration three times in twofold dilutions of a standard canine serum containing 222 micrograms/ml of CRP was y = 6.394 + 0.030x (r = 0.995). Capillary RPLA permitted quantification of CRP in the range 6.9-222 micrograms/ml. The coefficients of variation ranged from 10.28% to 12.40%. The recovery rates (percentage recovery) of CRP by capillary RPLA were within the range 87% to 106%. On measuring the CRP concentrations in sera from 78 dogs by capillary RPLA, single radial immunodiffusion (SRID) and enzyme-linked immunosorbent assay (ELISA), close correlations were demonstrated between SRID and capillary RPLA (y = 7.250 + 1.109x, r = 0.978), between SRID and ELISA (y = 3.042 + 1.059x, r = 0.967), and between capillary RPLA and ELISA (y = 1.778 + 0.929x, r = 0.962). Capillary RPLA may be considered useful as a routine biochemical technique for measurement of serum CRP concentration in the dog.

[Relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma)].

This investigation was undertaken to evaluate the relationship between Ga-67 uptake and radiotherapeutic response to primary lung cancer (squamous cell carcinoma), Ga-67 uptake of tumor was estimated on 16 patients with untreated primary lung cancer (squamous cell carcinoma). Ga-67 uptake was then compared with the response to radiation therapy (tumor reduction ratio). There was statistically significant inverse correlation between Ga-67 uptake and response to radiation therapy (r = -0.701, p less than 0.01). The fewer the Ga-67 accumulation in the tumor, the more effective radiotherapy in reducing tumor size. In conclusion, Ga-67 scintigraphy appears to be able to predict the response of primary lung cancer (squamous cell carcinoma) to radiation therapy.

[The influence of ferric metabolism on Ga-67 distribution in the human body].

This investigation was undertaken to make clear the influence of ferric metabolism on Ga-67 distribution in human body. Count ratios for each organ to femoral soft tissue (i.e. relative Ga-67 uptake) were calculated in 125 scintigrams obtained 48 hours following injection, and the relation between the relative Ga-67 uptake in each organ and serum Fe, or UIBC were investigated. The relative Ga-67 uptake in the liver and the lumbar vertebra had negative correlation to serum Fe, and had positive correlation to UIBC. However, there was no significant difference in the relative Ga-67 uptake in the lumbar vertebra between normal and high serum Fe group. Only in group with exceedingly low serum Fe, each vertebral body was visualized separately in posterior view of the abdomen. These findings indicated that in group with exceedingly low serum Fe, Ga-67 accumulated mainly in the bone marrow, and in group with high serum Fe, Ga-67 accumulated mainly in the bone. The urinary bladder was visualized only in group with high serum Fe, which suggested that the excretion of Ga-67 to the urine was continued yet at 48 hours after injection. Ferric metabolism affected remarkably on the relative Ga-67 uptake in the liver, the bone marrow and the bone, and also the excretion of Ga-67 to the urine.

[Comparative studies on the antitumor activities and side effects of segmental SMANCS/Lip-TAE with segmental SMANCS/Lip-TAI for hepatocellular carcinoma].

We compared the effectiveness of treatments and the influence of side effects on liver function and clinical symptoms between segmental SMANCS/ Lip TAI and segmental SMANCS/Lip-TAE. The early tumor response rate of the group treated by TAI was 23.6%, and that of the group treated by TAE was 80.0%. In the group treated by TAE, the therapeutic effects were better in the nodular type than in the diffuse type of HCC, and we were also able to obtain a good tumor response rate on the multiple HCC and large HCC. However, there was no difference in the response period between the groups treated by TAI and TAE. In both groups, there were no significant differences in the appearance rate and degree of side effects. In conclusion, segmental SMANCS/Lip-TAE seemed to be an effective treatment for HCC without any serious complications.

[A study on the dosage of carboplatin for bronchial arterial infusion in combination with radiation therapy].

Radiation therapy holds an important position as one of the multidisciplinary methods of treating lung cancer (non-small cell carcinoma). As a result of the development of platinum preparations such as cisplatin (CDDP) and wide use of digital subtraction angiography (DSA), selective bronchial arterial infusion (BAI) therapy made possible more effective use of anti-lung cancer drugs. The use of radiation therapy in combination with BAI is now recommended as a more effective method. Meanwhile carboplatin (CBDCA) has recently been developed as a second generation platinum preparation with less side effects, and is being used for BAI, too. However, the maximum tolerated dose (MTD) of CB DCA for BAI to be used in combination with radiation therapy is not known yet. We, therefore, carried out a phase-study to determine MTD of CBD CA for combination with radiation therapy. The results show that the MTD of CBDCA is 400 mg/m2, and that clinically recommendable infusion limit is 350 mg/m2. In an angiographic study performed at the same time, a plural number of tumor affected blood vessels were found in 81.3% of the patients with lung cancer. Therefore, infusion of a drug for such patients should be carefully applied.

[Efficiency of segmental SMANCS/Lip-TAE for hepatocellular carcinoma--comparative studies in the efficacy of segmental SMANCS/Lip-TAI].

We compared the segmental SMANCS/Lip-TAI and the segmental SMANCS/Lip-TAE and studied the effectiveness of both treatments and the influence and/or the side effects on liver function. In resected cases, we studied histopathologic examination. The response rate of the group treated by TAI was 28.6%, and that of the group treated by TAE was 76.5%. In the group treated by TAE, the therapeutic effects were good in nodular type HCC, using small doses of SMANCS. In both groups, the incidence and degree of side effects showed no significant difference. Hepatic insufficiency occurred in a few cases of the group treated by TAI. In resected cases, viable areas remained below the tumor capsule. In conclusion, segmental SMANCS/Lip-TAE seemed to be an effective treatment without any serious complications.