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The need to map regions of brain tissue that are much wider than the field of view of the microscope arises frequently. One common approach is to collect a series of overlapping partial views, and align them to synthesize a montage covering the entire region of interest. We present a method that advances this approach in multiple ways. Our method (1) produces a globally consistent joint registration of an unorganized collection of three-dimensional (3-D) multi-channel images with or without stage micrometer data; (2) produces accurate registrations withstanding changes in scale, rotation, translation and shear by using a 3-D affine transformation model; (3) achieves complete automation, and does not require any parameter settings; (4) handles low and variable overlaps (5-15%) between adjacent images, minimizing the number of images required to cover a tissue region; (5) has the self-diagnostic ability to recognize registration failures instead of delivering incorrect results; (6) can handle a broad range of biological images by exploiting generic alignment cues from multiple fluorescence channels without requiring segmentation and (7) is computationally efficient enough to run on desktop computers regardless of the number of images. The algorithm was tested with several tissue samples of at least 50 image tiles, involving over 5000 image pairs. It correctly registered all image pairs with an overlap greater than 7%, correctly recognized all failures, and successfully joint-registered all images for all tissue samples studied. This algorithm is disseminated freely to the community as included with the Fluorescence Association Rules for Multi-Dimensional Insight toolkit for microscopy (http://www.farsight-toolkit.org)., (© 2011 The Authors Journal of Microscopy © 2011 Royal Microscopical Society.)

The developing central neural circuits in teleosts are genetically controlled and temperature-initiated. We compiled a list of transcripts expressed in the developing tilapia (Oreochromis mossambicus) brain using expressed sequence tags derived from the developing brain, and investigated genes with thermosensitive ontogenetic expression. Of 1084 clones, 893 were unique genes, 445 of which were known. Fourteen of the latter were neural development-related, and the ontogenetic expression of nine was temperature-influenced. Discs large homolog 5, myelin expression factor 2, plasticity-related protein-2, tsc2 gene product-related genes, and an inhibitor of differentiation protein 2 (Id2) were differentially temperature-influenced according to their developmental stages. Endothelial differentiation-related factor 1, midkine-related growth factor b, and mitogen-activated protein kinase 14b were specifically influenced by elevated temperature, and beta-catenin-like isoform 1 by lower temperature. Neural development-related genes, particularly those with thermosensitive ontogenetic expression, might be important for developing central neural circuits in teleosts.

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.

The aim of this study was to investigate the pharmacokinetics of desflurane uptake into the brain and body by comparing desflurane concentrations in internal jugular-bulb blood (Jdes), arterial blood (Ades) and pulmonary arterial blood (PAdes) at a fixed inspired desflurane concentration. Thirteen patients (aged 42-72 years) undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 5% inspired desflurane concentration (CIdes) during the first hour of anaesthesia. Under constant volume-controlled ventilation, CIdes and end-tidal desflurane (CEdes) were measured with an infrared analyser. The desflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. It took 24 min for the Jdes to equilibrate with Ades. Both CIdes-CEdes and Ades-PAdes gradients persisted during the study period. There was no further uptake of desflurane into the brain after 24 min but there was near-constant uptake into the body.

99mTc ethyl cysteinate dimer (99mTc-ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in patients with acute carbon monoxide (CO) poisoning. Ten patients with acute CO poisoning and no past histories of psychoneurological disorders were enrolled in this study. After oxygen treatment, all of the 10 patients were investigated using 99mTc-ECD brain SPECT and brain computed tomography (CT) scan. Brain CT scan findings were normal in all of the 10 patients. 99mTc-ECD brain SPECT showed the hypoperfusion lesions of the basal ganglia and brain cortex in five and seven patients, respectively. Only three of the 10 patients had normal 99mTc-ECD brain SPECT findings. This study suggests that, in comparison with brain CT scan, 99mTc-ECD brain SPECT is a better tool for the early detection of hypoperfusion brain lesions in acute CO poisoning in patients with normal brain CT findings.

The aim of this study was to investigate the pharmacokinetics of sevoflurane uptake into the brain and body by comparing sevoflurane concentrations in internal jugular-bulb blood (Jsev), arterial blood (Asev) and pulmonary arterial blood (PAsev) over a fixed inspired sevoflurane concentration. Ten patients (aged 51-73 years), undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 3.5% inspired sevoflurane concentration (CIsev) during the first hour of anaesthesia. During constant volume-controlled ventilation, we measured CIsev and end-tidal sevoflurane (CEsev) using infrared analysis. The sevoflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. We found that it took 40 min for the brain concentration to equilibrate with arterial blood (Asev). Both CIsev-CEsev and Asev-PAsev gradients persisted during the study period. There was no further uptake of sevoflurane into the brain after 40 min; however, there was near-constant uptake into the body.

Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 32 female patients with primary Sjögren's syndrome (PSS) showing definite neuropsychiatric symptoms/signs and normal brain magnetic resonance imaging (MRI) findings. It demonstrated hypoperfusion brain lesions in 18 (56.3%) of the patients, most frequently in the parietal lobes, and appears to be a sensitive tool for this clinical application.

Water temperature has a differential influence on the development of central neurotransmitter systems according to the developmental period in tilapia (Oreochromis mossambicus). Aromatase and oestrogen receptors (ERs) represent important components of the mechanism of brain differentiation. Gene expression of aromatase and ERs is modulated by neurotransmitters in the developing brain. In the present study, the quantitative reverse transcription-polymerase chain reaction method was used to investigate the effects of temperature on the ontogenetic expression of aromatase and ERs in the developing tilapia brain. Before day 10 posthatching, exposure to a higher temperature (32 degrees C) resulted in a significant increase in the expression of brain aromatase; conversely, a lower temperature (20 degrees C) resulted in a decrease. ERalpha expression was depressed in accordance with the decrease of temperature, but ERbeta was unaffected by temperature. Between days 10 and 20, neither brain aromatase nor ERalpha expression was altered by temperature, whereas ERbeta expression was significantly enhanced by exposure to 32 degrees C. Between days 20 and 30, brain aromatase significantly increased at the higher temperature and decreased at 20 degrees C, but neither ERalpha nor ERbeta was affected by temperature. The expression of both brain aromatase and ERs, differentially regulated according to the temperature and to the developmental period, could be related to brain-sex differentiation.

High-affinity glycine transport in neurons and glial cells is a primary means of inactivating synaptic glycine. We have synthesized a potent selective inhibitor of glycine transporter 1 (GlyT1), and characterized its activity using a quail fibroblast cell line (QT6). The glycine transporters GlyT1A, GlyT1B, GlyT1C, and GlyT2 were stably expressed in QT6 cells. The transporters expressed in these cells exhibited appropriate characteristics as described previously for these genes: Na(+)/Cl(-) dependence, appropriate K(m) values for glycine uptake, and appropriate pharmacology, as defined in part by the ability of N-methyl glycine (sarcosine) to competitively inhibit glycine transport. Furthermore, the characteristics of the transporters in the cell lines recapitulate the characteristics of glycine transporters observed in tissue preparations. We developed a sarcosine derivative, (R)-(N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine (ALX 5407), and examined its activity against the cloned glycine transporters. ALX 5407 completely inhibited glycine transport in the GlyT1 cells, with an IC(50) value of 3 nM, but had little or no activity at the human GlyT2 transporter, at other binding sites for glycine, or at other neurotransmitter transporters. The inhibition of glycine transport was essentially irreversible. ALX 5407 represents a novel tool in the investigation of N-methyl-D-aspartate-receptor function. This class of drug may lead to novel therapies in the treatment of schizophrenia.

The period of maximal feminizing action of 17beta-estradiol (E(2)) upon sex ratio is before 10 days posthatching in tilapia (Oreochromis mossambicus). The effect of E(2) at this time is mimicked by para-chlorophenylalanine (p-CPA), a serotonin (5-hydroxytryptamine; 5-HT) synthesis inhibitor. The effect of E(2) on sexual differentiation may be mediated by the 5-HT system, which is consistent with the suggestion in mammals. The masculinizing actions of 17alpha-methyltestosterone (MT) are most potent later at up to day 20 of age, and may depend on MT induction of aromatase activity. In the present study, the effects of gonadal steroids and p-CPA on brain aromatase and estrogen receptor (ER) mRNA expression during the critical period of sexual differentiation were investigated. Treatment of tilapia with E(2) resulted in a significant decrease in the expression of brain aromatase and ERalpha between days 0 and 10, but not subsequently. The effect of E(2) at this time can be mimicked by p-CPA. Treatment of tilapia with MT, by contrast, resulted in a significant increase in brain aromatase, ERalpha and ERbeta mRNA expression when given between days 10 and 20. The downregulation of brain aromatase and ERalpha mRNA expression by E(2) before 10 days of age and, in turn, the upregulation of brain aromatase and ERalpha and ERbeta mRNA expression by MT at up to day 20 of age coincide with the period in which E(2) and MT have the maximal effect on gonadal feminization and masculinization, respectively., (Copyright 2001 S. Karger AG, Basel)

The alteration of gamma-aminobutyric acid (GABA) and glutamate (Glu) contents in the discrete brain of female tilapia during the certain stages of gonadal cycle was investigated. Both hypothalamic GABA and Glu showed a significantly higher content in the prespawning female than that in the recrudesced and regressed females, which there was no significant difference. In the different gonadal status of female, both telencephalic GABA and Glu showed a maximal content during the prespawning phase and a minimal content during the recrudesced phase. Neither GABA nor Glu content was altered with the gonadal phases in the optic lobe and cerebellum of female tilapia. These results indicate that the alteration of GABA and Glu contents in the hypothalamus and telencephalon, but neither in the optic lobe nor cerebellum, is consistent with the gonadal cycle.

The effects of gonadal steroids on brain serotonin (5-HT) and aromatase activity during the critical period of sexual differentiation were investigated in tilapia, Oreochromis mossambicus. Treatment of tilapia with 17beta-oestradiol (E2) between days 7 and 10 posthatching resulted in a significant increase in the female : male ratio as determined at day 90, and a significant reduction in brain 5-HT content. Treatment between days 10 and 20, or between days 20 and 30, had no significant effect. Since the 5-HT system may influence sexual differentiation, we examined the effects of para-chlorophenylalanine (p-CPA), a 5-HT synthesis inhibitor. As with E2, treatment of tilapia with p-CPA between days 7 and 10 posthatching resulted in a significant increase in the female : male ratio. Again, treatment between days 10 and 20, or between days 20 and 30, had no significant effect. Both p-CPA and E2 significantly depressed brain aromatase activity when administrated between days 7 and 10, but not subsequently. In tilapia treated between days 7 and 10, the brain 5-HT content was lowered by E2 to an extent similar to that seen with p-CPA, which is consistent with the suggestion that the effect of E2 on sexual differentiation may be mediated by the 5-HT system. Treatment of tilapia with 17alpha-methyltestosterone (MT), by contrast, resulted in a reduction in the female : male ratio, and treatment was most effective when given between days 10 and 20. The period of maximal effect of MT upon sex ratio appears to coincide with the ability of MT to induce an increase in brain aromatase activity.

The effects of temperature on the development of central neurotransmitter systems were investigated with tilapia, Oreochromis mossambicus. Zero-day-old (the hatching day) tilapia were kept at four different temperatures: 20 (lower), 24 (control), and 28 and 32 degrees C (elevated), respectively. On the 5th day, brain serotonin (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA), and glutamate (Glu) contents were quantified by a high-performance liquid chromatograph with electrochemical detection. Similar experiments were performed on the 5-, 10-, 15-, 20-, and 25-day-olds. The results showed that aquatic temperature influenced brain 5-HT, NE, Glu, and GABA contents during its respective restricted period. The influence of both lower and elevated temperatures on the neurotransmitter content, either increasing or suppressing, is dependent on its developing stage. The facts provide an evidence that the development of central neurotransmitter systems is influenced by aquatic temperature during its specific effective period.

The effects of gonadal steroids on the gamma-aminobutyric acid (GABA) and glutamate (Glu) contents of the early developing brain were investigated. Seven-day-old (7 days post-hatch) tilapia were divided into three groups which were continuously treated with 100 mg/kg diet 17beta-estradiol (E2), 100 mg/kg diet methyltestosterone (MT), and a normal diet, respectively. Until 10, 20, and 30 days old, the GABA and Glu contents of the brains were detected by HPLC-ECD. The brain GABA and Glu contents, before 30 days old, significantly increased with age. These results demonstrate that before 30 days old is a developing period of both GABA and Glu systems in the tilapia brain. During this period, both E2 and MT have a facilitative effect on the GABAergic and Gluergic system during a restricted effective period., (Copyright 1999 Elsevier Science B.V.)

The effects of gonadal steroids on serotonin (5-HT) synthesis and metabolism in the early developing brain were investigated. Seven-day-old (7 days post-hatch) tilapia, Oreochromis mossambicus were continuously treated with 17beta-estradiol (E2), methyltestosterone (MT) and para-chlorophenylalanine (p-PCA) up to the age of 30 days. The brain 5-HT content, before 30 days, increased with age. The result indicates that this is a developing period of the central 5-HTergic system. During this developing period, the activity of tryptophan hydroxylase (TPH) and monoamine oxidase (MAO) was not altered by age. Both E2 and MT influence the central 5-HT content during its restricted developmental period. E2 has an initial inhibitory effect and then a facilitative effect while MT only has a facilitative effect. The initial inhibitory effect of E2 is mediated by decreasing TPH activity and increasing MAO activity to decrease the 5-HT content. The facilitative effect of both E2 and MT is suppressed by p-CPA.

An 18-month-old girl was diagnosed as having GM1 gangliosidosis, on the basis of the clinical symptoms of muscle stiffness, developmental retardation, hepatosplenomegaly, and kyphoscoliosis and a laboratory study that revealed a deficiency in the lysosomal degradative enzyme beta-galactosidase. Magnetic resonance T1-weighted images showed persistent hyperintensity in the bilateral thalami, brainstem, and deep cerebellum at 14 and 18 months of age, indicating arrest of the myelination process in these areas, and that the arrest had occurred at the newborn stage. There was no myelination in the basal ganglia and diffuse leukomalacia developed in the cerebral hemispheres. Only supportive treatment was given; the patient died at 2 years of age. Myelination arrest at the newborn stage associated with progressive leukomalacia is a possible characteristic of GM1 gangliosidosis.

Effects of thermal acclimation on the serotonin (5-HT) and norepinephrine (NE) contents in the discrete brain of male and female tilapia, Oreochromis mossambicus were investigated. Sexually mature males and females were exposed to 26 degrees C, 29 degrees C, or 32 degrees C of water temperature for 3 weeks. The hypothalamic 5-HT content in the 29 degrees C and 32 degrees C acclimated male was lower than that in the 26 degrees C group. In females, the hypothalamic 5-HT content in the 32 degrees C acclimated group was less than those in the 26 degrees C and 29 degrees C groups. Similar results were found in the hypothalamic NE contents of males and females. In the optic lobe, the elevated temperature acclimation (29 degrees C and 32 degrees C) resulted in a higher 5-HT content in both males and females; whereas, the NE content was increased by the elevated temperature acclimation in females but not altered in that of males. In the telencephalon, the elevated temperature acclimation had no influence on the 5-HT content of males and females, but resulted in a lower NE content in both males and females. These results demonstrate that the neurotransmitter activity of teleost is influenced by the thermal acclimation in a sex- and regional-dependent pattern. The alterations of 5-HT and NE in the central nervous system might be involved in the physiological and biochemical responses that occur during thermal acclimation in fish.

Brain inflammation and paraplegia can be induced by an additional intraperitoneal (i.p.) and intracerebral (i.c.) restimulation in B6 mice after standard immunization with MBP in Freund's complete adjuvant (FCA) and Bordetella pertussis coadjuvant. Only the combination of i.p. MBP/FCA and i.c. MBP injection could induce clinical paraplegia; either one alone was not effective. Clinical symptoms would develop 2 days after the i.c. injection. The induction of paraplegia was MBP-specific, as irrelevant bovine serum albumin with the same protocol could not induce it. The i.p. restimulation was requisite and needed the MBP in FCA, as MBP in PBS was ineffective. Histopathological observation manifested cellular infiltration by leucocytes in perivascular spaces and cerebral cortex. Neutrophils were prominent at 12 h after i.c. injection, then were replaced by mononuclear cells 24 h later. There were dynamic changes in cell number and immunophenotype of VLA-4+ expression in cervical lymph node cells after i.c. injection. The cells derived from cervical lymph nodes had higher MBP-stimulated proliferation than that of distal lymph nodes. This additional i.p. and i.c. stimulation provides a new manipulation to study brain inflammation.

The MRL-lpr/lpr and MRL-(++) mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-alpha expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-(++) mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1 alpha, IL-6 and TNF-alpha in serum than MRL-(++) mice. Interestingly, in MRL-lpr/lpr but not MRL-(++) mice, the IL-6 concentration in cultured supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1 beta were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-(++) mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-alpha expression may predispose the development of autoimmune reactions. The expression of IL-1 beta and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.

In order to know the effect of mercury pollution on the serotonergic system of fish, serotonin concentrations in a discrete brain region of tilapia, Oreochromis mossambicus, were examined. Serotonin concentration was measured using a high performance liquid chromatography system with electrochemical detector. In male fish, the concentrations of serotonin were 1.468 +/- 0.350, 0.811 +/- 0.190 and 0.330 +/- 0.061 micrograms/g wet tissue in hypothalamus, telencephalon and optic lobe, respectively. The serotonin content was significantly different between each region; the hypothalamus had a higher content than that of the telencephalon and optic lobe. The serotonin concentration in female hypothalamus was 1.102 +/- 0.112 micrograms/g wet tissue which was significantly lower than that in males. However, serotonin concentration in the telencephalon and optic lobe showed no difference between male and female. After exposure to 0.015 and 0.03 ppm HgCl2 for 6 months beginning 7 days posthatching, male sample fish showed a significantly dose-dependent decrease in serotonin concentration in the hypothalamus. But a similar phenomenon was not found in other regions of the brain. These results suggest that exposure to HgCl2 results in an attenuated development of the serotonergic system in the hypothalamus of fish.

Polyclonal anticardiolipin antibodies purified from pooled serum samples of patients with systemic lupus erythematosus were shown to have inhibitory effects on cultured normal rat brain astrocytes (RBA-1 cells). Anticardiolipin antibodies at concentrations from 50 to 200 micrograms/ml inhibited the [3H]thymidine incorporation of RBA-1 cells in a dose dependent manner after three days of culture. A kinetic study showed that anticardiolipin antibodies (100 micrograms/ml) maximally inhibit the proliferation of RBA-1 cells (20.6 (5.1)% of the control value) after incubation for one day. In contrast, human gamma globulin (100 micrograms/ml) had no effect on these cells. In the presence of anticardiolipin antibodies (100 micrograms/ml), the RBA-1 cells attached to the bottom of wells became spherical and the expression of glial fibrillary acidic protein in the cytoplasm was slightly reduced. Using 3,3'-dihexyloxacarbocyanine iodide as an indicator, anticardiolipin antibodies depolarised the membrane potential of RBA-1 cells after one day of culture. In addition, the percentage binding of RBA-1 cells with anticardiolipin antibodies was greater than with gamma globulin as determined by flow cytometric analysis. Immunofluorescence staining of brain tissue from BALB/c mice with anticardiolipin antibodies was noted in the corpus callosum, the cellular zone near the corpus callosum, and cells scattered in brain tissue. These results suggest that anticardiolipin antibodies have an inhibitory effect on brain cells and elicit thrombus formation in brain vessels, which plays a part in neuropsychiatric lupus.

The ultimate capabibity and a detailed study of contrast and modulation in the context of photon transmission tomography (or computerized transverse axial tomography (CTAT)) is presented. Quantitative evaluation of atomic number, density and electron density of compound materials were made by X-ray fluorescence and combustion analysis, and the attenuation coefficients of photoelectric and Compton effect were measured with high resolution Ge(Li) and Si(Li) detectors. This study provides a guide to an understanding of the high resolution of the currently existing X-ray transmission CTAT scanner (EMI scanner) and to the future development of high resolution scanners.

This study compared the pain sensitivity, thermal capability, and brain monoamine turnover in normotensive and hypertensive rats. Either the spontaneously hypertensive rats, the experimentally (renal or deoxycorticosterone acetate) hypertensive rats, or their normotensive controls were tested for pain sensitivity by the hot-plate procedure, with the plate maintained at 55 degrees C. The spontaneously hypertensive rats, but not the experimentally hypertensive rats, showed an elevated level of spontaneous pain threshold compared with their appropriate controls. However, both the spontaneously and the experimentally hypertensive rats displayed a reduced sensitivity of analgesic responses to morphine administration. In addition the thermal responses to external stresses in these groups of animals were assessed. It was found that, over an ambient temperature range of 8-30 degrees C, either spontaneously or experimentally hypertensive rats maintained their rectal temperature within a normal limit displayed by their appropriate controls. However, the metabolic rate levels of both spontaneously and experimentally hypertensive rats were elevated at ambient temperatures less than 22 degrees C. Furthermore, compared with their appropriate controls, these hypertensive rats also showed a greater degree of hypothermic responses to chlorpromazine injection. Biochemical examination revealed that either the spontaneously or the experimentally hypertensive rats had a lower serotonin, but a higher catecholamine, turnover in both the hypothalamus and the brain stem compared with their appropriate normotensive controls. The data indicate that, in a hypertensive state, changes in the monoamine turnover of different brain regions may be correlated with the above-mentioned alterations in pain sensitivity and in thermal capability.

Ultrastructural and biochemical studies were carried out on three groups of experimental models which were induced by a single subcutaneous daily dose of 10 to 40 mg./kg. body weight of chlorphentermine hydrochloride. The first group consisted of 20 young adult rats which were sacrificed at intervals of from one to four weeks. The liver and lungs showed concentrically arranged memberanous bodies in the hepatocytes and alveolar cells during the first week after the first injection, while the CNS and pancreas showed no ultrastructural alterations. During the fourth week, the pancreas displayed abnormal cytoplasmic inclusion bodies in the A and B cells of the islets of Langerhans as well as in the exocrine portion. The brain showed various neuronal alterations at four weeks which consisted of irregular dense bodies to well-developed membranous structures which were similar to those of Tay-Sachs disease. Biochemically, thin layer chromatograms showed that the major ganglioside fraction in the brain at four weeks had an RF value similar to that of GM1-ganglioside. In an analysis of the total N-acetyl neuraminic acid the brains in the experimental group contained 90.9% GM1-gandlioside as compared with 44% in the controls. The total and fractions of phospholipids in the brains and livers of the experimental animals were within normal limits.

Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 78 SLE patients with neuropsychiatric manifestations. These patients were separated into two subgroups: group 1 including 48 cases with definite neuropsychiatric symptoms/signs and group 2 with 30 cases having no neuropsychiatric symptoms/signs. Tc-99m ECD brain SPECT demonstrated hypoperfusion brain lesions in 90% and 20% of patients in groups 1 and 2, respectively. In both groups, parietal lobe and cerebellum are the most and least common areas with hypoperfusion lesions, respectively. This study suggests that Tc-99m ECD brain SPECT may provide objective information for detection of hypoperfusion brain lesions in SLE patients. [ABSTRACT FROM AUTHOR]

The MRL-lpr/lpr and MRL-++ mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-α expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-++ mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1α, IL-6 and TNF-α in serum than MRL-++ mice. Interestingly, in MRL-lpr/lpr but not MRL-++ mice, the IL-6 concentration in culture supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1β were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-++ mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-α expression may predispose the development of autoimmune reactions. The expression of IL-1β and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice. [ABSTRACT FROM AUTHOR]