Neuronal activity in the globus pallidus in chorea caused by striatal lacunar infarction

Pallidotomy was performed in a patient with hemichorea caused by lacunar infarction in the striatum. Chorea in the lower limb was reduced after a neurosurgical lesion in the medial portion of the sensorimotor territory of the internal segment of the globus pallidus, and chorea in the upper limb disappeared after an additional lesion in the lateral portion of that same area. Intraoperative neuronal recording revealed that mean firing rates were low, and that firing was irregular in the globus pallidus compared with off-state parkinsonian patients. These results suggest that chorea with striatal infarction is driven by phasic neuronal activity with a low firing rate in the globus pallidus and that the neural pathway of chorea has a functional somatotopical organization in the globus pallidus.     

Astroglial function of schizophrenic brain: a study using lobotomized brain

The neurodevelopmental hypothesis is now being recognized as one of the most useful hypothesis for schizophrenia, and by using it, abnormalities in protein associated with neuron growth or neuronal migration have been reported. From neuron-glia interrelations in the neural development, it is important to study the function of astroglia in the schizophrenic brain. In this study, we examined the neuropathological reaction of astroglia using lobotomized brains, and a significant decrease of astroglia after artificial histological damage was observed in schizophrenic brains. We speculated that this may be due to the latent vulnerability of the dynamic function of astroglia in schizophrenia. Astroglia plays a guidance role on migration and if astroglia has latent vulnerability, we speculate that younger neurons may not sufficiently migrate during development. In further investigation of the neurodevelopmental hypothesis of schizophrenia, it will be necessary to examine the function of astroglia.     

Diffuse neurofibrillary tangles with calcification (a form of dementia): X-ray spectrometric evidence of lead accumulation in calcified regions

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of slowly progressive dementia in which no senile plaques are observed. The calcification is one of the most characteristic features of DNTC. We examined the elemental content of certain mineral deposits (lead, magnesium, phosphorus, calcium, iron, copper and zinc) in the calcified and non-calcified regions of eight cases of DNTC, five cases of Alzheimer's disease (AD) and in eight non-demented elderly controls. The study was performed using a combination of scanning electron microscopy and X-ray spectrometry on 10% formalin-fixed brain tissue. A marked abundance of calcium and phosphorus was observed in the calcified regions of DNTC and non-DNTC brains. Although no lead was observed in the non-calcified regions of DNTC and in non-DNTC brains, traces of lead were detected exclusively in the calcified regions of DNTC brains. The implications and possible significance of the lead accumulation in DNTC brains are discussed.     

Oral delivery of xeno-antigen combined with non-depleting anti-CD4 monoclonal antibody induces significantly prolonged survival of concordant skin xenograft

Abstract: Oral administration can induce unresponsiveness to protein antigens. Therefore, we examined whether oral administration of xeno-antigen could induce the prolonged survival of xenogeneic skin grafts. CBA mice were given 1 × 10⁷ SD rat splenocytes orally, 7 days before transplantation of a SD rat skin in the presence or absence of a non-depleting anti-CD4 monoclonal antibody (mAb) (YTS177, 200 µg/dose, −8 and −7 days relative to transplantation). All skin grafts survived with a median survival time (MST) of 62 days when xeno-antigens were administered orally in combination with anti-CD4 mAb. Mice treated with anti-CD4 mAb alone or oral administration of xeno-antigen alone induced modest prolonged survival of rat skin grafts (MST = 18 and 19 days, respectively) while naive mice rejected rat skin acutely (MST = 12 days). Oral administration alone or combined with anti-CD4 mAb reduced the level of xeno-antibody production compared with that in untreated mice after transplantation. Xenogeneic mixed leukocyte response was reduced when splenocytes from mice pre-treated with oral administration of xenogeneic cells were used as the responder compared with that in untreated mice. Oral delivery of xeno-antigen plus non-depleting anti-CD4 mAb can induce prolongation of concordant xenogeneic skin grafts.     

The Value of Ultrasound-Guided Fine-Needle Aspiration Cytology for Thyroid Nodules: An Assessment of Its Diagnostic Potential and Pitfalls

This study was conducted to assess the diagnostic potential and pitfalls of performing fine-needle aspiration cytology (FNAC) for thyroid nodules. We retrospectively analyzed 1012 aspirated samples obtained from 806 thyroid nodules by the ultrasound (US)-guided method. Of these 806 nodules, 226 (31%) had been surgically treated, 152 (67%) of which were histologically diagnosed as malignant. The rate of sufficient aspirate was 82%, being lower in nodules with a diameter of less than 5 mm (73%, P = 0.10); either calcified (77%, P = 0.043) or benign (72%, P = 0.0002). The accuracy of FNAC was 75%, the rate of indeterminate diagnosis was 16%, the false negative rate was 13%, and the positive malignancy rate was 99%. The rate of indeterminate diagnosis was higher in adenomatous goiter, follicular carcinoma, and malignant lymphoma, at P = 0.015, P = 0.0008, and P = 0.035, respectively. The accuracy was lower in follicular carcinoma and malignant lymphoma (both at P = 0.013). Sufficient aspirate was finally obtained from 701 (87%) of the 806 nodules by repeated aspiration. Of 152 malignant nodules, 28 (18%) were diagnosed after two or more aspirations, and the accuracy was improved to 81% by repeating the procedure. These findings indicated that repeated aspiration may be a simple and effective method of improving the diagnostic potential of FNAC. Received: November 1, 1999 / Accepted: September 26, 2000     

Assigning time-linked exposure status to controls in unmatched case-control studies: alcohol use and nearly lethal suicide attempts

In case-control studies, determination of alcohol consumption by cases immediately prior to the injury event is often conceptually straightforward. However, determination of consumption status by controls is difficult because they lack a reference point, especially when cases and controls are not individually matched. We describe a method of assigning alcohol consumption status to controls using a 24-hour drinking history, the distribution in time of case events, and the random assignment of a specific time period to each control subject. This methodology offers a practical approach for determining alcohol consumption status among control subjects immediately prior to a case event, when controls lack a reference point and have not been individually matched to cases. Published in 2001 by John Wiley & Sons, Ltd.     

Expression of mitochondrial thioredoxin-dependent antioxidant protein, SP-22, in normal human and inflammatory mouse placentae

The aim of this study was to elucidate whether a novel mitochondrial antioxidant protein, SP-22, is localized in placenta and whether its expression is induced in placenta of lipopolysaccharide (LPS)-exposed mouse. Western blot analysis of normal human placenta indicated that the SP-22 protein was located in the mitochondrial fraction. Immunohistochemical analysis of SP-22 in normal placenta showed that immunoreactive SP-22 was distributed mostly in cytotrophoblastic cells but with almost no signal in syncytiotrophoblasts. The positive signals were also detected in the decidual cells and stromal cells in stem villi of normal placenta. We also examined LPS-mediated inflammatory placenta on day 13 of pregnancy at various time points after LPS injection (50 microg/kg, intraperitoneally). Western blot analysis indicated that LPS approximately quadrupled the expression of SP-22 in placenta of LPS-exposed mouse. When the SP-22 protein was localized immunohistochemically, the decidua and the diploid trophoblasts in the basal zone were intensively stained in placenta of LPS-exposed mouse compared to the control. The localization and inducible expression of SP-22 protein in placenta suggest a possible role in antioxidant system in mitochondria of normal and inflammatory placentae.     

Inter-laboratory comparison of DNA preservation in archival paraffin-embedded human brain tissue from participating centres on four continents

DNA extracted from formalin-fixed and paraffin-embedded brain tissue is known to contain as yet ill-characterized inhibitors of the PCR process. As part of a project that aims to clarify the role of mitochondrial DNA sequence variation in human neurodegenerative diseases using DNA from various ethnic backgrounds, we have investigated factors that influence the preservation of archival DNA and its suitability for PCR. In this study, neuropathological tissue samples were analysed that had been routinely processed in 18 international centres on four continents. Following DNA extraction, PCR amplification of mitochondrial and nuclear DNA sequences was performed with and without additional purification of the template DNA. In addition, the DNA used for PCR was analysed by HPLC. Phosphate-buffered formalin proved to be a superior fixative compared with unbuffered aldehyde: DNA extraction resulted in greater yields, the molecular weight of the isolated DNA was higher and PCR was more successful. PCR inhibitors were identified as (1) high concentrations of small (<300 bp) DNA fragments that competitively compete with template DNA and (2) contaminants of the DNA template solution including denatured protein that cannot be completely removed by phenolic extraction. HPLC analysis did not reveal significant qualitative differences between DNA isolated from fresh-frozen tissue samples and DNA recovered from formalin-fixed, paraffin-embedded brain tissue. The fact that DNA could be amplified from the majority of tissue specimens in this study suggests that rare diseases and diseases where ethnic background plays an important role can be sampled for genetic polymorphism analysis on a global scale using archival neuropathological collections. Electronic Publication