Natural killer cell activity and serum immunoglobulins in epileptic patients

Serum immunoglobulins and the activity of natural killer (NK) cells of 50 epileptic patients (eight with idiopathic generalized epilepsy and 42 with cryptogenic partial epilepsy) and 28 controls have been studied. The values of IgA, IgG and IgM were the same-in patients and controls. The NK activity in controls was linearly related to the effector-to-target ratio, but this linear relationship was not observed in epileptic patients. The cytotoxic activity of NK cells at the lowest effector-to-target ratio was significantly greater in patients than in controls. This increase was observed in each therapy group. Our results seem to confirm a disturbance of the immune system in epileptic patients and suggest that this modification of cellular immunity is not a drug effect but is related to the illness itself.     

β-N-Acetylhexosaminadases in human cerebrospinal fluid and serum of patients with multiple sclerosis

β-N-Acetylhexosaminidase activity and isoenzyme have been investigated in normal human cerebrospinal fluid and that of patients with multiple sclerosis. β-N-acetylhexosaminidase activity in normal cerebrospinal fluids has been resolved into five components. The major component was in a form that eluted from DEAE cellulose at the same salt concentration as hexosaminidase As, the isoenzyme previously identified in human serum. Cerebrospinal fluid from patients exhibited a different isoenzyme profile, showing a remarkable increase in a form having a pI which was more acidic than that of As. These changes have a potential use in the diagnosis and further biochemical characterization of multiple sclerosis.     

Interaction of Nucleoside Analogues with the Sodium–Nucleoside Transport System in Brush Border Membrane Vesicles from Human Kidney

The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na⁺-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na⁺-driven ³H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na⁺–uridine transport was determined. At a concentration of 100 µM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na+-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na+-uridine uptake with a K _i of 26.4 µM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na⁺–nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The K _i of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside.     

Aspects of three dimensional reconstruction for a multi ring positron tomography

An important feature of multi ring positron tomographs is the inter plane septa, the purpose of which is to reduce random and scattered coincidences. In general, such septa also eliminate the coincidence lines of response between pairs of detectors more than one ring apart. The operation of a camera without septa must result in an increase not only in the true coincidence rate, but also in the singles, and therefore in the dead time and randoms rate, and in the scattered coincidences. A configuration option in the coincidence hardware of the 8 ring, 15 slice ECAT 931/08-12 enables a full set of 64 sinograms to be acquired when the septa are removed. The detector normalisation and transmission data for studies with the septa out can be obtained using a rotating pin source. To take maximum advantage of the additional signal, the emission data must be reconstructed using a fully three dimensional reconstruction algorithm. This paper presents an analysis of some phantom studies acquired without septa and reconstructed in three dimensions. The results are compared with data acquired with septa for the same phantoms imaged under similar conditions. It is found that, with the septa removed, the signal to noise for a uniform, 20 cm diameter cylinder improves by a factor of 2.8 in the centre of the field of view, whereas in regions distant from the centre in the axial direction, the signal to noise decreases due to the increase in scatter and randoms. An improvement in signal to noise is observed in 6 cm of the 10 cm axial length of the tomograph.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model

In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion. To test this hypothesis, healing bone was investigated within a rabbit incisor extraction socket, a subcritical size bone defect that resists significant soft tissue invasion by virtue of its conformity. After removal of the incisor teeth, one tooth socket was left as an empty control, one was filled with crosslinked polymer networks formed from the hydrophobic polymer poly(propylene fumarate) (PPF), and one was filled with a hydrogel formed from the hydrophilic oligomer oligo(poly(ethylene glycol) fumarate) (OPF). At five different times (4 days as well as 1, 2, 4, and 8 weeks), jaw bone specimens containing the tooth sockets were removed. We analyzed bone healing by histomorphometrical analysis of hematoxylin and eosin stained sections as well as immunohistochemically stained sections. The proposed hypothesis, that a hydrophilic material would hinder bone healing, was supported by the histomorphometrical results. In addition, the immunohistochemical results reflect molecular signaling indicative of the early invasion of platelets, the vascularization of wound-healing tissue, the differentiation of migrating progenitor cells, and the formation and remodeling of bone tissue. Finally, the results emphasize the need to consider biomaterial properties and their differing effects upon endogenous growth factors, and thus bone healing, during the development of tissue engineering devices.     

Association between presenilin-1 -48C/T polymorphism and Down's syndrome

Individuals with Down's syndrome (DS), i.e., trisomy 21, over 40 years of age, are likely to develop neuropathological changes characteristic of Alzheimer's disease (AD). The involvement of chromosome 21 both in DS and AD suggests a shared genetic susceptibility to these disorders, but genetic determinants are still undefined. The -48C/T polymorphism in the PSEN1 promoter is a possible candidate, since it has recently been associated with an increased risk of early onset AD. Based on the assumption that the excess of dementia in DS might be a consequence of a different distribution of the -48C/T polymorphism, we investigated the association between DS and this polymorphism in patients with trisomy 21 and controls. Overall, 260 DS patients and 197 controls were recruited at the Department of Neurosciences, Tor Vergata University of Rome. Cases and controls had similar age and gender distribution. High molecular weight DNA was extracted from whole blood samples collected in EDTANa(2) and -48C/T genotypes were determined. Genotype and allele frequencies were compared between cases and controls. Cases were less likely than controls to have the CC genotype ( P = 0.05). A significant difference for allele distribution between DS cases and controls was found, with DS showing a lower frequency of the allele C compared with the control population (OR: 0.57; 95% CI: 0.35-0.91; P = 0.01). No significant interaction of PSEN1 with age, gender, ApoE and -850 TNF-alpha polymorphisms was found. The association found suggests that the -48C/T polymorphism in the PSN1 gene promoter, which is involved in the modulation of amyloid beta load in human AD, is associated with DS. However, the biological role of this polymorphism in DS-related dementia remains unclear and merits further investigation.     

Performance characteristics of a rapid new immunochromatographic test for detection of antibodies to human immunodeficiency virus

A new immunochromatographic rapid test (Rapid Check HIV 1 and 2; Núcleo de Doen?as Infecciosas) for the detection of antibodies to human immunodeficiency virus type 1 and type 2 in human samples (whole blood, serum, and plasma) was evaluated and compared to the commercially available Determine (Abbott Laboratories). When whole-blood samples were evaluated, the specificity and sensitivity of both tests were 100%. However, when plasma samples were used, sensitivity for the Rapid Check HIV 1&2 and the Determine tests were 100 and 98.58%, respectively. The observed specificity for plasma samples was 98.94% for the Rapid Check HIV 1&2 and 96.97% for the Determine test. The results presented here are encouraging and support the adoption of both tests as an alternative to enzyme-lined immunosorbent assay and/or Western blots in regions where laboratorial infrastructure is not available or for use in the management of occupational accidents for healthcare workers.     

Towards improved clinical characterization of Leber congenital amaurosis: neurological and systemic findings

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy that presents in infancy. LCA is both clinically and genetically heterogeneous. The aim of our study was to clarify the clinical aspects of LCA and to contribute to improved characterization of the disorder. We studied 40 children affected by LCA (mean age at first observation: 19 months, range: 8-50 months), who underwent a comprehensive evaluation that included: neurophthalmological evaluation, electroretinogram (ERG), and visual evoked potentials (VEPs), general and neurological examinations, developmental assessment using scales for visually impaired children, neuroradiological examinations, hepatic and renal function and metabolic investigations, brainstem auditory evoked potentials (BAEPs), EEG, and hand radiographs. Analyses of known LCA genes are ongoing. The subjects are still being followed up at 6-/12-month intervals. All the subjects fulfilled De Laey's criteria for LCA. The neurological examination was abnormal in 31 cases (hypotonia, ataxia with/without associated cerebellar signs). Cognitive development was normal in 24 cases, borderline in five, and subnormal in 11. Mild and nonspecific alterations on MRI were present in seven cases, and "molar tooth" sign in four; all the others had a normal neuroradiological picture. Among the subjects presenting with neurological signs, a subgroup (13 patients) emerged that was characterized by systemic (skin, kidney, liver) involvement. Our data confirm that LCA is a heterogeneous entity that can present as an isolated ocular manifestation, or in association with neurological and systemic abnormalities and support the need for a multidisciplinary approach to this entity and for genotype-phenotype studies.     

Different patterns of 11q allelic losses in digestive endocrine tumors

Most foregut digestive endocrine neoplasms may be associated with the multiple endocrine type 1 (MEN-1) syndrome. In contrast, midgut/hindgut carcinoids never show such association. To investigate the pathogenetic involvement of the MEN-1 gene and of putative additional oncosuppressor gene(s) distal to it, a comparative analysis of loss of heterozygosity (LOH) at chromosome 11q13 to 11qter was performed in 27 foregut (pancreatic endocrine tumors [PETs]), 23 midgut (ileal and appendiceal), and 3 hindgut (rectal) endocrine tumors. LOH at the MEN-1 gene locus at 11q13 was observed in 52% of the 23 sporadic and in all 4 MEN-1-associated PETs and was found to consistently and continuously span to the most distal marker investigated at 11qter. In contrast, only occasional, discontinuous, and mostly interstitial LOH for 11q markers was observed in ileal (midgut) carcinoids, whereas no LOH was found in all appendiceal (midgut) and rectal (hindgut) carcinoids. The consistent extension of LOH from the MEN-1 region to 11qter in sporadic PETs suggests a mechanism of gene inactivation via chromosomal breakage and complete loss of chromosome 11q; furthermore, these results expand beyond the 11q13 region the search for additional oncosuppressor gene(s) potentially involved in the genesis of these neoplasms. The low frequency, limited extension, and discontinuous distribution of 11q deletions in midgut/hindgut carcinoids suggest that MEN-1 gene is not involved in the pathogenesis of these tumors.