Cerebellin-like peptide: tissue distribution in rat and guinea-pig and its release from rat cerebellum, hypothalamus and cerebellar synaptosomes in vitro

We have developed a specific radioimmunoassay for "cerebellin", a 16-amino acid peptide recently isolated from rat cerebellum. In both rat and guinea-pig, cerebellin-like immunoreactivity was highest in the cerebellum but was also present in high concentrations elsewhere in the central nervous system, especially in the hypothalamus. In both species, cerebellin-like immunoreactivity was found in other organs (heart, kidney and stomach) and at lower concentrations in the gastrointestinal tract. In the brain of both species, cerebellin-like immunoreactivity consisted of a single molecular form with an elution position on gel filtration and high-performance liquid chromatography identical to that of synthetic rat cerebellin. However, peripheral tissue contained an additional immunoreactive peak of higher molecular weight. Cerebellin was concentrated in synaptosomal preparations of rat brain, and its subcellular distribution pattern in rat brain was identical to that of two other known synaptosomal peptides, vasoactive intestinal polypeptide and substance P. Studies with superfused cerebellar synaptosomes and slices of rat cerebellum and hypothalamus demonstrated calcium-dependent cerebellin release when stimulated by high potassium concentrations as well as the addition of the calcium ionophore A23187. Cerebellin has therefore a widespread distribution and fulfils two criteria for a neurotransmitter, in that it is found in brain synaptosomes and shows calcium dependent, depolarization-induced release from nervous tissues and isolated nerve endings. It may, therefore, be a component of a novel neurotransmitter system.     

Preparation of a monospecific antiserum to thyroxine binding globulin for its quantitation by rocket immunoelectrophoresis

A simple technique is described for the preparation of a high titre monospecific antiserum to human serum thyroxine-binding globulin (TBG). This allows quantitation of the protein by rocket immunoelectrophoresis in 6 h with a day-to-day coefficient of variation of 2.9%. Using this technique serum concentrations of TBG have been determined in groups of patients in good health, in pregnancy and in women on oral contraceptive therapy     

Musculoskeletal manifestations of diabetes mellitus

Rheumatic complaints are common in patients with diabetes. Maintaining good glycaemic control by exercise, diet, and medication improves or prevents the development of rheumatic conditions.     

Fractionated conformal radiotherapy in vestibular schwannoma: early results from a single centre

AimsTo assess the local control and cranial nerve toxicity in vestibular schwannoma patients treated with fractionated conformal radiotherapy delivered using a linear accelerator.Materials and methodsNinety-five patients were referred for consultation to the Oncology Department in Addenbrookes Hospital between 1996 and 2005. The 42 cases who received fractionated conformal radiotherapy are the subject of this analysis. All patients had radiological or symptomatic progression. Conformal radiotherapy was prescribed at 50 Gy in 30 fractions over 6 weeks, delivered using a linear accelerator. Patients were immobilised using either a beam direction shell or a Gill Thomas Cosman relocatable stereotactic head frame.ResultsThe median age was 63 years (range 28–81) with 57% men. The average tumour size was 21.5 mm on magnetic resonance imaging. Before treatment, 20 (48%) patients were deemed to have useful hearing on the affected side. The median follow-up was 18.6 months (range 0.3–6.5 years) and the actuarial local control rate at 2.5 years was 96.9% (one patient progressed after treatment). In previously hearing patients, the actuarial rate of useful hearing preservation was 100%, and the rate of mild hearing loss was 20% at 1 year and 26.7% at 2.5 years of follow-up. There were five neurofibromatosis type 2 patients treated, two of whom had useful hearing before radiotherapy. In one patient this was affected, with a 20 dB loss, although he still has useful hearing. In those with normal facial nerve function before radiotherapy (n = 40), this was preserved in 96.8% at 2.5 years. Trigeminal nerve function was preserved in all patients (n = 38) who had normal nerve function before radiotherapy.ConclusionAlthough follow-up was relatively short in this single institution series, fractionated linear accelerator radiotherapy gave excellent local control, useful hearing preservation and retained cranial nerve function in vestibular schwannoma.     

Increased cortical neuronal responses to NMDA and improved attentional set-shifting performance in rats following prebiotic (B-GOS®) ingestion

We have previously shown that prebiotics (dietary fibres that augment the growth of indigenous beneficial gut bacteria) such as Bimuno^? galacto-oligosaccharides (B-GOS^®), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat brain. The current investigation examined the functional correlates of these changes in B-GOS^®-fed rats by measuring cortical neuronal responses to NMDA using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the attentional set-shifting task. Adult male rats were supplemented with B-GOS^® in the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing. Cortical neuronal responses to NMDA iontophoresis, were greater (+30%) in B-GOS^® administered rats compared to non-supplemented controls. The intake of B-GOS^® also partially hindered the reduction of NMDA responses by the glycine site antagonist, HA-966. In the attentional set-shifting task, B-GOS^® -fed rats shifted from an intra-dimensional to an extra-dimensional set in fewer trials than controls, thereby indicating greater cognitive flexibility. An initial exploration into the mechanisms revealed that rats ingesting B-GOS^® had increased levels of plasma acetate, and cortical GluN2B subunits and Acetyl Co-A Carboxylase mRNA. These changes were also observed in rats fed daily for 3 weeks with glyceryl triacetate, though unlike B-GOS^®, cortical histone deacetylase (HDAC1, HDAC2) mRNAs were also increased which suggested an additional epigenetic action of direct acetate supplementation. Our data demonstrate that a pro-cognitive effect of B-GOS^® intake in rats is associated with an increase in cortical NMDA receptor function, but the role of circulating acetate derived from gut bacterial fermentation of this prebiotic requires further investigation.     

Spironolactone as a source of interference in commercial digoxin immunoassays

Eight commercial digoxin immunoassay methods were tested in 17 subjects taking spironolactone (but not digoxin) to evaluate cross-reactivity from parent drug and/or metabolites. Four of these methods showed significant (up to 1.9 nmol/L) and variable "apparent digoxin" concentrations, despite the absence of digoxin in the drug regimen. The results suggest that clinical laboratories require a knowledge of their method with respect to spironolactone-related cross-reactivity and should exercise caution when interpreting digoxin results where spironolactone is coadministered. Further, the presence of concurrent renal and/or hepatic impairment could delay clearance of spironolactone metabolites (as well as digoxin metabolites and endogenous substances) and further distort a genuine digoxin result.     

The independent effect of body mass index on health-related quality of life among racial and ethnic subgroups

Purpose

To evaluate the impact of race/ethnicity on the relationship between body mass index (BMI) and health-related quality of life (HRQOL) among blacks, Hispanics, and whites.

Methods

We used the Sinai Urban Health Institute’s Improving Community Health Survey dataset to measure physical and mental HRQOL using the Physical Component Score (PCS-12) and the Mental Component Score (MCS-12) of the Short Form-12. Multivariate linear regression models were applied to the overall sample and in models stratified by race/ethnicity to evaluate the effects of BMI on physical and mental HRQOL outcome variables while controlling for confounders.

Results

Considering physical HRQOL, increasing BMI was independently associated with worse PCS-12 (β = ?0.22, p value <0.001) in the overall sample; the magnitude was not significantly different across racial/ethnic subgroups (blacks: β = ?0.18, p value = 0.02; Hispanics: β = ?0.28, p value = 0.01; whites: β = ?0.20, p value = 0.02). Overall, Hispanic participants reported a worse PCS-12 compared to whites (β = ?3.06, p value = 0.002). Considering mental HRQOL, BMI was not significantly associated with MCS-12 in the overall sample (β = ?0.06, p value = 0.21) nor was BMI significantly associated with MCS-12 in any racial/ethnic subgroups. Overall, black participants reported better MCS-12 compared to whites (β = 2.51, p value = 0.001).

Conclusions

BMI was associated with worse physical HRQOL to a similar degree among blacks, Hispanics, and whites. This finding suggests that interventions leading to obesity reduction should be associated with substantial and equal improvements in the physical HRQOL of all race/ethnicity groups.     

Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B beta 54-118) in degradation products of fibrin and of fibrinogen

Balb/c mice were immunized with a mixture of fibrin degradation products (XDPs) prepared by complete lysis of a human blood clot by tissue-type plasminogen activator and purified by immunoaffinity chromatography. Spleen cells of the mice were fused with P3 X 63 Ag 8653 myeloma cells. A clone (FDP 14) was selected that produces monoclonal antibodies (MoAbs) of the IgG1 kappa type that react with a neoantigenic determinant exposed in these XDPs, but not in intact fibrinogen or in fibrin monomers. Furthermore, the MoAb is reactive with some pure, individual degradation products of fibrinogen (fragments X, Y, E, and the N-terminal disulphide knot) and with the fibrinogen B beta-chain but not with A alpha- and gamma-chains or with fragments D, FCB-2 and FCB-3. Comparison of the known primary structures of these fibrinogen fragments indicates that the stretch B beta 54-118 comprises at least an important part of the epitope recognized by FDP-14. Apparently, this stretch contributes importantly to a neoantigenic determinant that is not functional in intact fibrinogen and fibrin monomer and that can be made functional by reduction of fibrinogen, or by digestion with plasmin or CNBr.     

Spondylometaphyseal dysplasia, corner fracture type: a heritable condition associated with coxa vara

The authors present the radiographic features of a previously incompletely delineated bone dysplasia, which they call spondylometaphyseal dysplasia, corner fracture type. This is a dominant heritable condition associated with short stature and developmental coxa vara. The progressive hip deformity usually causes significant disability requiring surgical correction. Developmental coxa vara, simulated corner fractures of long tubular bones, and vertebral body abnormalities result in a diagnostic constellation. Knowledge of these distinctive radiologic features allows accurate diagnosis, which in turn should lead to appropriate genetic counseling and possibly to earlier, more efficacious surgical treatment of the coxa vara.