Immunolocalization of transitional cell carcinoma of the bladder with intravesically administered technetium-99m labelled HMFG1 monoclonal antibody

The aim of this study was the immunolocalization of transitional cell carcinoma of the bladder with a radiolabelled murine tumour-associated monoclonal antibody and the measurement of the absolute uptake of the antibody by the tumour. Fourteen patients with transitional cell carcinoma of the bladder received 3–6 mCi (111–222 MBq) of technetium-99m labelled HMFG1 monoclonal antibody intravesically and one patient, 2 mCi (74 MBq) of iodine-131 labelled 11.4.1, which is a non-tumour-specific monoclonal antibody. Four of the 15 patients were evaluated with singlephoton emission tomography (SPET) 1 1/2 to 2 h post administration. All patients underwent transurethral resection of the bladder tumour within 12–20 h following intravesical administration of the radiolabelled antibody. The radioactivity of biopsy specimens from normal urothelium and tumour areas were counted in a gamma counter. The mean uptake of the radiolabelled antibodies from normal and tumour sites was expressed as a percentage of the administered dose per kilogram of tissue. Conventional histology and immunohistochemistry using HMFGI monoclonal antibody were performed on paraffin sections of the biopsy specimens. Although our results are preliminary, it can be concluded that: (a) bladder tumours are well imaged by SPET when using^99mTc-HMFG1; (b) intravesically administered radiolabelled antibody remains on the bladder tissue and does not escape into the systemic circulation; (c) the wide range of tumour uptake values (0%–9.3% administered dose/kg) observed probably can be attributed to heterogeneity of the antigenic expression of the tumour; (d) values of^99mTc-HMFGI monoclonal antibody uptake by the tumour do not justify future attempts at radioimmunotherapy.     

Lung volumes in infants who had mild to moderate bronchopulmonary dysplasia

New bronchopulmonary dysplasia (BPD) has been suggested to be a maldevelopment sequence with reduced alveolarisation of the lungs; affected infants then would be predicted to have low lung volumes. The aim of this study was to test that hypothesis by comparing the lung volumes of infants who had had mild-moderate BPD with those without BPD of similar postmenstrual age. Lung volumes of 17 infants who had mild-moderate BPD (oxygen dependent beyond 28 days, but not past term) (BPD infants) were compared to those of 17 infants without BPD (non-BPD infants). All were born at less than 33 weeks of gestation and studied at postmenstrual ages of 33 to 39 weeks. Lung volume was assessed by measurement of functional residual capacity (FRC). The BPD infants had lower lung volumes (median 19.1 ml/kg) than the non-BPD infants (median 26.5 ml/kg) (p=0.0001). The BPD compared to the non-BPD infants were of greater postnatal age (p=0.0003), born at a lower gestational age (p=0.0001) and of lighter birthweight (p=0.0001). Regression analysis, however, demonstrated that lung volume was significantly related to BPD status (p=0.005), independently of postnatal age, birthweight and gestational age. It is concluded that the lower lung volumes of the infants who had had mild-moderate BPD support the hypothesis that new BPD is associated with poor alveolarisation.     

Increased serum CA-15.3 levels in patients with megaloblastic anemia due to vitamin B12 deficiency

OBJECTIVES: To estimate the usefulness of serum tumor markers' monitoring, as predictors of gastric cancer in patients with pernicious anemia. PATIENTS AND METHODS: We investigated serum levels of carcinoembryonic antigen (CEA), alpha-fetal protein, cancer antigen (CA)-19.9, CA-125 and CA-15.3 in 50 patients with pernicious anemia and in 24 healthy controls, matched for age and sex. In 38 patients, the evaluation was repeated 1-6 months after the correction of cobalamin deficiency. RESULTS: All patients and controls had normal serum CEA and alpha-FP, and the levels of these markers as well as those of CA-125 and CA-19.9 did not differ between the two groups. All 50 patients, but only 2 controls exhibited increased serum CA-15.3, and the difference between the two groups was very significant (129.4 +/- 84.9 vs. 19.8 +/- 7.3 IU/ml, p < 0.001), while no difference between males and females was found. A thorough clinical examination of all patients, and mammographic study in 18 females did not reveal any finding suspicious of breast cancer. CA-15.3 levels were positively correlated with serum lactate dehydrogenase, and negatively with B(12) and hemoglobin, but they were substantially decreased after the correction of anemia, in all 38 patients tested, and in 33 of them they were restored to normal. After a median follow-up of 34 months, one patient developed a colon cancer, but none showed any sign suspicious of breast cancer. CONCLUSIONS: Serum CA-15.3 shows an aberrant increase in untreated patients with pernicious anemia, which is reversed after the correction of the anemia. The possible origin seems unrelated to mammary tissue, and may be released by the apoptosing bone marrow megaloblastic erythroblasts.     

A SERCA2 pump with an increased Ca2+ affinity can lead to severe cardiac hypertrophy, stress intolerance and reduced life span

Abnormal Ca(2+) cycling in the failing heart might be corrected by enhancing the activity of the cardiac Ca(2+) pump, the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) isoform. This can be obtained by increasing the pump's affinity for Ca(2+) by suppressing phospholamban (PLB) activity, the in vivo inhibitor of SERCA2a. In SKO mice, gene-targeted replacement of SERCA2a by SERCA2b, a pump with a higher Ca(2+) affinity, results in cardiac hypertrophy and dysfunction. The stronger PLB inhibition on cardiac morphology and performance observed in SKO was investigated here in DKO mice, which were obtained by crossing SKO with PLB(-/-) mice. The affinity for Ca(2+) of SERCA2 was found to be further increased in these DKO mice. Relative to wild-type and SKO mice, DKO mice were much less spontaneously active and showed a reduced life span. The DKO mice also displayed a severe cardiac phenotype characterized by a more pronounced concentric hypertrophy, diastolic dysfunction and increased ventricular stiffness. Strikingly, beta-adrenergic or forced exercise stress induced acute heart failure and death in DKO mice. Therefore, the increased PLB inhibition represents a compensation for the imposed high Ca(2+)-affinity of SERCA2b in the SKO heart. Limiting SERCA2's affinity for Ca(2+) is physiologically important for normal cardiac function. An improved Ca(2+) transport in the sarcoplasmic reticulum may correct Ca(2+) mishandling in heart failure, but a SERCA pump with a much higher Ca(2+) affinity may be detrimental.     

Neural stem/progenitor cells differentiate into oligodendrocytes,reduce inflammation,and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury

The central nervous system has limited capacity for regeneration after traumatic injury. Transplantation of neural stem/progenitor cells (NPCs) has been proposed as a potential therapeutic approach while insulin‐like growth factor I (IGF‐I) has neuroprotective properties following various experimental insults to the nervous system. We have previously shown that NPCs transduced with a lentiviral vector for IGF‐I overexpression have an enhanced ability to give rise to neurons in vitro but also in vivo, upon transplantation in a mouse model of temporal lobe epilepsy. Here we studied the regenerative potential of NPCs, IGF‐I‐transduced or not, in a mouse model of hippocampal mechanical injury. NPC transplantation, with or without IGF‐I transduction, rescued the injury‐induced spatial learning deficits as revealed in the Morris Water Maze. Moreover, it had beneficial effects on the host tissue by reducing astroglial activation and microglial/macrophage accumulation while enhancing generation of endogenous oligodendrocyte precursor cells. One or two months after transplantation the grafted NPCs had migrated towards the lesion site and in the neighboring myelin‐rich regions. Transplanted cells differentiated toward the oligodendroglial, but not the neuronal or astrocytic lineages, expressing the early and late oligodendrocyte markers NG2, Olig2, and CNPase. The newly generated oligodendrocytes reached maturity and formed myelin internodes. Our current and previous observations illustrate the high plasticity of transplanted NPCs which can acquire injury‐dependent phenotypes within the host CNS, supporting the fact that reciprocal interactions between transplanted cells and the host tissue are an important factor to be considered when designing prospective cell‐based therapies for CNS degenerative conditions. GLIA 2016;64:763–779     

Serum Vitamins D,B9 and B12 in Greek Patients with Inflammatory Bowel Diseases

Deficiencies in vitamin D, folate and cobalamin are common in Inflammatory Bowel Disease (IBD). The aim of the present study was to assess serum levels of these vitamins in IBD adults based on the respective serum cut off values for vitamin deficiencies, and to explore possible associations with IBD-related biomarkers and nutritional intake. A cross-sectional study was carried out and patients with Crohn’s disease (CD) or ulcerative colitis (UC) from Attica-Greece were enrolled. Medical and dietary history, clinical examination and blood/stool biomarkers were evaluated. In total, 87 patients participated in the study. Serum levels of 25(OH)D, folate and cobalamin were deficient in 36.8%, 18.4% and 5.7% of patients, respectively. Linear regression analysis in the overall patients showed positive associations between (a) serum 25(OH)D with serum iron (beta = 0.083, p = 0.005) and (b) serum cobalamin with total bilirubin (beta = 0.357, p = 0.020) and direct bilirubin (beta = 0.727, p = 0.033), adjusting for age, sex, body mass index (BMI), disease activity and duration, smoking, nutritional intake and season of recruitment. In CD patients (N = 54), a negative linear association between serum folate and fecal lysozyme was evident (beta = −0.009, p = 0.020). No associations were found for UC patients (N = 33). The serum vitamin profile may be a complementary biomarker for the evaluation of disease activity next to serum and stool inflammatory biomarkers.     

Changes in Vascular Tone Occur Early During Hemodialysis Treatments Independently of Volume Reduction

Hypotension commonly occurs during hemodialysis (HD). Hypotension can result from an absolute reduction in plasma volume following excessive ultrafiltration or from a reduction in vascular tone. We hypothesized that changes in vascular tone could occur during dialysis. Aortic pulse wave velocity (aPWV) was measured in 197 HD patients, mean age 63.3 ± 16.6 years, 62% male, 49% diabetic, during a single HD session. aPWV did not change (9.6 ± 2.2 vs. 9.6 ± 2.2 m/s) with HD. Systolic blood pressure (SBP) declined from 151 ± 31 to 147 ± 32 after 20 min and to 140 ± 36 mm Hg on completion of HD (P < 0.05), with an ultrafiltration volume of 2.2 ± 0.9 L over a 3.9 ± 0.4 h HD session. Aortic SBP declined from 154 ± 32 to 146 ± 29 after 20 min and 143 ± 35 at the end of HD, P < 0.001. Aortic augmentation index (Aortic Aix) decreased from 65% (52–79%) to 36.7% (23.3–52.9%) by 20 min and to 34.3 (15.1–49.1%) on completion of HD (P < 0.05), and brachial augmentation index (brachial Aix) from 5.7% (?25.2 to 27.5%) to ?1.9% (?2.2 to 30.1%) and ?6.6% (?44 to 22.7%), respectively, P < 0.05. Diastolic reflection area (DRA) increased from 36.7 (27.9–46.3) to 40.4 (32.2–51) after 20 min and 47.1 (34.2–60.5) on completion of HD, P < 0.05. We report changes in arterial tone within 20 min of starting HD, when minimal ultrafiltration has occurred, suggesting that volume changes may not be the only predisposing cause of intradialytic hypotension. The combination of a fall in SBP and a rise in DRA would suggest a reduction in coronary blood flow in keeping with reports of “myocardial stunning” during HD.