Heat-shock protein (HSP70-2) allelic frequencies in three distinct Mexican populations

The major histocompatibility complex (MHC) genes are highly polymorphic and therefore have been useful in population genetics and disease association studies. We analyzed restriction fragment length polymorphism of HSP70-2 alleles in healthy unrelated Mestizo, Mazatecan and Nahua populations. Both Indian groups, Mazatecans and Nahuas, were in Hardy-Weinberg equilibrium, while Mestizos were in disequilibrium (chi 2 = 0.399; P < 0.05). The Mazatecan Indians presented a high frequency of BB homozygosity (17.35%) compared to Mestizos (5%) (P = 0.01). Mexican ethnic groups present differences in distribution of BB genotype. The low frequency of BB genotype in Mestizos may be the result of a negative selection process.     

Expression and changes of HSP70 in the rat forebrain subjected to gamma knife (100Gy) irradiation targeted on the caudate putamen and survived for different times

Forebrain heat shock protein 70 (HSP70) immunohistochemical reactivity was investigated in rats subjected to gamma knife irradiation focusing on the right caudate putamen nucleus. The forebrain sections of all experimental animals were processed with anti-HSP70 antiserum and then by avidin-biotin peroxidase complex immunohistochemistry after gamma ray irradiation with a dose of 100Gy and they each survived for different times (from 30 min to 30 days). Some neurons, glial cells, and endothelial cells were HSP70-like immunoreactivity (HSP70-LI) positive. HSP70-LI was mainly distributed in the target area of irradiation, as well as in non-target regions, e.g. the cortex, hippocampus, and hypothalamus, etc. The expression and change of HSP70-LI from 3 h to 30 days after irradiation followed the following rules: (1) Within 3 to 24 h, the dilated vessels with HSP70-LI endothelial cells were found at first, and a few lightly stained HSP70-LI neurons and glias were observed in the target and non-target regions; (2) In 3-7 days, darkly stained HSP70-LI neurons and glias were apparently increased and formed an expression peak. From 14 to 30 days, HSP70-LI cells were distinctly decreased and became weakly stained or negative. These results suggested that although the irradiation target of the gamma knife was localized, the response to irradiation occurred extensively.     

Cooperative transformation of murine fibroblast NIH3T3 cells by hepatitis C virus core protein and hepatitis B virus X protein

Co-infection with hepatitis B virus (HBV) and hepatitis C Virus (HCV) is associated with increased frequency in the development of hepatocellular carcinoma (HCC). Here, we demonstrated that HBV X protein (HBx) and HCV core cooperate to transform mouse fibroblast NIH3T3 cells. They additively stimulated cell growth, especially in the absence of serum growth factors. In addition, co-expression of HBx and HCV core had additive effects on the induction of anchorage-independent cell growth as well as on the secretion of matrix metalloproteases, which may contribute to increased metastatic potential. Furthermore, the cells expressing both viral proteins exhibited higher tumorigenicity, as demonstrated in athymic nude mice.     

Projections from the hypothalamus and its adjacent areas to the posterior pituitary in the rat

Cholera toxin conjugated horseradish peroxidase was injected into the posterior pituitary and its afferents traced in 21 albino rats. The neuronal processes as well as the perikarya were elaborately displayed. The principal and retrochiasmatic supraoptic nuclei and the magnocellular paraventricular subnuclei were densely labelled. The accessory cell groups or nuclei labelled included: the medial preoptic and anterior hypothalamic areas, the anterior and posterior fornical nuclei, the lateral hypothalamic area, the nucleus circularis and nucleus of the forebrain bundle and hitherto unknown or not fully appreciated retrochiasmatic area, the dorsal accessory groups in an area between the stria medullaris and fornix, on the one hand, and the stria terminalis and internal capsule, on the other, and a well developed subependymalperiventricular zone. The medial preoptic nucleus, subfornical organ and organ vasculosum laminae terminalis were also weakly stained. Dendrites of the magnocellular paraventricular nucleus have been said by some to be largely confined to the subnuclei in which they lie. Immunohistochemical studies have proved that they extended beyond their nuclear confinement. The present study has found much wider extension of their dendritic fields. In fact, dendrites of the magnocellular neurosecretory cells in general were long and had a certain degree of directional bias. Several sites projecting to the posterior pituitary were closely related to the cerebrospinal fluid. Namely, the subependymal neuronal plexuses along the third ventricle and beneath the interventricular foramen, and the subpial dendritic plexuses of the supraoptic and retrochiasmatic supraoptic nuclei. Neurons were seen to squeeze in-between the ependymal cells, bringing themselves very close to the cerebrospinal fluid. No direct cerebrospinal fluid-contacting elements, either cell bodies or processes, however, could be ascertained. It is proposed that these plexuses may monitor changes in the cerebrospinal fluid. Besides the principal neurohypophysial tract the posterior pituitary was found in the present study to receive its afferents via two accessory fasciculi, one coursing in the medial forebrain bundle and the other running along the lateral wall of the infundibular recess subependymally.     

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; {"type":"clinical-trial","attrs":{"text":"NCT04619277","term_id":"NCT04619277"}}NCT04619277).     

An analogy between fetal haptoglobin and a potent immunosuppressant in cancer

In spite of the numerous reports indicating the presence of humoral immunosuppressive factors in cancer patients, only a few of these factors have been biochemically identified. Furthermore, their role as effective immunosuppressors in vivo remains to be established. Our laboratory has attempted to isolate and identify the major immunosuppressive factor in the malignant effusions derived from ovarian and lung cancer patients. We have previously demonstrated that the Mr 52,000 immunosuppressive factor isolated from the ascites fluid of an ovarian cancer patient inhibited T-dependent immune responses in vivo and in vitro including the inhibition of E-rosetting. Thus, this immunosuppressive factor was named "suppressive E-receptor" (SER). Our current study demonstrates that this SER factor purified from malignant effusions derived from ovarian, lung, or head and neck cancer patients had a common component which dissociated equally into Mr 38,000-42,000 and 17,000-19,000 moieties on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under vigorous reducing conditions. Electroelution of these two components followed by a limited amino acid sequence determination revealed these two components to have N-terminal amino acid sequences identical to the beta and alpha 2 subunits of normal adult haptoglobin. Immunoelectrophoresis of SER using a polyclonal antiserum to neonatal cord blood demonstrated that SER, unlike normal haptoglobin, has slower electrophoretic mobility than the normal adult haptoglobin. Western blotting analysis of SER separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under denaturing conditions failed to recognize a monoclonal antibody directed specifically to SER. However, this monoclonal antibody exclusively reacted with the SER separated by an analytical polyacrylamide gel electrophoresis gel under nondenaturing conditions while normal adult haptoglobins or purified but denatured haptoglobin obtained from the same malignant fluid as SER all failed to react with this antibody. Thus, SER appears to bear an additional epitope(s) that is absent in normal adult haptoglobin. Since the SER as well as the neonatal haptoglobin have at least 100 to 1000-fold more potent immunosuppressive activity than the normal adult haptoglobin, this additional epitope(s) present in SER may be responsible for the potent immunosuppressive property of SER.     

Outcomes and factors associated with early mortality in pediatric postcardiotomy veno‐arterial extracorporeal membrane oxygenation

Mortality and morbidity of children received veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) support after cardiac surgery remain high despite remarkable advances in medical management and devices. The purpose of this study was to describe outcomes and risk factors of applying VA‐ECMO in the surgical pediatric population. We retrospectively analyzed 85 consecutive pediatric patients (aged <18 years) who received postcardiotomy VA‐ECMO from January 2010 to December 2018. Median (IQR) age at ECMO implantation in this cohort was 12.7 (6.4, 43.2) months, median weight was 8.5 (6.0, 12.8) kg, mean ECMO duration was 143.2 ± 81.6 hours and mean hospital length of stay was 48.4 ± 32.4 days. Seventy‐five patients (88.2%) were indicated for postcardiotomy cardiogenic shock. The successful ECMO weaning rate was 70.6% and in‐hospital mortality was 52.9%. The most common diagnosis was transposition of great arteries (n = 18, 21.2%), while acute kidney injury occurred most often (n = 64, 75.3%). Multivariate logistic regression analysis showed that thrombocytopenia, hemolysis, and nosocomial infection were positively correlated with in‐hospital mortality. Multivariate Cox proportional hazard regression analysis presented that thrombocytopenia significantly increased the 180‐day mortality in patients with successful weaning. Therefore, multiple factors had adverse effects on prognosis. Patient selection and procedures from ECMO implantation to weaning need to be closely monitored and performed in a timely manner to improve outcome.     

Off-clamp Retroperitoneoscopic Tumour Evacuation for Sporadic Renal Angiomyolipomas with High RENAL Nephrometry Scores: A Novel Surgical Technique and Its Outcomes

BackgroundPartial nephrectomy or angioembolisation is commonly used for sporadic renal angiomyolipomas (RAMLs) with high RENAL scores, but there is a risk of reduced renal function, postoperative complications, and recurrence.ObjectiveTo describe a new technique for off-clamp laparoscopic evacuation of sporadic RAMLs with high RENAL scores that promotes maximal renal function maintenance and low postoperative complication and lesion recurrence rates.Design, setting, and participantsA retrospective cohort of patients undergoing off-clamp laparoscopic evacuation for sporadic RAMLs with RENAL scores ≥9 from January 2013 to June 2018 was included.Surgical procedureWe highlighted the curettage, suction, packing, and binding (CSPB) technique, a new off-clamp retroperitoneoscopic evacuation technique for sporadic RAMLs.MeasurementsDemographics, preoperative, intraoperative, and postoperative outcomes were assessed.Results and limitationsA total of 141 cases were included. The median (interquartile range [IQR]) tumour size was 7 (6.2–8.2) cm. The median (IQR) RENAL score was 10 (9–11). The median (IQR) operative time was 80 (65–125) min, with a median (IQR) estimated blood loss of 130 (90–362.5) ml. Conversion to neither open surgery nor standard laparoscopy occurred. The warm ischaemia time was zero for all cases. Postoperatively, 13 minor complications (Clavien grade 1) were recorded. No blood transfusions were reported. The glomerular filtration rate did not change significantly from preoperative period to 12-mo follow-up. Recurrence did not occur at the median follow-up period of 48 (36–60) mo. The retrospective design and lack of a control group are limitations of this study.ConclusionsOff-clamp retroperitoneoscopic tumour evacuation using the CSPB technique is feasible, safe, and effective for treating complex sporadic RAMLs.Patient summaryWe report a curettage, suction, packing, and binding technique for off-clamp retroperitoneoscopic evacuation of sporadic renal angiomyolipomas that leads to complete lesion clearance, excellent renal function preservation, and minimal perioperative complications.