Surface antigens on malignant Sezary and T-CLL cells correspond to those of mature T cells

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T- cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sezary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T- chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.     

The role of prolactin in the suppression of Crh mRNA expression during pregnancy and lactation in the mouse

Maternal stress is associated with negative health consequences for both the mother and her offspring. To prevent these adverse outcomes, activity of the hypothalamic‐pituitary‐adrenal (HPA) axis is attenuated during pregnancy and lactation. Although the mechanisms generating this adaptive change have not been defined fully, the anterior pituitary hormone prolactin may play a significant role. The present study investigated the role of prolactin in regulating the basal activity of the HPA axis during pregnancy and lactation in the mouse, focussing upon the corticotrophin‐releasing hormone (CRH) neurones. Using in situ hybridisation, a decrease in Crh mRNA‐expressing cell number in pregnant (55.6±9.0 cells per section) and lactating (97.4±4.9) mice compared to virgin controls was characterised (186.8±18.7, P<.01 Tukey‐Kramer test; n=6‐7 per group). Removal of the pups (24 hours) and thus the associated suckling‐induced prolactin secretion, restored CRH neurone number (180.1±19.7). To specifically test the role of prolactin in suppressing Crh mRNA expression in lactation, prolactin levels were selectively manipulated in lactating mice. Lactating mice were treated with ovine prolactin (1500 μg day^‐1, osmotic minipump, s.c.; n=7) or vehicle (n=6) for 24 hours following pup removal. This was sufficient to suppress Crh mRNA expression from 108.0±13.5 to 53.7±16.7 cells per section (P<.05 Student's t‐test). Additional cohorts of lactating mice were treated with bromocriptine (300 μg over 24 hours, s.c.; n=7) or vehicle (n=5) to suppress endogenous prolactin secretion; however, no change in Crh mRNA expression was detected. Thus, although prolactin was sufficient to suppress Crh mRNA expression in the paraventricular nucleus, it does not appear to be required for the ongoing regulation of the CRH neurones in lactation.     

The early luteal phase in successful and unsuccessful implantation after IVF-ET

The hormonal milieu at embryo implantation after in-vitro fertilization was investigated. Superstimulation was accomplished with clomiphene citrate and human menopausal gonadotrophin (HMG) injections followed by ovulation induction with human chorionic gonadotrophin (HCG). Venous blood samples were drawn on days 2 and 8, the day of oocyte recovery being day 0. Fifteen women with successful implantation, defined as an ultrasound-verified pregnancy, were compared to 42 women with unsuccessful implantation, using a three-way analysis of variance. Oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) did not differ between the two groups. However, the ratios of oestradiol/progesterone and of testosterone/SHBG were significantly higher in the non-fertile cycles, both on day 2 and on day 8 (P less than 0.05). Furthermore, there was a highly significant decrease in oestradiol, progesterone and testosterone between days 2 and 8 in fertile as well as in non-fertile cycles (P less than 0.001) and a highly significant increase in SHBG from day 2 to day 8 in both groups (P less than 0.001). The higher testosterone/SHBG ratio in the non-pregnant women implies a relative hyperandrogenicity in this group that might have adversely affected the uterine receptivity.     

Genomic instability occurs in colorectal carcinomas but not in adenomas

Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non-polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER⁺). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER⁺, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley-Liss, Inc.     

OPTN/SRTR 2018 Annual Data Report: Pancreas

The overall number of pancreas transplants continued to increase to 1027 in 2018, after a nadir of 947 in 2015. New additions to waiting list remained stable, with 1485 candidates added in 2018. Proportions of patients with type II diabetes waiting for transplant (14.6%) and undergoing transplant (14.8%) have steadily increased since 2016. Waiting times for simultaneous pancreas/kidney transplant have decreased; median months to transplant was 13.5 for simultaneous pancreas/kidney transplant and 19.7 for pancreas transplant alone in 2018. Outcomes, including patient and kidney survival, as well as rejection rates, have improved consistently over the past several years. Pancreas graft survival data are being collected by the Organ Procurement and Transplantation Network and will be included in a future report once there are sufficient cohorts for analysis.     

A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits

Background

Mild traumatic brain injury (TBI) is a serious public health concern affecting more than 1.7 million people in the United States annually. Mild TBI is difficult to diagnose and is clinically associated with impaired motor coordination and cognition.

Methods

We subjected mice to a mild TBI (mTBI-1 or mTBI-2) induced by a weight drop model. We assessed brain injury histologically and biochemically, the latter by serum neuron-specific enolase and glial fibrillary acidic protein. Systemic and brain inflammation were measured by cytokine array. We determined blood–brain barrier integrity by cerebral vascular leakage of micromolecular and macromolecular fluorescent molecules. We evaluated mice using a rotarod device and novel object recognition to measure motor coordination and cognition, respectively.

Results

Mice undergoing mTBI-1 or mTBI-2 had significant deficits in motor coordination and cognition for several days after injury compared with controls. Furthermore, both mTBI-1 and mTBI-2 caused micromolecular leakage in the blood–brain barrier, whereas only mTBI-2 caused macromolecular leakage. Serum neuron-specific enolase and glial fibrillary acidic protein were elevated acutely and corresponded to the degree of injury, but returned to baseline within 24 h. Serum cytokines interleukin-6 and keratinocyte-derived chemokine were significantly increased within 90 min of TBI. Interleukin-6 levels correlated with the degree of injury.

Conclusions

The current study provides a reproducible model of mild TBI in mice that exhibits pathologic features of mild TBI in humans. Furthermore, our data suggest that serum cytokines, such as IL-6, may be effective biomarkers for severity of head injury.     

Program‐specific transplant rate ratios: Association with allocation priority at listing and posttransplant outcomes

The Scientific Registry of Transplant Recipients (SRTR) is considering more prominent reporting of program‐specific adjusted transplant rate ratios (TRRs). To enable more useful reporting of TRRs, SRTR updated the transplant rate models to adjust explicitly for components of allocation priority. We evaluated potential associations between TRRs and components of allocation priority that could indicate programs' ability to manipulate TRRs by denying or delaying access to low‐priority candidates. Despite a strong association with unadjusted TRRs, we found no candidate‐level association between the components of allocation priority and adjusted TRRs. We found a strong program‐level association between median laboratory Model for End‐stage Liver Disease (MELD) score at listing and program‐specific adjusted TRRs (r = .37; P < .001). The program‐level association was likely confounded by regional differences in donor supply/demand and listing practices. In kidney transplantation, higher program‐specific adjusted TRRs were weakly associated with better adjusted posttransplant outcomes (r = ?.14; P = .035) and lower adjusted waitlist mortality rate ratios (r = ?.15; P = .022), but these associations were absent in liver, lung, and heart transplantation. Program‐specific adjusted TRRs were unlikely to be improved by listing candidates with high allocation priority and can provide useful information for transplant candidates and programs.     

Fractures after Stroke

Fractures are a serious complication after stroke. Among patients with femoral neck fractures, a large subgroup have had a previous stroke. This study aimed to investigate the incidence of fractures after stroke. Included in the study were 1139 patients consecutively admitted for acute stroke. Fractures occurring from stroke onset until the end of the study or death were registered retrospectively. Hip fracture incidence was compared with corresponding rates from the general population. Patients were followed up for a total of 4132 patient-years (median 2.9 years). There were 154 fractures in 120 patients and median time between the onset of stroke and the first fracture was 24 months. Women had significantly more fractures than men (χ² = 15.6; p < 0.001). In patients with paresis most of the fractures affected the paretic side (χ² = 22.5; p < 0.001) and 84% of the fractures were cause by falls. Hip fracture was the most frequent fracture and the incidence was 2–4 times higher in stroke patients compared with the reference population. Fractures are thus a common complication after stroke. They are usually caused by falls and affect the paretic side. It is necessary to focus on the prevention of post-stroke fractures, including the prevention of both falls and osteoporosis.