The p97-UBXD8 complex regulates ER-Mitochondria contact sites by altering membrane lipid saturation and composition.

The intimate association between the endoplasmic reticulum (ER) and mitochondrial membranes at ER-Mitochondria contact sites (ERMCS) is a platform for critical cellular processes, particularly lipid synthesis. How contacts are remodeled and the impact of altered contacts on lipid metabolism remains poorly understood. We show that the p97 AAA-ATPase and its adaptor ubiquitin-X domain adaptor 8 (UBXD8) regulate ERMCS.

Human Cytomegalovirus Uses a Host Stress Response To Balance the Elongation of Saturated/Monounsaturated and Polyunsaturated Very-Long-Chain Fatty Acids.

Stress and virus infection regulate lipid metabolism. Human cytomegalovirus (HCMV) infection induces fatty acid (FA) elongation and increases the abundance of lipids with very-long-chain FA (VLCFA) tails. While reprogramming of metabolism can be stress related, the role of stress in HCMV reprogramming of lipid metabolism is poorly understood.

Methodological Approaches Frame Insights into Endophyte Richness and Community Composition.

Isolating microbes is vital to study microbiomes, but insights into microbial diversity and ecology can be constrained by recalcitrant or unculturable strains. Culture-free methods (e.g.

Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study.

Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity.

Objective: To characterize IDH-inhibitor-associated DS (IDH-DS) and its effective management.

Impact of Age and Estimated Glomerular Filtration Rate on the Glycemic Efficacy and Safety of Canagliflozin: A Pooled Analysis of Clinical Studies.

Objective: Reduced efficacy has been reported in the elderly; it may be a consequence of an age-dependent decline in estimated glomerular filtration rate (eGFR) rather than ageing per se. We sought to determine the impact of these 2 parameters, as well as sex and baseline body mass index (BMI), on the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in people with type 2 diabetes.

Methods: Data were pooled from 6 randomized, double-blind, placebo-controlled studies (18 or 26 weeks; N=4053).

Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus.

The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure (BP) and osmotic diuresis- and intravascular volume reduction-related adverse events (AEs) were evaluated using pooled data from four placebo-controlled, phase 3 studies in patients with type 2 diabetes mellitus (T2DM; N=2313). At baseline, 1332 (57.6%) patients were taking an antihypertensive medication.

Efficacy and safety of canagliflozin in patients with type 2 diabetes and stage 3 nephropathy.

Background/aims: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m(2). The efficacy and safety of canagliflozin, an approved SGLT2 inhibitor, was evaluated in patients with stage 3 chronic kidney disease (CKD; eGFR ≥30 to <60 ml/min/1.

Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled analysis of phase 3 study results.

Background: Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed for treating type 2 diabetes mellitus (T2DM).

Methods: The safety/tolerability profile of canagliflozin 100 and 300 mg over 26 weeks was assessed using an integrated analysis of data pooled from 4 placebo-controlled, phase 3 studies representing a broad range of patients with T2DM (N = 2313; mean age, 56.0 years; glycated hemoglobin [HbA1c], 8.

Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR).

Objective: Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on serum electrolytes were evaluated using pooled data from studies of patients with type 2 diabetes mellitus (T2DM).

Research Design And Methods: Analyses were performed using two datasets, each including four placebo-controlled studies: Population 1 (N = 2215), patients with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) (mean = 89.

Properties of ornithine decarboxylase in human colorectal adenocarcinomas.

Ornithine decarboxylase (ODC) activity was measured in colon adenocarcinomas and adjacent normal-appearing colon mucosa from a total of 40 patients undergoing surgical resections. The enzyme activity was measured in the presence and absence of GTP, since recent work has demonstrated a GTP-activatable form of ODC in some murine and human tumors. In general, ODC specific activity was higher in adenocarcinomas than in adjacent normal-appearing mucosa.

Metaplastic carcinoma of the breast--diagnosis by aspiration biopsy cytology: report of two cases and literature review.

The unusual metaplastic carcinomas have a variety of names, each emphasizing the dominant histologic pattern. Components may include features of ductal, spindle, or squamous carcinoma with pseudosarcomatous, cartilaginous, or boney areas. A few reports from individual tumors examined by fine-needle aspiration biopsy have emphasized an array of findings.

Appraisal and cytomorphologic analysis of common carcinomas of the breast.

This work is based on 15 years experience with more than 9000 needle aspiration biopsies from the breast performed by a number of clinicians without syringe guns. From 1981 through 1983, 329 carcinomas were detected with a sensitivity of 90%. A positive or suspicious report was issued in 17 of the 32 minimal carcinomas.

Lymphadenopathy and aspiration biopsy cytology. Review of 376 superficial nodes.

The results of aspiration biopsy from 376 superficial lymph nodes were reviewed. Diagnosis of metastatic carcinoma based on "alien" cells and melanoma was easily made with an accuracy of 95%. The results of aspiration biopsy from lymphoma was much less accurate, and led to retrospective analysis of aspirates from 51 histologically verified cases of benign lymphadenopathy and lymphoma.

Early gastric cancer in a United States hospital.

Early gastric cancer (EGC) confined to mucosa and submucosa, described by Japanese physicians over 20 years ago, yields about 90% 5-year postoperative survival. EGC has been increasingly reported from centers outside Japan, but rarely from the United States. Between 1976-1981, EGC was found in six patients or about 8.

Small cell carcinoma of the ovary with hypercalcemia: a report of eleven cases.

Eleven cases of a small cell ovarian cancer associated with hypercalcemia that was reversed by removal of the tumor are reported and compared with three similar cases in the literature. The 14 cases account for 50% of recorded cases of ovarian-cancer-related hypercalcemia. The 14 tumors occurred in women between the age of 13 and 35, with an average of 22 years and, with two exceptions, behaved clinically in an aggressive fashion.

Bile reflux gastritis and esophagitis in patients without prior gastric surgery, with pilot study of the therapeutic effects of metoclopramide.

We reviewed our upper endoscopic records over a 27-month period, retrospectively for 23 months and prospectively for four months and identified patients with substantial bile reflux. Patients with prior gastrectomies were excluded. Of the remaining 36 patients, 23 had prior cholecystectomies.

Adequacies and inadequacies in assessing murine toxicity data with antineoplastic agents.

Previous retrospective analyses have suggested a very positive correlation in toxic doses of antineoplastic agents between mice and humans. Additional toxicological information has now been accumulated and reveals a noticeable variability in the existing data base. Nevertheless, it is likely that mouse toxicological studies will become a principal determinant for estimating initial doses to be used in humans.

Comparison of 5-fluorouracil and ftorafur. II. Therapeutic response and development of resistance in murine tumors.

The therapeutic activity of ftorafur was compared to that of 5-fluorouracil (5-FU) in a number of tumor systems. The drugs were active against ip L1210 leukemia when administered ip, sc, or orally. Administration every fourth day x 3 proved to be the most effective treatment schedule for both drugs, although significant activity was seen on all treatment schedules tested.

Comparison of 5-fluorouracil and ftorafur. I. Quantitative and qualitative differences in toxicity to mice.

5-Fluorouracil (5-FU) was compared to ftorafur, a fraudulent nucleoside analog which acts as a depot form of 5-FU, with respect to influence of dosage level and schedule of administration on toxicity in mice. When the drugs were administered daily and the duration of treatment was varied from a single dose to 32 daily treatments, the toxicity of 5-FU proved to be somewhat more than cumulative. On the other hand, the toxicity of ftorafur on daily treatment was less than cumulative.

Canine lung allograft lymphatic alterations.

Lymphatic obstruction has not been emphasized as a feature of lung allograft rejection. However, accumulation of fluid and cellular infiltrate, aggravated by lymph stasis, results in impaired lung function. In this study, lung specimens were recovered at varying times up to 133 days after either reimplantation (7 dogs) or allografting (29 dogs).

The metabolic clearance rate, head and brain extractions, and brain distribution and metabolism of progesterone in the anesthetized, female monkey (Macaca mulatta).

The brain distribution and metabolism of progesterone were studied in female, rhesus monkeys. Adult monkeys were anesthetized with ketamine and were given a constant infusion of [3H]- or [14C] progesterone. Blood samples were obtained from cannulae inserted into the carotid artery, the jugular vein and lateral (transverse) sinus.

Enhancement of the effectiveness of daunorubicin (NSC-82151) or adriamycin (NSC-123127) against early mouse L1210 leukemia with ICRF-159 (NSC-129943).

The LD50 of intraperitoneally (ip) injected daunorubicin in nonleukemic mice (1.8 mg/kg, q4d times 3) can be increased several fold by the concomitant ip injection of ICRF-159. In addition, the survival of leukemic mice treated with daunorubicin and ICRF-159 on Days 1, 5, and 9 after ip inoculation of L1210 tumor cells was substantially greater than after treatment with either drug alone.