SBDS rescues survival of zebrafish in a dose-dependent manner independently of Tp53.

Defects in ribosomal biogenesis profoundly affect organismal development and cellular function, and these ribosomopathies produce a variety of phenotypes. One ribosomopathy, Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, pancreatic exocrine insufficiency, and skeletal anomalies. SDS results from biallelic mutations in , which encodes a ribosome assembly factor.

Prostaglandin E attenuates lung fibroblast differentiation via inactivation of yes-associated protein signaling.

Prostaglandin E (PGE ) has been implicated in counteracting fibroblast differentiation by TGFβ1 during pulmonary fibrosis. However, the precise mechanism is not well understood. We show here that PGE via EP R and EP R inhibits the expression of mechanosensory molecules Lysyl Oxidase Like 2 (LOXL2), myocardin-related transcription factor A (MRTF-A), ECM proteins, plasminogen activation inhibitor 1 (PAI-1), fibronectin (FN), α-smooth muscle actin (α-SMA), and redox sensor (nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4)) required for TGFβ1-mediated fibroblast differentiation.

Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy.

Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities. Biallelic mutations in SBDS, which encodes a ribosome maturation factor, are found in 90% of SDS cases. Sbds-/- mice are embryonic lethal.

Influences of delay and rate of reinforcement on discrete-trial choice.

An adjusting procedure was used to measure pigeons' preferences among alternatives that differed in the duration of a delay before reinforcement and of an intertrial interval (ITI) after reinforcement. In most conditions, a peck at a red key led to a fixed delay, followed by reinforcement, a fixed ITI, and then the beginning of the next trial. A peck at a green key led to an adjustable delay, reinforcement, and then the next trial began without an ITI.

Undermatching in humans to amount of reinforcement.

Human subjects were exposed to a concurrent-chain procedure in which amount of reinforcement in the terminal links was varied. The experimental procedure was designed to resemble as closely as possible animal operant procedures: verbal instructions were eliminated, the key-press operant response was shaped, and a "consummatory" response was required to receive reward. In addition to varying amount of reward, three different pairs of initial-link values in the concurrent chain were studied.

Delay and amount of reward in a concurrent chain.

Eight pigeons responded under a concurrent-chain schedule for rewards differing in both delay and amount, the larger reward being associated with the longer delay. Preference was examined as the absolute durations of the terminal-link delays were increased at four different delay ratios. Difficulties with other experiments of this type were controlled for by the use of (a) a single-tape initial link to equalize terminal-link entries, (b) a blackout following the more immediate reward to equalize terminal-link length, and (c) a photocell to measure reinforcer duration more accurately.

Comparison of four-combination chemotherapy programs in metastatic breast cancer: comparison of multiple drug therapy with cytoxan, 5-FU and prednisone versus cytoxan and adriamycin, versus cytoxan, 5-FU and adriamycin, versus cytoxan, 5-FU and prednisone alternating with cytoxan and adriamycin.

In 126 postmenopausal women with metastatic breast cancer, four chemotherapeutic combination programs were tested. Patients were stratified and randomized to one of the four programs: (1) fluorouracil, cytoxan and prednisone (CFP): (2) fluorouracil, cytoxan and Adriamycin (CAF); (3) cytoxan and Adriamycin (CA); or (4) alternating combinations of CFP-CA. Objective response rates were 17% for 18 patients on CFP, 25% for 40 patients on CAF, 42% for 41 patients on CA and 63% for 19 patients on CFP-CA.

Choice between rewards differing in amount and delay: Toward a choice model of self control.

A concurrent-chain procedure was used to study pigeons' choices between rewards differing in both amount and delay. The shorter delay terminated with a 2-second access to grain whereas the longer delay terminated with a 6-second access to grain. The ratio of the delays was constant within a given condition while their absolute values were varied.

Immune complexes in breast cancer patients as detected by C1q binding.

Levels of Clq binding activity have been measured in the sera of patients with benign and malignant breast disease. Cancer patients showed significantly higher binding activity than patients with gross fibrocystic disease. Clq binding levels were not related to levels of carcinoembryonic antigen, or rheumatoid factor.

Potentiating role of previously administered agents in the combination chemotherapy of breast cancer.

91 women with metastatic breast cancer, who received prior CTX-5FU or CTX-5FU-PRD, were treated in 3 consecutive clinical trials with either CTX-5FU-PRD-MTX-VCR, MTX-VCR, or MTX-VCR-PRD in order to elucidate whether the effectiveness of 5 drugs was due only to the newly added drugs (MTX-VCR +/- PRD) or whether the previously used drugs (CTX-5FU) were necessary as potentiating agents. There were 17 or 39 responders (43%) in the 5-drug group, 3 of 25 (12%) in the MTX-VCR group and 3 of 27 (11%) in the MTX-VCR-PRD group. The survival in the group treated with 5 drugs was significantly longer.

Immunotherapy of chronic myelocytic leukemia: effects of different vaccination schedules.

In a clinical trial of immunotherapy in chronic myelocytic leukemia, 62 patients received repeated intradermal injections of BCG-cultured cell mixtures, while 16 were vaccinated with BCG alone. The lymphoblastoid cell lines used for vaccination were established from blood of patients with advanced myeloid leukemia and were reactive with "specific" primate antisera against myeloid leukemic cells. Both sensitization to target cell antigens and substantial general increases in delayed hypersensitivity responses were recorded among immunized patients.