Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling

d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant.     

Fifty Years On: Brown v. Board of Education and American Psychology, 1954-2004 An Introduction.

Introduces the current issue of the American Psychologist, which examines the ramifications of the Brown vs. Board of Education decision and its sequelae over the last 50 years, with a special focus on the mixed role of psychological research and practice. Despite the great strides toward a more just society since May 17, 1954, inequities remain in schooling, in social relations, and in economic opportunity. How will history judge American psychology 50 years from now vis-a-vis the possibilities it helped create via Brown? The articles in this special issue suggest several important directions of research and action our field will need to take if the verdict of history is to be a positive one. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cost of treating heart valve related complications

This paper presents 5 patients with repeated recurrence of osteosarcoma (RROS). The primary focus of 3 patients were in the distal portion of femur, and 2 patients were in the proximal portion of tibia. Three patients, whose chest X ray film were negative, were treated by amputation and chemotherapy. Two patients had isolated metastatic focus 1.5 cm in diameter in lung, were treated by amputation after 1 week of chemotherapy and then treated by lobectomy after 2 weeks of chemotherapy. After operation, the chemotherapy was carried out for 3 courses of treatment. The roentgenogram of chest and affected limb were taken once every two months. There were metastatic focuses found in the lung of 1 patient and in the distal portion of femur of 2 patients. One patient was operated on for 4 times. Up to now, 3 patients have been living for 5 years and 2 patients for 6 years after operation.     

A small region of the ecotropic murine leukemia virus (MuLV) gag gene profoundly influences the types of polytropic MuLVs generated in mice

The vast majority of recombinant polytropic murine leukemia viruses (MuLVs) generated in mice after infection by ecotropic MuLVs can be classified into two major antigenic groups based on their reactivities to two monoclonal antibodies (MAbs) termed Hy 7 and 516. These groups very likely correspond to viruses formed by recombination of the ecotropic MuLV with two distinct sets of polytropic env genes present in the genomes of inbred mouse strains. We have found that nearly all polytropic MuLVs identified in mice infected with a substrain of Friend MuLV (F-MuLV57) are reactive with Hy 7, whereas mice infected with Moloney MuLV (Mo-MuLV) generate major populations of both Hy 7- and 516-reactive polytropic MuLVs. We examined polytropic MuLVs generated in NFS/N mice after inoculation with Mo-MuLV-F-MuLV57 chimeras to determine which regions of the viral genome influence this difference between the two ecotropic MuLVs. These studies identified a region of the MuLV genome which encodes the nucleocapsid protein and a portion of the viral protease as the only region that influenced the difference in polytropic-MuLV generation by Mo-MuLV and F-MuLV57.     

Changes in muscle blood flow distribution during hyperthermia

Blood flow is a critical parameter for obtaining satisfactory temperature distributions during clinical hyperthermia. This study examines the changes in blood flow distribution in normal porcine skeletal muscle before, during and after a period of regional microwave hyperthermia. The baseline blood flow distribution during general anaesthesia and after the insertion of the thermal probes was established independently in order to isolate the changes due to hyperthermia. General anaesthesia alone and thermocouple insertion during anesthesia had no significant effect on the muscle blood flow distribution. Regional microwave heating generated a non-uniform blood flow distribution which was a function of the tissue temperature distribution. Blood flow was greater in those tissues samples in which higher temperatures were recorded and less in those sampled further from the applicators peak SAR (Specific Absorption Rate). The increase in blood flow appears to be primarily a local phenomenon. Although muscle blood flow may be considered to be uniform prior to heating, this does not hold during hyperthermia treatment. Therefore, the non-uniform nature of the blood distribution during heating should be incorporated into any practical bioheat transfer model.     

Human thalamic nucleus mediating taste and multiple other sensations related to ingestive behavior

Until now, taste was the only primary sensory modality for which the human central nervous system pathways were unknown. We report sensations evoked by stimulation at microampere current levels in the region of the human thalamic nucleus (ventralis caudalis parvocellularis internis) corresponding to the monkey taste relay nucleus. Stimulation in this region during awake neurosurgical procedures evoked special visceral/somatic (taste/pungent smell), general visceral (fullness of a hollow viscus), as well as painful and nonpainful general somatic sensations. General somatic or visceral sensation was evoked by stimulation at 80% of sites where special visceral/somatic sensation was evoked. These results suggest that primate taste relay mediates multiple sensations in addition to taste.     

Comparison of laparoscopic and minilap cholecystectomy for acute cholecystitis

The charts of all patients with acute cholecystitis undergoing either laparoscopic or minilap cholecystectomy at the Chinle Comprehensive Health Care Facility between October 1, 1991, and August 15, 1993, were retrospectively reviewed. During that period, 54 patients underwent laparoscopic cholecystectomy and 45 patients had minilap procedures. The two groups had similar mean age, sex distribution, temperature, leukocyte count, gallbladder wall thickness, and duration of preoperative symptoms. While laparoscopic cholecystectomy took an average of 16 min longer to perform than minilap cholecystectomy, patients who had laparoscopic cholecystectomy had less blood loss, reduced postoperative narcotic needs, and shorter hospital stays.     

Transitional cell carcinoma of the distal portion of ureter protruding into the sigmoid conduit six years after cystoprostatectomy

Bladder tumors develop after the diagnosis of upper urinary tract carcinoma in approximately 20% of cases, whereas the incidence of upper urinary tract tumor after the diagnosis of bladder cancer is low, approximately 2%. In a 64-year-old man who had undergone cystoprostatectomy treatment of bladder carcinoma 6 years previously, with the sigmoid conduit used for supravesicle diversion, a transitional cell carcinoma that developed in the conduit was not revealed with intravenous pyelography at regular follow-up intervals. The patient had only hematuria. After an obstructed left kidney, left ureteral stricture, and a filling defect in the conduit were observed radiologically and biopsy revealed a transitional cell carcinoma at the ureterosigmoid junction, the patient underwent left nephroureterectomy, partial resection of a third of the sigmoid conduit, and right ureteral reimplantation. The occurrence of upper urinary tract carcinoma after treatment of bladder cancer should be considered even in light of intravenous pyelography that shows no abnormality; and when such carcinomas occur in this situation, disease involving the conduit should be ruled out.