Analogues of geranyl pyrophosphate as inhibitors of prenyltransferase

Six analogues of geranyl pyrophosphate (the monophosphates of geraniol and tetrahydrogeraniol, and the pyrophosphates of nerol, octan-1-ol, tetrahydrogeraniol and citronellol) were synthesized, and were found to be inhibitors of pig liver prenyl- (geranyl-)transferase. The effects of each analogue were analysed in kinetic experiments, which showed the pyrophosphates of citronellol, tetrahydrogeraniol and octan-1-ol to be the most potent inhibitors. The results are interpreted to support a previous hypothesis that the main forces in the binding of substrates to prenyltransferase are non-specific lipophilic forces and a pyrophosphate-binding force.     

Microbiological Contamination of Hospital Air: I. Quantitative Studies

The levels of airborne contamination in various areas of two hospitals were determined during a 15-month sampling period, using Casella and Andersen volumetric samplers. Based on nearly 5,000 samples, the mean count per ft³ ranged from 4.5 in obstetric-gynecology delivery rooms to 72.4 in waste-handling areas. The mean count for the entire hospital environment was on the order of 20 contaminants per ft³; 48% were associated with particles >5 μ diam, 30% with particles between 2 and 6 μ diam, and 22% with particles <2 μ diam. The airborne contamination was influenced by traffic, activity, ventilation considerations, and gross surface contamination, but not markedly by seasonal changes. When suitable control measures were implemented, the level of contamination could be diminished and kept low.     

Microbiological Contamination of Hospital Air: II. Qualitative Studies

Over 10,000 airborne microorganisms, isolated from various areas of two hospitals, were characterized according to colonial and microscopic morphology and certain physiological reactions, including penicillin resistance and hemolysis. On the basis of all isolates examined during a 15-month period, 42.6% were gram-positive cocci, 19.2% were gram-positive rods, 14.0% were gram-negative rods, 17.1% were molds, 2.2% were actinomycetes, 1.2% were yeasts, and the remainder were assorted diphtheroids and coccobacillary types. The distribution of types varied according to hospital area, locations within a given area, and level of gross airborne contamination, but did not vary significantly with season of the year. There appeared to be some relationship between contaminant particle size and type of organism associated with the particle. Distribution of penicillin-resistant types differed markedly in different hospital areas, with proportions ranging from 21.4% in surgery areas to 4.3% in incinerator rooms. Of all gram-positive cocci isolated, 34.9% were hemolytic, and 16.4% were penicillin-resistant.     

Heat Shock RNA Levels in Brain and Other Tissues After Hyperthermia and Transient Ischemia

A number of studies have demonstrated increased synthesis of heat shock proteins in brain following hyperthermia or transient ischemia. In the present experiments we have characterized the time course of heat shock RNA induction in gerbil brain after ischemia, and in several mouse tissues after hyperthermia, using probes for RNAs of the 70-kilodalton heat shock protein (hsp70) family, as well as ubiquitin. A synthetic oligonucleotide selective for inducible hsp70 sequences proved to be the most sensitive indicator of the stress response whereas a related rat cDNA detected both induced RNAs and constitutively expressed sequences that were not strongly inducible in brain. Considerable polymorphism of ubiquitin sequences was evident in the outbred mouse and gerbil strains used in these studies when probed with a chicken ubiquitin cDNA. Brief hyperthermic exposure resulted in striking induction of hsp70 and several-fold increases in ubiquitin RNAs in mouse liver and kidney peaking 3 h after return to room temperature. The oligonucleotide selective for hsp70 showed equivalent induction in brain that was more rapid and transient than observed in liver, whereas minimal induction was seen with the ubiquitin and hsp70-related cDNA probes. Transient ischemia resulted in 5- to 10-fold increases in hsp70 sequences in gerbil brain which peaked at 6 h recirculation and remained above control levels at 24 h, whereas a modest 70% increase in ubiquitin sequences was noted at 6 h. These results demonstrate significant temporal and quantitative differences in heat shock RNA expression between brain and other tissues following hyperthermia in vivo, and indicate that hsp70 provides a more sensitive index of the stress response in brain than does ubiquitin after both hyperthermia and ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyrotropin-releasing hormone stimulates intestinal transit in young rats

The effect of intracisternal injection of thyrotropin-releasing hormone (TRH) on small intestinal transit of a charcoal bolus was investigated in 14-, 21-, 28- and 35-day-old and adult rats. Intracisternal TRH (15 micrograms in 2 microliters) was administered, and transit (distance traveled by the charcoal) was measured 120 min later. In all age groups, intracisternal TRH increased charcoal transit significantly (P less than 0.05) as compared to saline-treated controls. This increase in transit was not mimicked by intravascular TRH, and it was blocked in all age groups by prior intraperitoneal injection of atropine (2 micrograms/g body weight). Vagotomy blocked TRH-induced increases in small intestine transit in rats of 28 days and older. Prior intraperitoneal injection of the antiserotonin compound, cyproheptadine (1 microgram/g body weight) reduced TRH-induced increases in small intestine transit in all age groups. These results demonstrate that centrally administered TRH stimulates small intestine transit through both cholinergic and serotonergic mechanisms in rats as early as 14 days of age.