The increased prevalence of multidrugresistant bacterial pathogens motivated us to attempt to enhance the therapeutic efficacy of bacteriophages. The therapeutic application of phages as antibacterial agents was impeded by several factors: (i) the failure to recognize the relatively narrow host range of phages; (ii) the presence of toxins in crude phage lysates; and (iii) a lack of appreciation for the capacity of mammalian host defense systems, particularly the organs of the reticuloendothelial system, to remove phage particles from the circulatory system. In our studies involving bacteremic mice, the problem of the narrow host range of phage was dealt with by using selected bacterial strains and virulent phage specific for them. Toxin levels were diminished by purifying phage preparations. To

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A map of the location and relative concentration of a number of different proteins present in 25 distinct neuroanatomical regions of the male rat brain has been established utilizing two-dimensional polyacrylamide gel electrophoresis. The regions examined include cortical areas as well as nuclei from the hypothalamus, amygdala, thalamus, forebrain, and hindbrain. Tissue samples were obtained from each region of interest by microdissection. Proteins within these samples were first separated by charge using the technique of isoelectric focusing. In the second dimension, proteins were separated by mass on polyacrylamide slab gels containing sodium dodecyl sulfate. Proteins were visualized using a highly sensitive silver stain and quantitated by computerized scanning densitometry. The results demonstrate that all proteins examined varied somewhat in concentration among the different brain regions. The majority (53%) of polypeptides selected for quantitation were found to vary less than 4-fold in concentration between the neuroanatomical areas with the lowest and highest detected amounts. In contrast, approximately 10% of the proteins examined varied widely in the quantity measured in each brain region, with concentration values ranging more than 10-fold between the regions with the lowest and highest detected amounts. This atlas is a first attempt at systematically classifying the mass, charge, and relative concentration of proteins present in a variety of regions of the rat brain. The system presented here will serve as a basis for future studies in this area.

Protein profiles of brain areas mediating effects of steroid hormones on copulation were compared between animals in gonadal steroid states predictive of either the presence or absence of copulatory activity. A broad range of proteins present in micropunches of tissue from the medial preoptic area (MPO) and from the ventromedial hypothalamus (VMH) were compared between male and female rats with gonadal steroids present or absent. Half of the animals of each gender were gonadectomized 1 month prior to sacrifice. The remaining males were left intact, while the remaining females were gonadectomized, implanted with estrogen capsules, and injected with progesterone prior to sacrifice. These females were screened for sexual receptivity immediately prior to sacrifice. Proteins from the MPO and VMH of each animal were separated by two-dimensional gel electrophoresis, silver stained, and quantified by computerized optical densitometry. Several proteins differed in density between gels of high-steroid males and females and between high-steroid and absent-steroid animals of one or both genders. Two previously reported sex differences were replicated and found to depend on activational effects of gonadal steroids. Several interesting reversal patterns were noted between MPO and VMH, including three proteins that were affected by gonadectomy in the MPO of males, but not females, and in the VMH of females, but not males, thus correlating with sexual function. These included serum albumin (a possible index of local area blood flow) and neuron-specific enolase, a glycolytic enzyme of anaerobic metabolism. A probable genetic polymorphism was discovered at a locus whose expression appears to be regulated by gonadal steroids. In general, it appears that gonadal steroids exert a quantitative influence over several proteins in the MPO and in the VMH, and that the pattern of proteins affected and the direction of the effect are both area and gender specific.