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Biomedical subjects

J W Perry

Publications and source records attributed to J W Perry.

At least 19 recordsLinked to original sources

Design of organic molecules with large two-photon absorption cross sections.

A strategy for the design of molecules with large two-photon absorption cross sections, delta, was developed, on the basis of the concept that symmetric charge transfer, from the ends of a conjugated system to the middle, or vice versa, upon excitation is correlated to enhanced values of delta. Synthesized bis(styryl)benzene derivatives with donor-pi-donor, donor-acceptor-donor, and acceptor-donor-acceptor structural motifs exhibit exceptionally large values of delta, up to about 400 times that of trans-stilbene. Quantum chemical calculations performed on these molecules indicate that substantial symmetric charge redistribution occurs upon excitation and provide delta values in good agreement with experimental values. The combination of large delta and high fluorescence quantum yield or triplet yield exhibited by molecules developed here offers potential for unprecedented brightness in two-photon fluorescent imaging or enhanced photosensitivity in two-photon sensitization, respectively.

Aniline Compounds↗

Wound infections following spinal fusion with posterior segmental spinal instrumentation.

Twenty-three of 238 patients (9.7%) developed wound infections following segmental spinal instrumentation. When the infected group and a matched control group were compared, the infected group had a significantly higher number of patients with cerebral palsy and myelodysplasia (nonambulatory), patients with wound hematomas, patients with fusions that extended into the sacral region, and patients who were incontinent of urine. A high incidence of infections with gram-negative aerobic bacilli correlated with the extension of the surgery into the sacral region and bowel and/or bladder incontinence. Prophylactic antibiotics with broader coverage for gram-negative bacilli may be warranted for these procedures. Postoperative wound infections were managed by surgical drainage and debridement as well as antibiotics. Removal of the hardware was not necessary to control the infection in these patients who underwent segmental spinal instrumentation.

Adolescent↗

Implementation of information security and confidentiality policies, procedures, and standards.

The article describes one approach to developing and implementing a security program in response to the birth and growth of a computer-based patient record in a large teaching hospital. The discussion emphasizes the importance of the collaborative effort between the hospital and school of medicine in establishing one policy and set of standards because information is shared and electronically transferred between both institutions. The hospital's approach is summarized in five major steps: survey and literature search, development of key components or recommendations, institutional approval of the recommendations, feasibility analysis and projected time frame for implementation, and implementation of the recommendations with resolution of impediments to implementation.

Computer Security↗

Demonstration of lipopolysaccharide on sheathed flagella of Vibrio cholerae O:1 by protein A-gold immunoelectron microscopy.

Monoclonal antibodies with group and type specificity for lipopolysaccharide antigens were used in combination with protein A-colloidal gold labeling and transmission electron microscopy to demonstrate the presence of lipopolysaccharide antigens on both the sheathed flagellum and the cell surface of Inaba and Ogawa strains of Vibrio cholerae O:1. Labeling was associated with the sheath of the flagellum rather than the core, and flagellar cores were not labeled. Flagellum and cell shared a common set of lipopolysaccharide antigens characteristic of the strain serotype.

Antibodies, Monoclonal↗

Further characterization of the inhibition of casein production in a primary mouse mammary epithelial cell culture by epidermal growth factor. Antagonism by cyclic AMP.

Epidermal growth factor (EGF) inhibited casein production and the accumulation of casein mRNA activity induced by insulin (I), cortisol (F) and prolactin (P) in a primary culture of mammary epithelial cells from pregnant mice. The inhibitory effects of EGF were blocked by 8-bromo cyclic AMP (8-br-cAMP) in a dose-dependent manner. The effect of 8-br-cAMP was observed at a concentration as low as 20 microM and was maximal at 500 microM. Dibutyryl cyclic AMP (db-cAMP), cAMP, and 3-isobutylmethylxanthine (IBMX), an inhibitor of phosphodiesterase, also antagonized the inhibitory effect of EGF on casein production. 8-Br-cAMP had, however, no effect on the mitogenic activity of EGF in this system. These results suggest a possible modulatory role of cAMP in EGF-induced inhibition of casein production in cultured mammary epithelial cells.

8-Bromo Cyclic Adenosine Monophosphate↗

The study of differentiative potential of the lactating mouse mammary gland in organ culture.

The organ culture of the mammary gland of lactating mice was used to examine the response of the differentiated gland to lactogenic stimuli, insulin, cortisol, and prolactin. Time course studies showed that casein synthesis in cultured tissue decreased rapidly during the first 2 d despite the presence of the three hormones, but on the 3rd d tissue cultured with either insulin and prolactin or all three hormones regained the ability to synthesize milk proteins, casein, and alpha-lactalbumin: a greater increase occurred in the three hormone system. The delayed addition of prolactin on Day 2 to the culture system containing insulin and cortisol also stimulated casein synthesis. The addition of cytarabine, which inhibited insulin-dependent cell proliferation in cultured explants, did not block the rebound of milk protein synthesis. These results indicate that in the presence of insulin, cortisol, and prolactin mammary epithelial cells in culture first lose and then regain the ability of synthesizing milk protein without requiring the formation of new daughter cells.

Animals↗

The regulatory function of spermidine in hormonal control of the development of mouse mammary gland in culture.

The interplay of insulin, glucocorticoid, and prolactin induces differentiation of mouse mammary gland in culture. Earlier studies indicated that spermidine plays a key role in hormonal control of mammary development by mediating some of the lactogenic actions of glucocorticoid. In this study we examined the effect of progesterone, an inhibitor of lactogenesis, on milk protein synthesis and spermidine accumulation. The maximal degree of inhibition, which was attained at 300 nM, was about 40% for casein synthesis, 90% for alpha-lactalbumin synthesis, and 70% for spermidine accumulation. The increase in the activity of S-adenosyl-L-methionine decarboxylase and spermidine synthetase, two key enzymes in polyamine biosynthesis, was inhibited by 55 and 65%, respectively, by progesterone. The extent of progesterone inhibition of milk protein synthesis was greatest in cultured tissue from virgin mice, which contained a low level of spermidine, whereas mammary explants from lactating mice, which contained a high level of spermidine, were insensitive to progesterone. The inhibitory effect of progesterone can be partially antagonized by cortisol, which causes an enhancement of spermidine accumulation. These results suggest that the synthesis and accumulation of spermidine serve as targets for the inhibitory action of progesterone on lactogenesis.

Adenosylmethionine Decarboxylase↗

Putrescine and the regulation of S-adenosyl-L-methionine decarboxylase in cultured mouse mammary gland.

The activity of S-adenosyl-L-methionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase, EC 4.1.1.50) purified from mouse mammary gland can be stimulated by physiological concentrations of putrescine (Ka = 5 x 10(-7) M). In contrast, the elevation of the intracellular concentrations of putrescine in cultured mouse mammary tissue by exogenous addition of putrescine or by cultivation of the tissue in hypotonic medium results in the decrease in both the activity and the amount of the enzyme in tissue. Conversely, the addition of 1 mM alpha-methyl ornithine, an inhibitor of ornithine decarboxylase, causes augmentation of the activity and the amount of S-adenosyl-L-methionine decarboxylase, despite its inhibitory action on insulin-stimulated increase in the concentration of putrescine. These data suggest that putrescine can act as a 'negative' regulator of the enzyme in this system.

Adenosylmethionine Decarboxylase↗

Regulation of ornithine decarboxylase in cultured mouse mammary gland by the osmolarity in the cellular environment.

The biphasic increase of ornithine decarboxylase activity in mouse mammary gland in organ culture occurs with a hormone-independent first peak and a hormone-dependent second peak. The data presented indicate that a change in the osmolarity of the cellular environment is the major contributing factor for the emergence of the hormone-independent ornithine decarboxylase activity in mammary explants. Thus, incubation of mammary explants for 3 h in a medium diluted 53% with distilled water results in approx. 1000-fold stimulation of enzyme activity over the initial level, whereas a similar dilution of the medium with 0.18 M NaCl or 0.3 M sucrose blocks the increase. The increase in enzyme activity is similarly affected by a reduction of the concentration of NaCl in the culture medium. The hypoosmotic stimulation of ornithine decarboxylase activity appears to be affected at a posttranscriptional level, and is enhanced further by the actions of insulin and prolactin. The hypoosmotic enhancement of ornithine decarboxylase activity produces a large increase in the intracellular concentration of putrescine in mammary explants. However, neither the concentration of spermidine and spermine nor the activity of S-adenosyl-L-methionine decarboxylase is affected. In addition, studies of putrescine transport in mammary explants show that hypotonicity causes an increase in the rate of influx and a decrease in efflux of putrescine with enhancement of intracellular putrescine accumulation. On the other hand, the uptake of spermidine, spermine, amino acids, sugar, and a lipophilic cation, triphenylmethylphosphonium is unaffected. These data suggest a possibility that osmotic alteration in cellular environment causes an incresed need for putrescine in mammary cells, resulting in stimulation of ornithine decarboxylase activity, which may represent a cellular mechanism for maintaining the homeostasis of the intracellular cationic environment.

Animals↗

Cyclic AMP as a negative regulator of hormonally induced lactogenesis in mouse mammary gland organ culture.

In organ cultures of mammary glands from mice in midpregnancy, addition of both insulin and prolactin induces a marked accumulation of alpha-lactalbumin, whereas the augmentation of casein synthesis requires the presence of insulin, prolactin, and cortisol. Addition of 0.5 mM dibutyryl cyclic AMP resulted in complete inhibition of alpha-lactalbumin accumulation and partial inhibition of casein synthesis. Furthermore, either cholera toxin at 0.1-1.0 microgram/ml (a stimulator of adenylate cyclase) or 3-isobutyl-1-methylxanthine (an inhibitor of phosphodiesterase) in combination with 2 mM cyclic AMP, produced a similar pattern of inhibition of alpha-lactalbumin and casein synthesis in cultured tissue. During culture of mammary explants in medium containing no hormone, or insulin alone, or insulin, prolactin, and cortisol, the tissue content of cyclic AMP decreased rapidly, reaching half the initial level in 24-48 hr. These results indicate that cyclic AMP plays "negative" regulatory function in hormonal induction of milk protein synthesis during the development of the mammary gland.

1-Methyl-3-isobutylxanthine↗