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Biomedical subjects

D Burks

Publications and source records attributed to D Burks.

13 recordsLinked to original sources

Dopaminergic modulation of nNOS expression in the pituitary gland of male rat.

Nitric oxide is an unconventional transmitter since it is not transported and released by exocytosis. In the pituitary gland, nitric oxide is locally synthesised by gonadotroph and folliculo-stellate cells. Dopamine, the principal central inhibitory signal in prolactin release, may exert its inhibitory effects by stimulation of nitric oxide production. However, the effects of dopaminergic modulation on nitric oxide-producing pituitary cells have not been analysed. Therefore, we examined the effects of intraventricular administration of the dopamine antagonist haloperidol (40 microg) on the pituitary expression of neuronal nitric oxide synthase (nNOS) in male adult rats. In untreated and control animals, nNOS-positive cells were very similar. Two types of nNOS-positive cells appeared in the pars distalis: round or polygonal cells and stellate cells. Although some isolated cells were found, the nNOS-positive cells commonly appeared grouped in clusters close to blood vessels. nNOS immunoreactivity appeared as a uniform staining throughout the cytoplasm, including cell prolongations. The number and size of nNOS-expressing cells in the pituitary gland decreased significantly after treatment with haloperidol (p<0.01). To evaluate the potential direct effect of dopamine on pituitary cells, pituitary monolayer cultures were treated with dopamine during a time-course of 12 h. Our in vitro studies revealed that dopamine increases the percentage of nNOS-positive cells and augments cellular area (p<0.05). These results demonstrate that: (1) treatment of rats in vivo with a dopamine antagonist significantly decreases expression of nNOS in the pituitary and (2) in vitro dopamine exerts a direct effect on pituitary cultures by increasing nNOS-positive cells. Thus, these findings suggest that dopamine may function as a physiological stimulator of nNOS expression in the rat pituitary gland.

Animals↗

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

PURPOSE: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial. MATERIALS AND METHODS: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months. RESULTS: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports. CONCLUSIONS: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.

Adult↗

Postnatal differentiation of the immunohistochemical expression of aromatase P450 in the rat pituitary gland.

At our laboratory, we have recently demonstrated the immunohistochemical expression of aromatase P450 in the pituitary glands of adult rats; this expression was seen to be sex-dependent. In order to determine whether the changes in the expression of the enzyme are related to changes in the gonadal sphere and whether the expression of the enzyme is related to the postnatal differentiation of hypophyseal cytology, in the present work we performed an immunohistochemical study in the rat pituitary gland from birth to old age. The immunohistochemical reaction to aromatase was evident and very generalized at 7 days after birth, with no large differences between the male and female animals. At 14 days the immunohistochemical reaction was decreased in the females, with no changes in the males. At 17 days, aromatase immunoreactivity in the pituitary glands of female rats was very weak whereas the males showed large numbers of reactive cells. These observations were further pronounced at 21 days and 2 months of life. At 24 months, the immunoreactivity found in the pituitary glands of the male rats had almost completely disappeared. Our results show that a postnatal differentiation in the immunohistochemical expression of aromatase occurs; this is tightly linked to sexual activity and is lost in old age. This suggests that hypophyseal aromatase would be related to the mechanisms of action of gonadal steroids on hypophyseal differentiation and secretion.

Animals↗

Skin cleaning with kerosene facilitates passage of carcinogens to the lungs of animals treated with used gasoline engine oil.

Solvents such as kerosene or gasoline may be used by workers to clean their skin following contact with oily materials. This practice is not recommended, as it is well known that the solvent will defat the skin. Many also suspect that solvent washing may increase exposure by carrying materials through the skin; however, there is little documentation of this. Auto mechanics may be exposed to used gasoline engine oil (UGEO), an animal carcinogen which forms carcinogen-DNA adducts in skin and lung following topical application. This study was designed to determine if cleaning with kerosene following exposure to UGEO altered absorption of carcinogens from this material. UGEO or new oil (NO) was applied to the shaved skins of groups of HSD-ICR mice for five days. At 1 or 8 hours after application, the treated skins were cleaned with either kerosene or a commercial cleaner, or were not cleaned. Animals were sacrificed 24 hours after the last application, skins and lungs harvested, and DNA analyzed for carcinogen-DNA adducts by 32P-postlabeling. Five applications of UGEO significantly increased carcinogen-DNA adduct levels in both lungs and skin compared to animals treated with NO. DNA adduct levels in the skin were reduced significantly in groups washed with kerosene or commercial cleaner. Washing at one as opposed to eight hours after UGEO application resulted in lower adduct levels regardless of cleaner. DNA adduct levels in the lung were reduced when the commercial cleaner was used, again in a time-related fashion. However, cleaning with kerosene resulted in mean carcinogen-DNA adduct levels in the lung which were significantly higher than even the positive controls, regardless of cleaning time. This is the first demonstration that kerosene cleaning facilitates passage of carcinogens through the skin, resulting in higher levels of genetic damage in a critical internal organ.

Administration, Cutaneous↗

The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action.

Signal transduction by insulin and IGF-1, several interleukins (IL-2, IL-4, IL-9, IL-13), interferons, GH, and other cytokines involves IRS proteins, which link the receptors for these factors to signaling molecules with Src homology-2 domains (SH2-proteins). We recently reported the amino acid sequence of murine IRS-2; in order to examine a potential genetic role for this molecule in disease, we isolated the murine IRS-2 gene and compared the expression pattern of IRS-2 against IRS-1. Like IRS-1, IRS-2 is encoded by a single exon. Whereas IRS-1 is located on murine chromosome 1, IRS-2 is located on murine chromosome 8 near the insulin receptor. IRS-2 is expressed together with IRS-1 in many cells and tissues; however, IRS-2 predominates in murine hematopoietic cells where it may be essential for cytokine signaling; IRS-1 predominates in adipocytes and differentiated 3T3-L1 cells where it contributes to the normal insulin response. In 32D cells, IRS-1 and IRS-2 undergo differential tyrosine phosphorylation during insulin or IL-4 stimulation, as assessed indirectly by interaction with various recombinant SH2 domains. Thus, signaling specificity through the IRS proteins may be accomplished by specific expression patterns and distinct phosphorylation patterns during interaction with various activated receptors.

3T3 Cells↗

Impacts of foot orthoses on pain and disability in rheumatoid arthritics.

Rheumatoid arthritis (RA) frequently causes foot pain and swelling that affect ambulation. Pharmaceutical management of pain and disability is standard in clinical practice. The use of functional posted foot orthoses, as an adjunct to pharmaceutical treatment, is a promising treatment for managing foot pain and disability in RA. Its effectiveness, however, has not been rigorously evaluated. We performed a double-blind clinical trial using foot orthoses vs. placebo orthoses in the management of the rheumatoid arthritic foot, while subjects continued customary treatment. On the basis of findings of no effect on disability and pain measures, this study indicates no benefit of functional posted foot orthoses over placebos.

Adolescent↗

Recombinant mouse ZP3 inhibits sperm binding and induces the acrosome reaction.

Mammalian fertilization involves interactions of sperm surface receptors with ligands of the zona pellucida, an extracellular matrix surrounding the ovulated egg. In mouse, the zona is composed of three glycoproteins. One of them, ZP3, participates in primary sperm binding and in the subsequent triggering of the sperm's acrosome reaction. Considerable evidence suggests that carbohydrate determinants of ZP3 are responsible for binding to sperm and may be important for acrosomal exocytosis. A full-length cDNA encoding mouse ZP3 was assembled and cloned into expression vectors that contained either a cytomegalovirus (CMV) or a vaccinia (P11) promoter. Mouse L-929 cells were stably transformed with the pZP3-CMV constructs, and green monkey CV-1 cells were infected with a recombinant vaccinia virus containing ZP3. rZP3 was affinity purified from culture media and detected on Western blots as a single 60- to 70-kDa band, which differed in molecular weight from native ZP3 (mean, 83 kDa). Nevertheless, rZP3 is biologically active. rZP3 decreases sperm-zona binding with a potency equivalent to that of native zona pellucida and, like native ZP3, rZP3 triggers acrosomal exocytosis in capacitated mouse sperm. Thus, rZP3 isolated from both rodent and primate cells appears to contain those carbohydrate and protein structures necessary for ZP3's dual role in fertilization.

Animals↗

Evidence that cyclic adenosine 3',5'-monophosphate-dependent protein kinase activation causes pig ovarian granulosa cell differentiation, including increases in two type II subclasses of this kinase.

Agents that elevated intracellular cyclic adenosine 3',5'-monophosphate (cAMP) caused a 3- to 10-fold increase in the luteinizing hormone (LH) receptor level and in progesterone biosynthesis in primary cultures of pig ovarian granulosa cells. Associated with these effects was a 2- to 4-fold increase in the total activity of the catalytic subunit of cAMP-dependent protein kinase in the tissue. From quantitation by [3H]cAMP binding and changes in the specific labeling with the photoaffinity analog [32P]-8-azido-cAMP, these agents were found to cause a concomitant 5- to 15-fold increase in two isoforms of the type II R-subunit (Mr = 54,000 and 56,000) of the protein kinase. Since the two intrasubunit cAMP binding sites of the protein kinase have been found to be positively cooperative, the addition of a combination of an analog selective for site 1 and an analog selective for site 2 causes synergistic increases in protein kinase activation in vitro and synergistic increases in intact cell responses if mediated by the cAMP-dependent protein kinase. In the present study, the addition of such a combination of site 1- and site 2-selective analogs to granulosa cells caused a synergistic increase in LH receptor induction and progesterone production. For both responses, synergism did not occur when two analogs selective for the same site were combined. The results indicated that these responses are mediated by either of the two major isozyme types of cAMP-dependent protein kinase.

Animals↗

Urethral cyst in a man.

We report a case of a bulbous urethral cyst in a man. This rare lesion, probably arising from Cowper's gland, was treated successfully by endoscopic excision of the cyst wall.

Adult↗

Co-localization of enkephalin and cholecystokinin in discrete areas of rat brain.

A double-label immunofluorescence technique was used to demonstrate that immunoreactivities for the functionally antagonistic neuropeptides enkephalin and cholecystokinin octapeptide (CCK) are co-localized within individual neurons and processes in discrete areas of rat midbrain and forebrain. Coexistence was most prominent within varicose pericellular axons extending from the periaqueductal gray matter to a field overlying the medial lemniscus, axons and terminal-like puncta in the central medial, paracentral, interanterodorsal and ventral anterior thalamic nuclei, and perikarya and proximal axonal fragments in layers II and III of neo- and allocortex, and in the anterior olfactory nucleus. The former two systems of axons lie in areas of spinothalamic tract termination. These data suggest that some of the antagonism of opioid analgesia by CCK occurs at the synaptic level in nociceptive areas of brain-stem and thalamus where CCK and enkephalin are co-localized and presumably co-released.

Animals↗

Vicarious excretion of contrast medium in patients without azotemia.

Although excretion of urographic iodinated contrast agents via the biliary and gastrointestinal tract is not uncommon in patients with renal insufficiency, such vicarious excretion is unusual in the presence of normal renal function. The observation of such vicarious excretion in 2 patients with acute unilateral ureteral obstruction and no azotemia is reported in conjunction with review of the appropriate literature and suggestion of possible etiologies.

Adult↗

Effects of coronary flow reduction on capillary-myocardial exchange in dogs.

The effects of coronary flow reduction on tracer capillary permeability surface area (PS) and distribution volumes were studied in open-chest dog preparations. A mixture of 51Cr-labeled red blood cells, 125I-labeled albumin, [14C]sucrose, and tritiated water (3H2O) was introduced into a shunt connecting the carotid and left anterior descending coronary arteries. Sampling from the coronary sinus produced a multiple indicator curve from which [14C]sucrose PS and 3H2O volumes were computed. Curves were observed in control situations and after the cannula was partially clamped. In six dogs, cardiac lymph was collected and analyzed for total protein. Paired comparison of control and flow-restricted indicator curves showed that flow reduction decreased the absolute values of PS and tracer volumes. The ratio of sucrose volume to weight of perfused tissue increased with flow reduction. The ratio of sucrose PS to weight of perfused tissue increased with moderate flow reduction and decreased with severe flow reduction. The results suggest that flow reduction has two effects which competively affect exchange: 1) flow restriction reduces surface area by capillary derecruitment, and 2) the remaining functional capillaries appear to undergo an increase in permeability to small molecules.

Animals↗