Testosterone and postnatal ontogenesis of hypothalamic mu ([3H]dihydromorphine) opioid receptors in the rat.

Brain opioids modulate the activity of the hypothalamo-pituitary complex by binding to specific receptors which have been subdivided at least into 3 subclasses (mu, kappa, delta, etc). mu-Receptors and their ligands seem to be particularly involved in the control of gonadotropin and prolactin release. It is known that the neuroendocrine system, as well as the brain opioid systems and their receptors, are not fully mature at birth; it is also known that the postnatal maturation of many brain machineries is under the control of androgens secreted by the developing testes. Consequently, it has been investigated whether the presence or the absence of testosterone at time of birth may induce changes of the binding characteristics of hypothalamic mu-opioid receptors. The experiments have been performed by evaluating the maximal binding capacity (Bmax, an index of the number of receptors), and the affinity constant (Ka) of the specific mu-ligand dihydromorphine in hypothalamic plasma membrane preparations derived from normal male rats, normal female rats, male rats orchidectomized 2 days after birth and female rats treated 2 days after birth with 1.25 mg of testosterone propionate. Animals belonging to the 4 groups were killed at days 16, 26 and 60 of age. The results obtained show that, at 16 days of age, in the 4 groups of rats the number of hypothalamic mu receptors is identical. At 26 days a significant increase in the number of mu-receptors occurs in normal female animals, while their levels remain similar to those found at 16 days in the other 3 groups of animals. At 60 days of age, the number of mu-receptors in normal females remains elevated, while the number of mu-receptors increases to reach normal female levels in the hypothalamus of neonatally castrated males. At 60 days, there were no changes in normal males or in androgenized females. The variations here reported took place without any change of the Ka of dihydromorphine for the mu-receptors. These data show a sexual dimorphism of hypothalamic mu-receptors and suggest that their ontogenetic development may be linked to the presence or the absence of androgens at time of birth.     

Chimeric cytotoxin IL2-PE40 inhibits relapsing experimental allergic encephalomyelitis.

IL2-PE40 is a chimeric protein composed of human interleukin-2 (IL2) genetically fused to a modified form of Pseudomonas exotoxin lacking the cell recognition domain. IL2-PE40 is cytotoxic for IL2 receptor-bearing lymphocytes in culture and can inhibit activation of T cells in vivo. IL2-PE40 can significantly diminish antigen-stimulated proliferation of lymphocytes sensitized to myelin basic protein. Intraperitoneal administration of IL2-PE40 not only markedly inhibits the clinical manifestations of adoptively transferred relapsing experimental allergic encephalomyelitis but also dramatically reduces both inflammation and demyelination characteristic of the disease.     

Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Curriculum for musculoskeletal radiology.

Although general suggestions have been made regarding a radiology residency curriculum, no specific list of entities has been offered. Over the past ten years, we have developed a resident-run morning conference in musculoskeletal radiology that is supervised by faculty and covers a specific curriculum. We offer our curriculum as an example that may assist other departments in developing their own curricula.     

Family medical leave. An employee benefit for working caregivers of elderly family members

Future trends include a decrease in the number of adult children, an increase in the number of individuals over age 65, single parent families, working women, and individuals with no health care insurance. As more women with multiple roles and responsibilities enter and continue as part of the work force, employers recognize the need for support of family issues. Currently many employers lack initiative to make these needed changes. The occupational health nurses' role in relation to future policy for working caregivers includes assessment of how employment and caregiving impact work performance, job satisfaction, and health; and participation in defining public policy issues.     

Does chronic prenatal methadone exposure affect beta-receptor subtypes in placental, fetal and maternal brain homogenates?

Computer competition analysis of 3H-DHA (3H-dihydroalprenolol, a nonselective beta-adrenergic radioligand) binding in the presence of unlabeled metoprolol (a beta 1-selective antagonist) indicates the existence of both beta 1- and beta 2-adrenergic receptor subtypes in the rat placenta and confirms previous reports that both beta-adrenoceptors are present in adult rat cortex. In the fetal brain (20th day of gestation), however, only beta 1-receptors were detected. Pregnant rats were chronically exposed to methadone from day 7 to day 20 of gestation via implanted osmotic minipumps (6.3-9.0 mg/kg/day). This treatment schedule did not induce a change in the affinity and density of either beta-receptor subtype in the placental, fetal and maternal brain homogenates. The results are discussed in terms of the reported monoaminergic and opiate receptor functional interactions.     

Therapy of human cervical carcinoma with monoclonal antibody-Pseudomonas exotoxin conjugates.

Pseudomonas exotoxin A (PE) linked to the F(ab')2 fragment of 1H10, a murine monoclonal antibody recognizing a carbohydrate epitope of a glycoconjugate expressed on the surface of human cervical carcinoma tumor cells, was evaluated for in vitro and in vivo activity. PE can kill cells by ADP-ribosylating elongation factor 2 thus inhibiting protein synthesis. Disulfide- as well as thioether-linked immunotoxins (1H10-PE) killed cervical carcinoma cells in vitro and were 20-160 times more inhibitory to target than to control cells. Cell killing was antibody mediated as demonstrated by the reduction of 1H10-PE growth inhibition to target CaSki cells by free 1H10 F(ab')2. In addition, a control antibody immunotoxin was nontoxic to CaSki cells. Thioether-linked 1H10-PE administered either i.v. or i.p. suppressed the growth of established solid s.c. cervical carcinoma tumors xenografted in nude mice for over 30 days. Treatment with antibody alone or a control immunotoxin had no significant effect on tumor growth. Administration of immunotoxin i.p. was associated with less toxicity than administration i.v., but i.v. injections were more effective at suppressing the growth of established solid tumors.     

Paranasal sinus mucocele in cystic fibrosis

The relationship between cystic fibrosis, nasal polyposis and chronic sinusitis is clearly defined. Mucoceles of the paranasal sinuses, however, are a well-described complication of chronic sinusitis in adults; but they rarely occur in the pediatric age group. We report a three-year-old who presented with epiphora and fullness at the right medial canthus. Computed tomography confirmed a right ethmoid mucocele which was surgically drained, with resolution of symptoms. Approximately 12 other cases of mucoceles have been reported in the pediatric age group. Although many of these patients had recognized cystic fibrosis, some were previously undiagnosed. Only after presentation with a mucocele, did sweat testing reveal their underlying pathology. No pediatric patients in the literature were found with mucoceles and normal sweat tests. Paranasal sinus mucoceles may be diagnostic of cystic fibrosis and may be the presenting sign in some patients.     

Pediatric urology

Development of the genital and urinary systems is interwoven. Developmental abnormalities may cause problems in both systems, although the presenting problem may be ambiguous genitalia, hypospadias, undescended testis, or a urinary tract infection. The primary care physician must understand the underlying significance of pediatric urologic problems and seek appropriate consultation in a timely manner.