Propranolol, a beta-adrenergic antagonist, retards response to MSH in skin of Anolis carolinensis

Lacking sympathetic innervation, the skin of A. carolinensis, an iguanid lizard, darkens within minutes in response to circulating melanocyte stimulating hormone (MSH) or beta adrenergic agonists such as epinephrine (EPI). This change is produced by dispersion of melanin from a perinculear position within dermal melanophores into superficial dendritic processes. These melanophores possess alpha-2 and beta-2 adrenergic as well as MSH receptors except in a patch of skin behind the eye, the eyespot, which lacks alpha receptors. Activation of beta or MSH receptors leads to stimulation of adenyl cyclase whereas alpha stimulation inhibits the enzyme to override the others. In a series of trials, injection of saline or propranolol was followed after 30 minutes by saline, EPI, or MSH. Propranolol inhibited chromatophore response to EPI. It also, unexpectedly, retarded the response to MSH, increasing latency to eyespot formation and body color change as well as the duration of darkening for both. Alteration of MSH response by a beta blocker could be explained by linkage of both adrenergic receptors and the MSH receptor to a common adenyl cyclase molecule to form a functional unit in the membrane of the melanophore.     

A role for hyaluronan in macrophage accumulation and collagen deposition after bleomycin-induced lung injury

Elevated concentrations of hyaluronan (HA) are associated with the accumulation of macrophages in the lung after injury. We have investigated the role of HA in the inflammatory and fibrotic responses to lung injury using the intratracheal instillation of bleomycin in rats as a model. After bleomycin-induced lung injury, both HA content in bronchoalveolar lavage (BAL) and staining for HA in macrophages accumulating in injured areas of the lung were maximal at 4 d. Increased HA in BAL correlated with increased locomotion of isolated alveolar macrophages. HA-binding peptide was able to specifically block macrophage motility in vitro. Importantly, systemic administration of HA-binding peptide to rats before injury not only decreased alveolar macrophage motility and accumulation in the lung, but also reduced lung collagen alpha (I) messenger RNA and hydroxyproline contents. We propose a model in which HA plays a critical role in the inflammatory response and fibrotic consequences of acute lung injury.     

Heterogeneity of VP4 neutralization epitopes among serotype P1A human rotavirus strains.

We have used serotype-specific VP4 and VP7 neutralizing monoclonal antibodies (Nt-MAbs), as well as subgroup (SG)-specific MAbs, to characterize by enzyme immunoassay rotavirus strains isolated from diarrheic infants in the city of Monterrey, Mexico, from July 1993 to March 1994. Of a total of 465 children studied, 140 were rotavirus positive, including 3 patients infected with non-group A rotaviruses. The SG and VP7 (G) serotype specificities could be determined for 118 (84%) of the 140 rotavirus-positive stool specimens; 4 rotavirus strains were serotype G1 and SGII; 1 strain was serotype G2 and SGI+II; 112 strains were serotype G3 and SGII; 1 strain was serotype G3 and SGI; and none of the strains was serotype G4. Fifty-eight specimens, representing the 13 different group A rotavirus electropherotypes detected, were chosen for VP4 (P) serotyping. Of these, 48 (83%) strains reacted with the P1A serotype-specific Nt-MAb 1A10. None of the strains reacted with the serotype P2-specific Nt-MAbs tested. Not all viruses that reacted with Nt-MAb 1A10 were recognized by Nt-MAbs 2A3 and 2G1, which also recognize P1A strains, indicating heterogeneity of neutralization epitopes among serotype P1A human rotaviruses. This heterogeneity could be relevant for the specificity of the VP4-mediated neutralizing antibody immune response and indicates the need for antigenic characterization, in addition to genomic typing, of the VP4 proteins of circulating human rotavirus field strains.     

Potential uses of interleukin 2 in cancer therapy

Interleukin 2 (IL 2) has several potential uses in cancer therapy including: the augmentation of specific T cell mediated anti-tumor immunity and the activation of non-specific cytolytic effector cells, termed lymphokine-activated killer (LAK) cells. The current review will present data from our laboratory demonstrating in animal models the feasibility of both potential approaches. Studies to be reviewed show that: IL 2 can induce the proliferation and expansion in number of tumor-reactive T cells in vitro; T cells grown in culture in IL 2 can be effective reagents in vivo for specific tumor therapy; the administration of exogenous IL 2 can induce the growth and augment the function of cultured T cells in vivo; however, as a corollary, T cells cultured long-term in vivo with IL 2 are functionally limited in vivo without the administration of exogenous IL 2 in vivo; by contrast, T cells grown in vitro with specific antigen, as opposed to IL 2, as the major stimulus for proliferation are able to proliferate rapidly in vivo, distribute widely in host lymphoid organs, and mediate therapy of disseminated murine leukemia; importantly, such antigen-driven long-term cultured T cells can survive long-term in vivo and provide specific immunologic memory, and, the administration of low-dose IL 2 in vivo can induce the growth of antigen-driven long-term cultured T cells in vivo and thereby increase the number of functional memory T cells; the culture of lymphoid cells in high concentrations of IL 2 can induce LAK cells in vitro capable of lysing leukemia in vitro; LAK cells generated in vitro can mediate a small but detectable anti-tumor effect in vivo against disseminated leukemia as an adjunct to chemotherapy; and, high-dose IL 2 administered in vivo can activate LAK cells in vivo and cure disseminated murine leukemia. Therefore, it is highly likely that IL 2 can become an effective reagent for the therapy of human cancer.     

Familial Miller-Dieker syndrome associated with pericentric inversion of chromosome 17

Recently it has been shown that most cases of the Miller-Dieker syndrome (MDS) are caused by deletion 17p13.3. All familial cases have been associated with a balanced reciprocal translocation in a carrier parent and unbalanced translocations in their affected offspring. We report a new case of familial MDS in whom the mother carries a pericentric inversion of chromosome 17. She has had two children with MDS, one of whom was shown to carry a recombinant 17 consisting of dup(17q) and del(17p). The high frequency of familial MDS and its consistent association with balanced chromosomal rearrangements in one of the parents makes it important to do high-resolution chromosome analysis on all patients with MDS and possibly all patients with lissencephaly. Finding a familial balanced rearrangement makes prenatal diagnosis of this condition feasible.     

Serotypic and genotypic characterization of human serotype 10 rotaviruses from asymptomatic neonates.

Human rotaviruses were isolated from asymptomatic neonates at various hospitals and clinics in the city of Bangalore, India, and were found to be subgroup I specific and possess long RNA patterns (M. Sukumaran, K. Gowda, P. P. Maiya, T. P. Srinivas, M. S. Kumar, S. Aijaz, R. R. Reddy, L. Padilla, H. B. Greenberg, and C. D. Rao, Arch. Virol. 126:239-251, 1992). Three of these strains were adapted to tissue culture and found by serotype analysis and neutralization assays to be of serotype 10, a serotype commonly found in cattle but infrequently found in humans and not previously identified in neonates. By RNA-RNA hybridization, a high level of relatedness to a serotype 10 bovine rotavirus strain and a low-to-medium level of relatedness to a human rotavirus strain were observed. Since this human isolate shares a genogroup with bovine rotavirus, it is likely that it originated by interspecies transmission. A human rotavirus strain isolated from asymptomatic neonates and similar to bovine rotavirus might represent a good vaccine candidate.     

The "hyperacute" extraaxial intracranial hematoma: computed tomographic findings and clinical significance

Thirteen patients with acute subdural and epidural hematomas were found to have fresh, unclotted blood at the time of surgical decompression several hours after injury. Computed tomographic (CT) scans of these patients demonstrated areas of hyperdensity, corresponding to clotted hematoma, admixed with areas of isodensity, corresponding to liquid blood. Active bleeding from identifiable loci was found in 11 patients, 4 of whom had massive hemorrhages. Clotting abnormalities ranging from slightly elevated laboratory test results to a full-blown clinical picture of disseminated intravascular coagulation occurred in 8 patients. We describe the CT pictures of these "hyperacute" lesions, and we postulate that such CT presentations indicate either the presence of ongoing active intracranial bleeding or the onset of a coagulopathy complicating the management of these lesions.     

Serial Dexamethasone Suppression Tests and Clinical Outcome in ECT

Serial dexamethasone suppression tests (DST), obtained during a course of electroconvulsive therapy in 43 severely depressed patients, did not exhibit relationships between the initial DST, final DST, or the change in DST with clinical outcome measures at the time of discharge. In 37 patients reviewed six months after discharge, no relationship with the continuation of improvement, rehospitalization, or suicide was found. We are unable to confirm a clinical application for the DST in the management of patients during a course of convulsive therapy.     

Comparison of primary and secondary treatment in squamous oral cancer

A popular rule of thumb has often prevailed in treating oral cancer: Try one modality first; if it fails, try the other--the chance for cure will still be good. To study this dogma, a group of 160 consecutive patients with oral cavity squamous carcinoma were reviewed. A hypothesis was formed: secondary treatment for recurrent cancer, whether surgery after radiation failure or vice versa, would salvage essentially as many patients as primary treatment, say within 15%. Results show a large difference in success rates between first and second treatments when all stages are considered together, a difference well over 15 percentage points. Regarding each stage separately, the largest difference occurs in stage II (28 percentage points); other stages exceed 15 point differences. No significant differences in successful salvage occur between "home" failures and "elsewhere" failures. Local recurrence was a major cause of failure in both groups (55%). We conclude that recurrence of oral squamous cancer after first treatment markedly reduces patients' chance for cure.     

Lupus vulgaris responding to double antituberculous therapy

A patient with a 3 by 4 cm ulcerated lesion on the nose and upper lip in whom previous antibiotics and antifungal treatments for a "mixed infection" were of no avail is presented. Her history revealed that she has had pulmonary and pharyngeal tuberculosis and subsequently scrofuloderma of cervical lymph nodes. She eventually responded well to isoniazid, rifampin, and pyridoxine therapy.