Affective and Behavioral Stress Outcomes in Alzheimer's Caregivers

Few investigations have looked at behavioral stress outcomes in Alzheimer's caregivers. This study documented concentration deficits to examine behavioral outcomes of stress in 33 Alzheimer's Disease (AD) caregivers and in 33 age-, sex-, and race-matched controls. As hypothesized, caregivers showed less persistence than controls in solving problems from a standard test of problem-solving ability. In addition, caregivers tended to make more errors than controls on a standard proofreading task ( p < .09). In AD caregivers, cognitive deficits (represented by lower scores on problem-solving and concentration tasks) may be representative of a broader deficit in concentration that impairs the ability of caregivers to provide for their own needs and the needs of the family member for whom they are caring.     

New familial syndrome of unilateral upper eyelid coloboma, aberrant anterior hairline pattern, and anal anomalies in Manitoba Indians.

We report on 6 (3 male, 3 female) Manitoba Indian children with hypertelorism and variable combinations of unilateral eye malformations, aberrant anterolateral scalp hairline, and nasal and anal anomalies. These children belong to 4 related families. The parents and 7 other sibs are clinically unaffected. The family histories are otherwise unremarkable. The presence of 2 major malformations in sibs and related individuals (with unaffected parents) suggests that this is a newly described pleiotropic autosomal recessive syndrome. The differential diagnosis includes cryptophthalmos syndrome and several other related malformation syndromes. Although multifactorial determination cannot be excluded, the inbred, isolated population and distribution make autosomal recessive inheritance more likely.     

Irregular geometries in normal unmyelinated axons: A 3D serial EM analysis

Summary Axons have generally been represented as straight cylinders. It is not at all uncommon for anatomists to take single cross-sections of an axonal bundle, and from the axonal diameter compute expected conduction velocities. This assumes that each cross-section represents a slice through a perfect cylinder. We have examined the three-dimensional geometry of 98 central and peripheral unmyelinated axons, using computer-assisted serial electron microscopy. These reconstructions reveal that virtually all unmyelinated axons have highly irregular axial shapes consisting of periodic varicosities. The varicosities were, without exception, filled with membranous organelles frequently including mitochondria, and have obligatory volumes similar to that described in other neurites. The mitochondria make contact with microtubules, while the other membraneous organelles were frequently found free floating in the cytoplasm. We conclude that unmyelinated axons are fundamentally varicose structures created by the presence of organelles, and that an axon's calibre is dynamic in both space and time.These irregular axonal geometries raise serious doubts about standard two dimensional morphometric analysis and suggest that electrical properties may be more heterogeneous than expected from single section data. These results also suggest that the total number of microtubules contained in an axon, rather than its single section diameter, may prove to be a more accurate predictor of properties such as conduction velocity. Finally, these results offer an explanation for a number of pathological changes that have been described in unmyelinated axons.     

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.     

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.