Cytomegalovirus induces T-cell independent apoptosis in brain during immunodeficiency.

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic viral pathogen associated with HIV/AIDS or immunosuppressive therapy. Systemic pathology may be caused either through direct virus-mediated infection or by indirect mechanisms such as 'by-stander' apoptosis. CMV infection of the central nervous system (CNS) occurs late in disease progression and understanding of pathology in the brain is fundamental for selection of appropriate therapies. OBJECTIVES: Using a model of disseminated neurotropic CMV disease, these experiments are designed to identify cellular predilection of murine CMV (MCMV) within mature brain and to determine, if CMV induces apoptosis within CNS cells. STUDY DESIGN: Adult immunodeficient (SCID) and normal BALB/c mice were infected via the tail vein with 4.5 x 10(5)pfu recombinant MCMV expressing a green fluorescent protein reporter. Animals were perfused at various time periods from 3 to 35 days post inoculation and tissues were stained for MCMV, GFAP, NEU-N, MBP, TUNEL, and caspase-3. RESULTS: CMV infection within brain was observed in multiple, independent foci affecting several different cell types, including neurons, glial cells, meninges, ependymal cells, and cerebral vessels. Cellular changes included nuclear karyopyknosis and karyorrhexis, and associated meningitis, choroiditis, encephalitis, vasculitis, and necrosis. TUNEL and caspase-3 staining of brain-demonstrated apoptosis of nearby 'by-stander' meningial, glial, and neuronal cells, but only in immunodeficient mice lacking T- and B-lymphocytes. Generally, only large CMV infection foci were associated with apoptosis of non-infected adjacent cells. CONCLUSIONS: These results indicate that MCMV may cause both direct and indirect pathology to brain and that T-cell independent apoptosis of surrounding cells of the CNS may be an important mechanism of disease in the pathogenesis of neurotropic CMV.     

Olfactory neuroblastoma mimicking primary intracranial neoplasm

A case of esthesioneuroblastoma with an unusual clinical and radiographic presentation is reported. The presenting symptoms as well as the computed tomographic examination were compatible with a primary intracranial mass.     

Junctional epidermolysis bullosa keratinocytes in culture display adhesive, structural, and functional abnormalities.

An unusual, elongated, refractile cell morphology was observed in keratinocytes cultured from three patients with non-lethalis forms of junctional epidermolysis bullosa (JEB). To determine whether these changes might be related to altered cell adhesion, keratinocyte strains established from one patient were examined for adhesive, structural, and functional characteristics. JEB keratinocytes expressed keratin tonofilaments, as determined by staining with AE1 monoclonal antibodies and direct observation of tonofilaments by electron microscopy. JEB keratinocytes showed diminished cell-substratum adhesions, judged by interference reflection microscopy. Areas of diminished cell-substratum adhesion corresponded to F-actin-rich cell adhesions (focal adhesions) and not to cellular areas that abundantly express hemidesmosomal antigens. Analysis of cell-substratum adhesion by electron microscopy revealed extensive areas of cell-substratum separation in JEB keratinocytes that were not present in normal keratinocytes maintained in serum-free medium. Normal keratinocytes displayed numerous regions of focal contact between the ventral plasma membrane and the culture substratum, but these structures were not seen in JEB keratinocytes. Bundled actin filaments (stress fibers) were greatly diminished in expected regions of cell-substratum adhesion in JEB keratinocytes and, instead, displayed disorganized individual filaments. The growth rate of JEB keratinocytes was quite slow in culture, with a population doubling time of 2.7 d versus 1.5 d for normal keratinocytes under identical conditions. JEB keratinocytes also displayed a reduced ability to aggregate into colonies upon exposure to medium with increased extracellular calcium. JEB keratinocytes thus display adhesive, structural, and functional abnormalities that suggest this cell type may be central to the pathogenesis of junctional epidermolysis bullosa. Study of affected keratinocytes could be important to characterize associated molecular pathologies.     

Misdiagnosis of hysteria

The diagnosis of hysteria is often incorrect and must be made with great caution. A retrospective study demonstrates that an erroneous diagnosis of hysteria is most likely to be given to females, the psychiatrically ill, patients who embellish and patients who present plausible psychogenic explanations for their illness. Movement disorders and paralysis are the neurologic disorders most frequently mislabeled as hysteria.     

Manganese and arteriosclerosis

The relations between manganese and atherosclerosis were examined on rabbits with experimental atherosclerosis, on patients with atherosclerosis and on workers exposed to manganese. Here a favourable influence of manganese was shown which effected a decrease of the cholesterol content of serum, liver and aorta and inhibited the entry of lipids into the aorta. The influence of the manganese on various enzymes as well as a manganese-copper interaction are discussed as possible causes.     

Magnetic resonance imaging in planning limb-salvage surgery for primary malignant tumors of bone

In defining the linear extent of a malignant tumor in a long bone, radiographs, computerized tomography, and scintigraphy are routinely employed, especially when non-ablative surgery is being considered. The drawbacks of these modalities in defining the true intracompartmental extent of disease within a bone can largely be overcome with the use of magnetic resonance imaging. We did a prospective analysis of magnetic resonance imaging in sixteen consecutive patients with a primary malignant tumor of a long bone, and it showed that this modality has clinical promise of being more precise than the other modalities in defining the true proximal and distal extent of a tumor in a long bone. Coronal images permit easier planning of surgical techniques for salvage of a limb using an allograft than do a multiplicity of transverse images.     

Patient survival and local recurrence rate following radical prostatectomy for prostatic carcinoma

From 1970 to 1980, 153 patients with stages A2, B1 and B2 prostatic cancer and proved negative pelvic lymph nodes underwent radical prostatectomy (84 underwent radical perineal and 69 underwent radical retropubic prostatectomy). Seventeen patients were lost to followup. Of 136 patients who were followed for 5 years or until death 128 (94 per cent) were alive at 5 years, including 118 (87 per cent) who were without evidence of recurrence. Patients with microscopic invasion of the prostatic capsule have a better outcome at 5 years than those with microscopic involvement of the seminal vesicles. Only 46 of the patients could be assessed at 10 years or had died 6 to 10 years postoperatively. Results at 10 years are considered preliminary, since many more patients will reach the 10-year milestone within the next few years.     

Adrenergic and dopaminergic control of the canine paw microcirculation

Basal isolated canine paw blood flow was equally distributed between arteriovenous anastomosis (AVA) and capillary circulations. Norepinephrine decreased AVA flow by 92% and capillary flow by 41%. Dopamine significantly reduced AVA flow by 94% compared to baseline with a 37% reduction in capillary flow. However, with alpha-adrenergic blockade dopamine decreased AVA flow 66% while capillary flow increased 42%. Isoproterenol increased capillary flow almost twofold and appeared to decrease AVA flow, although the latter was statistically insignificant. Differential effects of adrenergic and dopaminergic agonists on canine paw AVA and capillary blood flow suggest the existence of independent regulation of these components of the microcirculation.     

Scar sign of renal oncocytoma: Magnetic resonance imaging appearance and lack of specificity

This case report illustrates the magnetic resonance imaging (MRI) appearance of a typically asymptomatic renal oncocytoma as a homogeneous mass of medium signal with a stellate central region of decreased signal, representing the central scar. The MRI was correlated with computed tomography (CT), ultrasound (US), and gross pathologic appearance. The appearance of a central scar is not specific for oncocytoma and does not exclude renal cell carcinoma, as illustrated by a second case.     

Myectomy versus myotomy as an adjunct to membranectomy in the surgical repair of discrete and tunnel subaortic stenosis

The results of membranectomy and deep myectomy in the left ventricular outflow tract were compared to those of membranectomy and myotomy in 42 patients who underwent surgical repair of discrete and tunnel subaortic stenosis. Fifteen consecutive patients (Group A) underwent membranectomy and myotomy, and 27 consecutive patients (Group B) underwent membranectomy and myectomy. Two patients of Group A and nine of Group B had tunnel subaortic stenosis. The preoperative mean (+/- standard deviation) peak systolic gradients across the left ventricular outflow tract in patients with discrete subaortic stenosis types I and II were 64 +/- 29 mm Hg in Group A and 52 +/- 3 mm Hg in Group B (p = not significant). In the patients with tunnel subaortic stenosis the preoperative mean gradients were 97 +/- 74 mm Hg in Group A and 73 +/- 26 mm Hg in Group B (p = not significant). In patients with discrete subaortic stenosis types I and II, postoperative catheterization at a mean follow-up of 21 months revealed residual mean gradients of 29 +/- 24 mm Hg in Group A and 10 +/- 13 mm Hg in Group B (p less than 0.01). In the patients with tunnel subaortic stenosis, the postoperative mean gradients were 25 +/- 7 and 30 +/- 30 mm Hg in Groups A and B, respectively (p = not significant). We conclude that in the surgical management of discrete subaortic stenosis types I and II, deep myectomy (in addition to membranectomy) produces better relief of the left ventricular outflow obstruction than do membranectomy and myotomy. In patients with tunnel subaortic stenosis myectomy is less effective than in the non-tunnel type but still produces acceptable results and may delay radical procedures to a later age.