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Biomedical subjects

I Frank

Publications and source records attributed to I Frank.

At least 73 records · Page 4Linked to original sources

A novel function of the herpes simplex virus type 1 Fc receptor: participation in bipolar bridging of antiviral immunoglobulin G.

We describe a novel function of the Fc receptor of herpes simplex virus type 1 (HSV-1), its ability to participate in antibody bipolar bridging. This refers to the binding of a single immunoglobulin G (IgG) molecule by its Fab end to its antigenic target and by its Fc end to an Fc receptor (FcR). We demonstrate that various immune IgG antibodies, including polyclonal rabbit antibodies to HSV-1 glycoproteins gC1 and gD1 and monoclonal human antibody to gD1 blocked rosetting of IgG-coated erythrocytes at IgG concentrations 100- to 2,000-fold lower than required for rosette inhibition with nonimmune IgG. Steric hindrance did not account for the observed differences between immune and nonimmune IgG since rabbit anti-gC1 F(ab')2 fragments did not block rosetting. Murine anti-gC1 or anti-gD1 IgG, a species of IgG incapable of binding by its Fc end to the HSV-1 FcR, also did not block rosetting. When cells were infected with a gC1-deficient mutant, anti-gC1 IgG inhibited rosetting to the same extent as nonimmune IgG. This indicates that binding by the Fab end of the IgG molecule was required for maximum inhibition of rosetting. Bipolar bridging was shown to occur even when small concentrations of immune IgG were present in physiologic concentrations of nonimmune IgG. The biologic relevance of antibody bipolar bridging was evaluated by comparing antibody- and complement-dependent virus neutralization of an FcR-negative mutant and its parent HSV-1 strain. By engaging the Fc end of antiviral IgG, the parent strain resisted neutralization mediated by the classical complement pathway. These observations provide insight into the role of the HSV-1 FcR in pathogenesis and may help explain the function of FcR detected on other microorganisms.

Animals↗

Long-term outpatient treatment of CMV retinitis with ganciclovir in AIDS patients.

Cytomegaloviral retinitis was diagnosed in nine eyes of seven patients with acquired immune deficiency syndrome (AIDS) on the basis of the characteristic ocular findings and a positive culture for cytomegalovirus (CMV) obtained systemically. Treatment with ganciclovir was begun on a protocol which provided two weeks of inpatient therapy at daily doses of 2.5 to 10 mg/kg followed by outpatient therapy at a reduced dosage three to six days per week. Outpatient maintenance dosage ranged from 15 mg/kg per week to 30 mg/kg per week. In seven eyes of six patients the treatment decreased retinal inflammation and stabilised the margins of the lesions. Six patients have tolerated long term maintenance therapy for 10-30 weeks. Six of seven patients (85%) in this study developed side effects from ganciclovir which required periods of a reduction in dosage or interruption of therapy. The side effects from ganciclovir included neutropenia, thrombocytopenia, drug fever, and neuropathy. Physicians using ganciclovir in AIDS patients must watch for the signs of drug toxicity and adjust treatment accordingly. Ganciclovir appears to be a promising therapy for CMV retinitis, but further work is necessary to determine the best regimen for optimal efficacy with minimal side effects.

Acquired Immunodeficiency Syndrome↗

Prototheca zopfii isolated from a patient with olecranon bursitis.

Prototheca zopfii was isolated from a patient with olecranon bursitis. Olecranon bursitis caused by Prototheca is a distinct clinical entity. Recognition of this infection was made by observing characteristic organisms in tissue and subsequent isolation of the organism.

Aged↗

[Hemorheologic studies for evaluating microcirculation in patients with peripheral arterial circulatory disorders and diabetes mellitus].

Haemorheological investigations in 73 male patients with chronic disturbances of the arterial blood supply of the lower extremities and 54 male non-insulin-requiring (type-II-) diabetics with and without micro- and macroangiopathy resulted in significant changes of the flow properties of the blood in contrast to 20 comparable clinically healthy males. In all groups of patients a clear increase of the aggregation of erythrocytes and the viscosity of plasma as well as a decrease of the deformability of erythrocytes were to be proved. The size of the deviations of all three parameters from the normal correlated with the degree of severity of the arterial obstructive disease and in diabetics with the occurrence of vascular complications (macroangiopathy, retinopathy) as well as with the situation of metabolism. The decreased fluidity of blood may lead to the development of further enlargement of disturbances of microcirculation. Therefore, haemorheological viewpoints should be included into the total diagnostic and therapeutic concept of the arterial obstructive disease and the diabetes mellitus.

Adult↗

Inhibition of fungal and mammalian sterol biosynthesis by 2-aza-2,3-dihydrosqualene.

2-Aza-2,3-dihydrosqualene (I) and a quaternary ammonium derivative (II) inhibited ergosterol biosynthesis in cells and cell-free extracts of the pathogenic yeast Candida albicans as measured by incorporation of radiolabelled precursors. The compounds inhibited squalene epoxidase and 2,3-oxidosqualene cyclase to varying degrees in microsomes from C. albicans and from rat liver. The rat liver epoxidase was 50% inhibited by I at 2.4 microM. In C. albicans cells, but not in cell-free extracts, I also inhibited lanosterol demethylation and led to accumulation of an unidentified polar product.

Animals↗

Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate.

The thiocarbamate antimycotics tolnaftate and tolciclate blocked sterol biosynthesis in fungal cells and cell extracts, with accumulation of squalene. This point of action was confirmed by the direct inhibition of microsomal squalene epoxidase from Candida albicans. There was no inhibition of other steps in ergosterol biosynthesis. In whole Candida cells, ergosterol biosynthesis inhibition was not complete at drug concentrations up to 100 mg/liter, whereas full inhibition occurred in a cell-free test system. Rat liver cell-free cholesterol biosynthesis was much less sensitive to the drugs. The biochemical action of tolnaftate and tolciclate is thus similar to that of the allylamine antimycotics naftifine and terbinafine.

Acetates↗

Large perilymph fistulas.

Perilymph fistulas may manifest themselves either by otologic symptoms, as in cases of small fistulas, or primarily through neurologic symptoms, as with large fistulas. A case history is presented of a 3-year-old girl with recurrent bouts of meningitis who was found to have a large perilymph fistula. She had a right undeveloped cochlea and labyrinth, as well as multiple defects of the medial wall of her middle ear. The only way of preventing the recurrent bouts of bacterial meningitis in cases of large perilymph fistulas is surgical repair. Our conclusion is that, considering the problems involved in cases of large congenital perilymph fistulas, a simple closure of the fistula is not sufficient and the method of choice is obliteration of a deeper structure--such as the vestibule itself.

Child, Preschool↗

Proliferation of primary sensory neurons in adult rat dorsal root ganglion and the kinetics of retrograde cell loss after sciatic nerve section.

This study was aimed at measuring the kinetics of retrograde death among primary sensory neurons axotomized by transection of the ipsilateral sciatic nerve in adult rats. Using electrophysiological and retrograde transport methods, we first determined that most sciatic afferents enter the spinal cord along the L4 and L5 dorsal roots (DRs), and that about 54% of the cells in the L4 and L5 dorsal root ganglia (DRGs) project an axon into the sciatic nerve. Knowing this value, we could then calculate the rate of loss of axotomized neurons from the overall rate of neuron loss in the DRGs at different times after the lesion. Following unilateral sciatic neurectomy, we found a steady falloff in the ratio of DRG neurons on the operated versus the intact control sides in cresyl-violet-stained serial paraffin sections. We were surprised to note, however, that on the control side there was a steady increase in the cell count with age. Counts done on a series of unoperated rats of various ages confirmed this natural increase. Overall, new neurons accrete at an average rate of 18.1 cells per day to the combined L4 and L5 DRGs, nearly doubling their numbers during the adult life of the animal. The new cells add mostly to the small-diameter neuronal compartment. Evidence from neonatally operated rats indicates that the decline in the ratio of neurons in operated versus control DRGs following sciatic nerve section in the adult results more from a halt in the accretion of new neurons to the sciatic compartment than from frank cell death. From our data, we calculate that the loss of axotomized neurons occurs at a rate of only about 8% per 100 postoperative days.

Animals↗

Light- and electron microscopic investigations of pulmonary tissue after high-frequency positive-pressure ventilation (HFPPV).

Narcotisized dogs were artificially ventilated for periods of two to five hours with HFPPV. During this time the blood gases, pH and bases were controlled. In spite of sufficient oxygenation and CO2-elimination, a metabolic acidosis developed which could not be fully compensated by the addition of buffer solutions. In light and electron microscopy these lungs did not differ significantly from control lungs. Haemorrhages or atelectases were never observed. Type I cells as well as Type II cells in the alveoli are unchanged, i.e. the Type II cells were not depleted but contained numerous typical lamellar bodies with a diameter of 0.4-1 mu. The blood gas barrier was not widened and was ca. 3000 A wide. The alveolar surface was coated by an often fragmented electron-dense film (monolayer of the surfactant).

Acid-Base Equilibrium↗