Experimental peripheral nerve repair: environmental control directed at the cellular level.

This study recognizes recent advances in the understanding of the anatomy and physiology of peripheral nerves at the cellular level. It has reproduced study conditions originally advocated by de Medinaceli and coworkers, with modifications. Eighty-four rats were divided into three groups. Group A underwent sciatic nerve transection and standard perineurial repair. Group B nerves were frozen, severed with a vibrating blade, and reconnected by tubulization with a rubber cuff while bathed in solutions designed to inhibit Ca++-calmodulin activation, maintain colloid osmotic pressure, and mimic ambient electrolytic conditions. Group C underwent a similar procedure as group B, with the rubber cuff replaced by a polyglycolic acid mesh. All animals were randomized and evaluated functionally in terms of a sciatic index. By post-operative day 225, animals of group A recovered 37% of function, group B recovered 74%, and group C recovered 67%. Compound action potential recordings revealed a velocity recovery of 41% in group A, 70% in group B, and 81% in group C. Microscopic evaluation provided evidence for corresponding structural improvement. This new method of nerve repair is uncomplicated, relatively inexpensive, and easily adaptable to other animal models.

Prolonged, progressive dementia with spongiform encephalopathy: a variant of Creutzfeldt-Jakob disease?

A 46-year-old female is described with prolonged, progressive dementia and a brain biopsy consistent with Creutzfeldt-Jakob disease (CJD). She had neither myoclonic jerks nor an electroencephalogram with periodic spikes and suppression. Five of her close relatives were also demented. The nosology of CJD was discussed in the light of this case in which histopathology was characteristic of spongiform encephalopathy but the clinical features were atypical. We concluded that it would be premature to expand the traditional diagnostic criteria to include such cases as having CJD but, at the same time, it would be prudent to handle tissue, linens and surgical instruments as if they were contaminated by the resistant agent of CJD.

Intracellular spiral inclusions in cerebral cell processes in Creutzfeldt-Jakob disease.

Electron microscopic examination of brain biopsy specimens from two patients with Creutzfeldt-Jakob disease revealed the presence of intracellular membranous spiral inclusions in the processes of cortical cells. These inclusions, 375 nm to 660 nm in length and 50 nm to 88 nm in width, resemble similar structures reported in a patient with the same disease by Bastian and, more recently, in a second patient by Gray et al. These inclusions bear close morphologic resemblance to spiroplasma organisms, a wall-free prokaryote known to cause a "slow-virus"-like disorder in mice.

Fine structure of contrasting choroid plexus lesions caused by tertiary amines or cyclophosphamide.

Hydropic alterations of the fine structure of the choroid plexus epithelium following administration of three different tertiary amines to rats were compared with alterations produced by cyclophosphamide and with normal choroid plexus. Single doses of 2,7-bis(2-diethylamino)-ethoxy)-4-methyl-1,8-naphthyridine HCl or 2,6-di-(omega-dimethyl aminoethoxy)-pyridine produced dramatic accumulations of membrane-limited vacuoles. Multiple doses of 2,7-bis-(diethylaminoethoxy)fluoren-9-one HCl (tilorone) produced accumulations of dense cytoplasmic bodies in choroid epithelial cells in addition to the hydropic vacuoles. Differential responses to these agents suggested functional specialization or temporal variation in function among adjacent choroidal cells. Despite the occurrence of pronounced plasma exudation in the plexitis following cyclophosphamide treatment, there was no hydropic vacuolization.

Nuclear bodies produced in astrocytes by tilorone.

Large, eosinophilic, nonglycogenic nuclear inclusions were produced in the central nervous system by the drug tilorone. At the light microscope level, the inclusions occurred predominantly in astrocytes. Ultrastructurally, they were identical to the nuclear bodies described in many cell types under many conditions. The bodies were produced by tilorone in small numbers in the median eminence, a part of the hypothalamus that lacks a blood-brain barrier. They were produced in only 2 or 3 days in large numbers adjacent to zones of thermal or traumatic necrosis or in areas of inflammation. These facts, and the distribution of affected astrocytes, indicated that permeability factors and cerebrospinal fluid flow were involved in the development of the nuclear bodies. The large size and large number of nuclear bodies produced by tilorone should facilitate studies of this poorly understood nuclear organelle.

Experimental adenovirus infection of the mouse adrenal gland. II. Electron microscopic observations.

A strain of mouse adenovirus, found to have a striking tropism for the weanling mouse adrenal gland, enabled electron microscopic examination of adrenals in various stages of infection. Nucleolar hypertrophy and the successive formation of three types of inclusion bodies in association with nucleoli preceded virion production. Angular crystals of virions formed in the affected nuclei. Virus was released by lysis of nuclear membranes; rapid degeneration of cytoplasmic organelles followed. Rupture of external cell membranes released virus into the extracellular spaces where virions crossed vascular basement membranes to enter endothelial cells. Virions were also phagocytized by inflammatory cells which reentered vascular sinusoids, and by adrenal parenchymal cells. Disruption of virus-laden phagocytic vacuoles in parenchymal cells released virions into the cytoplasm. Typical viral inclusion bodies also formed in vascular endothelial cells and in inflammatory cells, but virion replication was not detected. The possibility that virus directly entered parenchymal cells through the external cell membrane without phagocytosis is discussed.

Experimental adenovirus infection of the mouse adrenal gland. I. Light microscopic observations.

A murine type of adenovirus has been found to have a highly selective affinity for the adrenal of its natural host. In view of the adrenal pathology in Addison's disease, which consists of cortical atrophy and focal lymphocytic infiltration, the possibility of a viral causation is an attractive hypothesis. The striking adrenotropism of this agent offers, theoretically, a potential experimental animal model for investigation of this possibility. Most of our information about the acute biologic action of adenoviruses has been gained from study of virus-infected tissue culture cells. The sharply focused and severe attack of the murine agent upon a prime target organ facilitates correlative in vivo studies of the cytopathology of adenovirus infection at levels of light and electron microscopy.

A new form of localized allergic encephalomyelitis featuring polymorphonuclear neutrophilic leukocytes.

Mononuclear inflammatory infiltrates are characteristic of experimental allergic encephalomyelitis (EAE). Localized EAE was produced in rats in a single day by passive transfer of living lymphoid cells from immunized donors to non-immunized recipients with thermal brain injuries. When the recipients were pretreated with cyclophosphamide 1 or 2 days before cell transfer, neutrophils in the EAE infiltrates notably increased and mononuclear leukocytes decreased. This neutrophilic form of EAE was produced with cells from donors immunized with whole neural tissue or purified myelin basic protein and with adjuvants of different types. This lesion could not be reproduced if the EAE cells were replaced by EAE serum or by irrelevantly immunized cells, or if their activity was foiled by specific "desensitization" or by use of histoincompatible recipients. The 2-day period during which cyclophosphamide prepared recipients for neutrophilic EAE coincided with a transient lymphopenia and relative neutrocytosis caused by the drug. The passive transfer system made it possible for the drug to unbalance the recipient's hemopoietic system without risking adverse effects on the donor cells. The rapid development of the localized form of EAE made it possible to produce lesions before the recipient's transient imbalance gave way to pancytopenia. The new form of EAE may be useful for investigating autoimmune diseases because the neutrophils which indicate the immunologic injury are instantly recognized as reactive recipient cells. Preexisting conventional (mononuclear) EAE prevented subsequent production of neutrophilic infiltrates. This inhibitory effect may be due to local blockade of vessels by mononuclear cells, a concept for which there is evidence. These considerations suggest that the exudation of neutrophils in the new form of EAE may be due to suppression by cyclophosphamide of the mononuclear component of the inflammatory reaction, with loss of its blockading and protective influence on the vessels.

Allergic encephalomyelitis: passive transfer prevented by encephalitogen.

Allergic encephalomyelitis was produced in rats by passive transfer of lymph node cells from donors immunized intradernmally with nleural tissute or an encephalitogenic basic protein pluts adjulvants. The same basic protein, injected intravenously into the recipients before or after transfer of lymph node cells, prevented the disease. Even established lesions were reversed. Inhibition by basic protein was specific for encephalomyelitis; it had no effect onz passive transfer of allergic adrenalitis.