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Biomedical subjects

K P Johnson

Publications and source records attributed to K P Johnson.

At least 19 recordsLinked to original sources

The association of cervical spondylosis and multiple sclerosis.

The diagnostic and therapeutic considerations produced by the coexistence of cervical spondylosis and multiple sclerosis are complex. We have encountered six patients, affected by both multiple sclerosis and cervical spondylosis, in whom neurosurgical procedures were performed. The diagnosis of multiple sclerosis was confirmed by a combination of clinical, neuroimmunologic, electrophysiologic, and neuroradiologic findings. The diagnosis of spondylosis with spinal cord compromise was confirmed by myelography and computed tomographic scan in all cases, and by magnetic resonance imaging in four. Surgery was followed by lasting clinical improvement in two patients, transient improvement in one, and no change in the other three. Our experience confirms that multiple sclerosis and cervical spondylosis can coexist and suggests that this coexistence may result in an interaction that compounds the deleterious effect on the nervous system. Diagnostic evaluations of patients, particularly young patients, with symptoms of cervical spondylosis should include consideration of the possible coexistence of multiple sclerosis. The evaluation of a patient with known multiple sclerosis who develops new signs of cervical spinal cord dysfunction should always include spinal neuroimaging studies. When progression of symptoms coincides with documented progression of anatomic compression, surgical intervention can yield good results.

Adult

Interferon therapy for multiple sclerosis.

Laboratory findings that suppressor cell function is improved with beta interferon therapy and that gamma interferon activity is inhibited by beta interferon provide support for the hypothesis that beta interferon will have a significant therapeutic effect on relapse rates in multiple sclerosis.

Humans

Gamma-interferon induction in patients with chronic progressive MS.

Although gamma interferon (gamma-IFN) may be involved in the pathogenesis of exacerbations of multiple sclerosis (MS), whether it plays a role in chronic progressive MS is not known. To investigate this, we retrospectively analyzed serum samples from nine chronic progressive MS patients who were treated with monthly intravenous infusions of the interferon inducer polyinosinic acid polycytidylic acid polylysine in carboxymethylcellulose (poly ICLC). Using a bioassay we found that the mean peak total interferon level was 177 U/ml 12 hours after infusion, and using a radioimmunoassay we found that the mean peak gamma-IFN level was 15.9 U/ml 12 hours after infusion, so that gamma-IFN made up approximately 10% of the total. Greater gamma-IFN induction did not correlate with clinical worsening; induced gamma-IFN levels were not higher in two patients who worsened on treatment, and the highest levels were found in a patient who remained stable. Either chronic progressive MS is not sensitive to gamma-IFN or the effects of gamma-IFN are masked by other mediators induced by poly ICLC.

Antigens, CD

Guinea pig cytomegalovirus: transplacental transmission. Brief report.

A well characterized strain of guinea pig cytomegalovirus (GPCMV) was used to infect pregnant guinea pigs during various periods of pregnancy. Transplacental transmission of virus with invasion of the fetus was observed, even in some mothers with preinoculation evidence of GPCMV antibody. Fetal infection occurred during the middle third of pregnancy and GPCMV was isolated from many fetal tissues although histologic evidence of infection was not noted. During the last third, abortion of the pregnancy occurred in some animals. This report demonstrates that GPCMV may invade the fetus producing a sublethal, possibly mild infection which may be very similar to the usual type of CMV infection observed in the human newborn.

Animals

Enhancement of fluorescent antibody staining of viral antigens in formalin-fixed tissues by trypsin digestion.

The staining of viral antigens present in formalin-fixed, paraffin-embedded tissues by fluorescent antibodies is markedly enhanced by trypsin digestion. When the trypsin digestion method was used to detect viral antigens present in hamster brain following experimental infection with measles virus, the results were comparable to those obtained with acetone-fixed, freshly frozen tissues that had been sectioned with a cryostat. Measles antigens were readily identified in brain cells from a patient with subacute sclerosing panencephalitis and in lung and liver tissue from a patient with acute giant cell pneumonia, following preparation of the tissues for routine histologic examination. Viral antigens were detected in brain tissue that had been taken from patients with herpes simplex encephalitis and stored in paraffin for up to 15 years. Cells containing antigen could be precisely identified without loss of histologic detail by restaining the same tissue sections with hematoxylin and eosin.

Animals

Cytotoxic antibody to cells infected with measles virus in serum and cerebrospinal fluid of multiple sclerosis and control patients.

Sera and cerebrospinal fluids (CSFs) from 66 patients selected from a larger sample of multiple sclerosis (MS) and control patients were studied for presence of complement-dependent cytotoxic (CT) antibody against baby hamster kidney cells infected with measles virus, strain Lec. The MS group contained 26 patients with clinically definite disease and 7 with probable MS. Seventeen of the 33 patients selected from the MS group had hemagglutination-inhibiting (HI) antibody to measles virus in their CSFs. Specimens from 33 control patients with other identifiable neurological disorders were matched according to the time of specimen sampling and with the age of the donors. Seven of the controls had HI CSF antibody. The serum CT geometric mean antibody titer of the MS group was approximately twofold higher than that of the control group. Forty-two percent of the MS group and 18% of the control group had CT antibody in the CSF. With the exception of the ratio of one control patient, the serum/CSF ratios of CT antibody from all patients were 128 or less. Nine CSFs (six MS and three control specimens) had CT antibody but no detectable HI antibody. Conversely, 12 CSFs (eight MS and four control specimens) had HI antibody but no detectable CT antibody. Five patients in the MS group with both kinds of CSF antibodies had reduced CT ratios but normal HI ratios. The results suggest that the two tests detect CSF antibodies reactive with different antigens. In this study, where less than half of the MS patients displayed CSF CT antibody, it is unlikely that such antibodies play an active role in the pathogenetic mechanism operative in the disease.

Antibodies, Viral

Cerebrospinal fluid findings in asymptomatic patients with reactive serum fluorescent treponemal antibody absorption tests.

It is common to examine the cerebrospinal fluid in untreated or inadequately treated asymptomatic patients with a reactive serum fluorescent treponemal antibody absorption (FTA-ABS) test before initiating antibiotic therapy for syphilis. This prospective study evaluated the usefulness of such examination. Four hundred thirty-two patients over 40 years old, reporting for annual physical examination, had a serum FTA-ABS test. Thirty-seven (8.6%) patients and 2 of 4 spouses were reactive repeatedly. Of the 39 patients with reactive tests, 7 had a history of penicillin therapy for syphilis, 5 had received heavy metal therapy, and 27 had no history of syphilis. These 39 patients had a neurological examination, serum VDRL, Treponema pallidum immobilization (TPI), and repeat FTA-ABS tests by two other laboratories. The TPI test was reactive in 30 (77%). Four had nonspecific neurological signs. Routine CSF examination (cells, total protein, VDRL, glucose, IgG%) on 30 patients with a history of inadequate treatment had a low diagnostic yield. Two patients had an unexplained total protein elevation (57 and 61 mg/dl) and 1 had a mildly increased IgG% (15%). All cell counts, VDRL tests, and glucose levels were normal. Agarose electrophoresis demonstrated one or more CSF immunoglobulin bands in 10 (36%) of 28 patients, possibly representing an immunological marker of past or latent central nervous system infection.

Adult

CNS disease following dissemination of SSPE measles virus from intraperitoneal inoculation of suckling hamsters.

Acute encephalitis was observed in suckling Golden Syrian hamsters following intraperitoneal (ip) inoculation of a hamster brain adapted strain of subacute sclerosing panencephalitis (SSPE) measles virus (HBS). Virus was isolated from the brains of all encephalitic animals by cocultivation of tissue with Vero cells. The histopathology of the encephalitis was characterized by perivascular mononuclear infiltrates, necrosis, eosinophilic inclusion bodies, and rare giant cells. Association of encephalitis with systemic viral infection was observed with virus present in lung and a kidney-spleen pool in addition to brain. Viral dissemination in asymptomatic animals was documented with virus being isolated from multiple non-neural tissues (spleen, lung, liver) of animals having no recoverable virus in their brains and no signs of encephalitis. Treatment of animals with cyclophosphamide prior to ip virus inoculation did not increase dissemination to brain. Absence of encephalitis in asymptomatic animals with proven viral dissemination to parenchymal organs indicates that neither viremia alone, nor viremia in conjunction with dissemination are sufficient conditions to establish central nervous system disease. The association of encephalitis with systemic viral infection and the dissemination to brain establish this model's potential value for the study of the pathogenesis of measles encephalitis.

Animals

Viral antibodies in cerebrospinal fluid of multiple sclerosis and control patients: comparison between radioimmunoassay and conventional techniques.

Cerebrospinal fluid antibodies to measles, rubella, vaccinia, herpes simplex, and varicella-zoster viruses in four patient study groups (clinically definite multiple sclerosis [MS], early probable MS, optic neuritis, and control patients with other neurological diseases) were assayed by radioimmunoassay, complement fixation, hemagglutination-inhibition, or complement-enhanced plaque reduction methods. Antibodies were more frequently found and at higher dilutions by radioimmunoassay than by other techniques. Measles virus antibody, the most frequently found antibody, was present in the cerebrospinal fluid of 72% of MS patients and 5% of control patients. The differences between the numbers of MS patients and control patients with antibodies to other viruses were not as marked. Thus, 58% of MS patients versus 21% of control patients had antibody to rubella virus, 20 versus 3% had antibody to vaccinia virus, 50 versus 33% had antibody to herpes simplex virus, and 25 versus 8% had antibody to varicella virus. Sixty-seven percent of MS patients and 26% of control patients had antibodies to two or more viruses in their cerebrospinal fluid.

Adolescent

Subacute measles encephalitis complicating Hodgkin's disease in an adult.

A progressive neurological illness characterized by myoclonus, motor and sensory deficits, and lethargy occurred in a patient with Hodgkin's disease and was fatal within two months. A focal inclusion cell encephalitis was demonstrated by immunohistological means to be due to measles virus. Measles encephalitis must be considered a potential opportunistic agent in the immune-compromised host.

Antibodies, Viral

Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy.

Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-density lesions seen by computerized tomography. One of the patients was observed to excrete abnormal epithelial cells into the urine. These cells contained papovaviruslike particles, and JC virus was cultured from the urine sediment. The relative number of these abnormal cells declined during Ara-A treatment. Both patients died shortly after the conclusion of therapy without a change in the progression of the central nervous system disease. Systemic administration of Ara-A did not offer significant clinical benefit in the treatment of these 2 advanced cases of PML.

Aged

Multiple sclerosis: diagnostic usefulness of cerebrospinal fluid.

Early, atypical, or progressive cases of multiple sclerosis (MS) may be hard to diagnose. Until recently, assays of the most common abnormalities in cerebrospinal fluid were not available in clinical diagnostic laboratories, but now they can be done with relative ease and adequate standardization. With the newer techniques the CSF is abnormal in more than 90% of clinically definite cases of MS, and determination of such changes can be a major aid in diagnosis. The most common CSF abnormalities are discussed: elevation of immunoglobulin G(IgG), expressed as percentage of total protein; elevation of the IgG/albumin index; and presence of oligoclonal IgG bands. Not only does assessment of these CSF proteins provide an improved aid to diagnosis, but their study may furnish important clues to the cause and pathogenesis of MS as well.

Albumins

Effect of cyclophosphamide in vitro and on vaccinia virus replication in tissue culture.

The effect of cyclophosphamide on the growth of Vero, BSC-1, and HeLa cells in monolayer cultures was studied. By using hemocytometer counts and tritiated thymidine uptake as indicators of growth, it was found that cyclophosphamide significantly interfered with the metabolism of Vero and BSC-1 cells when sustained in Leibovitz medium. Vero cells and HeLa cells grown in Eagle medium were not affected by exposure to cyclophosphamide. Vaccinia virus replication in Vero cell monolayer cultures incubated with cyclophosphamide was markedly augmented, and this enhanced growth was reflected by virus quantitation techniques and metabolic studies using tritiated thymidine uptake. No difference in the distribution of infectious particles was found when cyclophosphamide-treated and control infected cultures were compared. Pathways other than through hepatic enzymes appear available to activate cyclophosphamide in vitro. These effects are dependent on both the cell type and the medium in which the cells are grown. Cyclophosphamide can facilitate vaccinia virus replication in vitro through metabolic interactions at the cellular level. The precise mechanisms underlying this effect require further study.

Cell Line

Agarose electrophoresis of cerebrospinal fluid in multiple sclerosis. A simplified method for demonstrating cerebrospinal fluid oligoclonal immunoglobulin bands.

The gamma globulins in cerebrospinal fluid from almost all patients with multiple sclerosis migrate in agarose electrophoresis as abnormal discrete populations, so-called oligoclonal bands. Such bands have also appeared in cerebrospinal fluid from patients with other types of inflammatory pathology such as neurosyphilis, acute idiopathic polyneuropathy, and subacute sclerosing panencephalitis. The demonstration of cerebrospinal fluid oligoclonal bands may aid in the evaluation of patients with early or atypical multiple sclerosis. This report describes a simple method for demonstrating cerebrospinal fluid oligoclonal bands using readily available commercial reagents and apparatus. Oligoclonal bands were seen in cerebrospinal fluid from all patients with clinically definite multiple sclerosis, even though some had normal cerebrospinal fluid gamma globulin levels, and in most patients with presumptive multiple sclerosis or other inflammatory conditions of the nervous system. They were not seen in cerebrospinal fluid of control patients with a variety of other neurologic diseases.

Adolescent

Measles antigen distribution in brains of chronically infected hamsters. An immunoperoxidase study of experimental subacute sclerosing panencephalitis.

Weanling (21-day old) hamsters were inoculated intracerebrally with hamster-adapted, HBS strain of subacute sclerosing panencephalitis virus and studied between days 6 and 51 of infection with light microscopic immunofluorescent and ultrastructural immunoperoxidase methods. Characteristic measles fuzzy nucleocapsids developed and persisted in brain cell cytoplasm while smooth nucleocapsids developed in both nucleus and cytoplasm. Measles virus antigens appeared not only in relation to nucleocapsid but also in cytoplasm and along the inner aspect of cytoplasmic membranes of brain cells including neuronal dendrites. No budding virions were seen. Focal concentrations of bound hamster IgG occurred within foci of infected cells during the chronic infection. These studies show that in hamsters, persistent central nervous system measles infection is due to morphologically identifiable virus structures even when the host serologic response is active. The finding of viral antigens within the cytoplasmic membrane along with focal collections of hamster IgG in the same areas suggests that a "blocking factor," possibly antibody, protects infected cells from immune surveillance and destruction.

Animals