Are population-genetic mechanisms responsible for clustering of cases of Creutzfeldt-Jakob disease?
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Biomedical subjects
Publications and source records attributed to V Mayer.
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Heterospecific autoantibodies to axonal neurofilaments of neurons in sera from five patients with Creutzfeldt-Jakob disease were detected with the use of cryostat section from normal human brain caudate nucleus. The antibody, visualized by the indirect immunofluorescence technique, was shown to bind complement. This allowed to achieve brighter staining either by the anticomplementary method alone or by a combination of both anti-C3 and anti-IgG conjugates
The lytic activity of splenocytes from C3H mice immunized with a highly attenuated line of Langat virus [tick-borne encephalitis (TBE) complex] was determined by the in vitro 51Cr release assay on TBE virus (western subtype)-infected target L929 cells. After the spleen cell suspensions were depleted of T cells with anti-mouse theta serum, or of B cells with anti-mouse immunoglobulin, the cytotoxic effect was found dependent on the presence of T lymphocytes. During immunization with Langat virus, cytotoxic T lymphocytes were generated, specific for both the foreign virus-specified antigen and the self component of the host system studied, coded by the K allele of the H-2 complex. The peak of T lymphocyte cytotoxic response was attained on the 6th day after administration of the live virus. T lymphocytes from mice, single-shot immunized with a flavivirus, displayed distinct cross-reactive lysis when studied on target cells infected with other flaviviruses but not on cells infected with an alphavirus.
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Splenocytes from mice immunized intravenously with one dose of Langat or Yellow fever viruses were cytotoxic for target cells infected with virulent tick-borne encephalitis (TBE) virus; cytotoxicity was measured by 51Cr release from target L929 cells. No significant lysis of the TBE virus-infected taget cells with splenocytes from Sindbis virus-infected mice was noted.
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In an attenuated variant of tick-borne encephalitis virus, western subtype (TBEV) with an ic+ sc s t e us character and lost virulence for monkeys, a distinct inhomogeneity together with a decrease in titre was observed after 8.7--9.6 years of storage at 4 and -14 (+/- 2) degrees C, with several interruptions due to failures in refrigeration systems. Proved by clonal analysis, the inhomogeneity concerned plaque polymorphism, increased thermo-resistance and degree of virulence for mice and monkeys. Marker studies of materials stored for up to 14.5 years yielded comparable findings. The possibility of the presence in the virus stocks in addition to a prevailing attenuated component also of minor component(s) having the advantage for survival under storage conditions, is discussed taking into account the intrinsic mutational capacity of the virus and known differences in resistance to environmental stresses between attenuated and virulent TBEV variants.
Transfer factor activity was demonstrated in the dialysable extract from lymphocytes from outbred donor mice, in which immunization with live attenuated Langat (E5 "14") virus induced a stage of high resistance against challenge with virulent tick-borne encephalitis virus. Administered to naive inbred recipient mice, the extract conveyed in them specific cytolytic activity, exerted by their T lymphocytes, as demonstrated by the 51Cr release assay on tick-borne encephalitis virus-infected syngeneic L-929 cells.
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In a long-term experiment, the features of humoral and cell-mediated immunity (CMI) were investigated in mice given intravenously (i.v.) a single dose of live attenuated Langat (E5 "14") virus of the tick-borne encephalitis (TBE) complex. The inapparent infection induced in mice specific resistance against challenge with virulent TBE virus, CMI was assayed by the capillary method of murine splenic lymphocyte migrarion inhibition (LMI) in the presence of partially purified TBE vurus. Significant LMI values were observed as early as 4 days after inoculation (p.i.), persisting for at least 15 months. Specific virus neutralizing (VN) antibodies were detected in the pooled serum of mice on the 4th day p.i. by a VN test potentiated with monospecific anti-mouse IgG serum. For the whole experimental period, significant antibody levels were found in the immunized mice which also displayed a complete resistance against 1000 s.c. LD50 of the virulent virus. Organ cultures of brain and spleen from these mice did not yield infections virus.
A peculiar grouping of Creutzfeldt-Jacob disease (CJD) and of other organic presenile dementia (OPD) cases in a small, prevalently rural area in Czechoslovakia to the east of 19 degrees 35' E and to the north of 48 degrees 15' N was studied. Between August, 1972 and November, 1976, three histologically proven CJD cases, bearing no sporadic of familial patterns, were observed. The distance between their dwellings was 13--17 km. In addition, seven cases of OPD were detected in the same area, two of them being suspected as possible CJD according to clinical evidence.
Histopathological findings in three temporo-spatially linked cases of Creutzfeldt-Jakob disease (CJD) are reported. The patients were males, unrelated and without positive family history. Their mean age at the onset of the disease was 52.3 years. The mean duration of the illness was 6.6 months; the clinical symptomatology differed considerably. Neurohistology revealed in all patients a neuronal loss, intracyoplasmic vacuolation, spongiosis and astrocytosis. Besides the cortical regions, basal ganglia and cerebella were severely affected. All cases were pathologically suggestive of the cortico-striato-cerebella variant of CJD. Attention is drawn to this apparent topical similarity of most pronounced lesions. The possible significance of the pathoanatomical consistency, observed in the cases studied, for the unusual pattern of natural occurrence of CJD is considered.
In 9 patients with coronary heart disease isovolumetric contractility indices and ejection phase parameters were measured simultaneously, using an angiographic catheter with a manometer at the tip (Millar). Regional wall motion at rest, after leg raising and during physical exercise (bicycle ergometer) was analyzed applying the hemiaxis method. Five weeks after aortocoronary bypass surgery the same examinations were repeated. Preoperatively left ventricular enddiastolic pressure (LVEDP) increased from 21 to 37 mm Hg following leg raising. The velocity mean of fiber shortening (Vcf) and of regional fiber shortening in the anterior wall decreased significantly.--All patients discontinued physical exercise due to angina pectoris. LVEDP increased from 21 to 39 mm Hg. Large hypokinetic and akinetic areas developed especially in the anterior wall. Velocity of fiber shortening of the anterior wall decreased from 1.43 to 0.76/s. Enddiastolic volume remained unchanged while endsystolic volume increased significantly. In six patients with patent grafts surgery had a beneficial effect. Comparing angiograms at rest no significant changes were found. After leg raising and physical exercise, however, marked improvement in ventricular function occurred, compared to the preoperative performance. All 6 patients were exercised without complaints at a load of 100 watts for 8 minutes. Velocity of fiber shortening in the anterior wall increased significantly from 0.76 to 2.56/s, mean Vcf from 1.11 to 2.12 circ/s, max dP/dt from 2302 to 4280 mm Hg/s and Vpm from 27.8 to 55.7/s. Functional improvement in individual wall segments amounted to 500% in the mean. Ejection fraction increased from 54 to 76%. Enddiastolic volume remained unchanged while endsystolic volume decreased from 67 to 33 ml/1.37 m2 (p less than 0.002). In three patients the bypass occluded or myocardial infarction occurred intraoperatively. Postoperative findings at rest and during exercise were unchanged as compared to preoperative values. Following successful bypass surgery ventricular function at rest did not change. During exercise, however, a marked improvement in overall and in regional ventricular function was found.
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