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Biomedical subjects

R J Blom

Publications and source records attributed to R J Blom.

16 recordsLinked to original sources
PubMed1997

[Favorable results of plasmapheresis in severe myasthenia gravis].

OBJECTIVE: Evaluation of the additional effect of plasma exchange in treatment with steroids of severe myasthenia gravis. DESIGN: Retrospective study. SETTING: Department of Neurology, University Hospital of Groningen, the Netherlands. PATIENTS AND METHODS: The clinical course was analysed in 24 patients with a total of 28 plasma exchange treatments. Prednisone was introduced or its maintenance dose was increased in 19 cases. Another 13 patients with severe myasthenia gravis were included to study the effect of prednisone monotherapy. RESULTS: Of the patients treated with plasma exchange and steroids 71% improved within the first week of treatment as against only 15% of the patients treated with prednisone monotherapy. After two weeks of plasma exchange plus prednisone or prednisone monotherapy, 88% and 69%, respectively were ameliorated. None of the patients receiving plasma exchange deteriorated or experienced adverse effects or complications due to plasma exchange. Of the patients receiving prednisone monotherapy 31% deteriorated in the first week of treatment. CONCLUSION: Patients with severe myasthenia gravis may safely be treated with plasma exchange in combination with prednisone. In our patient group, a state of rapid aggravation was cut short more quickly by prednisone plus plasma exchange than by prednisone monotherapy.

Adolescent↗
PubMed1996

Protective antitumor immunity induced by immunization with completely allogeneic tumor cells.

We have shown previously that immunization of B6 mice (H-2b) with tumor cells of B6 origin transformed by the human adenovirus type 5 early region 1 (Ad5E1) induces an H-2Db-restricted CTL response against an E1B-encoded CTL epitope. We now report that immunization of B6 mice with Ad5E1-transformed tumor cells of BALB/c origin (H-2d), apart from inducing a B6 anti-BALB/c allo-response, also induces a strong CTL response against the E1B-encoded H-2Db-presented CTL epitope. BALB/c Ad5E1-transformed tumor cells are not recognized by E1B-specific CTLs, indicating that nontumor cells have processed the E1B-encoded CTL antigen and have presented the E1B peptide to E1B-specific CTLs. These data also show that the B6 anti-BALB/c allo-response does not overwhelm the anti-E1B response induced by the allogeneic tumor cell vaccination. Moreover, B6 mice immunized with allogeneic BALB/c Ad5E1 cells are, in contrast to mice vaccinated with untransformed BALB/c cells, protected against a subsequent challenge with B6 Ad5E1-expressing tumor cells. These data show that immunization with completely allogeneic tumor cells can lead to protective syngeneic antitumor immunity, indicating that completely allogeneic tumor cell vaccines can be used for the induction of antitumor immunity.

Animals↗
PubMed1996

Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction.

Vaccination with synthetic peptides representing cytotoxic T lymphocyte (CTL) epitopes can lead to a protective CTL-mediated immunity against tumors or viruses. We now report that vaccination with a CTL epitope derived from the human adenovirus type 5 E1A-region (Ad5E1A234-243), which can serve as a target for tumor-eradicating CTL, enhances rather than inhibits the growth of Ad5E1A-expressing tumors. This adverse effect of peptide vaccination was rapidly evoked, required low doses of peptide (10 micrograms), and was achieved by a mode of peptide delivery that induces protective T-cell-mediated immunity in other models. Ad5E1A-specific CTL activity could no longer be isolated from mice after injection of Ad5E1A-peptide, indicating that tolerization of Ad5E1A-specific CTL activity causes the enhanced tumor outgrowth. In contrast to peptide vaccination, immunization with adenovirus, expressing Ad5E1A, induced Ad5E1A-specific immunity and prevented the outgrowth of Ad5E1A-expressing tumors. These results show that immunization with synthetic peptides can lead to the elimination of anti-tumor CTL responses. These findings are important for the design of safe peptide-based vaccines against tumors, allogeneic organ transplants, and T-cell-mediated autoimmune diseases.

Adenovirus E1A Proteins↗
PubMed1996

Efficient tumor eradication by adoptively transferred cytotoxic T-cell clones in allogeneic hosts.

Tumor-specific cytotoxic T cells (CTLs) can play an important role against cancer as illustrated by the observation that adoptive transfer of tumor-specific CTLs can mediate potent anti-tumor effects. Although such CTLs can be detected at the tumor site, relatively little is known about the mechanisms by which they enter the tumor. In this study, the role of major histocompatibility complex (MHC) class 1 molecules on vascular endothelium in the tumor in entry of, and tumor eradication by, tumor-specific CTL was investigated. Two H-2Db-restricted CTL clones recognizing peptide VNIRNCCYI on human adenovirus type 5 early region 1-(Ad5E1)-induced tumors were used to test whether CTLs were able to cross the vascular endothelium lacking the restricting MHC molecule. One CTL clone recognizes peptide VNIRNCCYI in the context of both H-2Db and H-2Dbm14 molecules. The other CTL clone recognizes this peptide only in the context of H-2Db. Adoptive transfer of these CTLs leads to eradication of Ad5E 1-induced, H-2Db-expressing tumors in B6(H-2Db+) and Bm14(H-2Db-) nude mice. Our data show that presentation of tumor-derived peptides by MHC molecules on endothelial cells of blood vessels in a tumor do not play a major role in eradication of tumors by adoptively transferred CTL in combination with interleukin-2. Moreover, our data show that successful adoptive CTL immunotherapy is possible across allogeneic barriers, without inducing severe side effects, provided the tumor expresses the MHC class 1-peptide complex recognized by the CTLs.

Amino Acid Sequence↗
PubMed1996

Enhanced tumor outgrowth after peptide vaccination. Functional deletion of tumor-specific CTL induced by peptide vaccination can lead to the inability to reject tumors.

CTL can play an important role in the defense against tumors. Protective CTL-mediated immunity can be established in animal tumor models after vaccination with synthetic peptides representing CTL epitopes. We now report that immunization with synthetic peptides can also lead to CTL tolerance associated with the inability to reject tumors. B6 tumor cells transformed by the human adenovirus early region 1 (Ad5E1) present an Ad5E1A- and an Ad5E1B-encoded CTL epitope to the immune system. CTL clones directed against either of these epitopes are able to eradicate established Ad5E1-induced tumors, showing that these CTL epitopes are targets of CTL that can mediate tumor regression. Here, we show that protective immunity against Ad5E1-expressing tumor cells can be established by immunization with Ad5E1-transformed cells and with an adenovirus vector containing the Ad5E1 region. Protective immunity, in either case, is associated with specific CTL memory. To test whether vaccination with synthetic peptides leads to protection against Ad5E1-expressing tumor cells, we vaccinated mice s.c. with a low dose of the Ad5E1B peptide. This peptide was chosen because the CTL response against the Ad5E1B-encoded CTL epitope contributes most to the antitumor response in B6 mice after vaccination with Ad5E1-transformed cells. Ad5E1B peptide-vaccinated mice were not protected against the outgrowth of Ad5E1-expressing tumor cells, but instead were no longer able to reject a tumor inoculum that was rejected by nonvaccinated mice. Moreover, the protection induced by tumor cell vaccination against Ad5E1B-expressing tumors was gone when the Ad5E1B-encoded CTL epitope was injected a few days before tumor challenge. This is associated with peptide-induced tolerance of Ad5E1B-specific CTL activity. These findings are relevant for the design of therapeutic approaches against both malignancies and T cell-mediated autoimmune diseases.

Adenovirus E1A Proteins↗
PubMed1995

An adenovirus type 5 early region 1B-encoded CTL epitope-mediating tumor eradication by CTL clones is down-modulated by an activated ras oncogene.

Mouse embryo cells (C57BL/6, H-2b) transformed by the E1A and E1B genes of adenovirus type 5 (Ad5E1 MEC) are highly immunogenic. Previously, CTL were cloned from mice immunized with Ad5E1 MEC. These CTL clones were capable of tumor eradication in nude mice, and were directed against the Ad5E1A-encoded decapeptide SGPSNTPPEI, presented by the H-2Db MHC molecule. We have now generated Ad5E1 MEC containing a mutated Ad5E1A-encoded epitope. The mutant Ad5E1 MEC induce a strong CTL response when injected into immunocompetent mice. CTL clones generated against mutant Ad5E1-transformed tumor cells recognize an Ad5E1B-encoded epitope (VNIRNCCYI) in the context of H-2Db. Because this epitope is also present on wild-type Ad5E1 MEC, it is concluded that Ad5E1-transformed tumor cells express at least two CTL epitopes. Interestingly, the lysis of Ad5E1 MEC by the Ad5E1B-specific, but not by the Ad5E1A-specific, CTL clones was strongly diminished by the action of the activated ras oncogene. CTL directed against the Ad5E1B-encoded epitope were, like Ad5E1A-specific CTL, able to eradicate large established Ad5E1-induced tumors in B6 nude mice, demonstrating that CTL activity directed against different CTL epitopes expressed by the same tumor can be exploited for immunotherapy of cancer.

Adenovirus E1 Proteins↗
PubMed1993

In vivo detection of fluorescent tumor-specific cytotoxic T cell clones.

Cytotoxic T lymphocytes (CTL) can be very effective mediators of tumor-specific immunity in vivo. Since little is known about the in vivo behaviour of cultured tumor-specific CTL, a fast and simple method has been developed utilizing a lipophilic carbocyanine, 1,1'-dioctadecyl 3,3,3',3'-tetramethylin-docarbocyanine perchlorate (DiI), for the in vivo detection of tumor-specific CTL clones in (tumor-bearing) mice. The two CTL clones used in this study are directed against human papillomavirus type 16- or human adenovirus type 5 early region 1 (Ad5E1)-transformed mouse embryo cells. Growth ability, cytotoxic capacity and tumor-eradicating potential remained unaltered when the CTL were labeled with this dye. Thus, in neither in vitro nor in vivo testing was the biological function of the CTL clones affected. The in vivo localization in the spleen of an adoptively transferred DiI-labeled Ad5E1-specific CTL clone is described. This adoptively transferred CTL clone was also detectable at the site of a subcutaneously growing human Ad5E1-induced tumor within 1 day after intravenous injection.

Adenovirus Infections, Human↗
PubMed1986

Clinical events following neuroangiography. A prospective study.

The authors prospectively evaluated the clinical event rate over a 72 hour period following femorocerebral angiography in 1002 procedures. The neurologic event rate was 1.3 per cent in the first 24 hours (0.1% permanent) and 1.8 per cent between 24 and 72 hours (0.3% permanent). The non-neurologic event rate (mostly hematomas) was 7.2 per cent. There were no deaths. One hundred and nine pieces of data per procedure were analysed statistically. Delayed cerebral ischemia does occur and could be secondary to the procedure. The low risk of judiciously performed cerebral angiography was confirmed. Carefully cataloguing all events for up to 72 hours neither verifies nor excludes angiography as the cause of deterioration.

Adult↗
PubMed1985

Intrapetrous intracavernous fusiform aneurysm of the internal carotid artery.

I report the computed tomographic and angiographic findings in a patient with an intracavernous intrapetrous fusiform aneurysm of the internal carotid artery. The patient presented with a third nerve palsy and was treated successfully by surgical "trapping" of the aneurysm. A review of the literature reveals one report of a similar case.

Adult↗
PubMed1984

Computed tomography in temporal lobe epilepsy.

Forty patients who had intractable temporal lobe epilepsy had surgery for treatment of their seizures following study by computed tomography (CT). Fifteen of 19 patients with tumors had good correlation between CT and pathological findings. Another group of patients had macroscopic changes that were demonstrated on CT and verified at surgery. Sixteen patients had microscopic pathological diagnoses including cytoarchitectural abnormalities, Chaslin gliosis, and ectopic neurons. Six of these had enlarged temporal horns on the ipsilateral and five on the contralateral side to the electroencephalographic-pathological abnormality. In the investigation of temporal lobe epilepsy we believe that CT, especially with the newer generation scanners, records tumors and other larger macroscopic changes but that temporal horn size is unreliable in predicting the abnormal side if only microscopic changes are present.

Adolescent↗
PubMedDate not supplied

Clinical events following neuroangiography: a prospective study.

Clinical events following cerebral angiography were prospectively evaluated in 1,002 procedures. The ischemic event rate between 0 and 24 hours was 1.3% (0.1% permanent). This incidence was higher (2.5%) in patients investigated for cerebrovascular disease, but the difference was not significant. In addition, 1.8% of the patients suffered ischemia (0.3% permanent) between 24 and 72 hours after angiography. Cerebral ischemic events occurred as a recurrence or worsening of a preexisting phenomenon. twice as often as de novo. All permanent ischemia was a worsening of a preexisting phenomenon. There was a significant increase in the incidence of neurologic events between 0 and 24 hours when the procedure lasted longer than 60 minutes and when there was systolic hypertension. Trends toward higher incidence were noted with the use of increased volume of contrast, with increased serum creatinine, when transient ischemic attacks or stroke were the indications, and when 3 or more catheters were used. The incidence of neurologic events between 24 and 72 hours increased significantly with the increase in the amount of contrast used, with age, and with diabetes. The occurrence of nonneurologic events (mostly hematomas) was significantly increased by multiple factors. This study shows that events can and do occur beyond the usual observation period of 24 hours but confirms the low risk of cerebral angiography when performed judiciously.

Age Factors↗
PubMedDate not supplied

Sneddon syndrome: CT, arteriography, and MR imaging.

We report a rare case of Sneddon syndrome, which consists of livedo reticularis and cerebrovascular lesions. The syndrome is characterized by occlusions of medium-sized arteries manifest particularly in the extremities and in the cerebrum. The spectrum of neuroradiological findings in this clinical entity are illustrated and discussed.

Adult↗