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J B Classen

Publications and source records attributed to J B Classen.

18 recordsLinked to original sources
PubMed2001

Vaccines and the risk of insulin-dependent diabetes (IDDM): potential mechanism of action.

Immunization with a number of different vaccines, including live and killed vaccines, has been linked to the development of insulin-dependent (type 1) diabetes in humans and animals. Multiple different mechanisms have been proposed to explain the association between vaccines and diabetes. The current paper reviews multiple different mechanisms by which vaccines are known to manipulate the immune system and can induce an autoimmune disease such as type 1 diabetes. Genetic variability may determine which of these pathways, or possible other pathways, predominate in an individual following immunization.

Animals↗
PubMed1999

Immunization in the first month of life may explain decline in incidence of IDDM in The Netherlands.

A low cumulative incidence of IDDM was reported in Dutch males born in 1962 (Diabetologia 1992: 35: 139-142) compared to males born in previous or later years. The cause for the decreased risk has not been previously explained. We propose that children born in 1962 during an European smallpox epidemic may have received the smallpox vaccine in the first month of life and this may have attributed to the decreased risk of IDDM in these children. We have shown that immunization with several different vaccines starting in the first month of life prevents diabetes in NOD mice and BB rats (Autoimmunity 1996: 24: 137-145) while immunization at birth with the BCG vaccine is associated with an decreased risk of IDDM in humans (Infectious Diseases in Clinical Practice 1997: 6: 449-454). An even bigger decline in diabetes is seen in rodents and associated in humans when one compares immunization starting in the first month of life to immunization starting after 2 months, since the later has been associated with an increased risk of IDDM. Immunization studies in the past have typically followed patients for only several weeks to determine any unplanned affects on autoimmune disease. Due to the potential benefit of reducing the incidence of diabetes by 50% through age 18 we believe clinical trials are warranted to study the effect of timing of immunization on IDDM.

Adolescent↗
PubMed1998

Cyclosporine induced autoimmunity in newborns prevented by early immunization.

It has been shown in animal toxicity models that administration of Cyclosporine, CsA, to a pregnant mouse greatly increases the risk that the offspring will develop autoimmunity. Immunization starting at birth has been shown to prevent autoimmunity in other animal models of autoimmunity and early immunization is associated with the prevention of diabetes in humans. Experiments were performed to see if early immunization could also prevent CsA induced autoimmunity. Mice were injected with CsA during the first week of life and then immunized with killed human vaccines, including common pediatric vaccines, starting in the second week of life for a total of 3-4 doses. Administration of CsA during the first week of life resulted in the development of antigastric autoantibodies which were measured at week 8 of life. Only 12% of mice treated with CsA alone lacked anti-agastric antibodies compared to 61% in the group receiving the CsA and the diphtheria, tetanus, pertussis, and anthrax vaccines (p = 0.0005). The results indicate early immunization can prevent CsA induced autoimmunity and provide further evidence that the effect of starting immunization in the first month should be compared to starting immunization after 2 months in humans.

Animals↗
PubMed1996

The timing of immunization affects the development of diabetes in rodents.

BACKGROUND: Insulin-dependant diabetes mellitus (IDDM) is an autoimmune disease that can be altered by immune modulation. NOD mice and BB rats have been used as models of spontaneous IDDM. The development of diabetes in these animals has been altered by several different immune modulators using relatively high doses for the size of the animal. The effect of pharmaceutical doses of vaccines on the development of diabetes in these rodents has not been adequately studied. METHODS: I studied the effect of administering killed human vaccines using low concentrations and as few as 3 doses. RESULTS: Administration of human vaccines to diabetic prone newborn animals starting before 2 weeks of age prevented the development of diabetes while administration of the pertussis vaccine starting at 8 weeks of life was associated with an increased incidence of diabetes. CONCLUSIONS: Animal studies have demonstrated the timing and content of human vaccines can affect the development of diabetes. Clinical trials of new human vaccines are not designed and generally not powered to detect an effect of immunization on the development of IDDM. These animal toxicology studies indicate that the effect of vaccines on human insulin dependent diabetes needs to be examined.

Age Factors↗
PubMed1993

Post-thymectomy organ-specific autoimmunity: enhancement by cyclosporine A and inhibition by IL-2.

It has previously been shown that the administration of cyclosporine A to newborn mice results in the development of autoimmunity later in life. It has been proposed that the neonatal administration of cyclosporine A results in altered thymic selection or inhibition of the development of suppressor cells. In the present study, treatment of day 3 thymectomized C3H/HeN mice with cyclosporine A (20 mg/kg/day) for 9 d post surgery increased the prevalence of antigastric autoantibodies. In contrast, the administration of IL-2 (300-600 Units/g/day) for 7 days after thymectomy inhibited the development of antigastric antibodies. We hypothesize that CsA may act by causing transient lymphokine abnormalities in the extrathymic environment during the first few weeks of life which lead to the development of antigastric antibodies. In contrast to the inhibition of development of antigastric antibodies, the administration of a similar course of IL-2 produced only a transient suppression of diabetes in NOD mice. These results and other data suggest that diabetes in NOD mice is probably due to a different immunologic defect.

Animals↗
PubMed1991

Evidence that cyclosporine treatment during pregnancy predisposes offspring to develop autoantibodies.

Cyclosporine was administered (11 mg/kg/day) to pregnant mice to study the effects of passively transferred CsA on the developing immune system. Placental transfer of CsA was shown by the detection of fetal-tissue levels ranging from 400 to 1500 ng CsA/g tissue. Treatment clearly altered the developing immune system. Thymuses from the day-18 embryos exposed to CsA were partially depleted of CD4+CD8- single positive cells. Eleven of 50 offspring born to CsA-treated mothers developed significant levels of IgG autoantibodies to gastric antigens. In addition, two animals that received CsA in utero developed an extensive mononuclear cell infiltrate in the gastric mucosa resembling autoimmune gastritis. These results raise the possibility that the administration of CsA during pregnancy may result in potential long-term effects on the developing immune system. Offspring of such pregnancies may suffer an increased incidence or severity of autoimmune diseases.

Animals↗
PubMed1989

ATP hydrolysis by ischemic mitochondria.

Cellular ATP levels are determined by the rates of ATP production and ATP hydrolysis. Both phenomena are affected by ischemia. Mitochondrial enzymes are damaged, inhibiting this organelle's ability to make ATP. Mitochondria are also uncoupled by ischemia and have the ability to hydrolyze ATP. We designed a series of experiments to determine whether decreased production or increased hydrolysis of ATP was the primary effect of mitochondrial damage. Rat hearts were subjected to 45 min of warm ischemia in order to induce irreversible cell damage. ATP or ADP was injected into cuvettes containing mitochondria isolated from normal myocardium or myocardium damaged by ischemia. Luciferin-luciferase, which fluoresces in the presence of ATP, was also added to the tubes as an indicator of ATP levels. Mixtures of uncoupled and coupled mitochondria were made and compared with the mitochondria damaged by ischemia. The results showed that mitochondria damaged by prolonged ischemia hydrolyze ATP more rapidly than normal mitochondria; however, normal mitochondria can easily compensate for increased ATP hydrolysis when in mixture with equal amounts of uncoupled mitochondria. These data suggests that the low cellular levels of ATP following irreversible ischemia are primarily due to decreased ATP synthesis and not to increased hydrolysis.

Adenosine Triphosphate↗
PubMedDate not supplied

Clustering of cases of type 1 diabetes mellitus occurring 2-4 years after vaccination is consistent with clustering after infections and progression to type 1 diabetes mellitus in autoantibody positive individuals.

OBJECTIVE: We previously analyzed data from a hemophilus vaccine trial and identified clusters of extra cases of type 1 diabetes mellitus (T1DM) caused by the vaccine that occurred between 36 and 48 months after immunization. Published reports indicate clustering of cases of T1DM occurring approximately 2-4 years after mumps infection. Others have reported a 2-4 year delay between the onset of autoantibodies and the development of T1DM. We attempted to determine whether similar clustering of cases of T1DM occurred after immunization with vaccines other than hemophilus. METHODS: We searched MEDLINE and reviewed references from published papers to find databases on the incidence of T1DM and then searched MEDLINE to determine whether changes in immunization occurred in these regions during the times the incidence of DM was being recorded. RESULTS: Distinct rises in the incidence of T1DM occurred 2-4 years following the introduction of the MMR and pertussis vaccines. A drop in the incidence of T1DM was detected between 3-4 years following discontinuation of pertussis and BCG vaccines. CONCLUSION: The identification of clusters of cases of T1DM occurring in consistent temporal time periods allowed a link between the hemophilus vaccine and T1DM to be established. The current findings indicate the there are also clusters of cases of T1DM occurring 2-4 years post-immunization with the pertussis, MMR, and BCG vaccine. The data are consistent with the occurrence of clusters following mumps infection and the progression to T1DM in patients with antipancreatic autoantibodies.

Autoantibodies↗