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M Kocova

Publications and source records attributed to M Kocova.

30 records · Page 2Linked to original sources
PubMed1993

Chimerism after liver transplantation for type IV glycogen storage disease and type 1 Gaucher's disease.

BACKGROUND: Liver transplantation for type IV glycogen storage disease (branching-enzyme deficiency) results in the resorption of extrahepatic deposits of amylopectin, but the mechanism of resorption is not known. METHODS: We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher's disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient. Samples of blood and biopsy specimens of the skin, lymph nodes, heart, bone marrow, or intestine were examined immunocytochemically with the use of donor-specific monoclonal anti-HLA antibodies and the polymerase chain reaction, with preliminary amplification specific to donor alleles of the gene for the beta chain of HLA-DR molecules, followed by hybridization with allele-specific oligonucleotide probes. RESULTS: Histopathological examination revealed that the cardiac deposits of amylopectin in the patients with glycogen storage disease and the lymph-node deposits of glucocerebroside in the patient with Gaucher's disease were dramatically reduced after transplantation. Immunocytochemical analysis showed cells containing the HLA phenotypes of the donor in the heart and skin of the patients with glycogen storage disease and in the lymph nodes, but not the skin, of the patient with Gaucher's disease. Polymerase-chain-reaction analysis demonstrated donor HLA-DR DNA in the heart of both patients with glycogen storage disease, in the skin of one of them, and in the skin, intestine, blood, and bone marrow of the patient with Gaucher's disease. CONCLUSIONS: Systemic microchimerism occurs after liver allotransplantation and can ameliorate pancellular enzyme deficiencies.

Adult↗
PubMed1993

Chimerism and donor-specific nonreactivity 27 to 29 years after kidney allotransplantation.

Chimerism was demonstrated with immunocytochemical and/or polymerase chain reaction techniques in kidney allografts and in the native skin, lymph nodes, or blood of 5 of 5 patients who received continuously functioning renal transplants from 1 or 2 haplotype HLA mismatched consanguineous donors (4 parents, 1 aunt) 27-29 years ago. In the 4 cases where the kidney donor still was alive to provide stimulator lymphocytes for testing, these provoked no (n = 2) or modest (n = 2) MLR in contrast to vigorous MLR to third party lymphocytes. In all 4 cases, the donor cells failed to generate in vitro cytotoxic effector cells (cell-mediated lymphocytotoxicity). These findings are in accord with the hypothesis that cell migration, repopulation, and chimerism are seminal events that define graft acceptance and ultimately can lead to acquired donor-specific nonresponsiveness (tolerance).

Adult↗
PubMed1993

A cold spot of IDDM incidence in Europe. Macedonia.

OBJECTIVE: To determine, for the first time, the incidence of IDDM among children 0-15 yr of age in Macedonia, the south republic of former Yugoslavia, and to compare these rates with those from neighboring countries. RESEARCH DESIGN AND METHODS: Children < 15 yr of age, with IDDM diagnosed between January 1985 and December 1991, were registered using the criteria established for the WHO Multinational Project for Childhood Diabetes. The primary source of case ascertainment consisted of clinical records from the University Pediatric Clinic in Skopje, the capital of Macedonia. The secondary source consisted of records for insulin supplies from the pharmacy in Skopje and from 15 local hospitals. RESULTS: During 1985-1991, 112 children < 15 yr of age were diagnosed with IDDM in Macedonia. The completeness of case ascertainment was 96.6%. The age-adjusted IDDM incidence rate was very low, only 2.45/100,000 per yr. No significant sex difference in incidence was observed. The highest incidence rate occurred in the 10- to 15-yr age-group. No temporal trends were observed. CONCLUSIONS: The incidence of IDDM in Macedonia is the lowest in Europe and among the lowest reported for Caucasian populations. However, the descriptive epidemiology is similar to that for high incidence populations. Further etiological studies are required to evaluate potential reasons for the very low incidence of IDDM in Macedonia.

Adolescent↗
PubMed1993

Non-radioisotopic typing of human leukocyte antigen class II genes on microplates.

We describe a new nonradioisotopic method for HLA class II molecular typing performed in 96-well plates of the same size as those used in enzyme-linked immunosorbent assays (ELISA) and radioimmunoassays (RIA). Biotinylated sequence-specific oligonucleotide (SSO) probes are bound to avidin-coated plates. Digoxigenin-labeled PCR-amplified DNA samples are hybridized, washed and detected with a peroxidase conjugated antibody assay. The method was tested by performing a partial HLA DQA1 and DQB1 typing on 69 randomly selected blood samples. The results are completely concordant with a traditional SSO-PCR typing performed on the same samples. This procedure is simple, fast and could be adapted for performance in semi-automated or automated fashion using equipment already available for ELISA and RIA assays.

Avidin↗
PubMed1992

Systemic chimerism in human female recipients of male livers.

We have previously reported data from clinical and laboratory animal observations which suggest that organ tolerance after transplantation depends on a state of balanced lymphodendritic cell chimerism between the host and donor graft. We have sought further evidence to support this hypothesis by investigating HLA-mismatched liver allograft recipients. 9 of 9 female recipients of livers from male donors had chimerism in their allografts and extrahepatic tissues, according to in-situ hybridisation and molecular techniques 10 to 19 years posttransplantation. In 8 women with good graft function, evidence of the Y chromosome was found in the blood (6/8), skin (8/8), and lymph nodes (7/8). A ninth patient whose transplant failed after 12 years from recurrent chronic viral hepatitis had chimerism in her lymph nodes, skin, jejunum, and aorta at the time of retransplantation. Although cell migration is thought to take place after all types of transplantation, the large population of migratory cells in, and the extent of their seeding from, hepatic grafts may explain the privileged tolerogenicity of the liver compared with other organs.

ABO Blood-Group System↗
PubMed1992

Autoimmunity and genetics contribute to the risk of insulin-dependent diabetes mellitus in families: islet cell antibodies and HLA DQ heterodimers.

The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody-negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies may be relatively common, it progresses only in those with variant HLA-DQ molecules.

Adolescent↗
PubMed1986

Translocation between chromosomes 1 and 9 in childhood acute lymphoblastic leukemia.

A case of a non-T, non-B acute lymphoblastic leukemia with a translocation between chromosomes #1 and #9 is described. The breakpoints in these chromosomes were determined to be at bands 1q23 and 9p22, respectively. The breakpoint in chromosome #1 was at the same site as that in a subgroup of acute lymphoblastic leukemia with t(1;19), and the breakpoint in #9 was the same as that in t(9;11)(p22;q23) in acute monoblastic leukemia. We discuss the possible association between these chromosome bands (1q23, 9p22, 11q23, and 19p13) and the morphologic features of the leukemic cells. The breakpoint in chromosome band 1q23 may be specifically associated with acute lymphoblastic leukemia.

Child↗
PubMed1986

Secondary acute myeloblastic leukemia with a Ph translocation in a treated Wegener's granulomatosis.

Ph-positive acute myeloblastic leukemia (AML) developing in a treated case of Wegener's granulomatosis is reported. The patient was a 70-year-old white male who received cyclophosphamide (150 mg/day) starting in July 1978; in May 1984 the patient was diagnosed as having AML, following a diagnosis of myelodysplastic syndrome lasting 3 months. Cytogenetic study of bone marrow cells at the diagnosis of the myelodysplastic syndrome revealed a standard Ph translocation in addition to numerical chromosome changes [i.e., 45,XY, -5, -7, -8, +19, +mar/45,XY, -5, -7, -8, +19, +mar,t(9;22)(q34;q11]). The events in this case suggest a strong possibility of the Ph-positive AML being a secondary disease related to prior cyclophosphamide therapy.

Aged↗
PubMed1985

Translocation 4;11 acute leukemia: three case reports and review of the literature.

Three children with acute leukemia and t(4;11)(q21;q23) are presented. Two of the cases showed very unusual karyotypic findings and long survival for the type of leukemia. In case B.T., the original karyotype change observed was t(4;11), with other changes (+4q-,+11q+,+6,+10) appearing during the last stages of the disease. In case R.B., the translocation was accompanied by many numerical and morphological chromosome changes, with a near-tetraploid chromosome number. In both of the above cases, remission was associated with a normal marrow karyotype. In case D.C., only the t(4;11) was observed. The number of cases with t(4;11) and acute leukemia published so far is 36, including the three cases presented by us. As this disease is usually characterized by a relatively short survival, the possible reasons for the remarkably long survival in two of our patients are discussed in relation to the rather unusual cytogenetic findings.

Acute Disease↗
PubMedDate not supplied

Pituitary pseudotumor with unusual presentation reversed shortly after the introduction of thyroxine replacement therapy.

Pituitary pseudotumor (pituitary thyrotroph hyperplasia) caused by unrecognized and untreated hypothyroidism has been described as a rare condition, mostly in adults. There are only a few reports on this condition in children. Here we describe an unusual association of pituitary pseudotumor with hypothyroidism, vaginal bleeding, and growth retardation in a girl at an early stage of puberty. Hormonal testing showed low thyroxine and high TSH levels, hyperprolactinemia, low growth hormone levels and prepubertal levels of gonadotrophins. Ovarian cyst was detected by ultrasound. A large intrasellar mass expanding beyond the sella turcica was detected on MRI. Homogeneous contrast enhancement confirmed pituitary hyperplasia. Therapy with L-thyroxine resulted in rapid improvement of the clinical signs, normalization of the hormone levels, and resolution of the pituitary hyperplasia on MRI within 40 days. In children, prolonged unrecognized primary hypothyroidism might be accompanied by growth deficiency and pubertal disharmony. Pituitary hyperplasia should be sought in these cases.

Child↗