Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and meta-analysis.

Objective: To further evaluate the controversial putative association between a Ser9Gly variant in the first exon of the dopamine D3 receptor gene (DRD3) and schizophrenia.

Methods: Swedish patients with schizophrenia ( n=156) and control subjects ( n=463) were assessed for the DRD3 Ser9Gly variant. Meta-analyses including previous and the present Swedish case-control results were performed.

Association study between dopamine D3 receptor gene variant and personality traits.

Dopamine receptor gene variation has been hypothesized to influence personality traits characterized by novelty seeking and related traits. We analyzed a dopamine D(3) receptor gene (DRD3) variant in a Swedish population (n = 373) investigated with one or more of several personality questionnaires. No significant relationships were found between DRD3 genotypes and any of the 15 Karolinska Scales of Personality (KSP) and five Health-relevant Personality 5 factor inventory (HP5i) scales.

The human small conductance calcium-regulated potassium channel gene (hSKCa3) contains two CAG repeats in exon 1, is on chromosome 1q21.3, and shows a possible association with schizophrenia.

Mutations in various ion channel genes are responsible for neuromuscular and other neurological disorders. We have previously identified the human small conductance calcium-activated potassium channel gene (hSKCa3) which has two tandemly arranged CAG repeats in its 5' region. Here we have isolated the first genomic clones containing the gene and have shown that both repeats are in exon 1.

Trend for an association between schizophrenia and D3S1310, a marker in proximity to the dopamine D3 receptor gene.

There is considerable controversy regarding a putative association between schizophrenia and a biallelic BalI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3), although meta-analyses of published data suggest an association. If such an association exists, it may be detectable at markers physically close to DRD3. Accordingly, we conducted a case-control association study using D3S1310, a short tandem repeat polymorphism located approximately 700 kb telomeric to DRD3 on chromosome 3q13.

Association between hSKCa3 and schizophrenia not confirmed by transmission disequilibrium test in 193 offspring/parents trios.

A possible association between the small conductance calcium-regulated potassium channel gene, hSKCa3, and schizophrenia has recently been described by Chandy et al using a case-control design with patients with schizophrenia (n=141) and matched controls (n = 158). The gene may be considered as an excellent candidate gene for psychiatric disorders, since it plays a role in modulating neuronal firing patterns by regulating the slow component of after hyperpolarisation. In addition, the gene contains a highly polymorphic trinucleotide sequence (CAG) within exon 1, which encodes a polyglutamine stretch.

No association between the tyrosine hydroxylase microsatellite marker HUMTH01 and schizophrenia or bipolar I disorder.

Linkage and association studies have implicated the involvement of the tyrosine hydroxylase (TH) gene on chromosome 11p15 in schizophrenia and bipolar disorder (BPD). An association of BPD with a polymorphic tetranucleotide repeat, HUMTH01, located in the first intron of the human TH gene has been reported. Subsequently a rare allele, Ep ([TCAT]10) of this microsatellite marker has been found in French and Tunisian schizophrenic patients only.

Analysis of the CAG repeats in the SCA1 and B37 genes in schizophrenic and bipolar I disorder patients: tentative association between B37 and schizophrenia.

We have genotyped unrelated French Alsatian schizophrenic and bipolar I disorder (BPD) patients and matched controls for the polymorphic CAG repeats within the genes for spinocerebellar ataxia type 1 (SCA1) and dentatorubral-pallidoluysian atrophy (B37), in order to test their possible involvement in these disorders. No alleles with abnormally expanded repeats were found in either gene in patients and controls. Differences in allele and genotype frequencies for the SCA1 CAG repeat between patients and controls were not significant, thus providing no support for its role as a possible positional candidate gene for schizophrenia and BPD in our patients.

Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia.

DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D3 receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients.

BalI and MspI polymorphisms of the dopamine D3 receptor gene in African Blacks and Caucasians.

An exonic BalI polymorphism and an intronic MspI polymorphism of the dopamine D3 gene were genotyped in 101 Caucasians from the Alsace and in 56 people from the Congo. This is the first study of the BalI polymorphism in sub-Saharan Africa and the first population study of the MspI site. BalI allele 1 was rare in the Congo (0.

Episodic central neurogenic hyperventilation in an awake child with systemic histiocytosis.

A 3 year old boy with systemic histiocytosis, diabetes insipidus and a lytic parietal bone lesion experienced episodes of central neurogenic hyperventilation 3 weeks after radiation to the head but was conscious and alert at presentation. At admission, the PaO2 was 133 mmHg, PaCO2 was 8 mmHg and pH 7.65.

Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study.

A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively.

Ewing's sarcoma metastatic at diagnosis. Results and comparisons of two intergroup Ewing's sarcoma studies.

Two Pediatric Intergroup Ewing's Sarcoma studies of patients with metastatic disease (IESS-MD) have used multimodal therapy consisting of intensive combination chemotherapy and radiation therapy (XRT) to areas of gross disease detected at the time of diagnosis. In IESS-MD-I, conducted from 1975 to 1977, 53 eligible patients were entered and received the chemotherapeutic agents vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and dactinomycin with concomitant XRT (VACA + XRT). In IESS-MD-II, conducted from 1980 to 1983, 69 eligible patients were entered and received 5-fluorouracil (5FU) in addition to the chemotherapeutic agents of IESS-MD-I; initial intensive chemotherapy was given and XRT was delayed until week 10 (VACA + 5FU, delayed XRT).

Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: intergroup study IESS-II.

Two hundred fourteen eligible patients with previously untreated, localized Ewing's sarcoma of bone were randomized on IESS-II to receive Adriamycin (ADR; doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vincristine, and dactinomycin by either a high-dose intermittent method (treatment [trt] 1) or a moderate-dose continuous method (trt 2) similar to the four-drug arm of IESS-I. Patient characteristics (sex, primary site, type of surgery) were stratified at the time of registration; these and other patient characteristics (age, time from symptoms to diagnosis, race) were distributed similarly between treatments. Surgical resection was encouraged, but not mandatory.

Hematologic disorders in 13 patients with acquired trisomy 21 and 13 individuals with Down syndrome.

To study the role of trisomy 21 in hematologic malignancies, we investigated the hematologic disorders of 13 patients with acquired trisomy 21 and 13 individuals with Down syndrome (DS). The most common hematologic malignancy among the patients with acquired trisomy 21 involved both granulocytic and monocytic lineages. By comparison, the hematologic disorders among the DS patients were predominantly acute lymphocytic leukemia and acute megakaryocytic leukemia.

Acute megakaryocytic leukemia (M7) in children.

We analyzed the clinical and laboratory features of eight children (median age, 20 months; range, 13 months to 11 years) with acute megakaryocytic leukemia (M7) and compared the findings with those reported in the literature. The diagnosis was supported by ultrastructural examination for platelet peroxidase or immunophenotyping for glycoprotein IIb/IIIa or the von Willebrand factor protein. Two patients had Down's syndrome.

Cardiopulmonary function in long-term survivors of childhood Hodgkin's lymphoma: a pilot study.

Twelve patients who had received mantle radiotherapy for Hodgkin's lymphoma during childhood underwent cardiopulmonary testing 7 years or more after the initial diagnosis and treatment. All but one patient had been asymptomatic. Results of echocardiography, pulmonary function tests, or exercise studies were abnormal in 9 of the 12 patients.

Cyclophosphamide-induced hemorrhagic cystitis in Ewing's sarcoma.

Recent improvements in survival of patients with Ewing's sarcoma have been made since the addition of cyclophosphamide-based adjuvant chemotherapy to primary surgery and radiation. A potential limitation to cyclophosphamide use is its urotoxicity, primarily in the form of hemorrhagic cystitis. The incidence of this adverse effect in patients treated for Ewing's sarcoma has not been established.

Abdominal Burkitt's lymphoma: role of early aggressive surgery.

Current surgical teaching advocates debulking of the abdominal Burkitt's lymphoma to decrease tumor burden and improve survival. The records of 16 children who had Burkitt's lymphoma were reviewed. Eleven of these children presented with abdominal tumors.

Ewing's sarcoma of bone. Experience with 140 patients.

The records of 140 patients with histologically verified Ewing's sarcoma of bone treated between 1969 and 1982 were studied retrospectively. Various factors thought to be relevant to prognosis were analyzed. Three statistically significant factors were found: presence of metastatic disease, elevation of the sedimentation rate, and location of the tumor in the pelvis.

Hereditary red cell disorders in Southeast Asian refugees and the effect on the prevalence of thalassemia disorders in the United States.

This investigation established the frequency and prevalence of hemoglobin E, alpha and beta thalassemia, and glucose-6-phosphate dehydrogenase deficiency in a group of Southeast Asian individuals and determined the impact upon the prevalence of thalassemia disorders in the United States. The resettlement program of Southeast Asian refugees has significantly increased the total number of serious thalassemic disorders in the United States. For several generations Southeast Asian children will be the principal thalassemic group.

Wilms' tumor in a 'lump' kidney associated with sacral agenesis.

Many cases of Wilms' tumor developing in a horseshoe kidney have been previously reported. We present a case of Wilms' tumor developing in a "lump" kidney, associated with sacral agenesis. We discuss the implications for staging and make recommendations for follow-up in these cancer-prone children.

Hematologic genetic disorders among Southeast Asian refugees.

Resettlement of Southeast Asian refugees has introduced into the Western Hemisphere many persons of all major ethnic groups from Indochina. They represent several distinctive cultural, genetic, and linguistic groups, and the prevalence of genetic traits among them varies accordingly. We studied 778 Southeast Asian persons resettled in the upper Midwest who belonged to 182 unrelated families from the five major Southeast Asian ethnic groups.

Randomized study of systemic chemotherapy following complete excision of nonosseous sarcomas.

Between June 1975 and April 1981, 61 of the 177 eligible patients whose nonosseous sarcomas of extremity or trunk origin had been completely excised primarily or after local recurrences agreed to participate in a randomized study of adjuvant chemotherapy. Dermatofibrosarcoma, lymphomas, myeloma, Kaposi's sarcoma, and embryonal rhabdomyosarcoma were excluded as were patients with significant second primary cancers and those who received either preoperative or postoperative radiation therapy. After stratification by anatomic status of disease, site of origin, and histologic grade, a random one half of the 61 participants began alternating courses of vincristine/cyclophosphamide/dactinomycin, and vincristine/doxorubicin/dacarbazine at six-week intervals for one year.

Intraoperative irradiation: a new technique in pediatric oncology.

Adverse effects on normal tissue are the principal limiting factor in the use of radiation therapy. Maturing tissues are most susceptible to these side effects, so high-dose applications can be a particularly difficult challenge in children. Intraoperative radiation therapy (IORT) enables the radiation oncologist to displace or shield dose-limiting organs or structures.

Sequential half-body irradiation (SHBI) and combination chemotherapy as salvage treatment for failed Ewing's sarcoma--a pilot study.

This study was undertaken to evaluate the toxicity of sequential half-body irradiation (SHBI) and combination chemotherapy (5-FU, VM-26 and BCNU) in patients who had failed primary aggressive therapy for their Ewing's sarcoma. A secondary goal was to evaluate the response of these previously treated patients to the combination of systemic radiation and multi-agent chemotherapy. The first patient in the study was treated with SHBI only and died 139 days following retreatment.