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R Haupt

Publications and source records attributed to R Haupt.

At least 55 records · Page 3Linked to original sources
PubMed1995

Molecular characterization of 12q14-15 rearrangements in three pulmonary chondroid hamartomas.

Chromosomal aberrations involving the chromosomal breakpoint region 12q14-15 are frequently seen in a variety of mesenchymal tumors as uterine leiomyomas, lipomas, myxoid liposarcomas, enchondromas, or hemangiopericytomas. Therefore, this breakpoint region seems to be one of the most frequent chromosomal abnormality associated with the initiation of human mesenchymal neoplasms. To narrow down the breakpoint region on a molecular level in cells of three pulmonary chondroid hamartomas with 12q14-15 aberrations, we performed fluorescence in situ hybridization analysis with different cosmid clones originating from a YAC and cosmid contig overspanning parts of the region 12q14-15. We were able to narrow down the breakpoint to a region of 175 kb belonging to an area designated multiple aberration region because it also includes the breakpoints of leiomyomas, lipomas, and pleomorphic adenomas with 12q14-15 abnormalities. Our molecular and cytogenetic data suggest that hamartomas of the lung molecularly belong to the benign group of mesenchymal tumors showing multiple aberration region involvement.

Cells, Cultured↗
PubMed1995

Alveolar surfactant subfractions differ in their lipid composition.

Alveolar surfactant consists of subfractions which are generated during normal lung function. Although subfractions obtained by differential centrifugation of lung lavage differ in structure, function and protein content, the phospholipid-pattern shows only minor differences. To correlate possible differences in composition between subfractions to their functional properties we did a more detailed analysis of lipid pattern. Subfractions of lung lavages from Wistar rats were obtained by differential centrifugation, lipid classes were separated by thin layer chromatography (TLC). Fatty acids and plasmalogens were determined as methylester and dimethylacetals by gas chromatography, respectively. Cholesterol and vitamin E were determined enzymatically and by HPLC, respectively. The patterns of fatty acids of total lipids and of the molecular species of phosphatidylcholine and phosphatidylethanolamine were very similar among the subfractions. The distribution of individual lavage lipids varied considerably. Three types of subfractions can be distinguished: The two dense subfractions (1000 g and 60,000 g) contain 70-88% of total phospholipids, dipalmitoylphosphatidylcholine, polyunsaturated phospholipids and polyunsaturated fatty acids present in lung lavage. The less dense subfraction (100,000 g) contains 44-60% of total cholesterol, choline plasmalogen, ethanolamine plasmalogen and vitamin E. The 100,000 g supernatant contains 40-50% of total tri-, diacylglycerols and free fatty acids. Our results support the concept that the 1000 g subfraction contains freshly secreted surfactant. The 60,000 g subfraction likely contains the monolayer and freshly secreted surfactant. The 100,000 g pellet probably contains material "squeezed out" from the monolayer at expiration. Most likely, the supernatant contains material destined for removal from the airspace.

Animals↗
PubMed1995

Cytogenetics of the tissue involved in neural tube defects.

Cytogenetic techniques were used to study the tissue involved in neural tube defects. Eighteen patients have been evaluated and no specific alterations have been detected. We conclude that, whatever are the mechanisms that lead to neural tube defect, their origins must be searched for at the molecular level.

Adolescent↗
PubMed1994

Educational attainment in long-term survivors of childhood acute lymphoblastic leukemia.

OBJECTIVE: To determine the impact of treatment on scholastic performance in the first cohort of survivors of childhood acute lymphoblastic leukemia who are old enough to have completed their educational experience. DESIGN: Retrospective cohort study. SETTING: Twenty-three institutions in the Childrens Cancer Group. SUBJECTS: A total of 593 adult survivors of childhood acute lymphoblastic leukemia and 409 sibling controls. OUTCOME MEASURES: Enrollment in special programs, grades during high school, graduation from high school, college admission, and college graduation. RESULTS: After diagnosis, survivors were more likely than their sibling controls to enter a special education (relative risk [RR] = 3.4; P < .01) or a learning disabled (RR = 3.6; P < .01) program, while just as likely to enter gifted and talented programs (RR = 1.0). The risk associated with special education and learning disabled programs increased with increasing dose of cranial radiotherapy. Despite these problems, survivors generally had the same probability as their siblings of finishing high school, entering college, and earning a bachelor's degree. However, survivors treated with 24 Gy and those diagnosed before 6 years of age were less likely to enter college (RR = 0.67 and 0.6, respectively; P < .01). CONCLUSIONS: This large study demonstrates that childhood acute lymphoblastic leukemia survivors have a greater likelihood of being placed in special education or learning disabled programs than their siblings, but that most are able to overcome these problems. Dose of cranial radiotherapy and age at diagnosis are the most important education-related risk factors.

Adolescent↗
PubMed1994

Synthesis and secretion of plasmalogens by type-II pneumocytes.

Alveolar surfactant (exposed to air and therefore a prime target of air oxidants) is supplied with antioxidants during its intracellular formation on type-II pneumocytes [Rüstow, Haupt, Stevens and Kunze (1993) Am. J. Physiol. 265, L133-L139]. Plasmalogens can protect animal cells against lipid peroxidation caused by u.v. radiation. It has been suggested that plasmalogens play a direct role in protecting animal cell membranes against oxidative stress [Zoeller, Morand and Raetz (1988) J. Biol. Chem. 263, 11590-11596]. We investigated biosynthesis and secretion of plasmalogens and phospholipids by type-II cells of adult rat lungs. The plasmalogens of type-II cells consist of 93% ethanolamine plasmalogens (EthPlas) and 7% choline plasmalogens (ChoPlas). Plasmalogens isolated from alveolar surfactant, however, consist of 36.5% ChoPlas and 63.5% EthPlas. The different incorporation rates of [14C]hexadecanol into both types of plasmalogen by type-II pneumocytes are reflected in the relative proportions of their total cellular plasmalogen content. Type-II cells cultured in the presence of labelled hexadecanol or labelled hexadecylglycerol and of labelled palmitate secrete labelled ChoPlas and labelled phospholipids, both spontaneously and in response to isoprenaline. The spontaneous and stimulated secretion rates of labelled ChoPlas are 3-6 times higher than those of labelled EthPlas. This higher relative secretion rate of ChoPlas corresponds to its higher proportion in the total plasmalogen content of alveolar surfactant compared with type-II cells. Added extracellular surfactant-specific protein A inhibits the secretion of plasmalogens as well as that of phospholipids by type-II cells. The molecular species of EthPlas and ChoPlas isolated from type-II cells or lung lavage do not differ significantly and consist mainly of molecular species containing poly-unsaturated fatty acids. We conclude that ChoPlas are secreted partly as integral constituents of the alveolar surfactant. Type-II cells select between both types of plasmalogens for secretion as a constituent of surfactant. The intramolecular sorting signal presumably is the choline moiety.

Animals↗
PubMed1994

Herpes simplex virus and oral mucositis in children with cancer.

The relationship between herpes simplex virus (HSV) and oral mucositis was investigated in children undergoing antineoplastic chemotherapy. HSV culture was performed in 20 children with stomatitis developing after antineoplastic chemotherapy. Viral isolates were typed and susceptibility to acyclovir was investigated. The virus was isolated from oral lesions in 10 of 20 children with severe oral mucositis. Viral reactivation was the most likely explanation in most cases, since HSV was isolated in 9 of 13 seropositive patients (and in 1 patient with unknown anti-HSV serology), but in no seronegative patient. HSV type 1 was isolated more frequently than HSV type 2 (8 versus 2). Acyclovir showed standard in vitro activity against all isolates. Our results suggest that oral mucositis in children receiving antineoplastic treatment is probably multifactorial in origin and that HSV can be an important cofactor, especially in children who are seropositive for HSV. In our Centre, acyclovir remains active in vitro against this opportunistic pathogen and could be employed in prophylaxis and therapy.

Adolescent↗
PubMed1994

Health status of long-term survivors after cancer in childhood. Results of an uniinstitutional study in Italy.

PURPOSE: This study aims at defining the frequency and severity of late effects in a series of 288 long-term survivors of childhood cancer treated from 1962 to 1982 at the Giannina Gaslini Children's Research Hospital of Genoa, Italy. PATIENTS AND METHODS: All cases with a diagnosis of malignancy in childhood and a minimum of 2.5 years from discontinuation of treatment were considered eligible. For all cases the study included physical, endocrinological, and psychological examination. Groups of patients selected according to treatment underwent cardiac, pulmonary, orthopedic, and ophthalmologic evaluation. The sequelae observed were scored according to a grading system in which asymptomatic subclinical defects are distinguished from those that are sufficiently symptomatic to require some type of corrective measure. RESULTS: Overall, 200 of 288 cases (69.4%) presented with some kind of abnormality. Symptomatic changes were present in 92 cases (42%); in these, severe and life-threatening late toxicity was reported in 61 (21.2%) and 12 cases (4.2%), respectively. The major risk factors appeared to be irradiation, type of tumor, and whether the patient had received therapy before 1974. CONCLUSIONS: In our experience, this study demonstrates that there was a true excess of morbidity caused by the disease and its treatment in long-term survivors from almost any kind of childhood cancer. It also sheds light on how to prevent, diagnose, and adequately treat these patients and proposes specific criteria for the evaluation of the severity of delayed toxicity in long-term survivors of cancer in childhood.

Adolescent↗
PubMed1993

Outcome after cessation of therapy in childhood acute lymphoblastic leukaemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP).

A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P < 0.0001). Thirteen patients died in continuous complete remission, 5 because of non-neoplastic central nervous system complications. There were 11 second solid malignancies, 8 of them in the central nervous system; 9 subjects presented an haematopoietic malignancy after ALL. The projected event-free survival at 8 years is 73%. Twenty-two of the 171 young adults (age > 20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

Adolescent↗
PubMed1993

Neuroblastoma IV-S in a patient with bilateral microphthalmia.

Neuroblastoma, a tumor of post-ganglionic sympathetic neurons, may be associated with a variety of genetic defects and congenital malformations (1). We report a case of neuroblastoma (NB) stage IV-S (2) in an infant with bilateral microphthalmia and other ocular malformations.

Abnormalities, Multiple↗
PubMed1993

Type II pneumocytes secrete vitamin E together with surfactant lipids.

Lung surfactant is exposed to strongly oxidizing conditions. We examined the hypothesis that in lung, lipophilic antioxidants are secreted together with surfactant to counteract the peroxidation of surfactant constituents. Lung lavage and the subfractions of the alveolar surfactant contain the lipophilic antioxidants vitamin E, vitamin A, and plasmalogens. The specific radioactivity of vitamin E isolated from serum, lung homogenate, lamellar bodies, and lung lavage increased linearly up to 3 h after intraperitoneal application of [3H]tocopherol. [3H]tocopherol was secreted in situ together with [14C]palmitic acid-labeled phospholipid in response to isoproterenol. Type II cells cultured in presence of [3H]tocopherol or of [3H]cholecalciferol and [14C]palmitic acid responded to isoproterenol by a time-dependent increase in secretion of [3H]tocopherol and of 14C-labeled phospholipids but not of [3H]cholecalciferol. The isoproterenol-stimulated secretion of [3H]tocopherol and of 14C-labeled phospholipids by type II cells is inhibited by surfactant protein A. We conclude that the alveolar surfactant contains lipophilic antioxidants as integral constituents. [3H]tocopherol seems to be secreted together with surfactant.

Animals↗
PubMed1992

Pentasomy 21 in leukemia complicating Diamond-Blackfan anemia.

We present the cytogenetic pattern of a leukemic infant with Diamond-Blackfan anemia (DBA). The karyotype was characterized by clonal evolution involving consecutive gains of chromosome 21 up to pentasomy. No chromosomal changes were present in normal lymphocytes. Such a karyotype evolution has been described in some cases of acute leukemia associated with Down Syndrome, but rarely in non-Down cases.

Chromosomes, Human, Pair 21↗
PubMed1992

Studies on the formation of dipalmitoyl species of phosphatidylcholine and phosphatidylethanolamine in pulmonary type II cells.

Endogenous content of and incorporation of labelled glycerol into alkenylacyl-, alkylacyl- and diacyl-glycerol, -glycerol-3-phosphocholine and -glycero-3-phosphoethanolamine of pulmonary type II cells were measured. On prolonged incubation of type II cells with labelled glycerol, the proportion of label incorporated into the diacyl subclass of these glycerolipids increased and the proportion of label incorporated into the ether lipids declined. Endogenous phosphatidylcholine (PtdCho) of type II cells contained 38.4% of the dipalmitoyl species, but endogenous phosphatidylethanolamine (PtdEtn) only 2.5%. In contrast, similar proportions of labelled glycerol were incorporated into dipalmitoyl-PtdCho and -PtdEtn after short-time incubation but, with prolonged incubation time the proportion of labelled dipalmitoyl-PtdCho increased from 11.3 to 18.8%, whereas that of dipalmitoyl-PtdEtn did not change significantly. Type II cell membranes were found to exhibit cofactor-independent and CoA-mediated transacylations of [1-14C]palmitoyl-lyso-PtdCho and -lyso-PtdEtn. The distribution of label among the palmitic acid-containing species of PtdCho and PtdEtn formed by both transacylation activities was determined. Cofactor-independent and CoA-mediated transacylation showed a strong selectivity for palmitate and arachidonate and a strong discrimination against oleate. The amount (nmol) of dipalmitoyl-PtdEtn formed by both transacylation activities after short-time incubation (2 min) decreased with prolonged incubation time (60 min). In contrast, the nmol of dipalmitoyl-PtdCho formed by cofactor-independent transacylation remains nearly the same after short-time and longer incubation. The nmol of dipalmitoyl-PtdCho formed by CoA-mediated transacylation increased strongly in the same time interval. Beside synthesis de novo via the CDP-choline pathway and reacylation of lyso-PtdCho with palmitoyl-CoA, the CoA-mediated transacylation of lyso-PtdCho may be an effective pathway for the formation of dipalmitoyl-PtdCho in pulmonary type II cells.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Smoking habits in survivors of childhood and adolescent cancer.

Because of their increased risk for second cancers, childhood cancer survivors are people who really should not smoke, but available evidence suggests that they do. We studied the smoking habits of long-term childhood cancer survivors in data collected from 1289 adult survivors of childhood cancer and 1930 of their sibling controls. Survivors were diagnosed with cancer between 1945 and 1974 when they were less than 20 years old. Using matched analyses that controlled for the influence of family, survivors were 8% less likely than controls to be current smokers, 13% less likely to be ever-smokers, but 12% less likely to have quit smoking; these differences were not statistically significant. In a logistic regression analysis there was a significant difference by year of diagnosis for current smoking rate ratios (RR); survivors were less likely to be current smokers if diagnosed in recent years (RR = 0.76; 95% confidence intervals = 0.58-0.98, between 1965-74) and quite similar to controls if diagnosed in earlier years (RR = 1.05 between 1945 and 1954). In our group of long-term cancer survivors, the reduction in current smoking came about because survivors were more inclined never to start smoking than controls. Once addicted to tobacco, they were less likely to quit. While the fact that survivors are less likely to start smoking is encouraging, the persistence of smoking habits strongly suggests the need for continuing efforts to prevent smoking in this most vulnerable group.

Adolescent↗
PubMed1992

Karyotype evolution in a patient with biphenotypic neonatal leukemia.

We present the case of a 4-day-old boy with acute lymphoblastic leukemia showing at onset a karyotype 46,XY,t(4;11)(q21;q23). At relapse an additional change, add(2), was present. Molecular analysis showed the same immunoglobulin rearrangement both at onset and at relapse, but immunohistochemical analysis revealed some cells having myeloid features. A continuous cell line derived from the leukemic blasts of the patient presented typical monoblastic features.

Cell Line↗