Chemotherapy-induced veno-occlusive disease of the liver.
Explore the source record for details and available documents.
Abdominal Muscles↗
Biomedical subjects
A C Lee
Publications and source records attributed to A C Lee.
Growth hormone treatment of short Chinese children with beta-thalassaemia major without GH deficiency.
OBJECTIVE: Despite regular transfusion and desferrioxamine treatment, growth failure is commonly seen in adolescent children with beta-thalassaemia major. The growth failure has been thought to be due to GH resistance rather than GH deficiency. We investigated the effect of GH on short non-GH deficient children with beta-thalassaemia. DESIGN: Recombinant human GH was given in a dose of 0.14 IU/kg/day subcutaneously in an open study. PATIENTS: Fifteen prepubertal Chinese children with beta-thalassaemia major (ranging from 7.16 to 14.7 years in age) with height -1.5 SD or more below the population mean for age and a growth velocity of less than 5 cm/year were treated with growth hormone for one year. All children had peak GH response > 15mlU/l to insulin induced hypoglycaemia and normal thyroid function and adrenal reserve. MEASUREMENTS: Anthropometric measurements were performed every 3 months. Morning urine was tested twice weekly for glycosuria. Blood count, renal and liver function tests, fasting blood glucose, IGF-I and fructosamine levels were assessed at entry and every 3 months during treatment. Fasting insulin was measured before and after 3 and 12 months of GH treatment. Skeletal maturity was assessed before and after one year of treatment. RESULTS: Treatment was stopped in two children after 6 months because of poor growth response and noncompliance with treatment and in one child at 9 months because of bone marrow transplantation. In the 13 children, the growth velocity increased from 3.6 +/- 0.7 cm/year to 8 +/- 1.2 cm/year after one year of GH treatment (P < 0.001). IGF-I was low before treatment (10.1 +/- 2.7 nmol/l), rising significantly to 15.8 +/- 4.8, 18.4 +/- 4.6, 19.3 +/- 6.4 and 21.9 +/- 7.5 nmol/l at 3, 6, 9 and 12 months of treatment (P < 0.005). The mean pretreatment bone age in the 13 children was 9.58 +/- 1.41 years and increased to 10.53 +/- 1.43 years after one year of treatment (delta BA/CA 0.95 +/- 0.3 years). None of the patients developed glycosuria or hypertension. There was no significant change in blood count, renal and liver function, thyroid function, fasting blood glucose or insulin concentrations during treatment. CONCLUSION: Growth failure in these children with normal GH reserve and low serum IGF-I concentrations would suggest GH insensitivity. Supraphysiological doses of exogenous GH can cause a significant increase in serum IGF-I levels and a significant improvement in short-term growth of short children with beta-thalassaemia major.
Adolescent↗
A cross-sectional study of growth, puberty and endocrine function in patients with thalassaemia major in Hong Kong.
METHODOLOGY: A cross-sectional study of growth, puberty and endocrine function was performed on 35 girls and 33 boys with thalassaemia major. RESULTS: Despite regular transfusion and chelation therapy, 75% of the girls and 62% of the boys over the age of 12 years were below the third percentile for height. Hypogonadotropic hypogonadism was found in a similar percentage of patients. Moderate to marked zinc deficiency secondary to chelation therapy was considered unlikely because normal serum zinc levels were found in all but three of our patients, but we could not exclude the possibility of a marginal status of zinc nutrition causing growth failure. Growth hormone deficiency and diabetes mellitus were sometimes encountered but hypothyroidism, hypoparathyroidism and adrenal insufficiency were rare among our patients. Most of the patients with growth failure had normal growth hormone (GH) response to insulin induced hypoglycaemia. The serum insulin-like growth factor-1 (IGF-1) levels were low in our patients and no significant difference in the serum IGF-1 levels was found between prepubertal children with or without growth failure (0.4 +/- 0.1 mU/mL vs 0.37 +/- 0.11 mU/mL, P = 0.39). Similarly, no difference in the serum IGF-1 levels was found between pubertal children with or without growth failure (0.48 +/- 0.2 U/mL vs 0.56 +/- 0.14 U/mL, P = 0.26). CONCLUSIONS: Delayed sexual maturation and a possible defect in growth unrelated to the GH-IGF-1 axis may be responsible for the growth failure in adolescent children with thalassaemia major.
Adolescent↗
Mixed chimerism following bone marrow transplantation for severe combined immunodeficiency: a study by DNA fingerprinting and simultaneous immunophenotyping and fluorescence in situ hybridisation.
We report a girl with severe combined immunodeficiency (SCID) who had a paternal T-depleted bone marrow transplant (BMT) when 11 months old. Engraftment was documented but karyotyping of marrow cells 1 year after BMT showed recipient metaphases (XX) only. However, she remained clinically well and further analysis y karyotyping of PHA-cultured peripheral blood mononuclear cells (PBMC) showed donor metaphases (XY) only. DNA fingerprinting confirmed mixed chimerism in the peripheral blood. The granulocytes were of recipient origin and the PBMC of mixed origin, the donor proportion of which increased after culture with PHA. Using simultaneous immunophenotyping and fluorescence in situ hybridisation (FISH) with chromosomes X and Y-specific probes, circulating T cells were demonstrated to be of donor origin whereas B cells and myeloid cells were mostly of recipient origin.
Adult↗
Beta-NADH decreases the permeability of the mitochondrial outer membrane to ADP by a factor of 6.
Mitochondria with intact outer membrane (99% intact based on cytochrome c impermeability) were isolated and used to measure the permeability of their outer membrane to ADP. beta-NADH reduced the permeability in a concentration-dependent manner (KD = 87 +/- 5 microM) by a factor of 6. alpha-NADH and beta-NAD+ cannot mimic the action of beta-NADH. The mitochondrial outer membranes become rate-limiting in the presence of beta-NADH at low, physiologically relevant, ADP concentrations (< 30 microM). beta-NADH has been shown to increase the voltage dependence of VDAC (a major pathway for metabolite transport across the outer membrane) in a reconstituted system and this may be the way it acts on the isolated mitochondria. Inhibition of beta-NADH dehydrogenases does not inhibit the action of beta-NADH indicating that it is not acting by delivering reducing equivalents. The ability of beta-NADH, produced by glycolysis, to inhibit mitochondrial function by reducing the permeability of the outer membrane may be one pathway responsible for the Crabtree effect.
Adenosine Diphosphate↗
Risks of radiation cataracts from interplanetary space missions.
Recognition of the human risks from radiation exposure during manned missions in deep space has been fostered by international co-operation; interagency collaboration is facilitating their evaluation. Further co-operation can lead, perhaps by the end of this decade, to an evaluation of one of the three major risks, namely radiation cataractogenesis, sufficient for use in the planning of the manned mission to Mars.
Aluminum↗
Helium-ion-induced human cataractogenesis.
Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoma patients treated with helium ions at LBL will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.
Adult↗
Monoamine oxidase activity in rat organs during pregnancy.
To elucidate the involvement of MAO activity in rat pregnancy, female rats exhibiting at least 3 consecutive 4-day estrous cycles were used. The day of sperm-positive smears was designated as day 0 of pregnancy. The rats were sacrificed on day 2 of diestrus (diestrus-2) and days 7, 14 and 21 of gestation. The organs were collected and weighted, and mitochondrial fractions were prepared for MAO analysis with kynuramine dihydrobromide as substrate. Specific activity (pmol/mg of protein/min) in the ovary is significantly lower in rats on diestrus-2 (792 +/- 127) (mean +/- S.D.) than on day 14 (1,038 +/- 140) and day 21 (1,580 +/- 61) of pregnancy. However, the levels of MAO activity in the uterus of rats on diestrus-2 (899 +/- 266) is higher than on day 21 (570 +/- 80) of pregnancy. The MAO activity in the placenta on day 21 (644 +/- 82) was higher than day 14 (356 +/- 88) of pregnancy. Total MAO activity per organ (nmol/min) of ovary on day 21 (27.2 +/- 5.2) is higher than on diestrus-2 (8.7 +/- 3.0) and on day 14 (14.2 +/- 3.6). Our results suggest that MAO activity in rat reproductive organs such as uterus, ovary, and placenta might fluctuate significantly near term, in correlation with steroid levels, tissue catecholamine contents and so on, in order to maintain pregnancy.
Animals↗
Catheter-associated nocardiosis.
Explore the source record for details and available documents.
Catheterization, Peripheral↗
Expression of basic fibroblast growth factor in primary human renal tumors: correlation with poor survival.
Explore the source record for details and available documents.
Adult↗
Disseminated mediastinal carcinoma with chromosomal translocation (15;19). A distinctive clinicopathologic syndrome.
BACKGROUND: A case of disseminated mediastinal carcinoma probably of thymic origin is reported in a 5-year-old boy with an anterior mediastinal mass associated with superior vena cava obstruction, tracheal deviation, right malignant pleural effusion, and evidence of bone metastasis. The diagnosis was based on findings of radiologic localization, light and electron microscopic study, and immunohistochemistry. The patient received combination chemotherapy but died of progressive disease. METHODS: Cytogenic study on the pleural fluid was attempted, and a literature search for similar chromosomal aberration was performed. RESULTS: Cytogenetic study of tumor cells from the pleural fluid revealed a clonal chromosomal abnormality of t(15;19)(q12;p13.1). Two patients with similar disease were reported in the English literature; their clinical courses, immunohistochemical findings, and t(15;19) were almost identical to those of the patient reported in this study. CONCLUSION: The authors suggest that this translocation may be specific to thymic carcinoma and may indicate a particularly aggressive form of the disease. Carcinomas are rare in children, so the chromosomal translocation may serve as a helpful marker for the diagnosis.
Adult↗
Effect of ethanol and progesterone on monoamine oxidase activity in cultured cells of human term placenta.
OBJECTIVE: The aim of this study was to evaluate the effect of ethanol and progesterone on the monoamine oxidase activity in cultured human term placental cells. STUDY DESIGN: Human placental cells were prepared from normal human term placentas by enzymatic dispersion in Dulbecco's modified Eagle medium. The viability of placental cells prepared by our method was 90%, and the yield of placental cells was 0.6 x 10(6) cells per gram of wet placental tissue. Five milliliters of Dulbecco's modified Eagle medium containing 3 x 10(5) placental cells was plated in a 25 cm2 flask and cultured for 8 days in an incubator at 37 degrees C under an atmosphere of 5% carbon dioxide and 95% oxygen with a saturated humidity. During the culture period the culture medium was replenished every 2 days. A confluent monolayer condition was achieved after 8 days in culture. The cultured placental cells were treated with different concentrations of ethanol (0, 34.6, and 69.2 mmol/L) and progesterone (0, 16, and 32 mumol/L) on day 8 of culture for 48 hours. At the end of treatment placental cells from control and treated flasks were harvested for the analysis of monoamine oxidase activity by spectrophotometry. The effects of ethanol and progesterone on cultured placental cells were statistically analyzed by one-way analysis of variance followed by Duncan's multiple comparisons procedure. RESULTS: A human placental cell culture system has been established from normal human term placentas. The monoamine oxidase activity in 8-day-cultured human term placental cells was significantly higher than that of freshly prepared placental cells. Ethanol concentrations at 34.6 and 69.2 mmol/L significantly increased and progesterone concentration at 32 mumol/L significantly decreased the monoamine oxidase activity. CONCLUSION: These results suggest that the cultured human term placental cells can be used to examine the in vitro effects of ethanol and progesterone on monoamine oxidase activity. However, the physiologic significance of progesterone's inhibitory effect and the stimulatory effect of ethanol monoamine oxidase activity in the in vivo system have yet to be further investigated.
Cells, Cultured↗
Neurophysiologic study of beta-thalassemia patients.
Neurophysiologic investigations were performed in 34 Chinese patients with beta-thalassemia major maintained on long-term desferrioxamine treatment to look for subclinical toxicity in the auditory, visual, peripheral, or central neural pathways. In the auditory pathway study, four patients (12%) had mild sensorineural hearing impairment. Two patients (6%) had increased P 100 latencies in the visual evoked potential study, and nine patients (26%) had abnormal electroretinogram results. All had normal electrooculograms. Ophthalmoscopic examination was abnormal in three patients (9%), and three (9%) had a visual field defect. In the peripheral or central nervous pathways, seven patients (21%) had sensory neuropathy, of which three cases were probably related to diabetes mellitus. All had normal motor conduction velocities. Four patients (12%) had increased cortical latencies of median or posterior tibial somatosensory evoked potential. Abnormalities in multiple neural pathways were seen in four patients (12%). There was a significant association between subclinical toxicity to the peripheral or central nervous systems and serum ferritin level (P < .03) and the presence of diabetes mellitus (P < .002). There was no significant relationship between the age, dosage, or duration of desferrioxamine used and the increased risk of neurotoxicity to the auditory, visual, peripheral, or central nervous systems. There was also no association between the risk of neurotoxicity and the serum zinc, copper, or fructosamine levels.
Adolescent↗
Hepatitis C virus antibody in multiply transfused Chinese with thalassaemia major.
Thirty-four of 99 multiply transfused Chinese (49 females, 50 males) with thalassaemia major were positive for antibody to hepatitis C virus. There was no sex predominance in seropositivity with 18 females and 16 males positive. The mean (+/- SD) age and units of blood transfused were significantly higher in the seropositive patients (167 +/- 48 months, 206 +/- 82 units respectively) than the seronegative patients (113 +/- 56 months, 124 +/- 80 units respectively). The seropositive patients had higher mean (+/- SD) serum alanine aminotransferase, aspartate aminotransferase and ferritin concentrations (91 +/- 82 IU/L, 67 +/- 38 IU/L, 4797 +/- 2522 ng/ml respectively) than the seronegative patients (38 +/- 29 IU/L, 48 +/- 28 IU/L, 3620 +/- 2140 ng/ml respectively). Serum ferritin had an independent and significant effect on serum alanine aminotransferase in addition to that of seropositivity to hepatitis C virus.
Alanine Transaminase↗
Bone marrow transplantation for thalassemia in Hong Kong: the early experience.
The first experience of bone marrow transplantation (BMT) for thalassemia in Hong Kong is reported. Of the three children transplanted using a matched allogeneic donor, two have been surviving disease free 291 and 256 days post-BMT respectively. The other child rejected the graft and remained transfusion dependent. Mild graft versus host disease occurred in one of the children which subsided on cyclosporin A alone. The regimen-related toxicities were mild and easily manageable. Thus the result is encouraging and the procedure is now accepted as an option of treatment for good risk patients in Hong Kong.
Bone Marrow Transplantation↗
Late cataractogenesis in primates and lagomorphs after exposure to particulate radiations.
Rhesus monkeys that were exposed in 1969, at the age of approximately 2 years, to low doses of "mixed-energy" protons (10- and 110-MeV) are exhibiting progressive (degenerative) lenticular changes. We have conducted regular examinations of this group of monkeys for cataractogenic development since 1987, i.e., 18 years after irradiation, and the animals began to show enhanced degrees of lenticular opacification two years later. The lenses of age-matched controls (median lifespan in captivity approximately 24 years) continue to exhibit much lower levels of opacification (senile cataracts). Trends in the new data are consistent with the cataractogenic patterns observed for other groups of monkeys that were exposed at similar ages in 1964 and 1965 to protons of different energies, and which we began to monitor only 20-21 years later. Therefore, the new information from the mixed-energy group of monkeys provides insight into the development of late cataractogenic sequelae in the other groups of animals during the 2-3 years before we began to measure them. Comparisons are also made here among recent results from the different groups of primates and from New Zealand white (NZW) rabbits that were exposed when young to 56Fe ions and monitored continuously thereafter. This is done because analogous expression of radiation-induced degenerative cataractogenesis also occurs late in the lifespan of the lagomorphs (control median lifespan in captivity approximately 5-7 years), but in this case the cataractogenic profile has been documented through most of the post-irradiation lifespan.
Animals↗
Ultraviolet radiation, solar dermatosis, and cutaneous neoplasia in beagle dogs.
Beagle dogs that were part of a life span study of the effects of low-level ionizing radiation during development were evaluated for the incidence of skin neoplasia and solar dermatosis. A total of 991 dogs up to 14 years of age were examined. The dogs were housed in gravel-based, outdoor pens with doghouses in a high-altitude, high-sunshine level environment. Solar dermatosis was restricted to the sparsely haired, nonpigmented abdominal skin. Skin neoplasms were either removed surgically or found at necropsy. Solar dermatosis was diagnosed in 363 of the 991 dogs, an incidence of 36.6%. There were 175 hemangiomas, hemangiosarcomas, or squamous cell carcinomas of the skin in the 991 dogs. Of these, 129 tumors occurred in dogs with, and only 46 in dogs without, solar dermatosis. Of the dogs with solar dermatosis, 93 (26%) had at least one of the three tumor types, compared to only 44 (7%) of dogs without solar dermatosis. Thirty-two dogs had multiple tumor types and solar dermatosis, compared to only two dogs with multiple tumor types and no solar dermatosis. There was a highly significant correlation (P less than 0.001) between the occurrence of these tumor types and solar dermatosis in the unpigmented abdominal skin. This correlation was strongest for the malignant neoplasms. Whole-body gamma-radiation exposures were delivered at one of three prenatal or three postnatal ages up to 1 year of age. There appeared to be an increased risk for hemangiosarcomas and squamous cell carcinomas in dogs with solar dermatosis and given gamma-ray exposures at 1 year of age. This suggests an interaction between exposures to ionizing and ultraviolet radiation.
Animals↗
Radiation carcinogenesis in dogs irradiated during prenatal and postnatal development.
To evaluate the lifetime hazards of ionizing radiation exposure, 1680 beagles received whole-body, 60-Cobalt gamma exposures or sham-exposures during development. Eight groups of 120 dogs each received mean doses of 16 or 83 cGy at 8 (preimplantation), 28 (embryonic), or 55 (late fetal) days postcoitus (dpc), or 2 (neonatal) days postpartum (dpp). One group of 120 dogs received 83 cGy at 70 dpp (juvenile), and one group of 240 dogs received 83 cGy at 365 dpp (young adult). Sham-irradiations were delivered to 360 controls. Sexes were equally represented. Young dogs, up to 4 years of age, had an increase in benign and malignant neoplasms after irradiation in the perinatal period at 55 dpc or 2 dpp. Among these, 4 fatal cancers were observed. No malignancies occurred in comparably-aged controls. The increase in both fatal neoplasms and all neoplasms in the perinatally-exposed groups were statistically significant. Over the full lifetime, dogs irradiated in the perinatal period also had the strongest evidence for an increased risk for fatal malignancies of all types. Though not as strong, there was a trend for increased risk for fatal cancer in dogs irradiated at all other ages. The risk of fatal malignancy after irradiation was greater in females than in males. Dogs exposed at 55 dpc had a significant increase in lymphoid neoplasia and dogs exposed at 8 and 55 dpc had increased risk for hemangiosarcoma. There was no evidence for an increased risk for mammary carcinoma in irradiated females. Dogs exposed as juveniles at 70 dpp had a significant increase in all benign and malignant thyroid neoplasms, including fatal thyroid carcinoma.
Aging↗