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Biomedical subjects

A C Lee

Publications and source records attributed to A C Lee.

At least 55 records · Page 3Linked to original sources
PubMed1998

The role of yeast VDAC genes on the permeability of the mitochondrial outer membrane.

In addition to the POR1 gene, which encodes the well-characterized voltage dependent anion-selective channel (YVDAC1) of the mitochondrial outer membrane, the yeast Saccharomyces cerevisiae contains a second gene (POR2) encoding a protein (YVDAC2) with 50% sequence identity to YVDAC1. Mitochondria isolated from yeast cells deleted for the POR1 gene (delta por1) had a profoundly reduced outer membrane permeability as measured by the ability of an intermembrane space dehydrogenase to oxidize exogenously added NADH. Mitochondria missing either YVDAC1 or both YVDAC1 and YVDAC2 showed a 2-fold increase in the rate of NADH oxidation when the outer membrane was deliberately damaged. Mitochondria from parental cells showed only a 10% increase indicating that the outer membrane is highly permeable to NADH. In the absence of YVDAC1, we calculate that the outer membrane permeability to NADH is reduced 20-fold. The low NADH permeability in the presence of YVDAC2 was not due to the low levels of YVDAC2 expression as mitochondria from cells expressing levels of YVDAC2 comparable to those of YVDAC1 in parental cells showed no substantial increase in NADH permeability, indicating a minimal role of YVDAC2 in this permeability. The residual permeability may be due to other pathways because cells missing both genes can still grow on nonfermentable carbon sources. However, YVDAC1 is clearly the major pathway for NADH flux through the outer membrane in these mitochondria.

Genes, Fungal↗
PubMed1998

Impairments of mental rotation in Parkinson's disease.

It is controversial whether parkinsonian patients are impaired on visuospatial tasks. In the present study, patients and normal control subjects judged whether pairs of wire-frame figures in different orientations were the same or different. The orientation difference between the figures was either in the picture plane (around the z-axis, or two-dimensional) or in depth (around the y-axis, or three-dimensional). Reaction times and error rates were measured. For the two-dimensional task, there were no significant differences in errors between the two groups, though Parkinsonian subjects were significantly slower to respond than the control group. In the three-dimensional task, patients had a different pattern of reaction times from the controls and made significantly more errors, which were systematic at large angular differences. The results suggest a visuospatial deficit in Parkinson's disease, which reflects problems in some aspect of the perception of extra-personal space.

Aged↗
PubMed1998

Penetrating pencil injury: an unusual case of child abuse.

OBJECTIVE: We report an unusual case of penetrating pencil injury in a young child that turned out to be a case of physical abuse. METHOD: This is a case report with review of the literature. RESULTS: A 4-year-old boy was brought by his mother to the accident and emergency department for a penetrating wound of the right hand. He was said to have injured himself during a fall at home while holding a sharpened lead pencil. The pencil broke after penetrating the hypothenar eminence, leaving the graphite tip embedded in the palm. On surgical exploration, a piece of graphite measuring 1.3 cm was removed. The injury was actually inflicted by his mother because he failed to complete his homework properly. Deep penetrating injuries associated with the lead pencil are uncommon events in the medical literature. They are often reported as accidental and usually involve the oropharynx and the orbit. CONCLUSION: Deep penetrating injury with a pencil is unusual in childhood and the public should be made aware of the possibility of nonaccidental injury.

Child Abuse↗
PubMed1998

Mortality in beagles irradiated during prenatal and postnatal development. I. Contribution of non-neoplastic diseases.

To evaluate the lifetime health effects of exposure to ionizing radiation during development, 1,680 beagles received whole-body exposures to 60Co gamma rays or sham exposures. Eight groups of 120 dogs each received mean doses of 15.6-17.5 or 80.8-88.3 cGy in early, mid- or late gestation, at 8, 28 or 55 days after breeding, or at 2 days after birth. Another group of 120 dogs received a mean dose of 82.6 cGy as 70-day-old juveniles and one group of 240 dogs received a mean dose of 81.2 cGy as 365-day-old young adults. Sham irradiations were given to 360 controls. Sexes were equally represented. There was no significant effect of irradiation on mean survival times in any groups. In 1,343 dogs allowed to live out their life span, chronic renal disease was a common cause of mortality, and irradiation in the late fetal or juvenile periods potentiated this disease, resulting in increased mortality due to renal failure. This was consistent with earlier findings of the high radiosensitivity of the kidney in the perinatal period. Hypothyroidism associated with atrophic thyroiditis was decreased by irradiation, a finding contrary to expectation and not easily explained. Diabetes mellitus was increased by irradiation in the mid- and late gestation and juvenile periods, a finding which is intriguing based on early reports of a similar finding in atomic bomb survivors. Though convulsive seizures were a common cause of mortality in the dogs, there was no evidence for increased risk associated with prenatal irradiation as has been reported in humans. Genetic analyses indicated that renal disease, hypothyroidism, diabetes mellitus and convulsive seizures all had a heritable component, but that this did not influence or bias the radiation responses evaluated.

Age Factors↗
PubMed1998

Mortality in beagles irradiated during prenatal and postnatal development. II. Contribution of benign and malignant neoplasia.

To evaluate the lifetime carcinogenic hazards of exposure to ionizing radiation during development, 1,680 beagles received whole-body exposures to 60Co gamma rays or sham exposures. Eight groups of 120 dogs each received mean doses of 15.6-17.5 or 80.8-88.3 cGy in early, mid- or late gestation, at 8, 28 or 55 days postcoitus or at 2 days after birth. Another group of 120 dogs received a mean dose of 82.6 cGy as 70-day-old juveniles and one group of 240 dogs received a mean dose of 81.2 cGy as 365-day-old young adults. Sham irradiations were given to 360 controls. Sexes were equally represented. In 1,343 dogs allowed to live out their life span, neoplasia was a major disease, contributing to mortality in 40% of the dogs. There was a significant increase in benign and malignant neoplasms occurring in young dogs (<4 years old), including fatal malignancies, after irradiation in the perinatal (late fetal and neonatal) periods. The lifetime incidence of fatal neoplasms was also increased in dogs irradiated perinatally. Three malignancies-lymphomas, hemangiosarcomas and mammary carcinomas-accounted for 51% of all fatal tumors. There was an apparent lifetime increase and earlier onset of lymphomas in dogs exposed as fetuses. Fatal hemangiosarcomas were increased in dogs irradiated early and late in gestation. Fatal mammary carcinomas were not increased by irradiation, although non-fatal carcinomas were increased after perinatal exposure. Myeloproliferative disorders and central nervous system astrocytomas appeared to be increased in perinatally irradiated dogs. These data suggest that irradiation in both the fetal and neonatal periods is associated with increased early onset and lifetime cancer risk.

Animals↗
PubMed1997

Making the female condom a "reality" for adolescents.

Alarming rates of pregnancy, sexually transmitted diseases, and human immunodeficiency virus infection among adolescents point to the need for expanding contraceptive options for adolescents. The female condom-a female-controlled barrier method that protects both partners from sexually transmitted diseases-marks an important breakthrough in contraceptive technology. This report reviews current research on the efficacy and acceptability of the female condom and considers the feasibility of its use in the adolescent population. Specifically, the authors first consider the factors that affect teenage condom (and other contraceptive) use (efficacy, cost and availability, and acceptability) and then apply the mechanics of the female condom to these issues. Based on this analysis, recommendations for future steps to be taken by researchers, adolescent health practitioners, and the manufacturer of the female condom are presented.

Adolescent↗
PubMed1997

Epidural haematoma and stroller-associated injury.

We present a severe case of head injury in an infant associated with stroller use and review similar reports from the literature. A case report and a literature search of the Medline database from 1966 to 6/1996 using the terms 'perambulator', 'parm', 'stroller', or 'baby carriage'. Reports in English describing injuries associated with their use are reviewed. We report a case of epidural haematoma in a 10 months old girl who sustained the injury after falling from a stroller. Safety harnesses were not worn during the incident. There was no skull fracture. Complete recovery followed surgical evacuation of the blood clot. Five reports describing stroller-related injuries were found in the English literature. Most injuries were mild. Three cases of death were reported of which two were classified as child abuse. The prevalence of unintentional stroller-associated injury is not clear. Mild injury, mostly to the head region, is probably common. Life-threatening injuries are rare but these are potentially preventable if strollers are properly designed and safety recommendations are followed.

Craniocerebral Trauma↗
PubMed1997

Intrathecal methotrexate overdose.

We report two cases of intrathecal methotrexate overdose. A 3-y-old girl with acute lymphoblastic leukaemia and a 4-y-old boy with Burkitt's lymphoma were to receive an intrathecal injection of methotrexate after completion of intravenous methotrexate infusion. Instead of 12.5 mg, they both received a dose of 125 mg. Both children developed generalized convulsion 3 h after the overdose, but afterwards recovered completely. Intravenous folinic acid and dexamethasone rescue were employed, but no attempt was made to exchange the cerebrospinal fluid. In addition to the staff's failure to check the drug label carefully, the marked resemblance of the two dose preparations of methotrexate (50 mg/5 ml and 500 mg/5 ml) may have been contributory.

Antimetabolites, Antineoplastic↗
PubMed1997

Non-neoplastic and neoplastic thyroid disease in beagles irradiated during prenatal and postnatal development.

To evaluate the lifetime hazards of exposure to ionizing radiation, 1,680 beagles received whole-body exposures to 60Co gamma rays or sham exposures during development. Eight groups of 120 dogs each received mean doses of 16-18 or 81-88 cGy at 8, 28 or 55 days of gestation, or at 2 days after birth. One group of 120 dogs received a mean of 83 cGy at 70 days of age and one group of 240 dogs received a mean of 81 cGy at 365 days of age. Sham irradiations were given to 360 controls. Sexes were equally represented. In 1,343 dogs allowed to live out their life span, heritable lymphocytic thyroiditis with hypothyroidism was a major contributor to mortality. Irradiated dogs had a decreased risk for hypothyroidism, a finding that was surprising and not easily explained. Of the 1,343 life-span dogs, those exposed as neonates at 2 days of age or as juveniles at 70 days of age had evidence for an increased risk for thyroid follicular cell neoplasia. Hypothyroid dogs had a significantly increased risk for thyroid neoplasia, including greater risk for carcinomas, but no evidence of a greater sensitivity to radiation-induced tumors. In dogs with normal thyroid function irradiated at 2 or 70 days of age there was increased risk for benign and malignant follicular cell neoplasms, including multiple neoplasms. No difference between sexes was noted. These findings related to age sensitivity in the dog were consistent with the high risk for radiogenic thyroid neoplasia in humans after exposure during early childhood.

Aging↗
PubMed1996

The role of pyridine dinucleotides in regulating the permeability of the mitochondrial outer membrane.

Both NADH and NADPH reduce the permeability of the mitochondrial outer membrane to ADP. This is specific for the outer membrane and uncorrelated with the respiratory control ratio. This could result in a 7-fold difference between the concentration of ADP in the intermembrane space and that in the external environment (at 5 microM ADP). In both cases the permeability declines by a factor of 5, but NADH is more potent: KD = 86 microM for NADH versus 580 microM for NADPH. The lower apparent affinity for NADPH is partly explained by Mg2+-NADPH being the active species, and under our conditions only 30% of the NADPH is in this form. The corrected KD is 184 microM. Free NADH has the same charge as the Mg2+-NADPH complex, and thus both likely bind to the same site. The ability of NADH and NADPH to induce the closure of reconstituted VDAC channels is consistent with VDAC being the main pathway for metabolite flow across the outer membrane. Oncotic pressure, effective at inducing VDAC closure, also decreases the outer membrane permeability. Thus, in the presence of cytosolic colloidal osmotic pressure NAD(P)H may inhibit mitochondrial catabolic pathways and divert reducing equivalents to anabolic pathways.

Binding Sites↗
PubMed1996

Aminoacetyl moiety as a potential surrogate for diacylhydrazine group of SC-51089, a potent PGE2 antagonist, and its analogs.

8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. During metabolism in cultured rat hepatocytes, SC-51089, which contains a diacylhydrazine moiety, has been shown to release hydrazine. Analogs of SC-51089, in which the diacylhydrazine functionality has been replaced by isosteric and isoelectronic groups, have been synthesized and have been shown to be analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure-activity relationships within these series.

Analgesics↗
PubMed1996

Malignant peripheral neuroectodermal tumor in an infant with neurofibromatosis type 1.

A case of multifocal malignant peripheral neuroectodermal tumor (PNET) arising from a plexiform neurofibroma in a 4-month-old Chinese boy with neurofibromatosis type 1 (NF-1) is described. Cytogenetic culture demonstrated hypotriploid karyotype with an abnormal clone characterized by 59-60, XY, +2, +3, +6, +8, +8, +12, +i(13)(q10), +der(14)t(1;14)(q21;q32), +16, +19, +20, +mar[cp3] with no apparent abnormality of chromosome 17. The child was treated with combination chemotherapy comprising ifosphamide, vincristine and doxorubicin. Despite initial partial response the child finally died of tumor progression and pulmonary metastases 8 months after diagnosis. We believe this is the first reported case of PNET in a child with NF-1 and may support an association between these two disorders of neural crest origin.

Fatal Outcome↗
PubMed1996

Associations between lymphocytic thyroiditis, hypothyroidism, and thyroid neoplasia in beagles.

The thyroids were evaluated in 276 control Beagles that were allowed to live out their full life span (mean = 12 years) in a closed breeding colony. Lymphocytic thyroiditis was found in 26.3% of the dogs. This lesion was characterized by lymphoplasmacytic inflammation accompanied by follicular destruction. The thyroiditis was progressive, resulting in severe atrophy of follicular tissue, and 44 dogs (15.9%) were diagnosed as hypothyroid at the time of death. In accordance with the experimental protocol, hypothyroid dogs were not given thyroxine replacement therapy. There was a high degree of heritability for the hypothyroidism. Hypothyroid dogs had an increased risk for thyroid follicular epithelial neoplasia and, in particular, for follicular adenocarcinomas. Twenty-four of the 44 hypothyroid dogs (54.5%) had one or more follicular thyroid neoplasms, whereas only 53 of the 232 (22.8%) clinically euthyroid dogs had similar tumors. Multiple thyroid tumors were present in 14 of the 44 (31.8%) hypothyroid dogs but in only 12 of the 232 (5.2%) euthyroid dogs. One or more follicular adenocarcinomas were present in 15 of the 44 (34.1%) hypothyroid dogs but in only 16 of the 232 (6.9%) euthyroid dogs. There was no difference in prevalence of hypothyroidism or tumors between the sexes. The strong association between progressive lymphocytic thyroiditis, hypothyroidism, and thyroid follicular neoplasia in these Beagles probably relates to promotion of residual follicular epithelium by chronic excess thyrotropin stimulation.

Adenoma↗
PubMed1996

The use of fiberoptic endoscopy in anesthesia.

The fiberoptic bronchoscope has contributed greatly to the practice of anesthesiology over the past 30 years. It has become an indispensable tool in the approach to the difficult airway, as well as the placement and positioning of double-lumen tubes for thoracic surgery. The equipment, preparation, and methods for using the endoscope in anesthesia, are presented here.

Anesthesia↗
PubMed1995

Paradoxical response of a pineal immature teratoma to combination chemotherapy.

A case of primary intracranial germ cell tumour is reported in a 5-year-old Chinese boy who presented with symptoms and signs of increased intracranial pressure. Computed tomography (CT) scan of the brain revealed a multicystic tumour over the pineal region. Stereotactic biopsy yielded enteric epithelium and isolated cells with hyperchromatic nuclei and high nuclear-to-cytoplasmic ratio, suggesting the diagnosis of an immature teratoma. Grossly elevated serum and cerebrospinal fluid (CSF) levels of alpha-fetoprotein and mildly elevated levels of beta human chorionic gonadotrophin suggested the simultaneous presence of embryonal tissues. Combination chemotherapy with cisplatin, etoposide, and bleomycin resulted in a gradual but complete normalisation of the serum and CSF tumour markers. Paradoxically, the patient's consciousness deteriorated and repeat CT scan after 3 months of treatment showed that the tumour was actually increasing in size. Complete surgical removal was attempted and histologic sections of the specimen revealed only mature teratomatous tissues. The child is now well and remains disease-free with minimal left hemiparesis 12 months after completion of treatment. This case illustrates the importance of combined neoadjuvant chemotherapy and surgery in the management of intracranial non-germinomatous germ cell tumour harbouring both germ cell and teratomatous components, while monitoring of both biochemical and radiological parameters are necessary in assessing the clinical behaviour of mixed germ cell tumours.

Antineoplastic Combined Chemotherapy Protocols↗