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Biomedical subjects

L Wolf

Publications and source records attributed to L Wolf.

At least 19 recordsLinked to original sources

Distribution of 17beta-hydroxysteroid dehydrogenases in human osteoblast-like cells.

In bone androgens and estrogens exert profound osteoprotective effects. Cultured human osteoblast (hOB)-like cells are able to metabolize circulating androgens or androgen precursors, such as testosterone and androstenedione, respectively, by aromatization (aromatase), 5alpha-reduction (5alpha-reductase) and reduction/oxidation at the 17beta-position (17-beta-hydroxysteroid dehydrogenases, 17beta-HSDs). In this study it was demonstrated that cultured normal human osteoblast-like cells as well as the osteosarcoma cell lines HOS and MG 63 express 17beta-HSDs types 1, 2, 3 and 4.

17-Hydroxysteroid Dehydrogenases↗

Ethical issues in early detection of HIV infection to reduce vertical transmission.

Proposals to make prenatal HIV testing routine and universal dramatize ethical issues regarding early detection of HIV. These proposals would abolish pretest counseling and written informed consent for prenatal HIV testing. Ethical concerns include whether pregnant women are adequately informed that they may refuse such testing and whether patients have an opportunity to obtain more detailed information about the benefits and risks of HIV testing in this context. Several pertinent research questions need to be studied, including whether pregnant women find routine universal HIV testing acceptable and whether safeguards adequately protect women who receive testing. If analogous policies to enhance early detection of HIV are considered in other clinical contexts, the important clinical and ethical differences between vertical transmission and other situations of HIV transmission must be kept clearly in mind.

Breast Feeding↗

Phase I trial of 6-hour infusion of glufosfamide, a new alkylating agent with potentially enhanced selectivity for tumors that overexpress transmembrane glucose transporters: a study of the European Organization for Research and Treatment of Cancer Early Clinical Studies Group.

PURPOSE: To determine the maximum-tolerated dose (MTD), the principal toxicities, and the pharmacokinetics of 6-hour infusion of glufosfamide (beta-D-glucosylisophosphoramide mustard; D-19575), a novel alkylating agent with the potential to target the glucose transporter system. PATIENTS AND METHODS: Twenty-one patients (10 women and 11 men; median age, 56 years) with refractory solid tumors were treated with doses ranging from 800 to 6,000 mg/m(2). Glufosfamide was administered every 3 weeks as a two-step (fast/slow) intravenous infusion over a 6-hour period. All patients underwent pharmacokinetic sampling at the first course. RESULTS: The MTD was 6,000 mg/m(2). At this dose, two of six patients developed a reversible, dose-limiting renal tubular acidosis and a slight increase in serum creatinine the week after the second and third courses of treatment, respectively, whereas three of six patients experienced short-lived grade 4 neutropenia/leukopenia. Other side effects were generally mild. Pharmacokinetics indicated linearity of area under the time-versus-concentration curve against dose over the dose range studied and a short elimination half-life. There was clear evidence of antitumor activity, with a long-lasting complete response of an advanced pancreatic adenocarcinoma and minor tumor shrinkage of two refractory colon carcinomas and one heavily pretreated breast cancer. CONCLUSION: The principal toxicity of 6-hour infusion of glufosfamide is reversible renal tubular acidosis, the MTD is 6,000 mg/m(2), and the recommended phase II dose is 4, 500 mg/m(2). Close monitoring of serum potassium and creatinine levels is suggested for patients receiving glufosfamide for early detection of possible renal toxicity. Evidence of antitumor activity in resistant carcinomas warrants further clinical exploration of glufosfamide in phase II studies.

Adult↗

Use of integrins to date the endometrium.

OBJECTIVE: To compare traditional histologic dating criteria of the endometrium with immunohistochemical criteria based on epithelial integrin expression during the menstrual cycle. DESIGN: Prospective clinical study. SETTING: An academic teaching hospital. PATIENT(S): Fertile and infertile women undergoing endometrial biopsy. MAIN OUTCOME MEASURE(S): Immunohistochemical staining intensity and distribution (HSCORE) of three integrins and traditional histologic endometrial dating. RESULT(S): In 1,501 endometrial specimens, phase assignment-based integrin staining was 95% and 85% concordant with histology for the proliferative and early secretory phase, respectively, but only 54% and 49% concordant for the middle and late secretory phase, respectively. The greatest disagreement occurred during the midluteal phase. Of 1,090 patients who underwent sampling 6-10 days after detection of a urinary LH surge (corresponding to cycle days 20-24), multiple logistic regression analysis revealed that endometriosis was positively correlated and male factor infertility was negatively correlated with absent beta3 integrin subunit expression. Diagnosis and absent epithelial alpha4beta1 expression were not related. Patient age was not correlated with the incidence of abnormalities in integrin expression. CONCLUSION(S): Traditional histologic dating of the endometrium has remained the gold standard for nearly 50 years. Although the use of marker proteins provides additional information and may reflect endometrial function or receptivity, such markers cannot yet replace traditional methods of endometrial assessment.

Adolescent↗

Temporal and spatial expression of Hoxa-2 during murine palatogenesis.

1. Mice homozygous for a targeted mutation of the Hoxa-2 gene are born with a bilateral cleft of the secondary palate associated with multiple head and cranial anomalies and these animals die within 24 hr of birth (Gendron-Maguire et al., 1993; Rijli et al., 1993; Mallo and Gridley, 1996). We have determined the spatial and temporal expression of the Hoxa-2 homeobox protein in the developing mouse palate at embryonic stages E12, E13, E13.5, E14, E14.5, and E15. 2. Hoxa-2 is expressed in the mesenchyme and epithelial cells of the palate at E12, but is progressively restricted to the tips of the growing palatal shelves at E13. 3. By the E13.5 stage of development, Hoxa-2 protein was found to be expressed throughout the palatal shelf. These observations correlate with palatal shelf orientation and Hoxa-2 protein may play a direct or indirect role in guiding the palatal shelves vertically along side the tongue, starting with the tips of the palatal shelves at E13, followed by the entire palatal shelf at E13.5. 4. As development progresses to E14, the stage at which shelf elevation occurs, Hoxa-2 protein is downregulated in the palatal mesenchyme but remains in the medial edge epithelium. Expression of Hoxa-2 continues in the medial edge epithelium until the fusion of opposing palatal shelves. 5. By the E15 stage of development, Hoxa-2 is downregulated in the palate and expression is localized in the nasal and oral epithelia. 6. In an animal model of phenytoin-induced cleft palate, we report that Hoxa-2 mRNA and protein expression were significantly decreased, implicating a possible functional role of the Hoxa-2 gene in the development of phenytoin-induced cleft palate. 7. A recent report by Barrow and Capecchi (1999), has illustrated the importance of tongue posture during palatal shelf closure in Hoxa-2 mutant mice. This along with our new findings of the expression of the Hoxa-2 protein during palatogenesis has shed some light on the putative role of this gene in palate development.

Amino Acid Sequence↗

A longitudinal study of siblings of children with chronic disabilities.

OBJECTIVE: To examine the unaffected siblings of 2 different groups with chronic disabilities, pervasive developmental disorder (PDD) and Down syndrome (DS), over 3 years, comparing their adjustment with each other and with the siblings of a nondisabled group. METHOD: This study examines 137 siblings of children with PDD, children with DS, and developmentally normal children (control group) initially and 127 siblings at follow-up 3 years later. Their adjustment is measured by the Survey Diagnostic Instrument (SDI), completed by caregivers and teachers. Predictor variables include sibling self-perception, social support, and relationship with sibling, as indicated by siblings; caregiver psychosocial factors such as parental stress, caregiver depression, and marital relationship; family systems characteristics as viewed by both caregiver and sibling; and difficulty that disabled child causes as perceived by the primary caregiver. RESULTS: Significantly more adjustment problems are found in the siblings of PDD children at both times when compared with siblings of DS and control children. Caregivers of PDD children report the highest levels of distress and depression, and this persists over time. Parent distress was found, at both times, to be related to sibling adjustment problems, regardless of study group. CONCLUSION: These results have implications for preventive intervention for the unaffected siblings of PDD children.

Adaptation, Psychological↗

Sharing medication data using the InterCare architecture.

Since June 1998 more than 20 partners from seven European countries are co-operating in the EC funded InterCare project. The primary objective of the InterCare project is to define, specify and implement cross-border products, called services here, that interoperate with one another in order to support shared care. These products should be based on the results of former European projects and must be validated in actual demonstration sites, one of which is located in the Schiedam region in the Netherlands. In this site the InterCare system is applied to medication information which involves integration of systems at the hospital, pharmacy and the general practitioners office. In this setting special attention is paid to security aspects.

Computer Security↗

Differential expression of Hoxa-2 protein along the dorsal-ventral axis of the developing and adult mouse spinal cord.

We have used synthetic oligopeptides derived from the coding sequence of the murine Hoxa-2 protein to produce polyclonal antibodies that specifically recognize the Hoxa-2 recombinant protein. Immunohistochemical studies reveal a distinct pattern of spatial and temporal expression of Hoxa-2 protein within the mouse spinal cord which is concomitant with the cytoarchitectural changes occurring in the developing cord. Hoxa-2 protein is predominantly detected in the nuclei of cells in the ventral mantle region of 10-day-old mouse embryos. Islet-1, a marker for motor neurons was also shown to be co-localized with Hoxa-2 in nuclei of cells in this region. As development progresses from 10-days to 14-days of gestation, Hoxa-2 protein expression gradually extends to the dorsal regions of the mantle layer. The Hoxa-2 protein expression pattern changes at 16-days of embryonic development with strong expression visible throughout the dorsal mantle layer. In 18-day-old and adult mouse spinal cords, Hoxa-2 protein was expressed predominantly by cells of the dorsal horn and only by a few cells of the ventral horn. Double labeling studies with an antibody against glial fibrillary acidic protein (GFAP, an astrocyte-specific intermediate filament protein) showed that within the adult spinal cord, astrocytes rarely expressed the Hoxa-2 protein. However, Hoxa-2 and GFAP double-labeled astrocytes were found in the neopallial cultures, although not all astrocytes expressed Hoxa-2. Hoxa-2 expressing oligodendrocyte progenitor cells were also identified after double-labeling with O4 and Hoxa-2 antibodies; although cells in this lineage that have begun to develop a more extensive array of cytoplasmic processes were less likely to be Hoxa-2 positive. The early pattern of Hoxa-2 protein expression across transverse sections of the neural tube is temporally and spatially modified as each major class of neuron is generated. This congruence in the expression of the Hoxa-2 protein and the generation of neurons in the cord suggests that the Hoxa-2 protein may contribute to dorsal-ventral patterning and/or to the specification of neuronal phenotype. Dev Dyn 1999;216:201-217.

Age Factors↗

Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Development of successful anabolic strategies to reverse the loss of lean body mass is of critical importance to increase survival in men with the AIDS wasting syndrome. Hypogonadism, an acquired endocrine deficiency state characterized by loss of testosterone, occurs in more than half of all men with advanced HIV disease. It is unknown whether testosterone deficiency contributes to the profound catabolic state and loss of lean body mass associated with the AIDS wasting syndrome. OBJECTIVE: To investigate the effects of physiologic testosterone administration on body composition, exercise functional capacity, and quality of life in androgen-deficient men with the AIDS wasting syndrome. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University medical center. PATIENTS: 51 HIV-positive men (age 42 +/- 8 years) with wasting (body weight < 90% of ideal body weight or weight loss > 10% of baseline weight) and a free testosterone level less than 42 pmol/L (normal range for men 18 to 49 years of age, 42 to 121 pmol/L [12.0 to 35.0 pg/mL]). INTERVENTION: Patients were randomly assigned to receive testosterone enanthate, 300 mg, or placebo intramuscularly every 3 weeks for 6 months. MEASUREMENTS: Change in fat-free mass was the primary end point. Secondary clinical end points were weight, lean body mass, muscle mass, exercise functional capacity, and change in perceived quality of life. Virologic variables were assessed by CD4 count and viral load. RESULTS: Compared with patients who received placebo, testosterone-treated patients gained fat-free mass (-0.6 kg and 2.0 kg; P = 0.036), lean body mass (0.0 kg and 1.9 kg; P = 0.041), and muscle mass (-0.8 kg and 2.4 kg; P = 0.005). The changes in weight, fat mass, total-body water content, and exercise functional capacity did not significantly differ between the groups. Patients who received testosterone reported benefit from the treatment (P = 0.036), feeling better (P = 0.033), improved quality of life (P = 0.040), and improved appearance (P = 0.021). Testosterone was well tolerated in all patients. CONCLUSIONS: Physiologic testosterone administration increases lean body mass and improves quality of life among androgen-deficient men with the AIDS wasting syndrome.

Adolescent↗

Effect of sibling perception of differential parental treatment in sibling dyads with one disabled child.

OBJECTIVE: To examine sibling perception of parental differential treatment in families of children with pervasive developmental disorder (PDD), Down syndrome (DS), and nondisabled controls. METHOD: Sibling self-concept and social support were studied in the context of sibling perceptions of parental differential treatment and caretaker plus teacher evaluations of sibling behavioral adjustment. Measures were completed at time 1 and time 2. The effect of parental stress and the difficulty of the disabled child, as well as the sibling relationship, were considered. RESULTS: For siblings of PDD children, internalizing and externalizing behavior problems identified by caretakers were evident at time 1 and more accentuated at time 2, at which time teachers also identified these difficulties. DS siblings were reported by caretakers and teachers to have only internalizing problems and only at time 2. These difficulties related to the perception for PDD siblings that they were preferred over their disabled sibling and for the DS sibling that their disabled sibling was preferred. Feelings of low competence predicted internalizing difficulties. Social support, especially over time, had a positive effect for all siblings, including the controls. CONCLUSION: The elucidation of specific mechanisms contributing to adjustment problems in the siblings of disabled children will allow for the development of specific preventive interventions.

Adolescent↗

Bioregeneration with maltose excreting Chlorella: system concept, technological development, and experiments.

ESA has been studying a small-scale bioregenerative system to support long-term biological experiments on-board spacecraft with oxygen, water and food. Core component of this system is a special photo-bioreactor in which a maltose-producing strain of the green micro alga Chlorella is cultivated. A number of auxiliary system components have been developed and are functioning on the ground according to the design specifications, among them a gas/liquid phase separator operating at the same time as a low shear-stress pneumatic pump, a dehumidifier, a maltose separator, and a liquid transfer system. All components have been designed so that--in principle--they will operate in weightlessness, though this has so far only been verified for the gas/liquid separator. The bioreactor and some of the auxiliary components have been integrated in a prototype system, which has been subjected to preliminary testing. The prototype has been sterilized successfully by autoclaving, except for the liquid transfer unit which is disinfected with isopropyl alcohol. Chlorella 241.80 has been cultured several times under controlled conditions for up to 8 weeks. Algal growth to a biomass concentration of 9 g.l-1 dry weight and maltose production to a concentration of 17 g.l-1 have been achieved. The low shear-stress pneumatic pump works reliably without the mechanical cell damage produced by other types of pumps. Contamination of the algal cultures by other micro-organisms has been avoided in most of the experiment runs. The maximum oxygen production rate observed was 2 ml.min-1, when the culture was aerated with air +0.5% CO2. This production rate is well below the CO2 gas transfer rate of 5 ml.min-1 under these conditions. It can probably be doubled by increasing the maximum light intensity of the illumination unit (currently 300 micro E.m-2S-1). In a preliminary closed gas loop experiment with Periplaneta as consumer, the possibility of controlling the Chlorella culture so as to match the needs of the consumer colony has been established. A maltose excreting Chlorella strain has been selected as the photosynthetic producer, because the technique for automatic culturing of this organism and harvesting its products was expected to be much less complex than that required for culturing higher plants. Although the prototype system developed in our laboratory has reached a high level of sophistication, there remain still a number of technical and biological problems to be solved before the feasibility of this concept is definitely demonstrated. The major problem is maintaining sterility, and eventually automatic cleaning and resterilization when contamination occurs during operation. The culture medium, which contains minerals, cell fragments and considerable amounts of sugars, is an ideal substrate for many other microorganisms. Another problem is long term operation. The prototype system contains many tubes and ducts which are perfused with culture medium. These may clog, which may lead to loss of sensor information essential for controlling the culture. Even when we succeed in demonstrating the feasibility of this concept, it will be a difficult task to demonstrate convincingly that the expected advantages of a bioregenerative system can outweigh the simplicity and reliability of a non-regenerative stored resource system in terms of volume, mass and amount of consumables required over the operational time.

Bioreactors↗

[The use of thermography for the laryngeal diagnosis].

Authors presented possibility of clinical appliance of the M 4128 thermocamera in monitoring thermal changes of the skin and mucosa in upper respiratory tract diseases in patients treated at ENT Department Medical University of Lodz. Basing on the obtained results authors conclude usefulness of thermocamera in diagnosis of the head and neck tumors and inflammatory diseases and monitoring of the photodynamic therapy.

Adolescent↗

Risk and protective factors affecting the adjustment of siblings of children with chronic disabilities.

OBJECTIVE: To examine the adjustment of nondisabled siblings of handicapped children. METHOD: In a 3-year longitudinal study, 46 siblings of children with pervasive developmental disorder (PDD), 45 siblings of children with Down syndrome, and 46 siblings of developmentally normal children (serving as controls) were examined at time 1 using the sibling, primary caretaker, and teacher as informants. Both direct and indirect variables related to sibling adjustment were considered. RESULTS: Significantly more difficulties were found in the siblings of children with PDD compared with the other two groups. Different correlates of adjustment were present in the siblings of the disabled compared with nondisabled children, and mediating factors differed in parent and teacher reports of internalizing difficulties in siblings of children with PDD. Marital satisfaction, lack of parental depression, a cohesive family, and a warm, nonconflictual sibling relationship were protective for normal control and Down syndrome siblings but not for PDD siblings. CONCLUSION: Findings underline the risks for the siblings of children with PDD and suggest the importance of a transactional mechanism rather than identification of single risk or protective factors in predicting sibling adjustment. Subsequent data analysis in this longitudinal study will assist in defining these mechanisms and allow for improved intervention strategies.

Adaptation, Psychological↗

Bioregeneration in space.

ESA has been studying a small-scale bioregenerative system to support long-term biological experiments on-board spacecraft with oxygen, water, and food. Core component of this system is a special photo-bioreactor in which a maltose-producing strain of the green alga Chlorella is cultivated. In initial experiments this bioreactor has been tested, and the physiology of Chlorella has been studied. The optimal conditions for CO2 to O2 conversion and maltose production have been determined, and the possibility of controlling the culture so as to match the needs of the consumer has been established. A microgravity-compatible photo-bioreactor, and a maltose separator have been developed and are functioning on the ground according to the design specifications. Tests in weightlessness will have to be performed in the future. The components are to be integrated to a complete bioregenerative life support system, which will then be subjected to extensive testing. The EXEMSI project afforded an opportunity to study the mutual influence of a Chlorella culture and real biological oxygen consumers, the four crew members in the laboratory module of the isolation facility. Chlorella 241.80 was batch cultured in an airlift bioreactor by the crew for 25 days with air aspirated from the module. The crew members determined pH and cell density in samples withdrawn from the culture. Microscopic observations showed no evidence of contamination of the culture by other organisms. Growth rates were smaller than those observed in laboratory conditions. This is attributed to the relatively low average CO2 concentration in the module atmosphere: 0.1% against 0.5% in the air supply during the laboratory experiments. The data show no evidence of trace contaminant accumulation in the Chlorella culture. The results are encouraging and suggest the value of further simulated operational testing of the system.

Cell Count↗

Oestrogen formation from androstenedione in human bone.

BACKGROUND AND OBJECTIVE: Peripheral aromatization of testosterone and androstenedione is the principal source for circulating oestrogens in men and in castrated and post-menopausal women. Since human bone is a target organ for androgens and oestrogens, aromatase activity was assessed in human spongiosa obtained from patients who were undergoing orthopaedic surgery. DESIGN AND PATIENTS: In initial experiments for assessing aromatization, oestrogen formation from 1,2,6,7-3H-androstenedione was compared with the release of tritiated water from 1 beta-3H-androstenedione. Since the rates of enzyme activity were similar with the two methods, rates of oestrogen formation were determined under standardized conditions with the tritiated water generation technique in bone specimens obtained from 4 men and 11 post-menopausal women. RESULTS: The apparent Km of the aromatase ranged between 6 and 50 nM (20.4 +/- 3.9; mean +/- SEM), values in the range of those reported for human placental microsomes. The maximum velocity (Vmax) of the aromatase activity ranged between 0.14 and 1.23 nmol/g DNA/h. CONCLUSIONS: Oestrogens formed in human bone may play a physiological role in steroid hormone action in this tissue.

Aged↗

A tuberculosis control plan for ambulatory care centers.

Tuberculosis and a multidrug resistant form of TB have reemerged in epidemic proportions. Tuberculosis is more prevalent among HIV-infected individuals, the homeless, foreign-born individuals from countries with high rates of TB, prison inmates, individuals in long-term care facilities, individuals from low-socioeconomic backgrounds, and intravenous drug users. Urgent care centers, which have gained popularity as an easy access to medical care, are at risk for seeing undetected infectious patients. By developing a TB control plan for ambulatory care centers, specific triage criteria can be instituted to promote early identification of the potentially infectious patient and provide guidelines for identification, prevention, environmental controls, education, and follow-up of exposed health care workers. This article discusses the mandatory OSHA policy for occupational exposure to tuberculosis based on the 1993 CDC guidelines for TB transmission and how a TB control plan for ambulatory care centers can be developed from these guidelines.

Ambulatory Care Facilities↗

[Digital method of assessing bone radiographs].

The computerized method of bone radiographs assessment has been presented. The radiographs were taken by standard technique with the aluminum wedge on the film and known exposition parameters as energy, time and the distance between the source and the subject. Specially designed software served to evaluate the intensity of film darkening. The method may be particularly useful for quantitative assessment of the callus in the healing phase of fractured bone. It may also be an alternative method (as cheaper one) to QCT or DPX in bone density evaluation in patients with metabolic bone diseases.

Absorptiometry, Photon↗