Search PubMed⌕ Search

Biomedical subjects

S Fisher

Publications and source records attributed to S Fisher.

At least 127 records · Page 7Linked to original sources

Expression of the amyloid precursor protein gene in mouse oocytes and embryos.

The amyloid precursor protein (APP) is thought to be processed aberrantly to yield the major constituent of the amyloid plaques observed in the brains of patients with Alzheimer disease and Down syndrome. However, the gene encoding APP is expressed widely in normal human tissues and in adult and fetal mouse tissues and is alternatively spliced in a tissue-specific pattern in the adult. There is evidence that APP may function as a growth factor and as a mediator of cell adhesion and in these roles could be important in morphogenesis. As a step toward determining the role of APP in development and in determining how the adult pattern of tissue-specific splicing is established, we have used reverse transcription and the polymerase chain reaction to demonstrate APP expression in mouse oocytes, preimplantation embryos, and postimplantation embryonic stages to the late embryonic period. All three splicing forms described in mouse were present at each stage, although there were changes in the ratios of the splicing forms at different stages. Screens for APP clones in embryonic cDNA libraries from the egg cylinder stage and the early somite stage were used to confirm the results of the polymerase chain reaction, and APP clone abundance was found to increase 10-fold between the two stages.

Alzheimer Disease↗

The focus of pessimism in performance assessments by the depressed.

The study concerns the microstructure of pessimistic judgements concerning personal performance in the depressed. The cognitive bias hypothesis was only supported for global estimates of performance and not for trial-by-trial decisions. This weakens the view that there is a fixed cognitive pessimistic bias and leaves open the possibility either that differences relate to the assessment of frequency or to protective strategies operated by the depressed.

Adolescent↗

Thirty-minute continuous sitting force measurements with different support surfaces in the spinal cord injured and able-bodied.

Able-bodied, paraplegic, and quadriplegic subjects sat for 30-minute intervals on various surfaces in a wheelchair with a forceplate mounted on the seat in order to determine factors that could contribute to the formation of decubitus ulcers. All three groups of subjects sat on ROHO and Jay cushions; in addition to sitting on the two cushions, the able-bodied subjects sat on a hard surface. Factors studied were: normal and shear seat forces, the location of the center of mass, and armrest force. The forceplate was under the cushions; therefore, the values reflect average forces over the buttocks and posterior thighs. These factors were compared between disability levels as well as between surface types. Larger, normal, and forward shear forces and a more anterior position of the center of mass were observed with the ROHO cushion. More frequent and larger lateral weight shifts occurred with the Jay cushion. The armrests tended to support from 5 percent of the body weight for quadriplegics to 9 percent for paraplegics. The results suggest that armrests reduce seat forces by carrying some of the body weight.

Adult↗

Evaluation of tartar control dentifrices in in vitro models of dentin sensitivity.

The effects of anticalculus dentifrices were compared with other commercially available dentifrices in in vitro models of dentin sensitivity. Changes in the hydraulic conductance of dentin discs were measured with and without a smear layer before and after treatment and also after a post-treatment acid etch. The capacity of dentifrices to occlude open dentinal tubules in vitro was also assessed by scanning electron microscopy (SEM). There was good correlation (R = 0.98) between our test and values reported in the literature. Tartar control dentifrices gave reductions in fluid flow rates through the dentin discs comparable to those obtained with Promise, Sensodyne, Thermodent and Denquel. Additionally, tartar control dentifrices did not remove microcrystalline debris (smear layers) from the surfaces of dentin in vitro. These results were confirmed by SEM. Thus, according to the hydrodynamic theory of dentin sensitivity, these in vitro results suggest that pyrophosphate-containing dentifrices should reduce dentinal sensitivity.

Dental Calculus↗

Effects of age on reporting of adverse clinical events: results from two postmarketing surveillance methods.

Two postmarketing surveillance methods were employed to determine the possible effects of age on reports by outpatients of adverse clinical events (ACEs) occurring shortly after treatment with targeted oral antibiotics or tricyclic antidepressants. One approach involved staff-initiated interviews of patients by telephone and the other involved patient-initiated telephone calls to report possible adverse drug reactions. Regardless of the method, the interviews obtained ACE reports both spontaneously and by review of organ systems. Both postmarketing methods confirmed monotonic relationships for age with treatment duration on the target drugs and with the number of concurrent medications. However, the expected positive correlation between age and spontaneously reported ACEs was evident only in the self-monitoring patients who initiated reports. Negative correlations between age and the number of reported valid ACEs were seen in six independent samples, whereas only two demonstrated a positive relationship. This disparity may elucidate a critical methodologic problem: careful attention must be paid to the means of eliciting information about possible adverse clinical events before attempting to study adverse drug reactions, which are necessarily a subset of ACEs.

Administration, Oral↗

Evaluation of flurbiprofen-exposed irises to acetylcholine anterior chamber irrigation.

Flurbiprofen (Ocufen), an antiprostaglandin, has been introduced into cataract surgery. It is used to prevent intraoperative miosis by blocking inflammatory mediator formation. Ocufen has been noted to diminish the controlled miosis produced by using acetylcholine in the operative period. This study evaluated the pupillary response to acetylcholine after it had been exposed to Ocufen. This was done using a control versus a study eye in 16 rabbits dilated with phenylephrine hydrochloride and cyclopentolate hydrochloride. The pupil diameters were measured at baseline, then the rabbits' anterior chambers were irrigated with an acetylcholine solution. The resultant pupillary diameters were measured at one and five minutes. At five minutes post-irrigation there was a statistically significant greater constriction in the control group than in the Ocufen group. This implies that Ocufen dampens the iris musculature's response to acetylcholine.

Acetylcholine↗

Postmarketing surveillance: accuracy of patient drug attribution judgments.

Data from two samples of ambulatory patients participating in a postmarketing surveillance study, one receiving antibiotics and another receiving tricyclic antidepressant agents, are presented, indicating that patients appear to be capable of correctly discriminating probable adverse drug reactions from other adverse clinical events. However, attribution accuracy depended both on the surveillance method and on how reports of the adverse clinical events were obtained. Discrimination was better when patients were reporting adverse clinical events spontaneously than when the interviewer probed for recall in a systematic inquiry. Discrimination was also better when the adverse clinical events were obtained from a staff-initiated surveillance method than from a self-monitoring, patient-initiated telephone-reporting method--probably because the latter method generates an excessively strong tendency to report mainly those adverse clinical events suspected of being drug related.

Adult↗

Sitting forces and wheelchair mechanics.

The effects of back angle and leg height on sitting forces in a wheelchair were studied, using a force plate mounted on a wheelchair seat. Readings of both normal force (perpendicular to the seat) and shear force were measured while the chair's back angle and footrest height were changed. Pressure under the ischial tuberosities was also measured during the footrest height adjustments. Five normal subjects sat directly on the plate as well as upon ROHO and Jay cushions placed on the force plate. Returning the back to the upright position after a recline caused the normal force (+/- SD) to increase 5.4 +/- 2.5, 9.5 +/- 4.0, and 10.0 +/- 2.3 kg for the hard surface, Jay cushion, and ROHO cushion respectively, while shear at the plate increased to 5.1 +/- 2.2, 11.6 +/- 2.6, and 12.3 +/- 2.7 kg for the hard surface, Jay cushion, and ROHO cushion respectively. Leaning forward (away from the back) caused all the forces to return to measurements close to the starting values. The results suggest that the wheelchair user should momentarily lean forward after a recline to reduce undesired forces. If a cushion with firm thigh support is used, ischial tuberosity pressure can be reduced by lowering the leg height as much as possible, which causes a levering action by lifting the pelvis.

Biomechanical Phenomena↗

Cognitive impairments in abstinent alcoholics.

Impaired cognitive functioning in alcoholics is widespread during the first months of detoxification. Between half and two thirds of abstinent alcoholics exhibit cognitive impairments during this period, with residual deficits persisting for years after detoxification in some patients. The most severe deficits have been observed in visuospatial abilities, perceptual-motor integration, abstract reasoning, and new learning. The most significant predictors of cognitive dysfunction in persons recovering from alcoholism are the time elapsed since the last drink and the person's age. Surprisingly, the pattern and duration of a patient's alcohol abuse are relatively weak determinants of neuropsychological impairment during abstinence. Research investigating the hypothesis that cognitive impairments may be related to alcoholic persons resuming drinking has yielded mixed results, but a higher level of neuropsychological functioning is associated with increased rates of completing treatment programs and with greater success in the work environment after discharge from treatment. The possibility of cognitive limitations should be taken into account in planning treatment programs for alcoholism.

Adult↗

The causes and control of anxiety.

The 20th century has been described as the age of anxiety. Many have claimed that the pressures of a modern technological and competitive society are too great. Anxiety is a normal part of reaction to threats created by life situations especially when control is low. Some people perpetuate constant anxiety by oversensitivity to environmental events. Anxiety can reduce daily efficiency and become self-enhancing. Biological mechanisms may also sustain anxiety further. Treatments include addressing both the cognitive and the biological aspects of the state. Training people to cope with life and to find forms of control may be the most beneficial in the long term.

Adaptation, Psychological↗

Developmental expression of the amyloid precursor protein, growth-associated protein 43, and somatostatin in normal and trisomy 16 mice.

The expression during development of 3 genes located on mouse chromosome 16 (MMU 16) which are implicated in neurobiological processes was examined by blot hybridization beginning at early gestational ages in the mouse. The 3 genes, amyloid precursor protein (App), preprosomatostatin (Smst), and growth-associated protein 43 (Gap43), exhibited distinct profiles of expression. App expression increased steadily throughout fetal and postnatal development. Smst expression peaked during the third postnatal week, then reached a plateau at a slightly lower level in adults, and Gap43 expression was highest in the early postnatal period, declining in adults to levels below those seen at the earliest timepoints examined. Smst message levels exhibited a 1.5-fold increase in the brains of trisomy 16 (Ts16) mice as compared to normal littermates on day 15 of gestation, while Gap43 and App message levels were elevated approximately 2-fold.

Amyloid↗

Improved anti-tumor reactivity with monoclonal anti-idiotypic antibody conjugated to syngeneic mouse red blood cells.

An anti-idiotypic (anti-Id) antibody (Ab), by resembling an epitope on an antigenic molecule may serve as a surrogate antigen and induce specific immune reactivity to the natural antigen. Anti-Id Ab are often conjugated to a foreign protein, such as keyhole limpet hemocyanin (KLH) to elicit a stronger response. However, KLH, a potent antigen itself, may provoke unnecessary and undesirable immune reactivity. In this study, syngeneic mouse red blood cells (RBC) were tested as carriers for anti-Id immunization. In a preliminary experiment, BALB/c mice were immunized with normal rat immunoglobulin G (NRIg)-MRBC or NRIg-KLH. Anti-NRIg responses induced by 2-0.2% of NRIg-MRBC (4-0.4 micrograms of NRIg) superseded those induced by NRIg-KLH (50 micrograms of NRIg). Immunization with NRIg-MRBC did not result in autoreactivity against self antigens on autologous RBC. Monoclonal antibody 2F10, which resembles an epitope on mouse mammary tumor virus (MMTV) envelop protein Gp52, was conjugated to MRBC and used as a surrogate antigen for Gp52. Immune sera were tested in cytotoxicity assay against MMT 68H which expresses Gp52. Between 2-4 weeks after the immunization, specific cytotoxic antibodies were detected in mice immunized with 2.0%, 0.2% and 0.02% 2F10-MRBC, with 0.2% 2F10-MRBC being the most effective dose. 2F10 immune sera did not react with autologous RBC. Therefore, MRBC are at least as effective, and may be more effective than KLH as carriers for Ig immunization. Repeated treatment will be feasible since MRBC are not immunogenic.

Animals↗

Testicular feminization in a cat.

Testicular feminization, caused by an inherited defect of the androgen receptor, was diagnosed in a domestic cat. Individuals affected with this syndrome are genetic males that have testes but fail to undergo masculinization because the internal and external genitalia cannot respond to androgens. The affected cat had the external appearance of a sexually normal female, but during surgery for ovariohysterectomy, only 2 abdominal gonads were found. Müllerian (uterus) or wolffian (epididymides) derivatives were not present. Only testicular tissue was found in histologic sections of the gonad. A normal male chromosome constitution (38,XY) was found in karyotypes prepared from lymphocyte cultures. High affinity binding of dihydrotestosterone was undetectable in fibroblasts cultured from genital skin of the affected cat, indicating that the cytosolic androgen receptor was nonfunctional. Pedigree analysis indicates that this is an X-linked disorder in cats, as it is in other mammals. Accurate diagnosis and genetic counseling are advocated to reduce the prevalence of the disorder.

Androgen-Insensitivity Syndrome↗