Self-recognition and the right hemisphere.
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Biomedical subjects
Publications and source records attributed to A Nelson.
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Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.
[reaction: see text] Scalar coupling between hydroxyl groups sharing a 1,4- or 1, 3-intramolecular hydrogen bond can be readily detected using standard 2D NMR techniques. Analyses of isotopically perturbed 2D J-resolved spectra have revealed (h2)J to be on the order of 0.3 Hz in systems such as diols 2 and 3. A standard 2D COSY experiment, modified to detect small coupling constants, is shown to be a convenient method for detecting (h2)J in these systems. Couplings derived from density functional finite perturbation theory (DFT/FPT) are found to be in general agreement with experimental data.
Late fetal CA1 hippocampal grafts and stem cell grafts from the conditionally immortal MHP36 clonal line derived from the H-2Kb-tsA58 transgenic mouse neuroepithelium both improved spatial deficits in rats with ischaemic CA1 damage induced by four-vessel occlusion (4VO). However, the distribution of fetal and MHP36 grafts differed. Fetal cells lodged in clumps around the implant sites and along the corpus callosum, whilst MHP36 grafts infiltrated the area of CA1 ischaemic damage, achieving apparent architectural reconstruction of the hippocampus. The migration of MHP36 cells is damage-dependent. Few cells were found in intact brain; after 15 min of 4VO cells repopulated only the discrete area of CA1 cell loss, whereas with more extensive damage after 30 min occlusion cells migrated to all hippocampal fields and to cortex. A higher proportion of grafted MHP36 cells differentiated into neurons in the host CA1 field than grafts of striatal or cortical expanded cell populations. Cortical population grafts were as effective as MHP36 grafts in improving water maze learning, whereas striatal or ventral mesencephalic cells were ineffective, indicating a degree of stem cell specificity. The efficacy of MHP36 cells extends to primates. In marmosets with profound impairments in conditional discrimination tasks after lesions of the CA1 field, MHP36 cells improved performance as effectively as fetal grafts and migrated evenly through the CA1 field, in contrast to clustered fetal cells. These findings suggest that MHP36 stem cell grafts are as effective as fetal grafts in functional repair of hippocampal damage, and that their preference for areas of cell loss and adoption of appropriate morphologies is consistent with a point-to-point repair mechanism.
In the human lower limb, the magnitudes of both Hoffmann (H) reflexes and primary somatosensory evoked potentials (SEPs) from scalp electrodes, are reduced by active and/or passive movement. We surmised that similar effects occur for the upper limb and specifically hypothesised that amplitudes of median nerve induced flexor carpii radialis H reflexes and cortical SEPs are reduced with passive movement about the wrist or elbow. The results showed (P<0. 05) that either movement significantly attenuated mean magnitudes of SEPs elicited from stimulation at elbow or wrist and that reflex magnitudes attenuated with wrist movement. Thus, the upper limb shows similar movement-induced modulation to the lower limb. These attenuations of fast conducting sensory paths consequent to movement per se, may be a basic level of motor control, initiated from muscle mechanoreceptor discharge. Upon this basic level, more complex modulations then may be laid as appropriate for the particular characteristics of active motor tasks.
Purpose: Dedicated PET-(fluorine-18)-fluorodeoxyglucose (FDG) studies were interpreted with the corresponding anatomic images (MR or CT) using image fusion display to improve spatial accuracy for the interpreter and the referring physician.Methods: The image-fusion display system was designed in-house and allows manual alignment and display of one image volume as an overlay on the other which has improved accurate correlation of physiological and anatomical information for more than 50 patient studies.Results: A case of a patient with left foot recurrent melanoma is presented for which the PET scan showed a large focus of activity just lateral to the urinary bladder. Image fusion confirmed that the PET focus corresponded to an abnormal lymph node on the follow-up CT scan. In a case of bladder carcinoma which included bladder augmentation, altered surgical anatomy rendered interpretation of the FDG-PET images difficult. The fusion with the patient's CT scan allowed evaluation of the altered physiology due to the altered surgical anatomy which permitted accurate image interpretation. In a case of pelvic lymphoma, the FDG-PET scan showed intense activity adjacent to the acetabulum and possibly within it. Image fusion allowed accurate localization of the patient's primary lesion with the additional benefit of showing activity extending into the adjacent bone.Conclusion: Image fusion of tomographic, anatomic and physiologic information permits accurate lesion localization including separation of soft tissue from bone. The image-fusion technique facilitates image-guided biopsy by providing accurate anatomic localization.
Despite the major strides made in birth control, which have produced a decline in unintended pregnancies over the past decade and the lowest rates of teen pregnancies seen since 1974 (1,2), significant problems still remain. Almost half (48%) of US pregnancies in 1995 were unintended (1) and many more that were "intended" were not planned or prepared for (3). To optimize maternal and fetal outcomes, it is incumbent that physicians both emphasize the need for women to be physically, emotionally, and socially prepared for pregnancy before they conceive as well as ensure the availability of effective methods to allow them to do so. Today, contraceptives are available that permit couples to choose if and when to have children. Although only 5% of women who are sexually active and say they do not want to become pregnant are using no method of birth control (4), that group accounts for nearly 40% of the unintended pregnancies. More than half of all unintended pregnancies occur in women who had used a method in the month of conception (1). The strategy with these women should be to find ways to make the method they select work better for them or to switch them to more effective methods. Unfortunately, the most effective reversible methods are among the least utilized--in part because they have the highest initial costs. Some states, such as California and Maryland, have passed Contraceptive Equity Acts, which require insurance companies that provide any prescriptive drug coverage to cover all forms of prescription contraception. Many other states, as well as the federal government, are now considering similar legislation. It is important, therefore, both from the perspective of quality patient care and also from a fiscal standpoint, that all who care for reproductive-aged women become familiar with the full array of contraceptive options. This article will review the methods of reversible birth control now available in the United States, including the most recent efficacy rates and new practical tips to achieve better utilization, as well as summarize the features of some of the new options that may be nearing introduction.
STUDY DESIGN: Literature review. OBJECTIVES: Upper extremity (UE) joint degeneration, particularly at the shoulder, detrimentally influences functional independence, quality of life, cardiovascular disease risk, and life expectancy of individuals following spinal cord injury (SCI). This review (1) describes UE use for transfers among individuals with SCI; (2) describes contributing factors associated with UE joint degeneration and loss of transfer independence; (3) summarizes and identifies gaps in existing research; and (4) provides suggestions for future research. RESULTS: Investigations of wheelchair transfer related UE joint and function preservation among individuals with SCI should consider factors including age and length of time from SCI onset, interface between subject-wheelchair, pain, shoulder joint range of motion (ROM) and muscle strength deficiencies or imbalances, exercise capacity and tolerance for the physical strain of activities of daily living (ADL), body mass and composition, previous UE injury or disease history, and transfer techniques. Existing studies of transfers among individuals with SCI have relied on small groups of either asymptomatic or non-impaired subjects, with minimal integration of kinematic, kinetic and electromyographic data. Descriptions of UE joint ROM, forces, and moments produced during transfers are lacking. CONCLUSIONS: Biomechanical measurement and computer modeling have provided increasingly accurate tools for acquiring the data needed to guide intervention planning to prevent UE joint degeneration and preserve function among individuals with SCI. The identification of stressful sub-components during transfers will enable intervening clinicians and engineers who design and modify assistive and adaptive devices to better serve individuals with SCI.
OBJECTIVE: Hyperparathyroidism (HPT) is a common endocrine disorder. Several loci of genetic interest have been identified in parathyroid tumours, including the MEN1 gene locus at 11q13; the HPT-JT region at 1q21-q32; and a putative tumour suppressor gene on 1p. We analysed these intervals, which harbour known genes or putative loci associated with familial hyperparathyroidism, in order to clarify the involvement of the respective regions in parathyroid tumourigenesis. DESIGN: We performed loss of heterozygosity (LOH) studies on 33 sporadic parathyroid tumours using a PCR based technique. A total of 22 microsatellite markers were used to analyse loci at 11q13, 1q21-q32 and 1p. Ten markers located distal on 1p, eight markers encompassed the HPT-JT region at 1q21-q32 and four markers surrounded the MEN1 gene locus at 11q13. MEN1 mutations were screened for using Single Strand Conformation Polymorphism analysis (SSCP) and automated sequencing of SSCP variants. PATIENTS: Thirty-three parathyroid glands and the corresponding blood samples were obtained from 33 patients (26 females and seven males) who underwent parathyroidectomy for primary hyperparathyroidism. RESULTS: Loss of heterozygosity was detected in 13 of 33 (39%) cases at 11q13, 6 of 33 (18%) cases at 1p, and in three of 33 (9%) cases at 1q (in conjunction with 1p loss). Only one of the 18 tumours in which LOH was detected, showed LOH at both chromosome 1 and chromosome 11. Additionally, those tumours found to exhibit LOH at 11q13 were screened for MEN1 mutations using single strand conformation polymorphism analysis (SSCP) and automated sequencing. Nine novel somatic mutations were found on the remaining allele in 13 (69%) tumours. CONCLUSIONS: This study consolidates the role of multiple loci in the pathogenesis of sporadic parathyroid tumours. The results indicate that there are at least two genetic loci involved in sporadic parathyroid tumourigenesis on chromosome 1, one of which has been linked to the distinct familial parathyroid condition, hyperparathyroidism-jaw tumour (HPT-JT) syndrome. The high frequency of loss of heterozygosity at 1p suggests the presence of a tumour suppressor at this locus.
Mesenteric venous thrombosis (MVT), an uncommon but important clinical entity, is one possible cause of ischemia or infarction of the small intestine. Diagnosis of this condition is sometimes difficult and treatment is often delayed because patients usually present with nonspecific abdominal symptoms. The hallmark is pain that is out of proportion to the physical findings. We report two cases of MVT, where the patients initially presented with vague abdominal symptoms. Diagnosis was made on the basis of computed tomography of the abdomen showing thrombus within the superior mesenteric vein. A search for a precipitating condition revealed no evidence of a hypercoagulable state, myeloproliferative disorder, or malignancy. These cases illustrate well the nonspecific clinical presentation of MVT. A high index of suspicion, recognition of known risk factors, or a previous history of venous thrombosis coupled with a history of nonspecific abdominal symptoms should alert clinicians to the possibility of MVT. Early diagnosis and prompt anticoagulation are the mainstay of therapy unless there are signs of peritonitis that necessitate surgical resection of the infarcted bowel.
Two distinct skeletal muscle ryanodine receptors (RyR1s) are expressed in a fiber type-specific manner in fish skeletal muscle (11). In this study, we compare [(3)H]ryanodine binding and single channel activity of RyR1-slow from fish slow-twitch skeletal muscle with RyR1-fast and RyR3 isolated from fast-twitch skeletal muscle. Scatchard plots indicate that RyR1-slow has a lower affinity for [(3)H]ryanodine when compared with RyR1-fast. In single channel recordings, RyR1-slow and RyR1-fast had similar slope conductances. However, the maximum open probability (P(o)) of RyR1-slow was threefold less than the maximum P(o) of RyR1-fast. Single channel studies also revealed the presence of two populations of RyRs in tuna fast-twitch muscle (RyR1-fast and RyR3). RyR3 had the highest P(o) of all the RyR channels and displayed less inhibition at millimolar Ca(2+). The addition of 5 mM Mg-ATP or 2.5 mM beta, gamma-methyleneadenosine 5'-triphosphate (AMP-PCP) to the channels increased the P(o) and [(3)H]ryanodine binding of both RyR1s but also caused a shift in the Ca(2+) dependency curve of RyR1-slow such that Ca(2+)-dependent inactivation was attenuated. [(3)H]ryanodine binding data also showed that Mg(2+)-dependent inhibition of RyR1-slow was reduced in the presence of AMP-PCP. These results indicate differences in the physiological properties of RyRs in fish slow- and fast-twitch skeletal muscle, which may contribute to differences in the way intracellular Ca(2+) is regulated in these muscle types.
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BACKGROUND: More than 50% of the elderly population has not received pneumococcal vaccination. Uncertainty regarding the benefits of immunization, particularly for noninvasive disease, may contribute to the underuse of pneumococcal vaccine. OBJECTIVE: To assess the health and economic benefits associated with pneumococcal vaccination. METHODS: We conducted a 2-year retrospective cohort study among all elderly members of a staff-model managed care organization who had a baseline diagnosis of chronic lung disease. The study outcomes were assessed over 2 years, from November 15, 1993, through November 14, 1995, and included hospitalizations for pneumonia and influenza, death, and hospitalization costs. Using administrative data, we compared these outcomes for vaccinated and unvaccinated subjects using multivariate models to control for subjects' baseline demographic and health characteristics. The additive benefits of combined influenza and pneumococcal vaccination were also assessed for the 2 influenza seasons included in the study. RESULTS: There were 1898 subjects. Pneumococcal vaccination was associated with significantly lower risks for pneumonia hospitalizations (adjusted risk ratio [RR], 0.57; 95% confidence interval [CI], 0.38-0.84; P=.005) and for death (adjusted RR, 0.71; 95% CI, 0.56-0.91; P = .008). For the control outcome of all nonpneumonia hospitalizations, rates did not differ significantly between the 2 groups (adjusted RR, 0.91; 95% CI, 0.77-1.07; P= .24). During the influenza seasons included in the study, the benefits of pneumococcal and influenza vaccinations were additive, with an adjusted RR of 0.28 (95% CI, 0.14-0.58; P<.001) for the number of hospitalizations for pneumonia and influenza among persons who had received both vaccinations compared with those who had received neither and an adjusted odds ratio of 0.18 (95% CI, 0.11-0.31; P<.001) for death. Over the 2-year outcome period, pneumococcal vaccination was also associated with direct medical care cost savings. CONCLUSIONS: Pneumococcal vaccination of elderly persons with chronic lung disease was associated with fewer hospitalizations for pneumonia, fewer deaths, and direct medical care cost savings.
BACKGROUND: Influenza vaccine is underused in groups targeted for vaccination. OBJECTIVE: To define the effects of influenza and the benefits of influenza vaccination in elderly persons with chronic lung disease. DESIGN: Retrospective, multiseason cohort study. SETTING: Large managed care organization. PATIENTS: All elderly members of a managed care organization who had a previous diagnosis of chronic lung disease. MEASUREMENTS: Outcomes in vaccinated and unvaccinated persons for the 1993-1994, 1994-1995, and 1995-1996 influenza seasons were compared after adjustment for baseline demographic and health characteristics. All data were obtained from administrative databases. RESULTS: Vaccination rates were greater than 70% for each season. Among unvaccinated persons, hospitalization rates for pneumonia and influenza were twice as high in the influenza seasons as they were in the interim (noninfluenza) periods. Influenza vaccination was associated with fewer hospitalizations for pneumonia and influenza (adjusted risk ratio, 0.48 [95% CI, 0.28 to 0.82]) and with lower risk for death (adjusted odds ratio, 0.30 [CI, 0.21 to 0.43]) during the influenza seasons. It was also associated with fewer outpatient visits for pneumonia and influenza and for all respiratory conditions. CONCLUSIONS: For elderly persons with chronic lung disease, influenza is associated with significant adverse health effects and influenza vaccination is associated with substantial health benefits, including fewer outpatient visits, fewer hospitalizations, and fewer deaths. Health care providers should take advantage of all opportunities to immunize these high-risk patients.
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OBJECTIVE: To assess the validity of self-reported influenza and pneumococcal vaccination status. DESIGN: Cross-sectional surveys of outpatients aged 65 years or older. SETTING: A Veterans Affairs Medical Center (VA) and a community managed care organization (MCO). Both organizations have organized influenza and pneumococcal vaccination programs. SUBJECTS: VA subjects included all elderly respondents to a mailed survey of 500 randomly selected outpatients. MCO subjects included all respondents to a telephone survey of 300 randomly selected elderly members of the MCO. MEASUREMENTS: The VA survey was conducted following the 1995-1996 influenza season while the MCO survey was conducted following the 1994-1995 season. Self-report from the mailed survey for VA subjects and from the telephone survey for MCO subjects was compared to medical record documentation (paper and computerized combined). RESULTS: The response rate was 77% (n = 369) for the VA subjects of whom 195 (53%) were aged 65 or older. The response rate for the MCO subjects was 84% (n = 237). Self-report of influenza vaccination had a sensitivity (SENS) of 1.0 and a specificity (SPEC) of .79 with a kappa of .72 (95% CI .58-.86) among VA patients. Among MCO patients, self-report of influenza vaccination had a SENS of .98 and a SPEC of .71 with kappa of .75 (95% CI .69-.89). Self-report of pneumococcal vaccination status among VA patients had a SENS of .97 and a SPEC of .53 with a kappa of .42 (95% CI .32-.52). Among MCO patients, self-report of pneumococcal vaccination had a SENS of .90 and a SPEC of .64 with a kappa of .54 (95% CI .40-.68). A secondary analysis excluding subjects living outside of the VA's catchment area improved the specificity and indices of concordance of self-report of both influenza and pneumococcal vaccination. A secondary analysis of MCO data which excluded subjects who received a pneumococcal vaccination > 2 years prior to the study also improved concordance and the negative predictive value of self-report. CONCLUSIONS: Self-report of influenza vaccination is a highly sensitive and moderately specific measure. Self-report of pneumococcal vaccination is also a highly sensitive but less specific measure of vaccination status. Lower rates of validity for pneumococcal vaccination may reflect both less accurate recall, particularly for more distant vaccination, and less complete documentation in medical records.
BACKGROUND: Although all epidemiologic subsets of Kaposi's sarcoma (KS) (i.e., sporadic, endemic, epidemic, and iatrogenic) have an association with human herpes virus 8 (HHV8), these subsets occur in patient populations with distinctive clinical features. To a variable degree men outnumber women in all subsets. OBJECTIVE: A retrospective study of women with histologically proven cutaneous KS was undertaken to determine the clinical and histopathologic features, as well as any associations. METHODS: Two hundred and fifty cases of cutaneous KS in women from 1975 to 1993 were reviewed. RESULTS: Of the patients, 80% were more than 60 years of age, and of the patients less than 60 years old, 28 were from areas of the world with endemic KS. All HIV+ patients but one were from areas of endemic KS. Two patients were renal transplant patients. Sixty-four percent of the patients had single lesions and 21% recurrent lesions. Twelve patients had, or were known to develop, internal involvement, and in six patients the cause of death was KS. All but four cases histologically showed areas of solid proliferations of tumour cells consistent with plaque or tumour stage. An angiosarcoma-like histologic pattern appeared to be associated with more aggressive epidemiologic subsets. High mitotic rates were rarely seen and did not correlate with aggressive epidemiologic subsets. CONCLUSION: Kaposi's sarcoma in women is diagnosed almost exclusively in plaque or tumour stage. The majority of women within our study fit within the epidemiologic subset of sporadic KS.
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