Differential expression of interleukin 1 alpha by Thy-1+ and Thy-1- lung fibroblast subpopulations: enhancement of interleukin 1 alpha production by tumor necrosis factor-alpha

The purpose of this investigation was to determine whether subpopulations of murine lung fibroblasts produced interleukin 1 (IL 1). We previously identified two major populations of pulmonary fibroblasts based on the presence or absence of Thy-1. Thy-1+ and Thy-1- subsets synthesize fibronectin and type I and III collagen, but only the Thy-1- population displays class II major histocompatibility complex antigens after stimulation with interferon-gamma and presents antigen to T helper clones. Interestingly, in the current study we determined that only Thy-1- fibroblast lines and clones synthesized IL 1. Although constitutive production was low, tumor necrosis factor -alpha (TNF-alpha) stimulated 5-20-fold increases in IL 1 production in Thy-1- fibroblasts. The Thy-1+ fibroblasts did not produce IL 1 even after TNF-alpha treatment. Northern blot analysis of TNF-alpha treated cells revealed that in the Thy-1- subset increased mRNA levels for IL 1 alpha were detected, while IL 1 beta mRNA was not detected. Furthermore, IL 1 activity from TNF-alpha-treated Thy-1- fibroblast membranes and supernatants was completely neutralized by IL 1 alpha-specific antibodies. These observations support the hypothesis that the antigen-presenting Thy-1- subset is important for promoting the inflammation associated with pulmonary fibrosis. In addition, the existence of functional subsets of lung fibroblasts is further substantiated by differential expression of IL 1.     

An effective regimen for early medical abortion: a report of 2000 consecutive cases

A combination of the anti-progesterone mifepristone and gemeprostprovides an effective non-surgical method for the inductionof abortion at gestations up to 63 days, achieving completeabortion rates of over 95%. We report our experience with analternate regimen, comprising a reduced dose of mifepristonein combination with vaginal misoprostol. A consecutive seriesof 2000 women requesting early medical abortion at gestationsup to 63 days was studied retrospectively. Each woman receivedmifepristone 200 mg orally, followed 36–48 h later bymisoprostol 800 µg vaginally. Of the 2000 women, 39 (2.0%)aborted completely following administration of mifepristonealone and a further 1912 experienced complete abortion followingadministration of misoprostol (a complete abortion rate of 97.5%).Surgical intervention was required in 49 women (2.5%): for incompleteabortion in 27 (1.4%), for missed abortion in seven (0.4%),for continuing pregnancy in 11 (0.6%) and to exclude ectopicpregnancy in four (0.2%). The surgical intervention rate wassignificantly higher among women at gestations 49 days thanamong those at 49 days (3.3 versus 1.5%, P = 0.0193). The regimenappears as effective, in terms of high complete abortion rateand low continuing pregnancy rate, as any published alternative.This regimen has the benefit of being less costly as the doseof mifepristone is 67% lower and misoprostol is substantiallyless expensive than gemeprost. Additionally, misoprostol doesnot require special transport or storage requirements. As such,the combination of mifepristone and gemeprost.     

Evidence for reactive synaptogenesis in the ventrolateral thalamus and red nucleus of the rat: changes in high affinity glutamate uptake and numbers of corticofugal fiber terminals

Summary High affinity glutamate uptake into corticofugal fiber terminals was measured in the ventrolateral thalamus and red nucleus at varying time intervals after lesions were made by kainic acid in the contralateral interpositus nucleus of the cerebellum in rats. Under similar conditions the density of cortical fiber terminals was estimated using the Fink-Heimer impregnation technique. 1. Glutamate uptake steadily increased in the ventrolateral thalamus up to 60 days after lesions in the contralateral cerebellum. 2. Similar changes were noted in the red nucleus. 3. The changes were dependent on the integrity of corticofugal fibers to the thalamus and red nucleus. 4. No changes in uptake of gammaaminobutyric acid were noted. 5. Saturation curves for glutamate uptake suggested a change in the maximal number of transport sites. 6. Fink-Heimer degeneration studies showed an increase in cortical terminals in the ipsilateral ventrolateral thalamus and in both rostral and caudal regions of the red nucleus following lesions in the contralateral interpositus nucleus. The data are consistent with an increase in the number of cortical fiber terminals in reaction to loss of cerebellar input to the ventrolateral thalamus and red nucleus. This study correlates anatomical and biochemical evidence for collateral sprouting in a model based on electrophysiologic data in the red nucleus and extends the model to include the thalamus.     

At-risk persons' attitudes toward presymptomatic and prenatal testing of Huntington disease in Michigan

One hundred fifty-five individuals at 50% risk of inheriting Huntington disease (HD) were given a questionnaire surveying their sociodemographic characteristics, experience with HD, and attitudes toward presymptomatic and prenatal testing in HD. About two-thirds (63.2%) of the persons indicated they would take a presymptomatic test even if no specific treatment was available. Although one-half (49%) of the respondents stated they would make use of a prenatal test, only 43% of these individuals would decide to terminate a heterozygous fetus. Presymptomatic test results indicating carrier status would influence some of the respondents' decisions about marriage and childbearing. This strong interest of at-risk persons to make use of both presymptomatic and prenatal diagnosis in HD indicates the need for well-organized testing programs. These programs must be designed to address the genetic, psychosocial, and ethical issues that may arise in the use of this type of genetic test.     

Impedance plethysmography: the origin of electrical impedance changes measured in the human calf

Electrical impedance plethysmography of the lower leg is now a widely used test for detection of deep vein thrombosis. The origin of the impedance signal is difficult to evaluate in the living subject, and experimental animals have important anatomic differences. A controlled study on human cadavers was therefore undertaken. Conductive and nonconductive fluids were injected into the lower legs of cadavers, while electrical impedance changes were recorded utilising a 4-electrode technique. X-ray studies confirmed the localisation of the injections. Results from ten cadavers showed that significant impedance changes occurred only in response to injections of saline in the region between the electrodes. Injections of nonconductive silicone oil caused a small increase in the measured impedance. It is concluded that electrical impedance plethysmography reflects changes in conductivity confined to the region between the electrodes; and that the ratio of deep to superficial impedance sensitivity is a function of the electrode spacing.     

Constrained least-squares restoration of nuclear medicine images: selecting the coarseness function

Image restoration using the constrained least-squares (CLS) method theoretically adapts to the image being processed. In addition, it only requires knowing the modulation transfer function of the imaging system when applied to nuclear medicine images. Prompted by these observations, a systematic evaluation of the effects of the form of the "coarseness function" [C(f)] used by the CLS method has been conducted. Nine C(f)'s are evaluated using an observer preference and a normalized mean-squared error (NMSE) criterion. This evaluation is conducted for three modulation transfer functions and a wide range of count levels. The results of the subjective studies support using the form of C(f) which has been most widely employed in previous studies, i.e., the form designed to minimize the energy in the second derivative of the restored image. A different form of C(f) is generally found to be optimal by the mean-squared error criterion. The CLS method is then compared to: (1) no processing, (2) count-dependent smoothing, and (3) count-dependent Metz restoration. When evaluated using objective measurements of error and contrast, the CLS method is found to be slightly inferior to the best method, Metz restoration. However, CLS restoration is found to be equal to or better than the other methods when judged by the results of observer preference studies.     

Concurrent and Close Temporal Administration of Lithium and ECT

The clinical effects of concurrent and close temporal administration of electroconvulsive therapy (ECT) and lithium (Li) were investigated by chart review. Three groups of patients were compared on the basis of ECT-related complications, total length of hospital stay (LOS), and post-ECT hospital stay. The groups consisted of patients administered concurrent ECT and Li (n = 27); patients administered Li within 24 h prior to ECT or within 48 h post-ECT (n = 49); and patients administered ECT without concurrent or close temporal administration of Li (n = 100). Prolonged or severe post-ECT confusion was significantly associated with close timing of administration of Li relative to the ECT course. The groups did not differ in the number of complications or the total LOS, although the post-ECT LOS was significantly longer in the group administered Li in close temporal association with ECT. These data suggest that caution should be exercised in the combined use of these treatment modalities.     

Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "re-presentation" of exogenous antigen by tumor-infiltrating antigen-presenting cells.

We show that interleukin 3 (IL-3) enhances the generation of tumor-specific cytotoxic T lymphocytes (CTLs) through the stimulation of host antigen-presenting cells (APCs). The BALB/c (H-2d) spontaneous lung carcinoma line 1 was modified by gene transfection to express ovalbumin as a nominal "tumor antigen" and to secrete IL-3, a cytokine enhancing myeloid development. IL-3-transfected tumor cells are less tumorigenic than the parental cell line, and tumor-infiltrating lymphocytes isolated from these tumors contain increased numbers of tumor-specific CTLs. By using B3Z86/90.14 (B3Z), a unique T-cell hybridoma system restricted to ovalbumin/H-2b and implanting the tumors in (BALB/c x C57BL/6)F1 (H-2d/b) mice, we demonstrate that the IL-3-transfected tumors contain an increased number of a rare population of host cells that can process and "re-present" tumor antigen to CTLs. Electron microscopy allowed direct visualization of these host APCs, and these studies, along with surface marker phenotyping, indicate that these APCs are macrophage-like. The identification of these cells and their enhancement by IL-3 offers a new opportunity for tumor immunotherapy.     

Stereotactic pallidotomy performed without using microelectrode guidance in patients with Parkinson's disease: surgical technique and 2-year results

OBJECT: Pallidotomy for the treatment of medically refractory Parkinson's disease (PD) has enjoyed renewed popularity. However, the optimal surgical technique, lesion location, and long-term effectiveness of pallidotomy remain subjects of debate. In this article the authors describe their surgical technique for performing pallidotomy without using microelectrode guidance, and the clinical and radiological results of this procedure. METHODS: Patients were evaluated preoperatively by using a battery of validated clinical rating scales and magnetic resonance (MR) imaging of the brain. Individuals with severe treatment-refractory idiopathic PD who were believed to be good candidates for surgery underwent computerized tomography scanning- and MR imaging-guided stereotactic pallidotomy. Intraoperative macrostimulation was used to optimize lesion placement and to avoid injury to nearby structures. Lesion location and size were calculated from MR imaging sequences of the brain obtained within the first 24 hours after surgery and again 3 months later. Clinical examinations were conducted at 1.5, 3, 6, 12, and 24 months after surgery. Seventy-five patients (mean age 61 years, range 38-79 years) underwent unilateral pallidotomy. Significant improvements were observed in the "off' period scores for the activities of daily living portion of the Unified Parkinson's Disease Rating Scale (UPDRS), the UPDRS motor scores, total "on" time, levodopa-induced dyskinesias, and contralateral tremor. These improvements were maintained 24 months postoperatively. The mean lesion volume measured on the immediate postoperative MR image was 73 +/- 5.4 mm3. Radiological analysis suggests that initial lesion volume does not predict outcome. The only permanent major complication was a single visual field defect. CONCLUSIONS: Pallidotomy performed without using microelectrode guidance is a safe and effective treatment for selected patients with medically refractory PD.