Analysis of HLA-DM polymorphism in juvenile dermatomyositis (JDM) patients.

Annually approximately 1:200,000 young children and adolescents are affected by juvenile dermatomyositis (JDM). Genetic factors are thought to contribute to the etiology. Since the discovery of the human leukocyte antigen class II associated DM molecule much has been learned about its role in the normal processing of HLA-class II molecules with a limited number of polymorphisms being found. Blood samples were collected from 30 patients who were seen in the clinic and 40 healthy volunteers. Exon 3 of the HLA-DM A and B genes were amplified and specific polymorphisms were identified given allele designations. The DMA*0103 allele was found in 43% of patient alleles versus 8% in the control group, this difference reached significance at a p value of 0.0004. The DMB*0102 allele was found in 20% of patients compared with 3% of the controls with a calculated p value of 0.037. Relative risk (RR) ratios with CI were as follows: DMA*0103 vs control RR = 5.7 and DMB*0102 vs control RR = 8. In conclusion, we feel that the polymorphisms represented in the DMA*0103 and the DMB*0102 alleles are increased in frequency in our JDM patients.

Effects of treatment for sound errors in apraxia of speech and aphasia.

This investigation was designed to examine the acquisition, generalization, and maintenance effects of a treatment for sound errors in speakers with co-occurring apraxia of speech and aphasia. Three speakers with chronic apraxia of speech and aphasia were studied in the context of a multiple baseline design across speakers and behaviors. Treatment combined the use of minimal contrast pairs with traditional sound production training techniques such as integral stimulation and articulatory placement cueing and was applied sequentially to sounds that were determined to be consistently in error before training. Results revealed increased correct sound productions for all speakers in trained and untrained words. Response generalization effects across sounds and stimulus generalization effects varied, but appeared to be limited for most speakers. Although positive maintenance effects were evidenced, some loss of treatment gains was noted following cessation of treatment.

Ethnopharmacology of Mexican asteraceae (Compositae).

Traditional herbal remedies have increased in popularity in Europe and the United States in recent years but have always been important to people living in rural Mexico and to their Mexican American/Chicano descendants in the United States. Mexican American patients will often be ingesting herbal teas at the same time that they are being treated for their ailments with antibiotics or antiinflammatory agents. The plant family Asteraceae (Compositae) has contributed the largest number of plants to this pharmacopoeia; the reasons for the importance of this family include its large number of species in Mexico and its wide array of natural products that are useful in the treatment of the maladies that have afflicted the inhabitants of rural Mexico. These natural products include sesquiterpene lactones, polyacetylenes, alkaloids, monoterpenes, and various phenolics such as flavonoids. In this review, we emphasize the sesquiterpene lactones, a large group of compounds with antiinflammatory properties and the ability to relax smooth muscles and thereby relieve gastrointestinal distress. These compounds also readily form adducts with glutathione or free thiols and can thereby affect the metabolism, activity, and toxicology of a wide array of pharmacological agents.

Knowledge-based patient screening for rare and emerging infectious/parasitic diseases: a case study of brucellosis and murine typhus.

Many infectious and parasitic diseases, especially those newly emerging or reemerging, present a difficult diagnostic challenge because of their obscurity and low incidence. Important clues that could lead to an initial diagnosis are often overlooked, misinterpreted, not linked to a disease, or disregarded. We constructed a computer-based decision support system containing 223 infectious and parasitic diseases and used it to conduct a historical intervention study based on field investigation records of 200 cases of human brucellosis and 96 cases of murine typhus that occurred in Texas from 1980 through 1989. Knowledge-based screening showed that the average number of days from the initial patient visit to the time of correct diagnosis was significantly reduced (brucellosis-from 17.9 to 4.5 days, p = 0.0001, murine typhus-from 11.5 to 8.6 days, p = 0.001). This study demonstrates the potential value of knowledge-based patient screening for rare infectious and parasitic diseases.

Purified X2 binding protein (X2BP) cooperatively binds the class II MHC X box region in the presence of purified RFX, the X box factor deficient in the bare lymphocyte syndrome.

The conserved X2 box sequence of MHC class II promoters is homologous to TRE/CRE elements, and is required for B cell expression and IFN-gamma induction of MHC class II genes. The X2 binding protein (X2BP) was initially identified as a DNA-binding activity that specifically interacts with the conserved X2 box sequence in both the MHC HLA-DRA and HLA-DRB promoters. To begin to demonstrate that X2BP is the X2 box factor responsible for class II expression in B cells, we have purified X2BP to homogeneity from B cell nuclear extracts using DNA-affinity chromatography. X-box DNA-affinity purification indicates that X2BP is most likely composed of two polypeptides of 120 kDa and 46 kDa. The 120-kDa protein was specifically cross-linked to an X-box probe by exposure to UV irradiation. The 46-kDa subunit of X2BP cross-reacted with anti-rat CREB polyclonal Abs but not to anti-human CREB Abs in Western analysis and supershift assays, indicating that it may be a novel member of the ATF/CREB family. Purified X2BP interacted with purified RFX, a factor that binds to the adjacent X1 box and is absent in some cell lines that are mutant for MHC class II transcription. This interaction increases the DNA-binding half-life of RFX from 5 to at least 60 min, suggesting that X2BP functions in class II MHC gene expression by forming a stable complex with RFX.

Isolated elevation of diastolic blood pressure. Real or artifactual?

Not infrequently, blood pressure measurement by the standard auscultatory technique yields a normal systolic pressure with an elevated diastolic pressure. The relatively narrow pulse pressure of such a measurement raises concern about the accuracy of the blood pressure measurement. The purpose of this study was to assess the accuracy of auscultatory blood pressure measurements in patients with an uncommonly narrow pulse pressure, particularly patients with an elevated diastolic but normal systolic pressure. Auscultatory blood pressure measurements were compared with an objective noninvasive standard, called K2 analysis, which has been shown to be more accurate than the auscultatory technique. Blood pressure was measured simultaneously by auscultatory and K2 techniques in 175 subjects. Comparisons were performed (1) in the group as a whole, (2) in four clinical subgroups (normotensive [< 140/< 90 mm Hg, n = 69], hypertensive [> or = 140/> or = 90 mm Hg, n = 53], isolated systolic hypertensive [> or = 140/< 90 mm Hg, n = 38], and isolated diastolic hypertensive [< 140/> or = 90 mm Hg, n = 15]), and (3) in two subgroups whose ratio of pulse pressure to diastolic pressure was greater than or equal to 0.45 (n = 151) or less than 0.45 (n = 24). Subjects in the isolated diastolic hypertensive group and in the group with a pulse pressure ratio less than 0.45 were considered to have a narrow pulse pressure. In the group as a whole, consistent with previous auscultatory-K2 comparisons, systolic pressure was slightly higher and diastolic pressure slightly lower when measured by K2 versus the auscultatory technique (auscultatory, 145/85 mm Hg; K2, 147/83 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

How should diastolic blood pressure be defined during pregnancy?

Controversy exists concerning the most accurate method for defining diastolic blood pressure in pregnancy. Both disappearance (phase V) and muffling (phase IV) of Korotkoff sounds have been advocated. We previously reported an objective noninvasive method for measuring blood pressure, called K2 analysis, which in nonpregnant subjects was not different from intra-arterial diastolic blood pressure and was more accurate than the auscultatory technique. For determination of the relation of diastolic blood pressure (using K2) in pregnancy with muffling and disappearance of Korotkoff sounds, 58 women (42 hypertensive, 16 normotensive) underwent 556 blood pressure evaluations in the supine position at various stages of pregnancy. K2 analysis was compared with simultaneous auscultation by two observers, A1 (n = 461 observations; 364 hypertensive, 97 normotensive) and A2 (n = 415; 316 hypertensive, 99 normotensive). Overall, muffling was detected by observer A1 52.9% (244/461) and by observer A2 44.3% (184/415) of the time. When evaluated by clinical classification, muffling was found by both observers to be present less often in the hypertensive group (A1: 47.5%; A2: 37.3%) compared with the normotensive group (A1: 73.2%; A2: 66.7%) (P < .0001). When both observers were present (n = 348), they agreed that muffling was present only 112 times. Disappearance of sound was detected by both observers 98.3% (A1: 453/461; A2: 408/415) of the time. Muffling overestimated K2 diastolic pressure by 7 to 10 mm Hg, whereas there was no statistically significant difference between disappearance and K2 diastolic pressure for hypertensive subjects and a 2.5-mm Hg underestimation of K2 diastolic pressure for normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of auscultatory gaps with wideband external pulse recording.

Three types of auscultatory gaps, called G1, G2, and G3, that occur during blood pressure measurement have been identified by using wideband external pulse recording. We have previously shown that the wideband external pulse recorded during cuff deflation can be separated into three components (K1, K2, and K3), one of which (K2) is closely related to the Korotkoff sound. G1 occurs with cuff pressure just below systolic and is characterized by the presence of K1 and K2 with intermittent disappearance of K2. G1 gaps are related to a phasic decrease of arterial (systolic) pressure and were exhibited by 13 of 60 hypertensive patients. G2 gaps are related to a phasic increase of arterial (diastolic) pressure, occur when cuff pressure is just above diastolic, and are characterized by the presence of K1, K2, and K3 with intermittent disappearance of K2. Seven of 60 hypertensive patients exhibited a G2 gap. G3 gaps occur with cuff pressure between systolic and diastolic and are characterized by an underdeveloped or blunted K2 signal. Three of 60 hypertensive patients exhibited a G3 gap. The identification of auscultatory gaps in relation to the wideband external pulse provides a qualitative measure of their existence, can be of significant value in better understanding aspects of the auscultatory blood pressure measurement technique, and provides an objective basis with which to better understand the mechanisms that cause them.

Wideband external pulse recording during cuff deflation: a new technique for evaluation of the arterial pressure pulse and measurement of blood pressure.

Analysis of the external brachial pulse recorded during standard blood pressure cuff deflation with use of a transducer with a wide frequency response has revealed a reproducible pattern with three distinct components that we have labeled K1, K2, and K3. K1 is a low-amplitude, low-frequency signal that is present with cuff pressures above systolic pressure. K2 is a triphasic signal appearing at systolic pressure and disappearing at diastolic pressure, which approximately corresponds to the audible Korotkoff sound. K3 appears with cuff pressure between systolic and diastolic pressure and continues to be present below diastolic pressure. Intra-arterial pressure recordings made with a high-fidelity Millar catheter-tip manometer revealed K2 and K3 analogs. K3 resembles the intra-arterial pressure waveform and when calibrated according to the pulse pressure, noninvasive dK3/dt determinations correlated well with intra-arterial dP/dt measurements. The appearance/disappearance property of K2 was designated as the "K2 algorithm" and represents a new, objective noninvasive method for measurement of blood pressure. The K2 algorithm compares favorably with intra-arterial measurements, is more accurate than the auscultatory technique, and may be especially useful in clinical situations in which the auscultatory technique does not work well.

Ciliary band formation in the doliolaria larva of Florometra. II. Development of anterior and posterior half-embryos and the role of the mesentoderm.

We report the results of cutting experiments on embryos of the crinoid Florometra serratissima, which produce, in the doliolaria stage, a striped pattern of ciliary bands. Embryos at gastrula and post-hatching elongation stages were divided into anterior and posterior fragments. Complementary fragments express parts of the total pattern without adding extra pattern elements, i.e. the pattern is a mosaic. Some fragments elongate which, from an examination of internal structures, we interpret as due to the elongation and displacement of the mesenteric sac. The number of pattern elements expressed correlates with degree of elongation and internal landmarks correlate with certain external pattern features. This suggests that the pattern mosaic may reside in the internal tissues, i.e. in the mesentoderm, but we are as yet unable to prove this. The results are discussed with reference to the roles of tissues of different germ layer origin in related embryos, including vertebrates, in which the mesentoderm has a significant instructive role.

Ciliary band formation in the doliolaria larva of Florometra. I. The development of normal epithelial pattern.

The development of ciliary band pattern in the doliolaria larva of Florometra serratissima is described based on scanning and transmission electron microscopy. The uniformly ciliated epithelium of the post-hatching larva develops four regularly spaced bands over a period of approx. 20 h generating an epithelial pattern that is, essentially, a series of stripes. The first visible events of pattern formation progress over the larval surface in a posterior-to-anterior and dorsal-to-ventral sequence, but the initial pattern is not, in fact, striped. It instead consists of a close-packed array of oval interband domains separated and surrounded by belts of band cells. Secondarily the interband domains expand laterally and coalesce to form continuous, broad stripes, while the bands remain as narrow stripes between them. Two possible explanations for this unusual sequence of events are discussed: that it can be understood in evolutionary terms with reference to band pattern in other echinoderm larvae, and that it is a morphogenetic necessity because limitations inherent in the patterning mechanism prevent the direct formation of regular stripes.

Bovine abortion and death associated with consumption of aflatoxin-contaminated peanuts.

Approximately 12% of a herd of 68 crossbred cows aborted third-trimester fetuses after consuming moldy peanuts for 4 days. Further investigation revealed that less than 20% of the herd had access to this supplemental feed. Results of serum biochemical analysis indicated liver damage in the affected cows. All of these cows died within 8 days of aborting. The peanuts contained 77 micrograms aflatoxin B1/g, as determined by liquid chromatography. Tissues were submitted from 1 cow, and liver contained 5 ng aflatoxin B1/g. Results of other laboratory tests were negative for common toxins and abortifacients.

Foil electret transducer for blood pressure monitoring.

A foil electret microphone for use under the cuff of an automatic blood pressure monitoring system is described. The transducer is designed to operate with relatively flat sensitivity over a static pressure range of 40 to 250 mm Hg (5.33 X 10(4) to 3.33 X 10(5) dyn/cm2). The new electret microphone differs from conventional microphones used for airborne sound reception in two ways: (1) the diaphragm thickness is 50 micron rather than the typical 12.5 or 25 micron, and (2) the backplate contains a set of annular ridges spaced at 4 mm rather than the typical 7-10 mm. This microphone offers three advantages over the piezoelectric microphone now in use: (1) greater tolerance in positioning the microphone over the brachial artery, (2) nearly 20-dB higher sensitivity and signal-to-noise ratio, and (3) the ability to obtain measurements with the microphone placed midway between the elbow and shoulder. Tests of the new foil electret microphone in conjunction with the automatic blood pressure monitoring system indicate that the automatic and conventional measurements of systolic and diastolic blood pressure agree to within 5 mm Hg at least 90% of the time. In addition, the electret microphone is able to obtain automatic measurements on subjects with a wider range of ages and sizes.