PubMed Health⌕ Search

Biomedical subjects

D Horwitz

Publications and source records attributed to D Horwitz.

At least 19 recordsLinked to original sources
PubMed1992

A revised estimate of twin concordance in systemic lupus erythematosus.

OBJECTIVE: Based on a small clinical series and previously published case reports, concordance for systemic lupus erythematosus (SLE) among monozygous (MZ) twins has been reported to be as high as 69%. Using a larger and less biased sample, we provide another estimate of this percentage. METHODS: We established a registry of twins with SLE, based upon self-reports and information provided by the patients' physicians. We used DNA fingerprinting to validate the reported zygosity in a sample of these twins. RESULTS: Of 107 twin pairs meeting the American College of Rheumatology 1982 revised criteria for the diagnosis of SLE, 24% of 45 MZ pairs and 2% of 62 dizygous (DZ) pairs were concordant. The frequency distributions of diagnostic criteria and disease symptoms in the SLE patients were similar to those in other published reports of SLE patients. Zygosity was confirmed by DNA fingerprinting in a subsample of 15 self-described MZ twins and 7 self-described DZ twins. All individuals had correctly predicted their zygosity. CONCLUSION: MZ concordance for SLE is similar to that for other autoimmune diseases and is much lower than previously believed.

Adolescent↗
PubMed1987

Natural killer (NK) cell immunodeficiency in patients with chronic myelogenous leukemia. II. Successful cloning and amplification of natural killer cells.

Defective natural killer (NK) cell populations from patients with chronic myelogenous leukemia (CML), that reacted with both HNK-1+ and B73.1+ antibodies, were obtained by a fluorescence-activated cell sorter (FACS). These fractions, along with NK fractions from normal donors which reacted with both antibodies, were expanded as bulk cultures or clones by limiting dilution, for 4 weeks in the presence of 10% interleukin 2 (IL 2), human type AB plasma, and irradiated human allogeneic mononuclear cells. Successfully established clones from patients with CML, with lytic activity against autologous and more differentiated neoplastic granulocytes, were generated more efficiently from B73.1+ than from HNK-1+ subsets. However, there were no significant differences among the generations of B73.1+ and HNK-1+ clones for both patients and normal donors with lytic activity against NK susceptible K-562 targets. Fresh myeloblast preparations from a blast crisis were found to be more susceptible to lysis by IL 2-proliferative B73.1+ and HNK-1+ clones than were fresh myelocyte preparations from a chronic phase CML patient, which were lytically susceptible to only B73.1+ clones. B73.1+ and HNK-1+ subsets from CML patients demonstrated major histocompatibility complex nonrestricted killing, and showed the following predominant phenotypes: B73.1+T3+T8+ or B73.1+T3+T8- from B73.1+ subsets; and HNK-1-T3+T8+ (initially HNK-1+) from HNK-1+ subsets. In contrast, B73.1+ and HNK-1+ clones from normal donors showed the following predominant phenotypes: B73.1+T3-T8-; and HNK-1-T3-T8- or HNK-1-T3-T8+ (initially all HNK-1+). Short-term in vitro IL 2 or interferon treatment of fresh NK defective subsets from CML patients resulted in minimal cytotoxic augmentation. In contrast, defective NK cells from CML patients, whether HNK-1+ or B73.1+ subsets, proliferated with complete regeneration of cytolytic activity after a 3-4 week exposure to IL 2, but differed in phenotypic profiles as compared to those of normal donors. These observations imply that not only fresh defective NK cells but also the cytotoxically restored clones from CML patients are derived from different NK subsets and may represent undifferentiated forms of NK cells that may be arrested at an early stage of development by yet unknown mechanism(s). In vitro substantiation of autologous leukemia cell killing by IL 2-proliferative NK cell clones is encouraging and may allow for new in vivo immunotherapeutic modalities in CML patients.

Antibodies, Monoclonal↗
PubMed1986

Natural killer-cell immunodeficiency in patients with chronic myelogenous leukemia. I. Analysis of the defect using the monoclonal antibodies HNK-1 (LEU-7) and B73.1.

Quantitative evaluation of natural killer (NK) cells using the HNK-1 (Leu-7) and B73.1 monoclonal antibodies (MAbs) was correlated with NK activity in 13 patients with chronic myelogenous leukemia (CML) and compared to normal donor controls. A consistent observation was the presence of normal absolute numbers of B73.1+ lymphocytes as well as normal to increased absolute numbers of HNK-1+ lymphoid cells in the peripheral blood of chronic-phase CML patients. Despite normal to increased numbers of B73.1+ and HNK-1+ lymphoid cells, these patients consistently demonstrated a significant impairment of lymphocyte-mediated NK activity in their peripheral blood. Further experiments demonstrated that chronic-phase CML patients, in contrast to normal controls, had significantly increased percentages of HNK-1+, E+ and B73.1+, E+ lymphoid cells and significantly decreased percentages of HNK-1+, E- and B73.1, E- lymphoid cells, which resulted in significant reversals of the HNK-1+, E+ to HNK-1+, E- and B73.1+, E+ to B73.1+, E- lymphoid cell ratios. (HNK-1+ [E+/E-] greater than B73.1+ [E+/E-]). Furthermore, as compared to normals, both FACS-sorted HNK-1+ and B73.1+ lymphoid cells from the E+ fraction of CML patients were consistently defective in NK activity, and could not be substantially augmented with alpha-interferon preparations. Although markedly defective in their ability to lyse K-562, HNK-1+ lymphoid cells from the E+ fraction of CML patients were not defective in their ability to bind to the NK-sensitive target, K-562. In contrast, NK-defective B73.1+ lymphoid cells were partially defective in their ability to bind to K-562.

Antibodies, Monoclonal↗
PubMed1986

Noninvasive determination of small vessel distensibility in man.

The present study describes and illustrates a noninvasive method for computing extensibility of the 'resistance vessels', from an experimentally obtained resistance vs transmural pressure plot, in a maximally dilated vascular bed of man. Limb blood flow was measured plethysmographically following 10 min of arterial occlusion, and blood pressure was measured by the arm cuff method. A ratio of two resistance values taken 30 mm Hg apart was used to compute percent change in radius and the extensibility, E. The computed values of E were 0.71 mm Hg-1 for normal hand and 0.13, 0.22 and 0.69 for the hypertensive forearm, hand and finger respectively. These results indicate that the method may prove useful in the understanding and management of diseases such as hypertension or other small vessel diseases.

Capillaries↗
PubMed1985

Plasma dihydroxyphenylglycol (DHPG) in the in vivo assessment of human neuronal norepinephrine metabolism.

We investigated the utility of deaminated norepinephrine (NE) metabolites in the study of human sympathetic nervous pathophysiology. Plasma levels of the NE metabolite dihydroxyphenylglycol (DHPG) appear to be related to intraneuronal NE stores. Plasma DHPG increases when sympathetic nervous activity or circulating NE increase and decreases when neuronal NE is depleted or neuronal NE reuptake is blocked. Changes in plasma dihydroxymandelic acid (DOMA) related less closely to changes in plasma NE. The coupling of measurements of plasma NE with its deaminated metabolites and DHPG may improve understanding of human NE metabolism and neuronal NE reuptake.

Glycols↗
PubMed1985

Maximal hand blood flow in hypertensive and normal subjects.

The present study examined whether patients with systemic hypertension have evidence of structural vascular changes, whether such changes can be detected in early stages of hypertension and whether they are reversible with treatment. Hypertensive and normal subjects were studied under conditions of maximal vasodilation in which flow at a given driving pressure was considered to give an index of structural changes in resistance vessels. Thirty-two subjects were separated into 4 groups: 8 with sustained hypertension, 8 with intermittent hypertension, 8 treated hypertensive subjects maintained at systolic pressures of less than 125 mm Hg with drugs for 5 years, and 8 normal subjects. Flow was measured by venous occlusion plethysmography after 10 minutes of ischemia, using a water-filled plethysmograph at 43 degrees C. Arterial blood pressure was measured by the arm cuff method. Transmural pressure, calculated as mean arterial minus external pressure, was varied by imposing varying external hydrostatic pressures. Flow at a transmural pressure of 85 mm Hg was calculated for each subject from the least-mean-square plot of transmural pressure vs flow. Mean flow for normal subjects was 41 ml/100 ml/min and differed significantly from that for sustained hypertensive patients (30 ml/100 ml/min), treated hypertensive patients (33 ml/100 ml/min), and intermittent hypertensive patients (32 ml/100 ml/min) (p less than 0.05). There was no overlap between sustained hypertensives and normal subjects, but half of the treated hypertensive patients were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Fludrocortisone suppression of sympathetic nervous activity.

Fludrocortisone depressed plasma norepinephrine in normal subjects but to a lesser degree than it depressed renin activity or urinary aldosterone excretion. Sympathetic nervous reactivity (defined as upright/supine plasma norepinephrine) was decreased more than supine plasma norepinephrine. Pretreatment supine plasma norepinephrine (but not plasma renin activity or aldosterone excretion) correlated with blood pressure changes during fludrocortisone dosing, which suggests participation of the sympathetic nervous system in the blood pressure elevations reported during exogenous steroid administration or primary aldosteronism. Suppression of sympathetic nervous activity and reactivity by fludrocortisone tends to explain its limited usefulness in patients with autonomic dysfunction and postural hypotension.

Adolescent↗
PubMed1983

Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.

We infused tracer-labeled l-[3H]-norepinephrine, d-[14C]norepinephrine, and d,l-[3H]-isoproterenol simultaneously into patients with essential hypertension and into normotensive control subjects, in order to determine whether abnormalities in the disappearance kinetics of these substances characterized the hypertensive patients. The mean preinfusion venous plasma norepinephrine concentration was somewhat higher in the hypertensive group (260 vs. 194 pg/ml, P = 0.06), but the groups did not differ in the disappearance kinetics of l- or d-norepinephrine or of isoproterenol. Preinfusion plasma norepinephrine was significantly positively correlated with calculated spillover rates in both the hypertensive and normotensive groups, but not with norepinephrine clearances. The d/l ratio in plasma norepinephrine was the same as in the infusate during and after the infusion, even after pretreatment with the neuronal norepinephrine uptake blocker, desipramine. Because isoproterenol is not taken up by nerve endings, the ratio of [3H]isoproterenol to l-[3H]norepinephrine increased after the infusion ended. This increase was almost completely abolished by pretreatment with desipramine. These results indicate that (a) increased plasma norepinephrine levels seen in some patients with essential hypertension result from increased sympathetic neural activity and not from decreased clearance of norepinephrine, (b) changes in the isoproterenol/norepinephrine ratio after simultaneous infusion of both provide an index of neuronal norepinephrine uptake in man, and (c) neuronal norepinephrine uptake is not stereospecific.

Adult↗
PubMed1982

Comparison of techniques for measuring baroreflex sensitivity in man.

Because discrepancies about baroreflex sensitivity in essential hypertension may have resulted from the use of different measurement techniques, we assessed the extent to which the results of different techniques agree in the same subjects. The eight techniques studied were the change in RR interval per unit change in systolic pressure during the Valsalva maneuver, upon release of the Valsalva maneuver, after injection of phenylephrine and after injection of nitroglycerin; the changes in RR interval and in systolic pressure per mm Hg externally applied neck suction; and the changes in RR interval and systolic pressure per mm Hg externally applied neck pressure. The average intercorrelation among these measures in 30 subjects was statistically significant (r = 0.36, p less than 0.01), but suggests that variance in one measure accounted for an average of about 13% of the variance in other measures. Standard deviations among subjects were often as large as the mean, indicating important interindividual variability as well. These findings demonstrate that baroreflex sensitivity varies widely among subjects and that different techniques for measuring baroreflex sensitivity probably measure different aspects of baroreflex function.

Adult↗
PubMed1982

Effects of restriction of sodium or administration of fludrocortisone on parotid salivary kallikrein in man.

Urinary kallikrein is increased by restriction of dietary sodium and by administration of fludrocortisone, a sodium-retaining steroid. In order to determine whether salivary kallikrein responds similarly, we studied 16 normal volunteers after 1-week periods of daily intake of 9, 109, and 259 mEQ of sodium; 10 subjects were studied after addition of 0.6 mg/day fludrocortisone for a week to a regimen of 109 mEq/day sodium. During sodium restriction, parotid saliva had a significantly higher mean concentration of kallikrein ad potassium and a significantly lower concentration of sodium than during periods of intake of 109 or 259 mEq/day sodium. Sodium restriction also caused significantly higher urinary excretion of kallikrein and aldosterone. Salivary amylase remained unchanged during the three sodium periods. Administration of fludrocortisone significantly increased the mean concentration of parotid kallikrein and excretion of urinary kallikrein in comparison with control levels, however the concentrations of parotid sodium and potassium did not change significantly. Four patients studied before and after removal of aldosterone-producing adenomas each showed decreased concentrations of parotid kallikrein and potassium and increased concentrations of parotid sodium after surgery. It is concluded that both salivary and urinary kallikrein increased in response to restriction of sodium and that these increases were mediated by levels of sodium-retaining steroid. Increased output of kallikrein in response to increased levels of sodium-retaining steroid may be a generalized response of organs that contain glandular kallikrein and can conserve sodium.

Adenoma↗
PubMed1981

Physiologic mechanisms opposing the hemodynamic effects of prazosin.

Prazosin was give for 10 to 14 days to eight hypertensive patients on a fixed intake of dietary salt. Except as limited by side effects, the dose was increased from 2 mg/day to a maximum dose of 24 mg/day. During treatment, when subjects were studied in supine and upright positions, mean arterial pressure (MAP) fell 6% and 12% (p less than 0.025 and p less than 0.005), heart rate rose 3% and 9% (p less than 0.05 and p less than 0.005), and plasma norepinephrine increased 95% and 107% (p less than 0.01 and p less than 0.001) over control. Daily excretion of the norepinephrine metabolites methoxyhydroxyphenyl glycol (MHPG) and vanillylmandelic acid (VMA) increased 42% and 17% (p less than 0.05 for each) during treatment. There were no changes in average body weight or plasma renin for the group, but patients whose body weight increased tended to show less reduction in blood pressure (correlation coefficient, r = 0.72, p less than 0.05) and smaller increases in heart rate (r = -.073, p less than 0.05) during treatment with prazosin. These data suggest that expansion of extracellular fluid and activation of the sympathetic nervous system oppose the hemodynamic effects of prazosin.

Adult↗
PubMed1979

Effect of indomethacin and adrenocorticotrophic hormone on renal function in man: an experimental model of inappropriate antidiuresis.

The effect of prostaglandin synthesis inhibition on basal and ACTH-stimulated adrenal and renal function was investigated in normal volunteers. Data were collected during control and experimental study periods (13 days each). Adrenocorticotrophic hormone (Cosyntropin, 80 U/day) was administered i.v. on days 8 and 9 of each period. Indomethacin (150 mg/day) was given on days 5 through 13 of the experimental period. The subjects ate a constant diet containing 9 mEq of sodium, 100 mEq of potassium, and 2,500 ml of fluid daily. Indomethacin markedly inhibited urinary PGE excretion and plasma PGE concentration. The effect of ACTH alone as compared to the effect of ACTH and indomethacin showed: plasma sodium concentration, 139 +/- 1 vs. 131 +/ 3 mEg/liter (P less than 0.01, mean +/- SEM); plasma osmolality, 287 +/- 3 vs. 270 +/- 3 mOsm/liter (P less than 0.01); free water clearance, 97 +/- 66 vs. -1100 +/- 380 ml/24hr (P less than 0.01); urine volume, 2,000 +/- 60 vs. 950 +/- 200 ml/day (P less than 0.01); and urine osmolality 282 +/- 12 vs. 720 +/- 144 mOsm/liter (P less than 0.01). We conclude that the effects of ACTH and prostaglandin synthesis inhibition interact to result in inappropriate antidiuresis.

Adrenal Glands↗
PubMed1979

Phenotypes of 'null' lymphoid cells in human blood.

F(ab')2 antibody fragments of heteroantisera directed against p28,33 (or 'Ia-like') antigen, T-cell antigen(s) (T), myeloid antigen (M), and immunoglobulin have been used along with rosetting techniques to analyse the antigenic heterogeneity of 'null' or 'unclassified' lymphoid cells purified 'negatively' from human blood by E rosette depletion of T cells and B removal on an anti-immunoglobulin immunoabsorbent. The results confirm that considerable heterogeneity exists within the 'null' cell population; the majority of cells are p28,33+ and Fcgamma-receptor-positive, and a proportion but not all of these p28,33+, Fcgamma+ cells are also C3-receptor-positive but negative for the other heteroantigens (T and M). 2-6% were 'pre-B' by the criteria of immunofluorescent staining for cytoplasmic IgM in the absence of detectable cell surface Ig. 1-3% stained intensely with anti-IgM, anti-IgG or anti-IgA, or anti-k plus anti-lambda and were presumed to be plasma cells or their immediate precursors. No null cells stained with antibody to terminal deoxynucleotidyl transferase enzyme, a marker for early T lineage cells, and less than 1% expressed an acute ('non-T, non-B') lymphoblastic-leukaemia-associated membrane antigen which is believed to be an 'early' lymphoid lineage differentiation marker. A minor subpopulation made sheep 'E' rosettes, and another made mouse 'E' rosettes after neuraminidase pretreatment of the lymphoid cells. A small proportion of 'lymphoid', 'null cells' were reactive with an anti-myelomonocytic (M) antibody. It is suggested that 'null' lymphoid cells in blood are heterogeneous and that most are not immature T or B precursors but either a relatively mature B lymphocyte population with a very low density of membrane immunoglobulin or a distinct non-T, non-B cell type.

Animals↗