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J S Simon

Publications and source records attributed to J S Simon.

At least 19 recordsLinked to original sources

Transfer of a salt-resistant renin allele raises blood pressure in Dahl salt-sensitive rats.

To evaluate the role of the renin gene in the development of hypertension in Dahl salt-sensitive rats (SS/Jr/Hsd), we derived a congenic strain of rats homozygous for the salt-resistant renin allele (S/renrr) and compared them with a control strain homozygous for the salt-sensitive renin allele (S/ren(ss). Mean arterial pressure was significantly higher in 12-week-old S/renrr rats fed a high salt (8.0%) diet for 3 weeks than in S/ren(ss) rats or in SS/Jr/Hsd rats rederived from the foundation colony we used to generate the cogenic strain (195 +/- 3 [n = 49] versus 168 +/- 3 [n = 17] or 161 +/- 3 [n = 16] mm Hg). Mean arterial pressure was also higher in S/renrr rats than in S/ren(ss) rats raised from birth on either a very low salt (0.1%) diet (119 +/- 9 [n = 6] versus 100 +/- 7 [n = 7] mm Hg) or a low salt (0.4%) diet (143 +/- 1 [n = 22] versus 117 +/- 3 [n = 10] mm Hg). Plasma renin activity of S/renrr rats was significantly higher than that of S/ren(ss) rats fed a very low salt diet (5.7 +/- 2.0 versus 1.8 +/- 0.3) ng angiotensin l/mL per hour), a low salt diet (4.4 +/- 1.0 versus 1.1 +/- 0.3), or a high salt diet (1.5 +/- 0.2 versus 0.9 +/- 0.1). Urinary protein excretion was greater in S/renrr rats than in S/ren(ss) rats fed a high salt diet (244.2 +/- 48.5 versus 43.6 +/- 19.5 mg/24 h), and this was associated with significant reductions in renal blood flow (3.3 +/- 0.6 versus 4.6 +/- 0.5 mL/min per gram kidney weight) and glomerular filtration rate (0.49 +/- 0.11 versus 0.82 +/- 0.08 mL/min per gram kidney weight). Captopril (20 mg/kg i.v.) had no effect on blood pressure in S/ren(ss) rats fed a low salt diet, but it lowered blood pressure by 20 mm Hg in S/ren(rr) rats to the same level seen in untreated S/ren(ss) rats. Chronic administration of captopril (5 mg/100 mL drinking water) reduced blood pressure in S/renrr rats fed a high salt diet (170 +/- 5 mm Hg) to the same level seen in untreated S/ren(ss) rats, whereas it had no significant effect on blood pressure in S/ren(ss) rats. These results indicate that transfer of a salt-resistant renin allele to SS/Jr/Hsd rats raises plasma renin activity and augments the severity of hypertension and renal disease.

Alleles

A reference cross DNA panel for zebrafish (Danio rerio) anchored with simple sequence length polymorphisms.

The ultimate informativeness of the zebrafish mutations described in this issue will rest in part on the ability to clone these genes. However, the genetic infrastructure required for the positional cloning in zebrafish is still in its infancy. Here we report a reference cross panel of DNA, consisting of 520 F2 progeny (1040 meioses) that has been anchored to a zebrafish genetic linkage map by 102 simple sequence length polymorphisms. This reference cross DNA provides: (1) a panel of DNA from the cross that was used to construct the genetic linkage map, upon which polymorphic gene(s) and genetic markers can be mapped; (2) a fine order mapping tool, with a maximum resolution of 0.1 cM; and (3) a foundation for the development of a physical map (an ordered array of clones each containing a known portion of the genome). This reference cross DNA will serve as a resource enabling investigators to relate genes or genetic markers directly to a single genetic linkage map and avoid the problem of integrating different maps with different genetic markers, as must be currently done when using randomly amplified polymorphic DNA markers, or as has occurred with human genetic linkage maps.

Alleles

Cytosolic phospholipase A2 gene in human and rat: chromosomal localization and polymorphic markers.

We report the chromosomal localization and a simple sequence repeat (SSR) in the cytosolic phospholipase A2 (cPLA2) gene in both human and rat. A (CA)18 repeat in the promoter of the rat gene was determined to exhibit length polymorphism when analyzed using the polymerase chain reaction (PCR) in 19 different inbred rat strains. Genotyping for this marker in 234 F2 progeny of a SHR x BN intercross mapped the gene to rat chromosome 13. Using a PCR strategy, a fragment of the promoter for the human gene was isolated, and a (CA)18 repeat was identified. Since this marker displayed a low heterozygosity index, we also identified a mononucleotide repeat in the promoter for cPLA2 that displayed a polymorphism information content value of 0.76. The human gene was mapped using fluorescence in situ hybridization (FISH) to chromosome 1q25. Of interest, the gene encoding the enzyme prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2), which acts on the arachidonic acid product of cPLA2, was previously localized to this same chromosomal region, raising the possibility of coordinate regulation. Identification of intragenic markers may facilitate studies of polymorphic variants of these genes as candidates for disorders in which perturbations of the eicosanoid cascade may play a role.

Animals

First-line therapy option with low-dose bisoprolol fumarate and low-dose hydrochlorothiazide in patients with stage I and stage II systemic hypertension.

This 30-center, randomized, double-blind, placebo-controlled, parallel-group study was designed to (1) establish that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemic hypertension; and (2) assess whether this formulation was more effective or possessed a safety advantage over standard monotherapy with bisoprolol or 25 mg of HCTZ. Results showed that HCTZ 6.25 mg contributed significantly to the antihypertensive effectiveness of bisoprolol 5 mg. Bisoprolol 5 mg/HCTZ 6.25 mg (B5/H6.25) produced significantly greater mean reductions from baseline in sitting systolic and diastolic blood pressure (-15.8 mm Hg/-12.6 mm Hg) than bisoprolol 5 mg alone (-10.0 mm Hg/-10.5 mm Hg) and HCTZ 25 mg alone (-10.2 mm Hg/-8.5 mm Hg). A 73% response rate was achieved with the low-dose formulation compared with 61% for the bisoprolol 5 mg (B5) group and 47% for the HCTZ 25 mg (H25) group. B5/H6.25 was found to be significantly more effective than B5 or H25 in all subgroups of patients, regardless of gender, race, age, or smoking history. Antihypertensive effects were maintained during the 24-hour dosing interval. The incremental effectiveness of B5/H6.25 was not accompanied by an increase in the frequency or severity of adverse experiences; the incidence of adverse experiences in the B5/H6.25 group was comparable to that in the placebo group. B5/H6.25 was shown to provide safety advantages over H25, as shown by less hypokalemia (< 1% with B5/H6.25 versus 6.5% with H25).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Arginine vasopressin stimulates protein synthesis but not proliferation of cultured vascular endothelial cells.

We previously showed that rat and cow blood vessels contain arginine vasopressin (AVP) of local origin. In the present study, to investigate potential roles for this locally produced peptide, we examined the effects of AVP on growth of cultured vascular endothelial and smooth muscle cells (EC, SMC). Treatment of cultured bovine aortic endothelial (BAE), murine cerebral microvascular endothelial (MME), or murine cerebral microvascular smooth muscle (MMSM) cells with AVP produced dose-dependent increases in total protein content with maximum increases of 11, 46, and 33% over vehicle-treated controls, respectively. AVP also dose-dependently increased new protein synthesis, as reflected by [3H]leucine incorporation into BAE and MME cell protein, with maximal increases of 34 and 24%, respectively. In addition, the AVP-stimulated increase in protein synthesis could be significantly attenuated in both BAE and MME cells by simultaneous addition of a specific AVP V1 receptor antagonist. In contrast, AVP did not affect total cell number or DNA synthesis, as reflected by [3H]thymidine incorporation, in any cell type. Neither was cell size, as measured by forward light scatter with a fluorescence-activated cell sorter (FACS), changed by treatment with AVP. However, the density of individual cells, as measured by orthogonal light scatter with FACS, was increased by AVP. These data demonstrate that AVP stimulates protein synthesis but not proliferation of cultured vascular EC and SMC and suggest that locally produced AVP may function as a growth factor for these cells.

Animals

Bisoprolol, a once-a-day beta-blocking agent for patients with mild to moderate hypertension.

The 24-h blood pressure control of bisoprolol, a new beta-selective, beta-blocking agent, was studied in 240 mild to moderate hypertensive patients in this 4-week, randomized, double-blind, placebo-controlled trial. A once-daily dosing schedule was evaluated by comparing bisoprolol's antihypertensive effectivness and safety at 24 h postdose and 3 h postdose, the latter time intended to correspond to peak effectiveness. Results from this trial demonstrated the antihypertensive effectiveness of once-daily bisprolol at doses ranging from 5-20 mg. Mean reductions from baseline diastolic blood pressure, measured 24 h postdose, were 6.3, 8.8, and 10.1 mmHg for patients receiving bisoprolol 5, 10, and 20 mg, respectively, compared with 1.6 mmHg for placebo-treated patients (p < 0.01); mean reductions from baseline systolic blood pressure for the bisoprolol groups were 8.6, 8.6, and 10.9 mmHg, respectively, versus 3.3 mmHg for placebo (p < or = 0.01); and mean reductions from baseline heart rate for the bisoprolol groups were 5.1, 7.1, and 10.2 beats/min, respectively, compared with a 0.9 beats/min increase in heart rate for the placebo group (p < 0.01). The response rates for bisoprolol-treated patients ranged from 47 to 70% compared with 18% for patients on placebo (p < 0.01). Antihypertensive effects were dose-related and sustained over the 24-h dosing interval. Near maximal antihypertensive effects were achieved within 1 week of initiation of therapy with bisoprolol and were sustained over the course of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Comparison of video thoracoscopic lung biopsy to open lung biopsy in the diagnosis of interstitial lung disease.

BACKGROUND: Up to one third of patients with interstitial lung disease will require a lung biopsy for diagnosis. Open lung biopsy is generally accepted as the most reliable method of biopsy and tissue diagnosis. The purpose of this study was to compare the efficacy and safety of video thoracoscopic lung biopsy, a minimally invasive technique, with open lung biopsy in the diagnosis of interstitial lung disease. METHODS: From December 1990 to January 1992, 43 patients were referred for diagnostic lung biopsy. Twenty-two consecutive patients undergoing video thoracoscopic lung biopsy (VTLB) over a 6-month period were retrospectively studied and compared with 21 consecutive patients who had undergone open lung biopsy (OLB) in the preceding 6-month period. RESULTS: VTLB (46 +/- 4 minutes) did not add to operative time when compared with OLB (38 +/- 3 min, p = 0.09). The same number of biopsies per patient were performed (VTLB, 1.9 +/- 0.1; OLB, 2.0 +/- 0.1; p = 0.48), the same amount of tissue was obtained per biopsy (VTLB, 6.69 +/- 0.82 cm3; OLB, 5.78 +/- 0.54 cm3; p = 0.36), and the diagnostic accuracy of each method was comparable (VTLB, 95 percent; OLB, 100 percent). However, patients undergoing VTLB demonstrated a significant reduction in length of pleural drainage (1.36 +/- 0.25 days) and hospital stay (2.57 +/- 0.46 days) relative to patients undergoing OLB (3.20 +/- 0.34 days, 5.71 +/- 0.63 days; p < 0.05). Complications occurred in 2/22 VTLB patients (9 percent, 0 deaths) and 4/21 OLB patients (19 percent, 1 death). CONCLUSIONS: When compared with OLB, VTLB does the following: (1) provides equivalent specimen volume; (2) achieves equal diagnostic accuracy; (3) does not add to operative time or complications; and (4) reduces the time necessary for pleural drainage and length of hospital stay. Our findings suggest that VTLB is an effective and safe alternative to OLB in the diagnosis of interstitial lung disease.

Adult

Characterization of a vasopressin-like peptide in rat and bovine blood vessels.

The present study examined the possibility that blood vessels of the rat and cow contain arginine vasopressin (AVP) and that the vascular stores of this potent vasoconstrictor are of local, rather than blood-borne, origin. Vessels from rat or cow were homogenized in acid, and the supernatants were assayed for AVP by radioimmunoassay. AVP immunoreactivity was detected in all vessels taken from the rat including aorta, mesenteric artery, renal artery, vena cava, and renal vein, as well as atria of the heart and also in cow aorta. Blood vessels from hypophysectomized and Brattleboro rats also contained AVP at levels similar to those of intact control rats. Further characterization of this immunoreactive material showed that, in both radioimmunoassay and radioreceptor assay, vascular extracts produced competition curves, which were parallel to those of synthetic AVP. Additionally, immunoreactive AVP in aortic extracts comigrated with synthetic AVP and pituitary extract on both high-pressure liquid chromatography and Sephadex G-25 chromatography. Furthermore, intravenous administration of the aortic extract produced pressor responses in conscious rats, and these responses were significantly attenuated by pretreatment with a specific AVP V1-receptor antagonist. These data demonstrate that blood vessels contain an AVP-like peptide that appears indistinguishable from authentic AVP and further suggest that this vascular peptide is of local origin.

Animals

The detection of depression by patient self-report in women with gynecologic cancer.

We examined the utility of patient self-report forms in identifying those gynecologic oncology patients who would be diagnosed by an experienced consultation-liaison psychiatrist as suffering from major depression. Sixty-five women with gynecologic tumors were evaluated by a consultation-liaison psychiatrist, using standardized (DSM-III) criteria. Each patient also completed a Carroll Rating Scale for Depression (CRS). The CRS demonstrated sensitivity and specificity of 87 percent and 58 percent, respectively. Used as a screening instrument to rule out depression, the CRS yielded a negative predictive value of 94 percent. We identified a priori forty items from the CRS which should not be influenced by the non-psychiatric biologic effects of gynecologic tumors, and compared the performance of this non-cancer related symptoms subscale (NCSG) to that of the CRS. The NCSG did not significantly outperform the CRS; its sensitivity and specificity were 87 percent and 62 percent, respectively. Because our study population was relatively homogeneous (i.e., non-ovarian gynecologic oncology patients without severe debilitation who were not receiving chemotherapy, radiation therapy, or other invasive procedures), the findings should not be generalized to other oncologic populations at this time. Our results suggest that patient self-report forms can be effective screening devices for identifying those non-ovarian, gynecologic oncology patients who should then be carefully evaluated for coexisting clinical depression.

Adult

The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders.

We determined the frequency of antithyroglobulin and antimicrosomal antibodies in 173 consecutively admitted psychiatric inpatients. (We found antithyroid antibodies in 8% (5/65) of patients with DSM-III major depression, 13% (4/31) with biploar disorder, and in 0% (0/4) of those with schizoaffective disorder.) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole. The overall frequency of positive antithyroid antibody titers in patients with DSM-III affective disorder, 9% (9/99), did not differ from that in patients with nonaffective disorders, 10% (7/68). However, patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients. Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder, even in the absence of lithium exposure. However, as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders, the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation.

Adolescent

Subclinical hypothyroidism: a review of neuropsychiatric aspects.

The authors review current information about the prevalence, causes, course, and consequences of subclinical hypothyroidism. There is evidence that subclinical hypothyroidism may be associated with cognitive dysfunction, mood disturbance, and diminished response to standard psychiatric treatments. Recommendations are presented for the screening, evaluation and treatment of patients in whom subclinical hypothyroidism may be contributing to neuropsychiatric dysfunction.

Humans

The dexamethasone suppression test and antidepressant response in major depression.

UNLABELLED: We conducted a prospective open pilot study of 34 consecutively admitted patients with the DSM-III diagnosis of MD who were admitted to a general psychiatric unit. Patients underwent a 1 mg DST and were randomly assigned to treatment with either maprotiline or trazodone. Antidepressant dosages were increased as tolerated clinically and according to treatment response. RESULTS: mean final oral doses were 193 mg for maprotiline and 328 mg for trazodone. The mean treatment duration was 4.5 weeks for maprotiline and 5.9 weeks for the trazodone group. Of these 34 patients 44% showed DST nonsuppression (41% maprotiline, 45% trazodone). Seventy-six per cent of the patients responded to treatment (76% for both drugs) as defined by GAS. Eighty-seven per cent of the nonsuppressors responded to treatment (86% maprotiline, 88% trazodone) and 68% of the suppressors responded (70% maprotiline, 67% trazodone). Of the eight treatment nonresponders six showed DST suppression. The implications of these findings are discussed.

Adolescent

An outbreak of recurrent acute and chronic hypersensitivity pneumonitis in office workers.

Three episodes of an acute, flu-like illness, one studied in detail, were associated with manipulations on the central air handling system of an office building in Tennessee in the summer and early fall of 1981. Symptoms were compatible with acute hypersensitivity pneumonitis, although the time of onset revealed a biphasic epidemic curve. Breathing air not supplied through the central air handling system protected against disease. Ill persons had significantly more precipitins to agents cultured from the building than did controls. Symptoms suggestive of chronic hypersensitivity pneumonitis were also found. Chronic disease was associated with the presence of humidifiers at home, asthma, and longer work in the building. Acute disease occurred less frequently in smokers and persons who had previously worked in the building before 1976. Persons with acute disease were more likely to have chronic disease. No single etiologic agent could be identified. Because of difficulties with demonstrating safety for reoccupancy, the building was vacated and remains empty at this time.

Acute Disease

Abdominal surgery in patients undergoing chronic hemodialysis.

The reports on surgical techniques that specifically focus on the management and outcome of patients on chronic hemodialysis (CHD) who undergo major intra-abdominal procedures--particularly of an emergency nature--are few. It is hoped that by analysis of our experience the nature of the problem can be further clarified and guidelines for clinical care can be formulated. Thirty-two cases which encompass a 7-year period (1978 to 1985), were reviewed. Seventeen patients underwent elective surgery and fifteen underwent emergency intervention. There was a wide range of cases that were similar to those most generally seen in an acute-care teaching hospital. The morbidity and mortality rates in elective surgery patients were 12% and 6%, respectively, while in the emergency cases, these rates were 62% and 47%. Patients with diabetes had the highest morbidity and mortality. These results were analyzed, and we conclude that CHD patients at risk with a surgically correctable condition should be considered for elective intervention, even if they are currently free of symptoms. This may be particularly true for CHD patients with diabetes.

Abdomen