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Biomedical subjects

S Rosen

Publications and source records attributed to S Rosen.

At least 109 records · Page 6Linked to original sources

Tumefactions as an extravascular manifestation of Wegener's granulomatosis.

Wegener's granulomatosis appeared as localized or infiltrative tumefactions in six patients. The tissue swellings affected the retroperitoneum, mediastinum (two), breast, retroorbital tissue (two), and gingiva. There was extensive fibroblastic proliferation in each case with a predominantly granulocytic inflammatory component, microabscess formation, and collagen necrobiosis. In one of the mediastinal lesions and in the gingiva, there was a granulomatous component as well. In the breast were scattered multinucleated histiocytes. Necrotizing vasculitis was absent or limited in all cases. All patients responded dramatically to cyclophosphamide and/or prednisone after the diagnosis was established. These observations indicate a role for tissue destruction in Wegener's granulomatosis mediated by granulocytes without a vasculitic component.

Adult↗

Level of functioning, severity of illness, and smoking status among chronic psychiatric patients.

It was hypothesized that chronic psychiatric patients who had quit smoking would be more functional and have lower Brief Psychiatric Rating Scale (BPRS) scores than those who continued to smoke. We interviewed 300 chronic psychiatric patients followed in the community. Fourteen percent were former smokers and nearly 11% had never smoked. Fifty-six percent of the sample were current smokers who had no intention of quitting, 13% were considering quitting, and 6% were seriously preparing to quit or had actually quit for a short period. When compared with current smokers, former smokers were more likely to live independently (p < .026) and less likely to have a drug or alcohol problem (p < .013). A random sample of current smokers were compared with former smokers on the BPRS. Former smokers had lower total BPRS scores (p < .03), and lower withdrawal/retardation subscale scores (p < .0058) than current smokers. We concluded that better functioning patients who smoked would be more likely to quit.

Adult↗

Vascular permeability factor (vascular endothelial growth factor) is strongly expressed in the normal male genital tract and is present in substantial quantities in semen.

PURPOSE: Vascular permeability factor (VPF) is a potent inducer of microvascular hyperpermeability and stimulates endothelial cell growth and angiogenesis. This study examines expression of VPF in the male genital tract. MATERIALS AND METHODS: Vascular permeability factor in seminal plasma was quantified by immunoassay. Vascular permeability factor mRNA and protein expression in tissue were studied by situ hybridization and immunohistochemistry. RESULTS: All seminal plasmas studied contained high levels of VPF. Prostatic and seminal vesicle epithelium labeled strongly for VPF mRNA and protein. CONCLUSIONS: The strong expression of VPF in prostate and seminal vesicle and the high concentration of VPF in semen suggest an important role for this cytokine in male fertility.

Adult↗

Nine members of the myomodulin family of peptide cotransmitters at the B16-ARC neuromuscular junction of Aplysia.

1. Neuromodulation by multiple related peptides with different spectra of physiological effects appears an effective way to integrate complex physiological functions. A good opportunity to examine this issue occurs in the accessory radula closer (ARC) neuromuscular circuit of Aplysia, where, extensive previous work has shown, acetylcholine-induced contractions of the muscle are variously modulated by several families of peptide cotransmitters released under appropriate behavioral circumstances from the muscle's own two motor neurons. 2. In this work we focused on the myomodulins (MMs) released from motor neuron B16. Previous work has characterized MMA (PMSMLRLamide) and MMB (GSYRMMRLamide). We now similarly purified from ARC neuromuscular material and sequenced MMC (GWSMLRLamide), MMD (GLSMLRLamide), MME (GLQMLRLamide), and MMF (SLNMLRLamide). Three additional MMs, MMG (TLSMLRLamide), MMH (GLHMLRLamide), and MMI (SLSMLRLamide), are encoded by a known MM gene. B16 probably synthesizes, and coreleases, all nine MMs. Further MMs have been found in other mollusks. All evidence indicates that the MMs are a major, widely distributed family of molluscan neuropeptides important as neuromuscular modulators and probably also central transmitters or modulators. 3. MM effects on motor neuron B16-elicited ARC muscle contractions were best analyzed as the sum of three distinct actions: potentiation, depression of the amplitude of the contractions, and acceleration of their relaxation rate. We compared the effectiveness of all nine MMs in these respects. We correlated this with their effectiveness in enhancing the L-type Ca current and activating a specific K current in voltage-clamped dissociated ARC muscle fibers, effects we previously proposed to underlie, respectively, the potentiation and the depression of contractions. 4. All nine MMs were similarly effective in enhancing the Ca current and, as far as it was possible to determine, potentiating the amplitude as well as accelerating the relaxation rate of the contractions. 5. In contrast, the MMs' ability to activate the K current and depress the contractions varied greatly. MMB and MMC, in particular, were weak, whereas the other seven MMs were considerably more effective in both respects. 6. Altogether, we were able to explain the potentiating and depressing strengths of the MMs by the magnitude of their modulation of the Ca and K currents, providing further support for our hypothesis that the effects on contraction amplitude are mediated by the effects on the two currents. 7. The net effect on contraction amplitude was determined by the balance between the potentiation and depression. Although most MM concentrations had both potentiating and depressing actions, potentiated contractions predominated at low and depressed contractions (but with accelerated relaxation rate) at high concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Biosensors: where do we go from here?

In the 1980s, researchers predicted that biosensors would dominate hospital POC, POL, and home testing. While that hasn't quite come to pass, here's what biosensors have accomplished and a look at their future.

Biosensing Techniques↗

FK506 nephrotoxicity: morphologic and physiologic characterization of a rat model.

BACKGROUND: FK506 is a useful agent in the prevention of allograft rejection but has recently been shown to be nephrotoxic. EXPERIMENTAL DESIGN: Sprague-Dawley rats (n = 40) were divided into four groups: control (C); low-salt (LS); FK506, 3 mg/kg daily by gavage (FK); and FK506-low-salt (FK-LS). After 6 weeks, the animals underwent physiologic studies and were sacrificed with perfusion fixation of the kidneys. Semiquantitative analysis of morphologic injury was performed as well as grading of juxtaglomerular apparatus (JGA) granularity (1-micron plastic sections). Computer-assisted morphometry was used to measure medullary thick ascending limb (mTAL) size within the inner stripe. RESULTS: Serum creatinine and plasma renin activity were significantly elevated only in the FK-LS group, but both FK groups had significantly increased fractional excretion of Mg. Tubular atrophy and fibrosis involving medullary rays and inner stripe (areas of low oxygen availability) was minimally present in FK, but prominent in FK-LS (P < 0.001). Injury correlated with decreased function (P < 0.001). Variance of mTAL size, an expression of co-existent tubular atrophy and hypertrophy was significantly greater in FK-LS and correlated with decreased renal function and urine osmolality (P < 0.001). JGA granularity was increased by FK506 (P < 0.006) with the highest values in FK-LS (P < 0.001), and strongly correlated with injury (P < 0.001). JGA granularity did not correlate with circulating renin activity levels, suggesting local activation of a renin-angiotensin system. CONCLUSIONS: FK506 compromises renal parenchymal zones which are known to have limited oxygen availability (medullary ray and inner stripe), a pattern that has been observed with other nephrotoxins. The injury is potentiated by salt depletion and may be mediated by the renin-angiotensin system. Furthermore, these findings illustrate the close correlation between the medullary injury that was observed and the impaired function that was documented.

Animals↗

Characterising auditory filter nonlinearity.

An important aspect of auditory nonlinearity is that psychoacoustically measured auditory filters broaden as the level at which they are measured increases. However, it is not yet clear whether the change in filter shape is controlled primarily by the level of the probe or that of the masker. We have therefore developed a new method for fitting filter shapes to notched-noise data in which filter parameters depend explicitly on signal level (either probe or masker). By applying this technique to a set of notched-noise data in which both fixed-probe and fixed-masker paradigms have been used at a range of levels, we have been able to show that models in which filter parameters depend on probe level are considerably more successful than models in which filter parameters depend upon masker level. The results from this new procedure have enabled us to describe the nonlinear changes in auditory filter shape at 2 kHz with only five parameters. Also discussed are the implications of these findings for the generation of excitation patterns and for the computational implementation of simple, yet reasonably realistic nonlinear auditory filters whose shape depends on their output.

Acoustic Stimulation↗

Intraocular pressure after neodymium:YAG laser treatments in the anterior segment.

Intraocular pressure (IOP) increase soon after neodymium:YAG (Nd:YAG) treatments in the anterior segment has been reported. To evaluate this complication in a large sample of patients, we conducted a retrospective study of all Nd:YAG treatments during three years. Three hundred forty capsulotomies and 212 iridotomies were performed with the Q-switched Nd:YAG laser. An IOP elevation of 10 mm Hg or more within two hours of laser surgery was seen in 15 eyes (4.4%) that had a capsulotomy but in 45 eyes (21.2%) that had an iridotomy. In 13 of the 15 eyes in which the IOP increased after capsulotomy, additional risk factors (glaucoma, high myopia, aphakia) were found. Our results indicate that posterior capsulotomy with the Nd:YAG laser in otherwise healthy, pseudophakic eyes is usually not accompanied by immediate IOP elevation. Elevation can be predicted by risk factors and therefore anticipated in a small group of vulnerable patients.

Aged↗

Loop diuretics reduce hypoxic damage to proximal tubules of the isolated perfused rat kidney.

The straight portion (S3) of the proximal tubule lies in close proximity to the thick ascending limbs (TALs) at the cortico-medullary junction. Since a delicate balance exists between oxygen demand and the limited oxygen supply in this region, we hypothesized that reduction of thick limb metabolic activity might augment oxygen availability to S3 segments, which depend heavily upon aerobic metabolism, and prevent hypoxic damage. The degree of functional deterioration and morphological damage to S3 was assessed in isolated rat kidneys perfused with an erythrocyte-free medium. Bumetanide (10(-5) M) and furosemide (10(-4) M) reduced S3 fragmentation from 9.8 +/- 3.9% of tubules in controls to 0 and 1.4 +/- 0.9%, respectively (P < 0.0005). Tubular glucose reabsorption was better preserved in kidneys exposed to loop diuretics than in control kidneys (P < 0.01), and urinary alkaline phosphatase (P < 0.05) and the total amount of LDH released into the perfusate and urine (P < 0.01) were lower in the treatment groups. Morphological damage to S3 was closely correlated with medullary TAL necrosis (r = 0.66, P < 0.001), urinary alkaline phosphatase excretion (r = 0.89, P < 0.001) and glycosuria (r = 0.83, P < 0.001). We conclude that under hypoxic conditions TALs and S3 segments may compete with each other for a limited oxygen supply. Reduction of active transport in the mTAL might augment oxygen availability to S3 segments and improve their survival.

Alkaline Phosphatase↗

Experimental nephrotoxicity, hepatotoxicity and pharmacokinetics of cyclosporin G versus cyclosporin A.

Cyclosporin G (CsG) is an analogue of cyclosporin A (CsA) with strong immunosuppressive activity. We compared these two drugs in a rat model in which salt depletion promotes irreversible renal interstitial fibrosis with renal dysfunction in animals given CsA for three weeks. When both drugs were given in the same dosage on a weight basis (15 mg/kg/day, subcutaneously), CsA blood levels were higher than CsG (3305 vs. 1824 ng/ml, P < 0.001). This could be explained by a higher CsG clearance (6.4 vs. 4.3 ml/min/kg in CsA, P < 0.0001) resulting in smaller CsG area under the curve. There was also lower renal and hepatic CsG tissue concentrations. CsA induced a dramatic decrease in GFR, 0.14 in CsA versus 0.67 ml/min/100 g in control, P < 0.001, and increased urinary excretion of N-acetyl beta-D-glucosaminidase (NAG), 21 in CsA versus 13 IU/gCr in control rats, P < 0.001. CsG-treated and control rats had similar GFR and urinary NAG. When CsA dosage was decreased to 7.5 mg/kg blood levels were similar to those found with CsG 15 mg/kg. CsA at this dose caused a reduced GFR (0.29 ml/min/100 g) and an increased urinary NAG (20 IU/gCr) (P < 0.01 vs. control for both). Both dosages of CsA induced considerable cortical and medullary injury (interstitial fibrosis and tubular atrophy), more severe than the histological damage found in CsG-treated rats. Neither drug promoted significant changes in liver function or histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

FRF peptides in the ARC neuromuscular system of Aplysia: purification and physiological actions.

1. One preparation that has proven to be advantageous for the study of neuromuscular modulation is the accessory radula closer (ARC) muscle of Aplysia californica and its motor neurons B15 and B16. In this study three members of a new peptide family have been purified from this well-characterized preparation. Because these peptides terminate in Phe-Arg-Phe-amide, we have named them FRFA, FRFB, and FRFC. The FRFs are thus RFamide peptides and are related to the widely studied neuropeptide FMRFamide. 2. The FRFs are present in the ARC motor neuron B15 in small quantities. 3. When they are exogenously applied, the FRFs decrease the size of ARC muscle contractions elicited by stimulation of either motor neuron B15 or B16. They appear to do this by a combination of presynaptic and postsynaptic actions. 4. Presynaptically, the FRFs appear to act like the buccalins, another family of inhibitory ARC neuropeptides. Both families of peptides reduce the size of motor neuron-elicited excitatory junction potentials (EJPs) presumably by decreasing presynaptic acetylcholine (ACh) release. 5. Postsynaptically, the FRFs appear to depress contractions because they activate a characteristic voltage-dependent, 4-amino-pyridine-sensitive K current in the ARC muscle. The same current is activated by a second class of ARC modulators: those that exert potentiating actions at low doses and inhibitory actions at high doses, i.e., serotonin, the small cardioactive peptides (SCPs), and particularly the myomodulins. Receptors mediating activation of the K current by the FRFs and the other modulators do, however, appear to be different. 6. We hypothesize that the inhibitory actions of the FRFs prevent excessively large muscle contractions. If contraction size is limited, then contraction duration is also limited. This may allow faster and more energetically favorable switching between contractions of antagonistic muscles.

Acetylcholine↗

Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat.

Human radiocontrast nephrotoxicity is predicted by the presence of multiple risk factors, often associated with compromised renal circulation. To produce a simple model of radiocontrast nephropathy, rats were pretreated with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME, to inhibit nitric oxide synthesis) before the administration of iothalamate. Acute renal failure consistently developed, with a decline in creatinine clearance from 1.05 +/- 0.10 to 0.27 +/- 0.05 ml/min (P < 0.001) associated with selective necrosis of 49 +/- 9% of medullary thick ascending limbs. Hemodynamic studies using laser-Doppler probes revealed that when injected alone, iothalamate increased outer medullary blood flow to 196 +/- 25% of baseline (P < 0.001). Pretreatment by L-NAME or indomethacin both reduced basal medullary blood flow and transformed the medullary vasodilator response to radiocontrast into vasoconstriction, with a prolonged reduction of medullary blood flow to less then half of baseline. Combined administration of indomethacin, L-NAME, and iothalamate lowered medullary blood flow to 12 +/- 4% of baseline. We conclude that prostanoids and nitric oxide have an important protective role in the renal response to radiocontrast material. Reduced synthesis of these vasoactive substances in renal/vascular diseases may predispose patients to radiocontrast nephropathy.

Acute Kidney Injury↗

Holistic nursing in New Zealand.

New Zealand nurses are active and dynamic emerging holistic practitioners. Despite an economic recession and dramatic changes in their health care delivery systems, the country's holistic nurses have mobilized to develop and begin a holistic nurses' association. Holistic nurses from both islands have begun independent practices using complementary therapies and modalities. Although New Zealand is distant from North America geographically, there have been increasing numbers of exchange visits and subsequent influence on international holistic nursing practice. New Zealand, being a lush, green, clean, semitropical country in the South Pacific, is a wonderful place for North American nurses to experience cross-cultural nursing while still being in an English-speaking country.

Holistic Health↗

Effects of salt depletion on the kidney: changes in medullary oxygenation and thick ascending limb size.

Previous studies have shown that salt depletion enhances the susceptibility of the kidney to nephrotoxins (amphotericin, cyclosporine, and contrast). To study the renal response to salt depletion, Sprague-Dawley rats were fed a sodium-deficient diet (N = 12) with pair-fed controls (N = 13) for 4 wk. In addition, rats from each group underwent 24-h water deprivation studies (N = 9; four salt deprived, five normal). Plastic 1-micron horizontal sections of mid-inner stripe were examined, and cross-sectional areas of the medullary thick ascending limb (mTAL) were analyzed. The mTAL of the salt-deprived rats were smaller (P = 0.04) and showed greater variance in size (P = 0.02) than control (618 +/- 106 versus 693 +/- 50 microns2). However, mean glomerular and collecting duct cross-sectional areas were unaffected by salt intake. Cross-sectional areas of long- and short-loop mTAL were significantly different, regardless of group (518 +/- 78 versus 732 +/- 92 microns2). Maximal urinary concentrating ability was found to correlate with mTAL cross-sectional area (r = 0.85; P = 0.004) and with long-loop mTAL size (r = 0.77; P = 0.016). However, it did not significantly correlate with short loop mTAL size (r = 0.53; P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗