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Biomedical subjects

P Kaufman

Publications and source records attributed to P Kaufman.

At least 19 recordsLinked to original sources

Atropine reduces but does not eliminate the age-related decline in perfusion outflow facility in monkeys.

Accommodative amplitude and outflow facility decline with age in rhesus monkeys and humans. In monkeys, there is an age-related reduction in ciliary muscle (CM) mobility due to stiffening of its posterior and outer attachments. Since the CM inserts into the trabecular meshwork (TM) and CM contraction deforms the TM so as to increase outflow facility, we asked whether the age-related decline in outflow facility observed in anesthetized monkeys is consequent to the age-related reduction in CM mobility. One eye of 19 pentobarbital-anesthetized rhesus monkeys aged 4-24 years underwent 2-level constant pressure perfusion of the anterior chamber (AC) for 40 min to measure baseline total outflow facility. Both eyes then received 100 micrograms of atropine, given topically to the central cornea. The AC of the second eye was cannulated 40 min after atropine treatment. Facility was measured simultaneously in both eyes for 40 min beginning 45 min after atropine treatment. Baseline facility declined with age by -0.0160 +/- 0.0059 microliters min-1 mmHg-1 yr-1 (P = 0.009). The average facility at baseline was approximately 50% higher in the youngest (ages 4-10 years) compared to the oldest (ages 21-25 years) animals (P < or = 0.03). Following atropine facility decreased by approximately 25% in the youngest monkeys (N.S.), but not at all in the oldest animals when compared to baseline. Thus, the age-related facility decline persisted after atropine in both eyes, but was not as dramatic as prior to atropine (-0.0092 +/- 0.0050 [P < or = 0.09] and -0.0078 +/- 0.0044 [P < or = 0.10] microliter min-1 mmHg-1 yr-1 respectively). Apparently, atropine inhibits facility-relevant anesthetic-induced ciliary muscle tone to a greater extent in younger than in older monkeys, presumably because stiffening of the posterior and outer attachments of the CM in the older animals has already reduced its ability to move and thereby deform the TM. The inability of atropine to completely eliminate the age-related facility decline indicates the presence of atropine-independent, facility-relevant age-dependent changes in the TM itself, such as loss of cells or build-up of extracellular material.

Aging↗

Association of a choroidal ganglion cell plexus with the fovea centralis.

PURPOSE: After recently demonstrating an NADPH-diaphorase-, nitric oxide synthase (NOS)-positive ganglion cell plexus in the human choroid that was absent in rabbit and rat eyes, the authors extended their comparative studies to nonhuman primates and to subprimate mammals. METHODS: The authors investigated the choroids of diurnal cynomolgus monkeys with well-developed fovea centralis and accommodative systems; diurnal tree shrews without a fovea centralis or accommodative capacity; nocturnal owl monkeys with substantial accommodative capacity but without a fovea centralis; cats with an area centralis but no fovea centralis; and pigs without an area centralis or a fovea centralis. The latter two species have moderately developed ciliary muscles. Wholemounts of the choroid of eight cynomolgus monkey, two owl monkey, four tree shrew, four cat, and four pig eyes were stained for NADPH-diaphorase. In addition, frozen sections through the cynomolgus monkey choroid were stained for NOS and vasoactive intestinal polypeptide (VIP). RESULTS: In all species, the choroidal vessels were surrounded by NADPH-diaphorase-positive nerve fibers. A ganglion cell plexus, however, was seen only in cynomolgus monkey eyes. The ganglion cells stained for NOS and VIP. CONCLUSIONS: The presence of intrachoroidal nitrergic nerve cells restricted to species with a fully developed fovea centralis may indicate a functional correlation of these structures.

Amino Acid Oxidoreductases↗

[Semi-invasive diffuse pulmonary aspergillosis with antineutrophil cytoplasmic antibodies. 2 cases].

We report two cases of semi-invasive pulmonary aspergillosis with a thoracic wall extension in the first case and a parietal vasculitis without Aspergillus invasion in the second. Semi-invasive pulmonary aspergillosis is an identifiable entity. It is characterized by impairment of local pulmonary defense mechanisms and/or a mild systemic immunosuppression as well as a slowly progressive course. Pulmonary symptoms are not specific. The thoracic wall involvement subsequent to a contiguous pulmonary lesion occurs rarely and indicates poor prognosis. CT scan improves diagnosis significantly, confirmed by histology and/or by the biopsy growth of Aspergillus. Itraconazole, tolerated better than amphotericin B, is an efficient treatment though prognosis remains poor (28% of deaths). Detection of anti-neutrophil cytoplasmic antibodies (diffuse cytoplasmic staining) evolving conversely to this disease seems to be associated with infectious vasculitis. These antibodies are found in vasculitis and especially in Wegener's granulomatosis with a high specificity. They have also been described in a few patients with infectious diseases.

Aged↗

Hemodynamic response to volume stress in awake late-pregnant and nonpregnant rats.

The present study was designed to determine whether the often observed gestational rise in blood volume alters the hemodynamic response to volume stress relative to the nonpregnant state. Late-pregnant and nonpregnant Wistar rats, prepared with an electromagnetic flow probe around the ascending aorta and/or intravascular catheters were used for this study. One of the following sets of measurements were performed either before and after volume loading or before and after volume depletion (24 h thirst): 1) continuous monitoring of cardiac output, blood pressure, heart rate, and fluid balance (only during volume loading); 2) measurement of cardiac output and regional blood flows (microspheres); and 3) measurement of the inferior vena cava diameter (x-ray). Both rapid (bolus) and slow volume loading (infusion) led to a rise in cardiac output. The generated surplus in cardiac output was distributed to the kidneys, skeletal tissues, and intestines (only in nonpregnant rats), and was paralleled in the pregnant rats by a consistent fall in placental blood flow. Slow volume depletion had neither a consistent effect on cardiac output nor on its distribution, with even a preserved maturational rise in placental blood flow during the 24 h of thirst. Slow volume loading and depletion led to an increase and decrease of the caliber of the inferior vena cava, respectively. The nonnuterine hemodynamic response to all forms of volume stress had not changed in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interaction of soluble pig heart glutamate-aspartate transaminase with various beta,gamma-unsaturated amino acids.

beta-Ethylidene-DL-aspartate (beta EA) and beta-methylene-DL-glutamate (beta MG) were synthesized and tested as potential suicide inhibitors of soluble pig heart glutamate-aspartate transaminase (sGAT). beta MG was found to be a) a substrate with a very low turnover number relative to glutamate and b) a competitive inhibitor with respect to aspartate (albeit with a large binding constant). At high concentrations beta MG inactivated the enzyme but only very slowly. beta EA was also found to be a substrate with a very low turnover number; it did not inactivate the enzyme (1 hr, 25 degrees C) even at a high concentration. However, beta EA was found to bind to the enzyme with an affinity comparable to that of aspartate and glutamate. beta-Methylene-DL-aspartate (beta MA) has been shown to rapidly inactivate glutamate-aspartate transaminase. Therefore, it appears that glutamate-aspartate transaminase can bind analogues of aspartate with alkene groups in the beta position. The conjugated carbonyl groups of beta MA and beta EA will enhance Michael addition in comparison with that expected for vinylglycine. On the other hand, the presence of the methyl groups should reduce the electrophilicity of the double bond of beta EA compared to beta MA. This deactivation and/or steric hindrance to Michael attack may account for the inability of beta EA to inactivate sGAT. Therefore, it may be possible to design selective suicide inhibitors of glutamate-aspartate++ transaminase with the following structure: HO2CC(= CHX)CH(CO2H)NH2, where X is an electron-withdrawing group. Ideally, X would increase the reactivity of the double bond while affording a minimum of steric hindrance to susceptible enzyme-bound bases.

Amino Acids↗

Investigations into the possible regulation of negative gravitropic curvature in intact Avena sativa plants and in isolated stem segments by ethylene and gibberellins.

Using Avena sativa L. cv. Victory oat seedlings and excised p-1 stem segments (including the p-1 and p-2 internodes) the effect of exogenously supplied ethylene and the removal of ethylene on internodal extension and gravitropic bending was assessed. Similarly, the ability of the excised system to respond to gravistimulation was assessed in the presence of inhibitors of ethylene action (AgNO3) and ethylene synthesis (3,5-diiodo-4-hydroxybenzoic acid and benzyl isothiocyanate; BITC). The production of ethylene from both intact and excised systems was also measured from 0 to 48 h after gravistimulation, relative to vertical controls. Although gravitropic curvature is initiated, and indeed enters the most rapid phase of upward bending during the first 6 h, there is no difference in ethylene production between vertical and geostimulated plants during this period. The ethylene production of gravistimulated plants rises sharply to a maximum at 24 h, then decreases steeply to almost the control level by 48 h, at which time the rate of upward curvature is diminishing. Neither the addition nor removal of ethylene, nor the addition of inhibitors affecting ethylene-action (AgNO3) or synthesis (DIHB) influence gravitropic bending or internodal extension in excised segments. Although the ethylene synthesis inhibitor BITC slowed down the rate of upward bending, this effect could not be reversed by addition of ethylene. We conclude that the burst in ethylene production that develops in leaf-sheath bases (pulvini) after they have started to curve upwards is not primary to the induction of curvature. We further suggest that ethylene has no major effect or role in the induction of upward bending after gravistimulation. The metabolism of high specific activity gibberellin A1 ([3H]-GA1) in the excised system was assessed during 1, 2 and 4 h of gravistimulation. Changes in endogenous GAs and GA metabolism have been shown previously to be correlated (at the later stages) with gravistimulated bending in intact Avena shoots. The excised segments "leaked" free [3H]-GAs and [3H]-GA glucosyl conjugate-like substances into the bathing medium, and this was a confounding factor. Nevertheless, gravistimulated stem segments, and especially the bottom half of the segment, were significantly less leaky then vertical segments. Thus, just 1 h after gravistimulation, bottom segment halves retained 22% more precursor [3H]-GA1, 36% more free [3H]-GA-like metabolites, and 48% more [3H]-GA glucosyl conjugate-like metabolites than vertical segments. In contrast, the 1 h gravistimulated top halves retained slightly less (1-4%) precursor [3H]-GA1 and free [3H]-GA metabolites, but 21% more [3H]-GA glucosyl conjugate-like radioactivity than vertical segments.

Avena↗

[The importance of HLA antigens in alcoholic cirrhosis].

The existence of a relationship between HLA and the possibility of the development of an alcoholic cirrhosis is researched in this paper. This work was done from 1982 to 1984, by the staff of four clinics of the Medicine School of the University of Uruguay. We studied 47 alcoholics with portal cirrhosis, 19 non-cirrhotic alcoholics and 250 healthy nonalcoholic controls. We confirmed with liver biopsy the cirrhosis in the first group and in the second, liver biopsy was performed in order to assure that they had no cirrhosis. Table I shows the histocompatibility antigens which were tested in the 3 groups. Levels of significance were obtained from exact Fisher test with Yates correction for discontinuity; Pc (corrected P) and RR (relative risk) were also determined. In the alcoholics with portal cirrhosis, the HLABW40 showed a Pc less than 0,005 (RR = 3,93). In the non-cirrhotic alcoholics no significative association was found. We conclude that the carrier of the genetic marker HLABW40, has almost 4 times more chances to develop a cirrhosis as consequence of chronic alcoholic abuse. The presence of this marker, in our patients, has no association with the possibility that an individual becomes an alcoholic abuser. We think that if this data are confirmed in a wider study, some guidelines for the prevention of alcoholic cirrhosis may be established.

Adult↗

Tear lithium concentration: a measurement of dubious clinical value.

A mean tear/serum lithium ratio of 0.77 +/- 0.06 was found in 13 volunteers who were given lithium carbonate for 7 days. This finding differs considerably from those of another study, which reported tear and plasma lithium levels to be quite similar. It is suggested that measurement of tear lithium concentration has no clinical utility and that further research along these lines should be discouraged.

Adult↗

Long-term results of valve implants in filtering surgery for eyes with neovascular glaucoma.

Filtration surgery was performed with a pressure-sensitive, unidirectional valve implant in 79 eyes with neovascular glaucoma. The device consisted of an open Supramid tube (outside diameter 0.58 mm) sealed to a Silastic tube with a slit valve. The Supramid tube was inserted at the corneoscleral limbus 1 to 4 mm into the anterior chamber. The Silastic portion was located under a scleral flap. Of the 79 eyes, 53 had postoperative intraocular pressures less than or equal to 24 mm Hg after a mean follow-up period of 23.7 +/- 10.9 months. Bleb revision for external scarring was required in ten of these 53 eyes and postoperative medical therapy was required in 26. The valve implant failed to control intraocular pressure in 26 of the 79 eyes. Failure was secondary to scarring of the external bleb in 18 eyes and to closure of the internal Supramid tube in five eyes. Mortality during the follow-up period was high: 12 of the 53 successfully treated patients and five of the unsuccessfully treated patients died.

Adolescent↗

Filtering valve implant surgery for eyes wtih neovascular glaucoma.

We performed filtration surgery with a unidirectional, pressure-sensitive valve implant in 40 eyes with neovascular glaucoma. The device consisted of an open Supramid tube (outside diameter 0.58 mm, inside diameter 0.38 mm) sealed to a Silastic tube with a slit valve. The Supramid tube was inserted at the corneoscleral limbus 1 to 4 mm into the anterior chamber and the Silastic portion was located under a lamellar scleral flap. Twenty-seven of 40 eyes (68%) had a postoperative IOP less than or equal to 24 mm Hg with a mean follow-up of 13.8 months. Ten of these 27 eyes required postoperative medical therapy to achieve this level of IOP control. The glaucoma valve implant failed to return IOP to normal in 13 of the 40 eyes (32%), 11 of these as a consequence of scarring of the external bleb.

Adult↗

The Structure of Plant Cell Walls: VI. A Survey of the Walls of Suspension-cultured Monocots.

The primary cell walls of six suspension-cultured monocots and of a single suspension-cultured gymnosperm have been investigated with the following results: (a) the compositions of all six monocot cell walls are remarkably similar, despite the fact that the cell cultures were derived from diverse tissues; (b) the cell walls of suspension-cultured monocots differ substantially from those of suspension-cultured dicots and from the suspension-cultured gymnosperm; (c) an arabinoxylan is a major component (40% or more by weight) of monocot primary cell walls; (d) mixed beta-1,3; beta-1,4-glucans were found only in the cell wall preparations of rye grass endosperm cells, and not in the cell walls of any of the other five monocot cell cultures nor in the walls of suspension-cultured Douglas fir cells; (e) the monocot primary cell walls studied contain from 9 to 14% cellulose, 7 to 18% uronic acids, and 7 to 17% protein; (f) hydroxyproline accounts for less than 0.2% of the cell walls of monocots. Similar data on the soluble extracellular polysaccharides secreted by these cells are included.

Journal Article↗