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Biomedical subjects

R Goldstein

Publications and source records attributed to R Goldstein.

At least 181 records · Page 10Linked to original sources

Structure and copy number of gene clusters related to the pap P-adhesin operon of uropathogenic Escherichia coli.

The structurally related pap and prs operons of the uropathogenic Escherichia coli isolate J96 encode a P and an F adhesin that mediate bacterial attachment to the human P blood group antigen and the Forssman antigen, respectively. Using probes prepared from different segments of the pap operon, Southern blot hybridizations were performed to characterize pap-related sequences of 30 E. coli clinical isolates expressing different adhesin phenotypes. Gene clusters encoding P and F adhesins displayed no restriction site polymorphism in sequences homologous to the papH, papC, and papD genes that encode proteins essential to the transport and polymerization of the subunits of the P-pilus adhesin. In contrast, pap-related genetic elements associated with a null phenotype either lacked homology to the papH, papC, and papD genes or displayed a restriction site polymorphism in this region. Sequences within and surrounding the J96 papG and prsG adhesin genes that determine the binding specificities to the P and F antigens, respectively, were not conserved. However, gene clusters encoding different binding specificities could not be distinguished based on such restriction site polymorphisms. The majority of clinical isolates had more than one copy of pap-related sequences that involved gene clusters similar to the J96 pap operon, as well as genetic elements that were related only to a part of this operon. The implications of this unexpected copy number polymorphism with respect to possible recombination events involving pap-related sequences are discussed.

Adhesins, Escherichia coli↗

Applicability of a threshold loading device for inspiratory muscle testing and training in patients with COPD.

We evaluated application of a Pth device for testing inspiratory muscle endurance among patients with severe but stable COPD. Endurance time in five patients was reproducible. Magnitude of variability was +/- 1.26 minutes with a range of +/- 0.19 to +/- 2.28 minutes. Eleven inpatients completed inspiratory muscle training twice daily for four weeks in addition to their usual program of respiratory rehabilitation. The mean age of our experimental cohort was 65 years; FEV1, 33 +/- 12 percent predicted; and Dsb, 42 +/- 7 percent predicted. Baseline measurements showed no significant differences in pulmonary function, exercise tolerance, inspiratory muscle strength or inspiratory muscle endurance between control and study groups. Following training, the study group significantly improved inspiratory muscle endurance as evidenced by an increase in endurance time while breathing against the same absolute external Pth load used during baseline assessments. There were no associated changes in lung mechanics, muscle strength or exercise tolerance.

Aged↗

In vitro IgM and IgM rheumatoid factor production in response to Staphylococcus aureus Cowan I and pokeweed mitogen: the contribution of CD5+ (Leu 1) B cells.

The relation between the percentage of circulating CD5+ CD20+ B cells and the ability to synthesize IgM and IgM rheumatoid factor (RF) in vitro in response to pokeweed mitogen (PWM) and Staphylococcus aureus Cowan I (SAC) was assessed in 21 healthy controls. CD5+ CD20+ cells ranged from 7.3 to 19.9% of total CD20+ B cells. By Spearman's rank correlation, there was an inverse relation between the percentage of CD5+ CD20+ B cells and IgM production in response to PWM (rs = -0.452, p less than 0.05) and a direct correlation with RF production in response to SAC (rs = 0.450, P less than 0.05). The percentage of CD5+ CD20+ B cells was not related to any serologic HLA-A, B, C or D antigen. Healthy individuals may be predisposed to producing IgM or autoantibodies based on the percentage of circulating CD5+ Cd20+ B cells.

Antigens, CD20↗

Gold sodium thiomalate compared to low dose methotrexate in the treatment of rheumatoid arthritis--a randomized, double blind 26-week trial.

Thirty-five patients with definite or classic rheumatoid arthritis (RA) entered a prospective, double blind, randomized study of 26 weeks duration. All patients had active RA that was unresponsive to greater than or equal to 2 nonsteroidal antiinflammatory medications and/or antimalarials. Eighteen patients were randomized to receive methotrexate (MTX) 12.5 mg weekly (oral and noncycled) + placebo, and 17 patients to gold sodium thiomalate (GSTM) 50 mg IM weekly + placebo (schedule I) after initial test dose of 10 and 25 mg. Dose reductions from Schedule I to Schedule II (i.e. MTX 5.0 mg and GSTM 25 mg) were permitted at Weeks 6 and 12. The GSTM group showed statistically significant improvement at Week 26 compared with baseline status in all of the clinical efficacy variables and the MTX group in 7. There were no statistically significant differences in these outcome variables between the 2 groups at Week 26. However, this small sample size may not have detected a clinically significant difference between treatment groups (alpha = 0.05, beta = 0.20). Two of the 18 patients treated with MTX and 6 of the 17 patients treated with gold withdrew because of drug toxicity, but this difference was not statistically significant. In conclusion, GSTM and MTX are similarly efficacious in the short term treatment of RA.

Activities of Daily Living↗

Major histocompatibility complex genes in systemic lupus erythematosus, Sjögren's syndrome, and polymyositis.

Current concepts about the roles of human leukocyte antigen (HLA) and complement genes in predisposing to connective tissue diseases are reviewed. Precise localization of disease conferring alleles and epitopes is confounded by two major phenomena: (1) clinical and serologic heterogeneity of the diseases and associations of several different HLA alleles with different and often overlapping autoantibody responses; and (2) linkage disequilibrium of many potentially relevant gene loci located on the disease-associated HLA haplotypes. Using molecular genetic tools in serologically homogeneous patient populations, and across racial lines, the Ro (SS-A) and la (SS-B) autoantibody responses in systemic lupus erythematosus and Sjögren's syndrome appear to associate most strongly with HLA-DQ alleles, whereas the anti-Jo-1 autoantibody in myositis correlates best with HLA-DRw52. A gene deletion of C4A within HLA predisposes to systemic lupus erythematosus in both white and black patients.

Alleles↗

Molecular heterogeneity of complement component C4-null and 21-hydroxylase genes in systemic lupus erythematosus.

C4A-null alleles (C4A*Q0) and hereditary complete C4 deficiency (homozygous C4A*Q0,C4B*Q0) are associated with systemic lupus erythematosus (SLE). Using Southern blot analysis with C4 and 21-hydroxylase (21-OH) DNA probes, we studied SLE patients and normal control subjects with or without C4A*Q0, and 2 C4-deficient SLE patients. A previously reported large C4A,21-OHA gene deletion associated in normal subjects with the HLA-A1;B8;DR3;C4AQ0 haplotype was detected by the appearance of a new C4 Hind III 8.5-kb fragment and disappearance of a 3.2-kb 21-OH Taq I fragment. In 3 SLE patients with homozygous C4A*Q0 and 15 with heterozygous C4A*Q0, this deletion pattern occurred almost exclusively in association with the HLA-B8;DR3;C4A*Q0 phenotype; the one exception was a black SLE patient. Other C4A*Q0-bearing HLA phenotypes in white patients and black patients with SLE, and the 2 completely C4-deficient SLE patients, had normal DNA hybridization to both C4 and 21-OH probes. The genetic basis for C4-null alleles in SLE is heterogeneous. A large C4A,21-OHA deletion occurs mainly on the HLA-B8;DR3;C4AQ0 haplotype in SLE and controls. Other HLA haplotypes bearing C4A*Q0 have normal C4 and 21-OH genes, as demonstrated by Southern blot analysis.

Alleles↗

Opposite effects of vasotocin and of a specific vasotocin antiserum on active sleep of kittens.

The effects of intracerebroventricularly administered synthetic arginine vasotocin (AVT) or undiluted AVT, vasopressin (AVP) and oxytocin (OT) antisera on active sleep (AS) of newborn kittens have been investigated in comparison with rabbit serum control. In contrast to AVP and OT antisera, AVT antiserum has produced opposite effects on AS as AVT itself. Since after 10 microliter of undiluted AVT antiserum the percentage of AS did not decrease under 20% and even after 100 microliter AS did not decrease under 5%, it is concluded that, at least during perinatal life, AVT could be considered as a neuromodulator with AS-promoting effect.

Animals↗

Early event-related potentials with passive subject participation.

An oddball paradigm was used to elicit event-related potentials from 10 normal-hearing young adult subjects. The frequent signal (90% probability) was a 1000 Hz tone burst at 75 dB nHL and the oddball signal (10% probability) was a similar tone burst at 60 dB nHL. A mock or control condition in which both frequent and oddball signals were 60 dB nHL also was run. The subjects were given no instructions other than to lie quietly on a cot in a test booth. They were awake throughout the test session. The identical procedure was repeated in a second session at least 24 hr after the first. Subtraction of the frequent (60 dB nHL) from the oddball (60 dB nHL) averaged evoked potential (AEP) in the mock condition yielded virtually a straight line. However, subtraction of the frequent (75 dB nHL) AEP from the oddball (60 dB nHL) AEP revealed a negative difference that peaked at about 175 ms. Subtraction of either the frequent or the oddball AEP obtained in the mock condition from the 60 dB nHL oddball of the experimental condition also produced a negative peak at about 175 ms and, in addition, a smaller negative difference that peaked at about 75 ms. Observations were consistent across sessions.

Adult↗

An emulsion formulation of amphotericin B improves the therapeutic index when treating systemic murine candidiasis.

Incorporating amphotericin B into liposomes was reported to decrease amphotericin B toxicity without a concomitant loss of antifungal efficacy. We formulated an alternative emulsion-based delivery system for amphotericin B and compared it with Fungizone. The maximal tolerated dose (MTD) in mice was 1 mg of Fungizone/kg; however, the MTD was greater than 9 mg of the Intralipid emulsion formulation/kg. The emulsion formulation and Fungizone were equipotent for treating systemic candidiasis in mice. Amphotericin B nephrotoxicity, as manifested by polyuria that was resistant to antidiuretic hormone, was markedly diminished when amphotericin B was administered as an emulsion to rats. Loss of potassium from human red blood cells was also reduced by formulating this agent within emulsions. The emulsion formulation extended the survival time of mice that had established Candida albicans infections, when compared with the Fungizone treatment. The efficacy and reduced toxicity of the amphotericin B emulsion are findings suggesting that the emulsion formulation is preferable to Fungizone.

Amphotericin B↗

Postpartum restoration of pregnancy-induced cholecystoparesis and prolonged intestinal transit time.

Pregnancy-induced cholecystoparesis and prolonged intestinal transit are well known, but their duration after delivery and any relation to the rapid decline of serum progesterone have not been studied in the early postpartum period. We studied gallbladder and small intestinal motor function in 10 women during the third trimester of pregnancy and in the second and fourth days postpartum, comparing the results to a control group of 8 women during the follicular phase of the menstrual cycle. Gallbladder motor function was evaluated by real-time ultrasonography and intestinal transit time was measured by the lactulose hydrogen breath test. Postpartum correction of gallbladder and intestinal motor function is early and is initially related to the fall of serum progesterone. Other as yet unknown mechanisms operate later to achieve normalization of gallbladder motor function.

Breath Tests↗

Natural history of fetal ventriculomegaly.

The natural history of in utero ventriculomegaly was defined by a retrospective review of the outcome of 47 fetuses evaluated during a 5-year period by the Fetal Treatment Program at the University of California. In 20 fetuses, a diagnosis of ventriculomegaly associated with other severe abnormalities was made early in pregnancy. Termination of pregnancy was elected in 19 of 20 cases, and no fetus survived. In five fetuses, the diagnosis was made late in pregnancy and was associated with severe abnormalities. Fetuses were handled in a routine obstetric fashion and none survived. Of the other 22 fetuses 19 had stable and two had progressive ventriculomegaly; in one case, ventriculomegaly resolved in utero. Nineteen of these fetuses have survived, 13 with normal intellectual development and six with moderately to severely delayed development. Associated abnormalities were detected with ultrasonography in 74% of fetuses; there was a 20% false-negative rate of detection. Ventriculomegaly was isolated and progressive in two fetuses. In both cases, fetuses were delivered at term, and postnatally a shunting procedure was performed. Both children are neurologically normal. From our results and a review of the literature, which supports our findings, we were unable to define a group of fetuses with in utero ventriculomegaly that would benefit from in utero shunting.

Abortion, Therapeutic↗

Myo-osseous intercostal pedicle flaps for tracheal reconstruction in puppies.

We evaluated a myo-osseous intercostal pedicle flap for distal tracheal reconstruction. Mongrel puppies, 6 to 10 weeks old, underwent tracheal repair, 12 for primary defects and seven for stenotic lesions created in the distal trachea. A composite flap was constructed from the anterior portion of the fourth rib with the overlying pleura and periosteum and a posteriorly based intercostal muscle/neurovascular pedicle. The animals did well following tracheal reconstruction without evidence of airway obstruction. Bronchoscopy documented normal tracheal diameter and the repair site could not be discerned from the surrounding mucosa. Histologically, there was complete respiratory epithelial ingrowth with no inflammatory changes. The rib graft had active hematopoietic marrow. This work suggests that the myo-osseous intercostal pedicle flap provides a surface for normal epithelial ingrowth of tracheal mucosa without stimulating granulation tissue, interposes a stent capable of growth, therefore minimizing anastomotic stricture, and is an effective alternative in the management of distal tracheal stenosis.

Animals↗

Controlled multicenter study of the antihypertensive effects of lisinopril, hydrochlorothiazide, and lisinopril plus hydrochlorothiazide in the treatment of 394 patients with mild to moderate essential hypertension.

Lisinopril (LIS) is a lysine analog of enalaprilat, the active metabolite of enalapril, an angiotensin-converting enzyme inhibitor (ACEI). Unlike enalapril, the precursor of enalaprilat, LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration. Short-term (12 weeks) and long-term (24 weeks) blood pressure control has been studied with LIS, hydrochlorothiazide (HCTZ), and LIS + HCTZ when given once a day. Drug treatment had three phases: (i) 2-4 weeks of single-blind placebo washout; (ii) 12 weeks of double-blind comparison therapy with LIS 20, 40, and 80 mg vs. HCTZ 12.5, 25, and 50 mg, vs. LIS + HCTZ 20 + 12.5, 40 + 25, and 80 + 50 mg; (iii) 13-24 weeks single-blind LIS vs. LIS + HCTZ. Starting double-blind therapy at the lowest dose, all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP (SDBP) less than 90 mm Hg. At the end of 12 weeks of double-blind therapy, uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped. Mean BP reductions (systolic/diastolic, mm Hg) for all three groups after 12 weeks of double-blind comparison therapy were: (i) LIS (n = 162), -16.6/-12.5; (ii) HCTZ (n = 155), -10.4/-6.8; (iii) LIS + HCTZ (n = 74), -23.9/-18.2 with p less than 0.01 for all groups compared to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of antihypertensive efficacy of lisinopril compared to metoprolol in moderate to severe hypertension.

A double-blind controlled, randomized, parallel, multicenter 12-week study was conducted to compare the antihypertensive efficacy of lisinopril with that of metoprolol in treatment of moderate to severe hypertension. Initially, 118 patients were recruited on lisinopril and 61 on metoprolol; and for the purpose of efficacy analysis at week 8, 115 patients on lisinopril and 60 on metoprolol were included. The doses of lisinopril or metoprolol were 40-80 mg/day and 100-200 mg/day, respectively. At week 4, the pretreatment diastolic blood pressure of 111 mm Hg was decreased to 97 mm Hg (p less than 0.01) with lisinopril: metoprolol decreased the diastolic blood pressure from 110 to 99 mm Hg (p less than 0.01). Similar decreases were noted at week 8; however, the drop in blood pressure with lisinopril was not significantly different from that with metoprolol. Systolic blood pressure also demonstrated a decrease of about 18 mm Hg with lisinopril and 12 mm Hg with metoprolol (p less than 0.01). This larger decrease in systolic blood pressure with lisinopril was statistically significant at week 4 (p less than 0.05). These decreases in systolic blood pressures were maintained at week 8, again with statistical significance (p less than 0.01). Of the 118 lisinopril-treated patients, four were discontinued from lisinopril therapy because of headache, dizziness, rash, flushing, or lymphadenopathy. Four patients out of 61 (9.8%) were discontinued from metoprolol therapy because of fatigue, somnolence, asthenia, weight gain, flatulence, tremor, or bronchospasm. In conclusion, lisinopril 40-80 mg once daily is as effective as metoprolol 100-200 mg once daily in reducing diastolic blood pressure in patients with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗