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Biomedical subjects

R Goldstein

Publications and source records attributed to R Goldstein.

At least 127 records · Page 7Linked to original sources

Loss of serum antibodies to a conformational epitope of HIV-1/gp120 identified by a human monoclonal antibody is associated with disease progression.

Serum antibody reactive with epitopes within the CD4 binding site (CD4BS) of HIV-1/gp120 on infected cells was measured by inhibition of binding of a human monoclonal antibody, F105, which recognizes a conformational epitope within this region. Serum samples from 27% of ARC/AIDS patients blocked binding of F105 to this epitope, while samples from 100% of asymptomatic seropositive patients blocked binding. F105 blocking activity increased in 87% of asymptomatic donors who maintained stable disease over a 3-6 year period and decreased in 50% of asymptomatic patients with progressive disease. Moreover, serum samples from patients with stable disease exhibited higher titers of F105 blocking activity. The presence of F105 blocking activity also correlated with serum neutralization of virus. When diluted 1:640, serum with low F105 blocking activity neutralized only 20-30% of viral cytopathic effect (CPE), while serum with high F105 blocking activity neutralized > 80%. Serum neutralization was enhanced by the addition of F105. Seroreactivity to infected cells was detectable within 6 months of seroconversion, but F105 blocking activity was delayed by an additional 6-12 months, as was the development of high titers of neutralizing antibody. These data support the notion that the humoral response to the CD4BS on gp120 may be important in the maintenance of health.

AIDS-Related Complex↗

Vasotocin effects in depressive patients with eating disorders.

Since arginine vasotocin (AVT) effects are mediated by serotonin, which was involved in the production of eating disorders, disorders which show many common mechanisms with the depressive disorders, and since AVT was used as treatment of depressive disorders, we investigated the AVT effects in a double-blind study with patients with eating disorders. We compared AVT effects on 15 patients with eating disorders to 18 patients with eating disorders which received tricyclic antidepressants or cognitive-behavioral psychotherapy. The severity of depression was assessed by means of the Hamilton Depression Scale and of Beck's Depression Inventory, before and after three months therapy. Data showed a significant improvement of depressive symptomatology after AVT treatment. Comparison of AVT effects on depression of eating disorders subgroups versus tricyclic antidepressant or psychotherapy treatment are discussed.

Adolescent↗

A review of the results of laparoscopic versus open appendectomy.

Proponents of laparoscopic appendectomy emphasize the advantages of laparoscopic operation--decreased hospitalization, paralytic ileus, postoperative pain and wound complications, including infection. This study compared open laparoscopic appendectomy with laparoscopic appendectomy. To compare the two techniques, patients undergoing laparoscopic appendectomy at four hospitals were compared with patients undergoing open appendectomy during a six month period. Excluded were incidental appendectomies and patients with perforated appendicitis. An equal number of pediatric patients undergoing laparoscopic and open procedures were included in the analysis to avoid bias, because most of the laparoscopic appendectomies were performed in the adult patient population (age of more than 16 years). A University Medical Center, a Veterans Administration and two community hospitals were the settings. Patients undergoing laparoscopic appendectomy (n = 54) had an average age of 25.7 +/- 1.5 (range of six to 59 years). These patients were compared with 121 patients undergoing open appendectomy whose average age was 23.7 +/- 1.8 (range of three to 83 years). The race and gender distribution were similar in the two groups. Traditional open appendectomy was compared with a group of patients undergoing laparoscopic appendectomy. Variables evaluated were operating room time, number of patients who reported nausea, days until patient tolerated a regular diet, days of hospitalization, postoperative pain medication and wound infection rate. Results are expressed as the mean plus or minus standard error of the mean. Analysis of variance was used to compute continuous variables and Fischer's exact test was used for discrete variables. The laparoscopic approach was attempted in 61 patients and completed in 54 patients. Open appendectomy was performed upon 121 patients. Nineteen patients (18 who underwent open operation and one patient who underwent laparoscopic operation) were excluded from further analysis because of perforated appendicitis. The open procedure took less time (p < 0.05). However, there were more wound infections than in the laparoscopic group (seven of 103 versus zero of 53; p = 0.09). Patients with acute appendicitis recuperated more quickly from the laparoscopic procedure, as evidenced by the time until eating regular diet, period of hospitalization, incidence of nausea and pain medications on postoperative day one (p < 0.05). The absence of wound infections after laparoscopic appendectomy can be attributed to the practice of placing the appendix in a sterile bag or into the trocar sleeve before removal from the abdomen. Laparoscopic appendectomy reduces the period of hospitalization, postoperative ileus, nausea and postoperative pain in patients with acute appendicitis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Surveillance for colorectal neoplasia: is patient adherence following treatment a problem?

This study was conducted in order to assess prospective adherence to surveillance colonoscopy and fecal occult blood testing (FOBT) at 1 year following treatment for an index lesion among colorectal cancer and polyp patients. The investigation was carried out in cooperation with two gastroenterology and two surgical practices in Philadelphia and surrounding communities. Subjects in this study were patients who were treated for colorectal cancer (N = 9) or polyps (N = 169) and were recommended to undergo surveillance colonoscopy at 12 months following treatment. Overall, 96 (54%) subjects underwent surveillance colonoscopy. Of the 178 subjects included in the study, 52 (29%) were willing to participate in an assessment of FOBT sensitivity in surveillance. Of the 52 subjects who were mailed an FOBT packet, 24 (46%) actually returned specimen. Of the 24 patients who returned FOBTs, 17 (71%) also underwent colonoscopy, whereas only 10 (36%) of 26 patients who did not do FOBTs underwent colonoscopy. These findings indicate that adherence to surveillance is low, and that adherence to FOBT may be a marker for adherence to colonoscopy.

Adenomatous Polyps↗

Anderson's disease: no linkage to the apo B locus.

We describe three patients with Anderson's disease who are members of one family; the father and mother are close relatives and three of seven children show symptoms of the disease. All patients suffered from diarrhea, failure to thrive, and recurrent infections during infancy. Although these symptoms disappeared later in life, biochemical disorders (such as low plasma levels of apolipoproteins A1 and B and cholesterol, resulting in avitaminosis E, plus failure to secrete chylomicrons after a fat meal) persisted. Electron microscopy of enterocytes of one of the patients showed accumulation of lipid vacuoles with no significant aberration of the Golgi apparatus itself. It is possible, therefore, that the disease reflects a defect in chylomicron assembly. We found that low levels of apolipoprotein (apo) B48 were present in the patients' plasma. This suggests that the processing of the B100 message resulting in apo B48 functions normally. The possibility that a mutation in the apo B gene results in an abnormal apo B48 protein is very unlikely since a variable number tandem repeat (VNTR) polymorphism probe mapped to chromosome 2 failed to show correspondence of the parent alleles with the disease. These observations confirm the suggestion that Anderson's disease is not linked to the apo B locus.

Apolipoprotein B-48↗

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 2. Synthesis and biological activity of 8-(benzenesulfonamido)-7-(3-pyridinyl)octaonic acid and related compounds.

A series of arylsulfonamide alkanoic acids substituted with a 3-pyridinyl group along the aliphatic chain were synthesized and tested in vitro for their ability to antagonize thromboxane A2 (TxA2) receptors and inhibit thromboxane synthase. These compounds were found to potently inhibit the U 46619-induced aggregation of human platelets and to also inhibit TxA2 biosynthesis in a human microsomal platelet preparation. However, some members of the series, notably compound 21, were found to display agonist activity on the rabbit aorta TxA2 receptor. This unwanted agonist activity appeared to be related to the presence of a substituent beta to the arylsulfonamido group.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 3. Pyridinylalkyl-substituted 8-[(arylsulfonyl)amino]octanoic acids.

A series of 8-[(arylsulfonyl)amino]octanoic acids substituted with a pyridinylalkyl group along the chain were synthesized and tested in vitro for their ability to both antagonize the binding of thromboxane A2 to its receptors and to inhibit the thromboxane synthase enzyme. This series of compounds were found to inhibit the U 46619-induced aggregation of human platelets and the U 46619-induced contraction of dog saphenous vein. The compounds also inhibited TxA2 biosynthesis in a human microsomal platelet preparation. The relative position of the pyridinylalkyl and arylsulfonamide groups had significant effects on the thromboxane receptor antagonist (TxRA) activity and thromboxane synthase inhibitor (TxSI) activity. Compounds with the pyridine ring at the 7- or 8-position of the octanoic acid side chain were weakly active as TxSI but behaved as potent TxRA at the platelet receptor for TxA2. However, these compounds were agonists at the vascular receptor. Substitution of the pyridinylalkyl group at the 2- or 3-position resulted in compounds with potent TxSI activity and weak TxRA activity. The activity profile of the compounds with the pyridinylalkyl substitution at the 4-, 5-, or 6-position was very desirable. Compound 22 with a pyridinylpropyl substituent at the 4-position was found to display extremely potent TxRA and TxSI properties.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Racial differences in the frequencies of scleroderma-related autoantibodies.

OBJECTIVE: To determine demographic differences in scleroderma-related autoantibodies. METHODS: One hundred fifty-six patients with systemic sclerosis were prospectively examined for anticentromere antibodies (ACA), anti-topoisomerase I (anti-topo I, or Scl-70), antinucleolar, and anti-U1 RNP autoantibodies. RESULTS: ACA was found in 36% of Caucasians and 4% of American blacks (P = 0.002, odds ratio [OR] 15). Anti-topo I was found in 37% of American blacks, compared with 17% of Caucasians (P = 0.04, OR 3). No significant differences in the frequencies of antinucleolar and anti-U1 RNP autoantibodies were found. CONCLUSION: These data suggest important demographic differences in scleroderma-associated autoantibodies.

Autoantibodies↗

The effect of desogestrel for hormone replacement therapy on the blood lipid profiles of postmenopausal women.

OBJECTIVE: To determine the effect of a hormone replacement protocol containing conjugated equine estrogens and desogestrel (which has a highly selective progestogenic and low androgenic effect) as the progestogen, on the plasma lipid profile, as compared with two other hormone replacement treatments (HRT). METHOD: Eighty-nine healthy postmenopausal women were divided prospectively into four groups. A control group of 24 women did not receive HRT. Twenty-nine women received conjugated equine estrogen and medroxyprogesterone, and 13 women received a protocol containing estradiol, estriol and norethisterone acetate. Fasting blood lipid was taken at the end of each third cycle. The cumulative therapeutic response was calculated in each group as compared with initial values and between groups. Significance was analyzed by t-tests. RESULTS: A protocol containing desogestrel significantly decreased low-density lipoprotein cholesterol (27%; P < 0.05) and increased high-density lipoprotein cholesterol (HDL-C) by 30% (P < 0.05%) after 9 months. The ratio of total cholesterol to HDL-C also decreased significantly (44%; P < 0.05). CONCLUSION: The most beneficial effect on plasma lipid profile was obtained with an HRT protocol containing desogestrel as the progesterone.

Cholesterol↗

Effect of task difficulty and interstimulus interval on blink parameters.

The effects of task difficulty and interstimulus interval (ISI) on blink rate, blink latency and blink duration, were studied in a modified Sternberg memory task in which either two or six characters were to be memorized. Stimuli were presented in ISI blocks at either 5.3 or 9.3 s (SOAs of 6 or 10 s). While blink rate and blink duration declined prior to each stimulus, the difficulty of the expected task (the length of the memory set) did not affect the rate of decline or the final prestimulus level. Concerning ISI, blink rate declined more rapidly during shorter ISIs but the final prestimulus level, as was the case with task difficulty, was unaffected by the ISI duration. Presentation of the 6-character memory set produced a marked immediate inhibition of blinking. The data suggest that the encoding of visual stimuli is more akin to processes invoked in preparation for input than to ensuing processing stages since both encoding as well as preparation are accompanied by inhibition of blinking.

Adolescent↗

Auditory distortion products measured with averaged auditory evoked potentials.

The purpose of this investigation was to describe the properties of averaged auditory evoked potential distortion products (AEP-DPs) in guinea pigs. This study provided a step toward developing a clinical index of nonlinear processing of auditory signals and supplied a baseline for studies evaluating the effect of cochlear damage on AEP-DPs. The amplitude of the AEP-DPs was evaluated as a function of f2/f1 ratio (1.12-1.52) and primary frequency (500 Hz-2000 Hz). The amplitude of the AEP cubic difference tone (AEP-CDT) increased with increasing f2/f1 ratio for the 500-Hz f1 primary and remained constant for the 800-Hz and 1700-Hz f1 primaries. The AEP-CDT generated by the 1100-Hz and 1400-Hz f1 primaries was maximum for the middle f2/f1 ratios (1.22, 1.32, and 1.42). The AEP-CDT could not be distinguished from the noise floor for the 2000-Hz f1 primary. The AEP difference tone (AEP-DT) was larger and more frequently identified than the AEP-CDT. The amplitude of the AEP-DT decreased with an increase in f2/f1 ratio. The decrease was more pronounced for low-frequency f1 primaries than for high-frequency f1 primaries.

Acoustic Stimulation↗

Studies of the HLA class II alleles involved in human responses to ragweed allergens Ambrosia artemisiifolia V (Ra5S) and Ambrosia trifida V (Ra5G)

Previous studies have associated skin test sensitivity and specific IgE response to Ambrosia artemisiifolia V (Amb a V) with HLA-DR2, and to Ambrosia trifida V (Amb t V) with HLA-DRw52 haplotypes in atopic individuals. Using HLA class II typing by restriction fragment length polymorphism (RFLP) analysis with DRB, DQB and DQA DNA probes to define the HLA-D alleles, we have demonstrated the association of the DQw6 in 16 out of 16 (100%) Amb a V-responsive individuals, compared to 3 out of 18 (17%) ragweed-sensitive but Amb a V-nonresponsive individuals (p = 5.7 x 10(-6), RR greater than 75). We suggest that the DQw6 association with Amb a V sensitivity may be a reflection of an association with the DQA*0102 allele. This suggests an association of a particular HLA class II allele with an immune response to a well-characterized antigen (Amb a V). The HLA-DRw52 haplotypes in the Amb t V-sensitive individuals are not of one particular subtype. The HLA-DRw52 association with Amb t V sensitivity may reside in homologous DRB1 alleles linked on HLA-DRw52-bearing haplotypes.

Alleles↗

Association of polar amino acids at position 26 of the HLA-DQB1 first domain with the anticentromere autoantibody response in systemic sclerosis (scleroderma).

HLA class II alleles (detected by DNA typing) were determined in 116 Caucasians with systemic sclerosis positive and negative for anticentromere autoantibodies (ACA). Significantly increased frequencies of HLA-DR5(DRw11) (P = 0.009) and the Dw13(DRB1*0403, *0407) subtypes of DR4 (probability corrected, Pc = 0.005) were seen in ACA positive patients, and HLA-DR1 and DRw8 were also increased. These findings appeared to reflect linkage disequilibrium of DR5(DRw11) and many DR4(Dw13) haplotypes with HLA-DQw7 and DR1 with DQw5. In fact, the presence of a DQB1 allele having a polar glycine or tyrosine at position 26 of the DQB1 first domain versus a hydrophobic leucine accounted for 100% of ACA positive Caucasian systemic sclerosis patients compared to 69% of the ACA negative SS patients (P = 0.0008) and 71% of Caucasian controls (P = 0.0003) as well as all 7 ACA patients of non-Caucasian background. Furthermore, the genotype frequency of DQB1 alleles lacking leucine at position 26 was 73% in ACA positive SS patients, compared to 42% of ACA negative patients (P = 1.2 x 10(-5)) and 38% of controls (P = 5.8 x 10(-7)). These data, then, suggest that the second hypervariable region of the HLA-DQB1 chain may form the candidate epitope associated with the ACA response.

Alleles↗