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Biomedical subjects

J Goldstein

Publications and source records attributed to J Goldstein.

At least 415 records · Page 23Linked to original sources
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Increased potency of Fc-receptor-targeted antigens.

A major challenge for using native and modified T cell epitopes to induce or suppress immunity relates to achieving efficient uptake and processing by antigen-presenting cells (APC) in vivo. IgG Fc receptors, which are expressed constitutively by professional APC including monocytes and dendritic cells, have long been known to mediate antigen uptake in a manner leading to efficient T cell activation. We have previously demonstrated enhanced presentation of antigenic and antagonistic peptides by targeting them to the type I Fc receptor for IgG (Fc gamma RI, CD64) on human monocytes. In the present report we review the literature suggesting that CD64-targeted antigens are likely to be effective in vivo, and present data demonstrating enhanced immunogenicity in CD64 transgenic mice of a fusion protein that combines the specificities of HIV gp120 and the humanized anti-CD64 monoclonal antibody H22. Overall, these studies suggest that targeting antigens to CD64 represents an effective approach to enhancing the effectiveness of vaccines in vivo.

Animals↗
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Memory deficits associated with chronic fatigue immune dysfunction syndrome.

Performance on tests of memory in 39 patients who met Center for Disease Control (CDC) criteria for chronic fatigue immune dysfunction syndrome (CFIDS) was compared with 23 depressed patients (DSM-III-R) and 129 healthy controls. Although the CFIDS patients had normal neuropsychological profiles, they significantly overestimated their ability (metamemory), performed significantly worse on tests of recall as context increased (e.g., recognition), made more errors when rehearsal was prevented, and had delayed mental scanning as memory load increased. The overall pattern indicated that CFIDS patients had a significant memory deficit, far worse than implied by CDC criteria. The pattern for CFIDS patients was consistent with temporal-limbic dysfunction and significantly different than depressed patients and control subjects.

Adult↗
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The isolated major histocompatibility complex class I alpha3 domain binds beta2m and CD8alphaalpha dimers.

The MHC class I molecule plays a crucial role in cytotoxic lymphocyte function. The heavy chain of the MHC class I molecule can form many non-covalent interactions with other molecules on multiple domains and surfaces. We have generated an isolated alpha3 domain of a murine MHC class I molecule and evaluated the contribution of this domain to binding with the MHC class I light chain, beta2m, and CD8. The alpha3 domain binds beta2m at a thousand-fold higher concentration than the whole MHC, and binds CD8alphaalpha with a dependence on the alpha3 CD loop. Our results are relevant for models of MHC folding and CD8-MHC function. The study of individual domains of complex molecules is an important strategy for understanding their dynamic structure and function.

Binding Sites↗
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Comparison of butorphanol nasal spray and fiorinal with codeine in the treatment of migraine.

Butorphanol tartrate is a synthetic mixed agonist-antagonist opioid analgesic. Its transnasal dosage form, which may be self-administered when the use of an opioid analgesic is appropriate, was previously shown to provide rapid relief of migraine pain. In this double-blind, parallel-group, outpatient study, we compared butorphanol nasal spray 1 mg followed in 1 hour by an optional second 1-mg dose with the orally administered analgesic, Fiorinal with Codeine (one capsule containing butalbital 50 mg, caffeine 40 mg, aspirin 325 mg, and codeine phosphate 30 mg). Patients (N=321) were assigned by randomization to one of two treatment groups (butorphanol or Fiorinal with Codeine) and instructed to self-administer medication when migraine pain reached an intensity of moderate or severe and to record study-related events in a diary for 24 hours posttreatment. Efficacy analyses were performed on data from 275 patients who took study medication and returned a patient diary; 136 in the butorphanol group and 139 in the Fiorinal with Codeine group. During the first 2 hours after treatment, butorphanol was more effective than Fiorinal with Codeine in treating migraine pain as measured by pain intensity difference scores, percentage of responders (pain decreased to mild or none), percentage of pain-free patients, and degree of pain relief, with a more rapid time to onset of 15 minutes. A similar percentage of patients in the two groups used rescue medication during the first 4 hours, after which more butorphanol-treated than Fiorinal with Codeine-treated patients used rescue medication. Butorphanol patients had more side effects, less improvement in digestive symptoms, and less improvement in functional ability than Fiorinal with Codeine patients.

Administration, Intranasal↗
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Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Rizatriptan Protocol 046 Study Group.

Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.

Adult↗
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Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Rizatriptan Multicenter Study Groups.

Rizatriptan is a novel, selective 5-HT1B/1D receptor agonist with a rapid onset of action after oral dosing for the acute treatment of migraine. We conducted a long-term (up to 1 year), multicenter, randomized study in 1831 patients treating more than 46,000 attacks to compare the efficacy and tolerability of rizatriptan 5 mg and 10 mg to standard care medications routinely used for the acute treatment of migraine attacks. Both doses of rizatriptan were highly effective, without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior (P < 0.05), both to the 5-mg dose and to standard care, in providing relief in 90% of attacks, with 50% pain-free by 2 hours after dosing. The most common dose-related adverse events were nausea, somnolence, and asthenia/fatigue. Based on this large, multicenter, long-term trial, rizatriptan is an important new oral agent for the acute treatment of migraine.

Administration, Oral↗
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Frequency of delayed hemolytic transfusion reactions following antibody screening and immediate-spin crossmatching.

In view of the continuing controversy regarding the use of immediate-spin crossmatch procedures in preparing blood for transfusion to patients in whom unexpected clinically significant antibodies have not been found by antibody screening by the indirect antiglobulin test (IAT), a review of 8 years' experience with such a policy was conducted. In that period, 54,725 units of packed red cells or whole blood were transfused to 10,146 patients. Four clinically overt delayed hemolytic transfusion reactions and 18 clinically silent delayed serologic transfusion reactions were found. In 3 of the 22 patients, the offending antibody(ies) were detectable in the pretransfusion serum by an enzyme IAT, but none was detectable by routine saline IAT against either a three-cell screening panel or the transfused cells. Thus, the incorporation of saline indirect antiglobulin crossmatch would not have prevented the delayed reactions. It can be concluded that the use of a saline indirect antiglobulin crossmatch offers no significant advantage over the current policy of using only immediate-spin crossmatch for those patients whose pretransfusion serum gives negative results in a three-cell screen using a saline IAT.

Aged↗
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Multiple-unit and second transfusions of red cells enzymatically converted from group B to group O: report on the end of phase 1 trials.

BACKGROUND: It has previously been shown that 1 and 2 units (200 - 400 mL) of red cells (RBCs) enzymatically converted from group B to group O by treatment with alpha-galactosidase (ECO RBCs) are safe and efficacious when transfused to normal group O or A persons. STUDY DESIGN AND METHODS: The current report describes studies in which 1) normal group A and O subjects received large volumes of these cells (3 units), 2) some group O subjects underwent transfusion several months later, and 3) ECO RBCs were prepared by the use of recombinant coffee bean alpha-galactosidase and transfused to a group O subject, to demonstrate the in vivo equivalence of ECO RBCs, whether prepared with native or recombinant alpha-galactosidase. RESULTS: Clinical evaluation (hematologic tests, chemistry analysis, urinalysis) and serologic analyses did not reveal any evidence of subtle or acute transfusion reaction or significant increase in preexisting anti-B titer. ECO RBC survival within the circulation of the recipients was normal (24-hour survival, 95.5 +/- 0.9%; t1/2, 34.7 +/- 6.1 days; n = 8 transfusions), and the efficacy of the transfusions was manifested in elevations in recipient hemoglobin and hematocrit (hemoglobin increase, 1.5 +/- 0.6 g/dL; hematocrit increase, 3.6 +/- 1.6%; n = 8 transfusions). CONCLUSION: ECO RBCs are safe and efficacious when transfused more than once or in multiple-unit volumes to group O or A subjects, and ECO RBCs prepared with recombinant or native enzyme are equivalent in vivo.

ABO Blood-Group System↗
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Water channel proteins AQP3 and AQP9 are present in syncytiotrophoblast of human term placenta.

The syncytiotrophoblast of human term placenta (HST) is a continuous, multinucleated structure with minimal tight junctions, which results from the fusion of the underlying cytotrophoblast cells. Consequently, the transport of metabolites, ions and water from mother to fetus could take place primarily via transcellular routes. Transcellular water flux may be facilitated by aquaporins, membrane proteins functioning as water channels that are widely expressed in cells and tissues. Here, we report the presence of AQP3 and AQP9 in the apical membranes of HST using RT-PCR, immunoblotting and immunohistochemistry. Since AQP3 is not only a water channels, but also permits the rapid passage of both urea and glycerol, while AQP9 also mediates the passage of carbamides, polyols, purines, and pyrimidines, we have speculated that these proteins could be involved in the transport of water and solutes from mother to fetus.

Amino Acid Sequence↗
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Fourier transform infrared microspectroscopy as a quantitative diagnostic tool for assignment of premalignancy grading in cervical neoplasia.

The early diagnosis and proper identification of cervical squamous intraepithelial lesions plays an important role in a good prognosis for the patient. However, the present practice of screening based on PAP (Papanicolaou) smear and histopathology makes it tedious and prone to human errors. We assess the validity of FTIR microspectroscopy (FTIR-MSP) of biopsies as a method to properly assign the correct stage of premalignancy in patients with symptoms of cervical intraepithelial neoplasia. For the first time we evaluate the biopsies based on the FTIR spectra for different grades of neoplasia in tandem with probabilistic neural networks (PNNs) and histopathology. The results show that the grading of neoplasia based on FTIR-MSP and a PNN differentiates the normal from premalignant with a high level of accuracy. The false positive identification of the normal as cervical intraepithelial neoplasia 1 (CIN1), CIN2, and CIN3 patients is 9.04, 0.01, and 0.01%, respectively. The false negative identification of CIN2 patients as normal and CIN1 patients is 0.01 and 4.4%, respectively. Similarly, the false negative identification of CIN3 patients as normal, CIN1, and CIN2 is 0.14, 6.99, and 9.61%, respectively. The small errors encountered in the grading are comparable to current methods, encouraging advanced studies for the development of mechanized equipment for the diagnosis and grading of premalignant cervical neoplasia.

Algorithms↗