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Biomedical subjects

A Goldstein

Publications and source records attributed to A Goldstein.

At least 127 records · Page 7Linked to original sources
PubMed1986

Morphine and codeine from mammalian brain.

Recently, we described the presence of six immunoreactive (ir) morphinans in bovine adrenal and hypothalamus and identified one as morphine [Goldstein, A., Barrett, R. W., James, I. F., Lowney, L. I., Weitz, C. J., Knipmeyer, L. L. & Rapaport, H. (1985) Proc. Natl. Acad. Sci. USA 82, 5203-5207]. We now report that ir morphinans corresponding to the previously reported peak 1 (morphine), peak 4, and peak 5 are consistently present in extracts of bovine hypothalamus and variably present in extracts of bovine adrenal and rat brain. We no longer detect the previously reported peaks 2, 3, or 6, and we have established that they were contamination artifacts. Peak 1 is coeluted with morphine in two distinct reversed-phase HPLC systems, as is peak 4 with codeine. We have purified peak 1 and peak 4 compounds from bovine hypothalamus and determined their identities by gas chromatography/mass spectrometry (GC/MS): peak 1 is confirmed to be morphine and peak 4 is codeine.

Adrenal Glands↗
PubMed1986

Early open reduction and internal fixation of the disrupted pelvic ring.

Early open reduction and internal fixation (ORIF) of extremity fractures in patients with multiple injuries has been demonstrated to be safe, improve survival, and decrease the incidence of respiratory failure. Complications leading to abandonment of planned operative fixation and death in several patients with pelvic fractures led us to initiate a policy of early ORIF of the disrupted pelvic ring. Early ORIF of the pelvis was performed in 15 multiply injured patients between May 1984 and August 1985. Patients ranged in age from 13 to 79 years, their Hospital Trauma Index-ISS scores ranged from 14 to 68, and number of preoperative transfusions ranged from 0 to 42. Types of fractures were A-P compression, two, lateral compression, one, vertical shear, seven, complex, two, and acetabulum with ring disruption, three. All patients were resuscitated, transported in pneumatic antishock garments, and evaluated by abdominal and pelvic CT scan (in two patients following celiotomy). Preoperative angiograms to assess retroperitoneal hemorrhage in eight patients resulted in identification and control of significant bleeding in five. The mean time from injury to pelvic stabilization was 38 hours. Seven patients underwent ORIF within the first 24 hours. In most cases simultaneous anterior and posterior internal fixation was performed with the patient in the lateral decubitus position. Excluding associated procedures, operative time averaged 5.1 hours. Intra-operative transfusions averaged 4 units (range, 0-11). Rigid fixation was achieved in all patients. Most patients were out of bed by the third postoperative day. No patient developed respiratory failure. Two patients developed wound infections. Modification of our technique has avoided this complication in the latter part of this series.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Use of the contrast-enhanced CT enema in the management of penetrating trauma to the flank and back.

There have been few innovations in the management of penetrating trauma of the flank and back since that reported by Peck and Berne in 1981. During 1984-1985 our Trauma Service treated 119 patients with injuries in these areas. In 56 patients management was based on the results of the contrast-enhanced CT enema (CECTE), a computerized tomographic technique designed to delineate all of the retroperitoneal viscera by simultaneously opacifying the small bowel, duodenum, colon, GU tract, and major vessels. Specific radiographic findings were present on 44 scans. Twelve scans were negative. Six scans were considered indications for angiography because of the proximity of the identified missile wounds or their hematomas to major vascular structures. One of these arteriograms revealed a renal artery pseudoaneurysm which would otherwise have remained undiagnosed. In 30 cases the penetrating wounds were well delineated by CECTE, and their nature and location were considered appropriate for nonoperative management. None required subsequent exploration. In eight cases CECTE demonstrated that the wounds were located so as to place specific viscera at risk for significant injury, but no definite injury was identified. Five of these patients were successfully managed by further evaluation and close observation, two were explored, and one signed out of the hospital. No scan demonstrated extravasation from a hollow viscus. Overall, 52 of our 56 patients (92%) were successfully managed nonoperatively on the basis of the interpretation of their CECTE findings. CECTE can be useful in the management of stable patients with penetrating trauma to the back and flank by identifying the nature and location of the resulting retroperitoneal injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1986

An analysis of 161 falls from a height: the 'jumper syndrome'.

Vertical deceleration injuries represent a distinct form of urban blunt trauma. We reviewed 161 adult patients, admitted over 36 months, who jumped or fell from a height of one to seven stories and survived emergency department resuscitation. Charts and radiographs were analyzed to identify common injuries, complications, and causes of death. Those who fell five or more stories had a mean ISS of 41, for a predicted survival of 50% but actual survival of 83%. Virtually all these patients had multiple fractures. Sixty per cent of them presented in shock, yet more than two thirds had angiographically demonstrated retroperitoneal hemorrhage as their major source of bleeding. Thirteen patients had significant intra-abdominal injuries, with only one associated with major hemorrhage. Utilizing early diagnostic peritoneal lavage, ten of 13 patients explored had a therapeutic laparotomy. Hollow viscus perforations accounted for about one half of the abdominal injuries, including three duodenal injuries. Conclusions. 1) Patients who present in shock after falls from height are much more likely to be bleeding from retroperitoneal than intraperitoneal sources. 2) Early tap and lavage followed by emergency angiography and transcatheter embolization is the treatment of choice in this group of patients. 3) Although these patients often have multiple complex injuries, the prognosis for long-term survival is good. Therefore, we advocate early aggressive operation stabilization of fractures to permit patient mobilization, facilitate pulmonary toilet and nursing care, and to decrease long-term disability.

Abdominal Injuries↗
PubMed1986

Conversion of leumorphin (dynorphin B-29) to dynorphin B and dynorphin B-14 by thiol protease activity.

Dynorphin B (rimorphin) is formed from leumorphin (dynorphin B-29) by the action of a thiol protease from rat brain membranes, in a single step. This represents a "single-arginine cleavage" between threonine-13 and arginine-14 of the substrate. We have observed that in addition to dynorphin B, dynorphin B-14 is formed from dynorphin B-29. Among the various protease inhibitors tested, none except p-chloromercuribenzensulfonic acid inhibited the formation of the two products. Both temperature and pH had similar effects on the formation of dynorphin B-14 and dynorphin B. The inhibitory potencies of adrenocorticotropic hormone, peptide E, and dynorphin A were virtually identical for the formation of the two products. These results suggest that the same enzyme may be responsible for the formation of dynorphin B-14 and dynorphin B.

Adrenocorticotropic Hormone↗
PubMed1985

Neuropeptide processing by single-step cleavage: conversion of leumorphin (dynorphin B-29) to dynorphin B.

Dynorphin B (rimorphin) is formed from dynorphin B-29 (leumorphin) by the action of a thiol protease from rat brain membranes. This represents a "single-arginine cleavage" between threonine-13 and arginine-14 of the substrate. In isotope dilution experiments we find that the radioactivity from radiolabelled dynorphin B-29, which appears in dynorphin B during incubation with the enzyme preparation, is not diminished by addition of a high concentration of dynorphin B-Arg14. Moreover, in pulse-chase experiments, radioactivity that appeared in dynorphin B-Arg14 did not decrease, nor did the radioactivity in dynorphin B increase, after chasing with a high concentration of non-radioactive dynorphin B-29. These results indicate that although some dynorphin B-Arg14 is formed by the impure enzyme preparation, it is not an intermediate in the conversion of dynorphin B-29 to dynorphin B. Thus the formation of dynorphin B does not involve the action of a trypsin-like enzyme followed by removal of arginine-14 by a carboxypeptidase B-like enzyme. It appears that a single enzyme converts dynorphin B-29 to dynorphin B in a single step.

Animals↗
PubMed1985

A linkage analysis of the Gm locus and multiple sclerosis.

We conducted linkage analyses of immunoglobulin G heavy chain marker (Gm) phenotypes and multiple sclerosis (MS) in 30 families, each having at least two first-degree relatives with definite/probable MS. These families yielded positive evidence for linkage to human leukocyte antigen (HLA) loci in previous analyses. In the present analysis, however, the results for Gm were negative. Most lod scores were negative, particularly at the smaller recombination values (theta). We explored the possibility of heterogeneity by subgrouping our data on the basis of specific HLA types (A3, B7) and Gm types (Gm1, Gm1,2) within the pedigrees. The results were again negative with no substantial differences in estimates of theta between subgroups.

Gene Frequency↗
PubMed1985

A monoclonal antibody specific for a dynorphin precursor.

Murine monoclonal antibodies were produced against dynorphin-32 (D32), a naturally occurring opioid peptide containing the sequence of dynorphin A (Dyn A) at its amino terminus, followed by Lys-Arg, then by the sequence of dynorphin B (Dyn B). Initial characterization using an enzyme-linked immunosorbent assay revealed that one clone (17.M) recognized D32 but not Dyn A or Dyn B. A solid-phase radioimmunoassay using 125I-labeled antibody 17.M was developed and showed a maximum sensitivity of 45 fmol for synthetic D32. Dyn B crossreacted only 0.05%; Dyn A and other related opioid peptides crossreacted less than 0.001%. Immunoreactive D32 was detected in extracts of rat brain and anterior pituitary but not neurointermediate lobe of pituitary. The unique specificity of monoclonal antibody 17.M should make it useful in investigations of the differential localization and release of Dyn A and Dyn B and the precursor D32.

Animals↗
PubMed1985

Sequence and expression of the rat prodynorphin gene.

We report here the isolation of a lambda genomic clone that contains the nucleotide sequence coding for the main exon of the rat prodynorphin (proenkephalin B) gene. This exon codes for the majority of the translated region of prodynorphin mRNA including the opioid peptides alpha-neo-endorphin, dynorphin A, and dynorphin B. The entire 3' untranslated region is also contained on the lambda clone. Nucleotide sequence comparison with the main exon of the human prodynorphin gene reveals both structural and sequence homology. RNA blot analysis reveals that prodynorphin transcripts can be seen in numerous regions of the rat brain and in the adrenal gland, spinal cord, testis, and anterior pituitary.

Animals↗
PubMed1985

Morphine and other opiates from beef brain and adrenal.

We describe nonpeptide opioids found in extracts of beef hypothalamus and adrenal, which are recognized by antisera raised against morphine. Four have been purified to homogeneity. One is morphine. The structures of the other three have not been determined yet. None of them are derived from morphine or normorphine after extraction from the tissues. It is not known whether the opiates described here are of endogenous or exogenous origin.

Adrenal Glands↗
PubMed1985

Antinociception and paralysis induced by intrathecal dynorphin A.

Intrathecal administration of dynorphin A in rats produced dose-dependent antinociceptive effects in the tail-flick test to radiant heat and on a limb-flexion test to pressure. The potency of dynorphin A as an analgesic agent on the tail-flick test was dependent upon the duration of cannula implantation. When a short-term procedure was used (drug injected 1 day after catheter implantation) dynorphin A was approximately equipotent to morphine, whereas in animals with long-term implants (drug injected 7 or more days after catheter implantation) dynorphin A was an order of magnitude less potent than morphine. [D-Ala2,D-Leu5]enkephalin was the most potent opioid tested, and in the tail-flick test (long-term procedure) it was about 2 orders of magnitude more potent than dynorphin A and 7 times more potent than morphine. [Leu]enkephalin had no detectable antinociceptive effects. Low doses of naloxone (1 and 2 mg/kg s.c.) completely blocked the antinociceptive effects of morphine and [D-Ala2,D-Leu5]enkephalin, but neither low nor high (40 mg/kg s.c.) doses clearly blocked the antinociceptive effects of dynorphin A. Thus, dynorphin A has an antinociceptive action at the level of the spinal cord, and mu opioid receptors do not mediate these effects. In addition, high doses of dynorphin A (20 nmol or greater) produced long-lasting hindlimb paralysis, which suggests that dynorphin peptides may play a role in motor function in the spinal cord. This paralytic action of dynorphin A was not antagonized by naloxone in doses up to 32 mg/kg s.c.

Animals↗
PubMed1984

Analgesia induced by intrathecal injection of dynorphin B in the rat.

A dose-dependent analgesic effect of intrathecally injected dynorphin B was observed in rats using the tail flick as nociceptive test. Intrathecal injection of 20 nmol of dynorphin B increased the tail flick latency by 90 +/- 23%, an effect that lasted about 90 min. For the same degree of analgesia, dynorphin B was 50% more potent than morphine on a molar basis. The analgesic effect of this dose of dynorphin B was partially blocked by 10 mg/kg, but not by 1 mg/kg, of subcutaneous naloxone, showing a relative resistance to naloxone reversal as compared with morphine analgesia. The analgesia produced by dynorphin B was unchanged in morphine-tolerant rats but was significantly decreased in rats tolerant to ethylketazocine. These results suggest that dynorphin B produces its potent analgesic effect by activation of kappa rather than mu opioid receptors in the rat spinal cord.

Analgesics↗
PubMed1984

No evidence for linkage between an insulin-dependent diabetes mellitus-susceptibility locus and immunoglobulin loci KM or GM.

We studied 52 families having more than one member affected with insulin-dependent diabetes mellitus (IDDM) for linkage of an IDDM-susceptibility locus to the immunoglobulin loci KM and GM. Linkage was analyzed by the LOD score method using single-locus recessive and dominant models of IDDM inheritance, with penetrances of the disease-susceptible genotypes being dependent on age and reaching a maximum of 20% by age 40. We found no evidence for linkage of IDDM to KM or GM. Close linkage (recombination fraction less than 5%) was rejected for KM under the recessive model and for GM under both models. These results suggest either that there are no IDDM-susceptibility loci closely linked to KM or GM or that use of a single-locus model of IDDM (which ignores the effects of the susceptibility locus in the HLA region) is inadequate for their detection.

Adult↗
PubMed1984

Improved control of bulky prostate carcinoma with sequential estrogen and radiation therapy.

Patients with bulky prostate cancer have usually been treated by palliative measures because the likelihood of tumor control with definitive irradiation has been low and the development of distant metastases high. The addition of estrogen to irradiation has not been shown to be of value. However, we believe the method of estrogen administration may have been the cause for the apparent lack of benefit. Estrogen had been started either concurrent with irradiation or had been used for palliation and was given for long and unscheduled time periods prior to irradiation. We have used estrogen for two months prior to and concurrent with irradiation. We postulated that in those patients with estrogen responsive cancer, the reduced tumor burden prior to irradiation could enhance tumor control and survival. Between 1975 and 1980, 25 patients with bulky prostate cancer received sequential estrogen and irradiation, 12 patients irradiation alone and six patients irradiation after having become refractory to long-term estrogen use. One patient was lost to follow-up. Eighteen of 25 (72%) treated by sequential estrogen and irradiation, 14/17 (82%) with estrogen responsive cancer and 4/8 (50%) with estrogen resistant cancer had a complete tumor response. Six of 11 (55%) patients treated by irradiation alone and 2/6 (33%) treated by irradiation for estrogen refractory cancer had a complete tumor response. Disease-free survival was observed in 13/25 (52%) treated by sequential estrogen and irradiation, and 8/17 patients (47%) with irradiation. It is also possible the improved survival in the estrogen responsive group was a direct result of improved local control. Persistent local disease can act as a source for distant metastases. Distant metastases was observed in 15% of patients when the primary tumor was controlled and 30% when there was persistent or recurrent local disease. Also, progressive local disease can be an important cause of death. This was most evident in our patients with estrogen refractory cancer. Almost all patients in this group had progressive local disease that caused serious urinary bleeding and urinary infection that were considered the major cause of death. Our results suggest bulky prostate cancer should be aggressively treated when first diagnosed. The value of adjunct estrogen is unproven. Our results with the use of estrogen prior to and concurrent with irradiation is encouraging. Estrogen may shrink the cancer and allow for a more favorable geometry for external irradiation. Tumor control and survival may be thereby improved.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗