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Biomedical subjects

J Goldstein

Publications and source records attributed to J Goldstein.

At least 145 records · Page 8Linked to original sources
PubMed1992

Lipopolysaccharide (LPS) from Brucella abortus is less toxic than that from Escherichia coli, suggesting the possible use of B. abortus or LPS from B. abortus as a carrier in vaccines.

Brucella abortus may be useful as a component of vaccines. This is because it possesses several unique properties as a carrier that enable it to stimulate human B cells even in the relative absence of T cells. Human immunodeficiency virus type 1 proteins conjugated to B. abortus could induce neutralizing antibodies against human immunodeficiency virus type 1. Recently we showed that the characteristics of lipopolysaccharide (LPS) derived from B. abortus are similar to those of the whole bacterium in that the LPS acts as a T-independent type 1 carrier in mice. In this study we wanted to determine whether LPS derived from B. abortus is associated with the adverse effects seen with other bacterial endotoxins. LPS purified from B. abortus by butanol extraction was shown to have less than 2% (wt/wt) contamination by protein and less than 1% (wt/wt) contamination by nucleic acids and to contain 1% (wt/wt) ketodeoxyoctanic acid. Compared with LPS derived from Escherichia coli, B. abortus LPS was 10,000-fold less potent in eliciting fever in rabbits, 268-fold less potent in killing D-galactosamine-sensitized mice, and 1,400-fold and 400-fold less potent in inducing interleukin-1 beta and tumor necrosis factor alpha production, respectively. These results suggest that B. abortus LPS is much less likely than the LPS from E. coli to evoke endotoxic shock; therefore, it may be feasible to incorporate B. abortus as a component of vaccines.

Animals↗
PubMed1992

Identification of the promoter region of the Escherichia coli major cold shock gene, cspA.

The major cold shock protein of Escherichia coli, CS7.4, is produced at a level of 13% of total protein synthesis upon a temperature shift from 37 to 10 degrees C. The transcription of its gene (cspA) was found to be tightly regulated and induced only at low temperature. In addition, the cspA mRNA was extremely unstable at 37 degrees C, so that CS7.4 production was hardly detected when the culture temperature was shifted from 15 degrees C to 37 degrees C. The transcription initiation site (+1) was identified. In vivo footprinting demonstrated that the region from bases -35 to -73 was protected from chemical modification, and gel mobility shift analysis showed that a cold-shocked cell extract contained a factor(s) specifically bound to the fragment containing the sequence between bases -63 and -92. This factor was synthesized de novo only at low temperature, and its synthesis was inhibited by chloramphenicol. Possible functions of this factor are discussed.

Amino Acid Sequence↗
PubMed1992

Alternate pathways for chloride conductance activation in normal and cystic fibrosis airway epithelial cells.

Using whole cell patch-clamp and perforated patch recording techniques on human cystic fibrosis (CF) and non-CF airway epithelial cells, we sought to determine whether a single Cl- conductance (GCl) could be modulated via different regulatory pathways or whether multiple conductances could be identified. Cl- current in both CF and non-CF cells was activated by cellular swelling as well as by an elevation in intracellular calcium ([Ca2+]i). While the adenosine 3',5'-cyclic monophosphate (cAMP)-activated GCl was absent in CF cells, its activation in non-CF cells was only observed in the perforated patch configuration at lower temperatures (24 degrees C) or infrequently in the whole cell configuration at elevated temperatures (33 degrees C). Currents activated by all three regulatory pathways were sensitive to the Cl- channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Further increases in current activation could be produced by cellular swelling after maximal Ca2+ or cAMP-induced current activation. Intracellular application of a peptide inhibitor of Ca(2+)-calmodulin-dependent protein kinase selectively blocked the Ca(2+)-dependent current activation while leaving the swelling-induced current increase intact. These results are consistent with the presence of multiple anion conductances in both CF and non-CF airway cells. The heterogeneity of the responses to the three regulatory stimuli, however, prevented the correlation of a specific anion conductance with a separate modulatory pathway based on characteristic voltage-dependent kinetics and conductance.

Calcium↗
PubMed1992

Curability of solitary bone plasmacytoma.

PURPOSE: The effects of involved-field radiotherapy were assessed in patients with a solitary plasmacytoma of bone (SBP). PATIENTS AND METHODS: Forty-five consecutive patients with an SBP received megavoltage irradiation of at least 3,000 cGy. The median age was 53 years, 67% of patients showed a myeloma protein, and uninvolved immunoglobulins (Igs) were preserved in 93% of patients. RESULTS: Permanent control of presenting disease was achieved in all but two patients, but 46% of patients developed multiple myeloma. When it occurred, progression of myeloma occurred within 3 years in two thirds of the patients, suggesting that the extent of disease was understaged at diagnosis. Myeloma protein disappeared in nine patients (30%) whose disease has not yet recurred. The median survival for all patients was 13 years and the myeloma-specific survival fraction at 10 years was 53%. CONCLUSION: In patients with an SBP, the disappearance of myeloma protein with involved-field radiotherapy predicted long-term disease-free survival and possible cure. Nonsecretory disease and persistent myeloma protein after treatment were adverse prognostic factors for which adjuvant therapy with interferon alfa should be considered.

Adult↗
PubMed1992

Ergot pharmacology and alternative delivery systems for ergotamine derivatives.

Dihydroergotamine mesylate (DHE) has been used in migraine therapy since the 1940s. Renewed interest in its use has been kindled by research in receptor pharmacology and by efficacy of DHE-45 in breaking the cycle of chronic daily headache. Nasal and oral routes of administration may widen the applicability of DHE.

Dihydroergotamine↗
PubMed1992

Prostaglandin E1 infusion for right ventricular failure after cardiac transplantation.

The infusion of prostaglandin E1, a vasodilating substance with predominant effects on the pulmonary vasculature, has been found effective in the management of pulmonary hypertension associated with various diseases. The reported experience with prostaglandin E1 after cardiac transplantation is, however, limited. We used prostaglandin E1 in 18 patients in whom acute right ventricular failure developed after orthotopic cardiac transplantation. The infusion was started within 24 hours after operation in 16 patients and was continued for up to 7 days. Maximal doses of prostaglandin E1, administered via a central venous catheter, ranged from 30 to 120 ng/kg/min. Norepinephrine was simultaneously infused via a left atrial catheter in 10 patients to prevent a reduction in systemic arterial pressure. The prostaglandin E1 infusion resulted in significant reductions in mean arterial pressure and pulmonary vascular resistance and simultaneous increases in cardiac index and stroke index. Mean arterial pressure was stable and left ventricular stroke work increased. The alveolar oxygen tension/forced inspiratory oxygen index tended to decrease during the infusion. Three patients died, two of right heart failure and one of multiple organ failure associated with cardiac allograft rejection. In patients in whom right ventricular failure associated with pulmonary hypertension develops after cardiac transplantation, prostaglandin E1, combined with norepinephrine whenever the arterial pressure declines, can effectively reduce pulmonary artery pressures and improve global cardiac function without compromising systemic perfusion.

Adult↗
PubMed1991

Expression of class I histocompatibility antigens in transitional cell carcinoma of the urinary bladder in relation to survival.

The expression of class I histocompatibility antigens (HLA) in transitional cell carcinoma of the bladder was studied by the immunoperoxidase technique and correlated with tumor differentiation and survival. Tumors of 33 patients who underwent cystectomy were examined; 57% of the tumors expressed HLA class I antigens. Positive expression was observed in 5 of 6 cases with Grade 1 tumors, 8 of 13 with Grade 2, and 6 of 14 with Grade 3. The 5-year survival was significantly better in patients with HLA class I-positive tumors (74%) compared with those with negative tumors (36%, P less than 0.05). The expression of HLA class I on tumor cells may serve as a target for the immune response and control the metastatic potential of the tumor. These results suggest that HLA class I expression in bladder carcinoma is a prognostic indicator that should be considered in treatment planning.

Adult↗
PubMed1991

In vivo effect of asparagine in the hydrophobic region of the signal sequence.

On the basis of the biophysical studies on the synthetic mutant (Ile-8----Asn) OmpA signal peptide in the preceding paper (Hoyt, D. C., and Gierasch, L.M. (1991) J. Biol. Chem. 266, 14406-14412), the in vivo effects of the same mutation were examined by fusing the mutant OmpA signal sequence to Staphylococcus aureus nuclease or TEM beta-lactamase. The mutation in which the isoleucine residue at position 8 of the OmpA signal sequence of Escherichia coli was replaced with a neutral polar residue, asparagine, resulted in a defective signal peptide. The mutant signal sequence was unable to be processed, and the precursor molecule accumulated in the cytoplasmic as well as in the membrane fractions, indicating that the Ile-8----Asn OmpA signal sequence is not competent for translocating nuclease A or beta-lactamase across the membrane. This result is consistent with the in vitro studies on the Ile-8----Asn OmpA signal peptide, which indicated that the mutant signal peptide was unable to penetrate into the hydrophobic core of the lipid bilayer. Other asparagine or glutamine substitution mutations in the hydrophobic region of the OmpA signal sequence were also examined. Interestingly, the OmpA signal sequence with either Ile-8----Gln, Val-10----Asn, or Leu-12----Asn mutation was completely defective as the Ile-8----Asn OmpA signal sequence, while the Ile-6----Asn and Ala-9----Asn OmpA nucleases were able to be processed to secrete nuclease, although the processing occurred at a much slower rate than the wild-type OmpA nuclease. These results indicate that the defects depend on the position of the lesion in the hydrophobic core of the OmpA signal sequence.

Amino Acid Sequence↗
PubMed1991

Reductive alkylation of DNA by mitomycin A, a mitomycin with high redox potential.

The mitomycins are a group of antitumor antibiotics that covalently bind to DNA upon reductive activation. Mitomycin A (1b; MA) is more toxic than its clinically useful mitomycin C (1a; MC). The greater toxicity of mitomycin A has been previously attributed to its higher reduction potential. In this report, the DNA alkylation products of reductively activated MA were isolated and characterized by conversion to the known 7-amino mitosene-deoxyguanosine adducts. The three major adducts formed were identified as a monoadduct, N2-(2"beta-amino-7"-methoxymitosen-1"alpha-yl)- 2'-deoxyguanosine (5), a decarbamoyl monoadduct, N2-(2"beta-amino-10"-decarbamoyl-7"-methoxymitosen-1"alpha-y l)-2'- deoxyguanosine (6), and a bisadduct, N2-(2"beta-amino-10"-deoxyguanosin-N2-yl-7-methoxymitosen-1" alpha- yl)-2'-deoxyguanosine (7). Under all reductive activation conditions employed, MA selectively alkylated the 2-amino group of guanine in DNA, like MC. In addition, both MA and MC alkylated DNA and cross-linked oligonucleotides to a similar extent. However, variations in the reductive activation conditions (H2/PtO2, Na2S2O4, or enzymatic) affected the distribution of the three major MA adducts in a different manner than the distribution of MC adducts was affected. A mechanism is proposed wherein the 7-methoxy substituent of MA allows initial indiscriminate activation of either of the drugs' two electrophilic sites. While oxygen inhibited cross-linking by MC, similar aerobic conditions exhibited little influence on the cross-linking ability of MA. Hence, the greater toxicity of MA may be influenced by increased and nonselective activation and cross-link formation in both aerobic and anaerobic cells. This effect is a direct consequence of the higher redox potential of MA as compared to MC.

Alkylation↗
PubMed1991

Single-unit transfusions of RBC enzymatically converted from group B to group O to A and O normal volunteers.

Full-unit transfusions of RBC enzymatically converted from group B to group O by treatment with alpha-galactosidase (ECO RBC) to group O and A normal healthy individuals exhibit excellent in vivo survival times (24-hour survival 95.1% +/- 2.3%, T50 36.9 +/- 4.6 days). These results confirm our earlier findings describing ECO RBC in vitro viability and normal in vivo survival time after small-volume infusions. No significant increase in pretransfusion anti-B titer or score is observed in either group O or A subjects provided that sufficient enzyme is used to treat the cells: Cells transfused to group O recipients require higher levels of enzyme (185 to 200 U/mL RBC) than those infused to group A (90 U/mL RBC). Two separate single-unit transfusions of ECO RBC to one group O recipient (4.5 months apart) also survived normally (24-hour survival 96% and 92%, T50 40 and 36 days) and did not increase preexisting anti-B levels in this subject. ECO RBC were not agglutinated or lysed by recipient sera before or after transfusion. Similarly, no antibody development to the alpha-galactosidase used in cell treatment (and washed from the product before transfusion) could be detected in any subject. The sustained increase in hemoglobin levels after transfusion of ECO RBC suggests that this product will be useful in treatment of acute and chronic anemia.

ABO Blood-Group System↗
PubMed1991

Ovarian hormones enhance 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated increases in cell proliferation and preneoplastic foci in a two-stage model for rat hepatocarcinogenesis.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in rodents. However, liver tumor incidence is increased by TCDD in female Sprague-Dawley rats but not male rats in chronic carcinogen bioassays. Our studies have investigated this finding by evaluating histological and biochemical parameters in a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats (intact and ovariectomized), using diethylnitrosamine (DEN) as the initiating agent and TCDD as the promoting agent. Increases in gamma-glutamyl transpeptidase-positive foci were greater in intact female rats than in ovariectomized (OVX) animals. For example, in intact rats receiving both DEN and TCDD, the percentage of liver occupied by gamma-glutamyl transpeptidase-positive foci was 0.37, compared to 0.08 in OVX rats. Values for intact or OVX rats receiving either DEN or TCDD only were 0.04 or less. Similar results were obtained when using placental glutathione S-transferase to detect hepatic preneoplastic lesions. Cell proliferation data, obtained using bromodeoxyuridine in osmotic minipumps, were consistent with preneoplastic foci data in that the hepatocyte labeling index was increased in DEN/TCDD intact rats but not in DEN/TCDD OVX rats. Analysis of data from individual animals revealed a strong correlation (P less than 0.01) between cell proliferation and placental glutathione S-transferase-positive foci/cm3 in liver. These findings did not reflect effects of ovariectomy on TCDD tissue distribution, since livers of OVX rats contained more TCDD than livers of intact rats, although both groups of rats received a dose of 1.4 micrograms TCDD/kg once every 2 weeks for 30 weeks. Hepatic cytochrome P-450d (IA2) was induced approximately 6-8-fold in all TCDD-treated groups, and the magnitude of induction was not influenced by ovariectomy. This cytochrome efficiently catalyzes metabolism of 17 beta-estradiol to catechol estrogens. Our data suggest that ovarian hormones (probably estrogen) play a significant role in the hepatocarcinogenic actions of TCDD.

Animals↗
PubMed1991

[Histiocytic necrotizing lymphadenitis of Kikuchi and Fujimoto].

Histiocytic necrotizing lymphadenitis of Kikuchi and Fujimoto (HNL) is a benign, self-limited disease of unknown etiology. It can easily be mistaken for lymphoma, both clinically and on pathological examination. We report a 25-year-old woman who presented with fever and painful unilateral lymphadenopathy, clinically compatible with, and histologically diagnosed as HNL. Only 2 previous cases of HNL have been reported from Israel.

Adult↗
PubMed1991

Bilateral coronary artery to left ventricular fistulas.

Congenital coronary artery fistulas are important coronary artery anomalies. Bilateral coronary artery fistulas are very rare and coronary artery to left ventricular communications are even more infrequent. This report describes a patient with bilateral right and left coronary artery fistulas draining into a common channel and emptying into the left ventricular cavity.

Aged↗
PubMed1991

Immunogenicity of lipopolysaccharide derived from Brucella abortus: potential as a carrier in development of vaccines for AIDS.

In view of its unique ability to stimulate human B cells, we have considered using Brucella abortus (BA) as a carrier for human vaccines. Recently we showed that HIV-1 coupled to BA, but not unconjugated HIV-1, was able to stimulate murine responses even in the relative absence of CD4+ T cells. This result suggested that HIV-BA may be useful in boosting the immunity of individuals infected with HIV-1 and who have impaired CD4+ T cell function. In order to refine this carrier we purified lipopolysaccharide (LPS) from BA and examined its effects on immune responses. Similar to LPS from E. coli (LPS-EC), LPS-BA was capable of stimulating mouse B cells to proliferate. In addition, LPS-BA could activate mouse spleen cells to secrete antibodies in vitro. Isotype analysis revealed that IgM and all the IgG subclasses were elicited. When comparing these responses to those of LPS-EC, LPS-BA induced a greater percentage of IgG2a and LPS-EC evoked more IgG3. IgG2a is probably important in protection against murine viral infection. LPS-BA was haptenated with trinitrophenol TNP-LPS (BA) and tested for carrier effect. Similar to TNP-BA and TNP-LPS (EC), TNP-LPS (BA) triggered anti-TNP antibody of the IgM and all IgG subclasses. In contrast, TNP-ficoll induced mainly IgM and only small amounts of IgG3. These results suggest that LPS-BA, like intact BA, behaves as a T-independent type 1 carrier, and as such may be advantageous as a carrier for human vaccines development.

AIDS Vaccines↗
PubMed1991

Posttraumatic headache and the postconcussion syndrome.

Although headache is the most common sequelae of head injury, the posttraumatic headache is associated frequently with dizziness, irritability, lack of concentration, and intolerance to alcohol ingestion as a part of a symptom complex known as the postconcussion syndrome. This article clarifies the definitions of acute traumatic headache, posttraumatic headache, and the postconcussion syndrome and improves diagnostic ability, making the assessment and treatment of patients with these three conditions more accurate and effective.

Brain Concussion↗