Pathological case of the month. Primary oxalosis (primary hyperoxaluria).
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Child↗
Biomedical subjects
A Friedman
Publications and source records attributed to A Friedman.
Induction of experimental autoimmune encephalomyelitis by native myelin basic protein-activated T lymphocyte lines.
Self antigens bind to MHC class II molecules in vivo. The capacity of class II molecules to bind native self antigen, namely antigen that has not been processed through an endososomal pathway, could increase susceptibility to autoimmune diseases if recognized by autoreactive T lymphocytes. To confirm this prediction we designed experiments to show that: (a) native myelin basic protein (BP) activates encephalitogenic T lymphocyte lines, and (b) these activated lines cause experimental autoimmune encephalomyelitis (EAE) in naive rats. We show that two encephalitogenic T lymphocytes lines, LEW and BN, are activated by native BP in the presence of paraformaldehyde pre-fixed antigen-presenting cells (APC). The degree of activation, as measured by T lymphocyte proliferation, was equal to that obtained in response to BP processed by APC prior to paraformaldehyde fixing. The response to native BP was confirmed by demonstrating insensitivity to the presence of the lysosomotropic agent chloroquine or protease inhibitors. Activation of T lymphocytes by BP required the presence of syngeneic APC. The activated T lymphocyte lines were injected into naive recipient rats that developed EAE within 5 days. Both disease incidence and severity were equal to that observed in rats that were treated with T lymphocytes activated by processed BP. Hence, at least in EAE, the risk of an autoimmune event could be precipitated by a complex of native antigen and class II molecules on cells that do not possess an endososomal pathway for antigen processing and presentation.
Animals↗
Lymph node sampling in patients with epithelial ovarian carcinoma.
Lymph node sampling is part of the FIGO staging of patients with ovarian carcinoma and is usually part of a meticulous second look operation. We analyzed the primary lymph node status of patients and compared this to the lymph node status at second look operation. From 3/86-3/91, 97 patients with epithelial ovarian tumors were treated at this institution. Seventy-one of the 97 patients (73.2%) had lymph node sampling at primary surgery. Thirty of the 71 patients had positive lymph nodes (42.2%) and 41 patients were lymph node negative (57.8%). Of the initial 97 patients, 58 were eligible for second look operation (59.8%), and 48 of these patients had lymph nodes sampled at second look operation. Nine of the 48 patients had positive lymph nodes (18.7%) and 39 had negative lymph nodes at second look operation (81.3%). Of the patients with negative lymph nodes at primary surgery, 25 patients had second look operation and 24 of these patients had lymph node sampling at second look operation. All patients with negative lymph nodes at primary surgery had negative lymph nodes at second look operation. Of the 30 patients with positive lymph nodes at primary surgery, 12 underwent second look operation. Four patients had persistent positive lymph nodes and 8 patients had negative lymph nodes. Our data suggest that patients with negative lymph nodes at primary surgery are unlikely to have positive lymph nodes at second look operation. Therefore, we believe that lymph node sampling under these circumstances is unnecessary.
Adolescent↗
Immunological parameters in meat-type chicken lines divergently selected by antibody response to Escherichia coli vaccination.
Our group has established two lines of meat-type chickens divergently selected for early (HC line) and late (LC line) antibody responsiveness at 10 days of age to immunization with inactivated pathogenic Escherichia coli bacteria. The question addressed in the study presented here is whether this selection has changed other immunological responses, increasing the overall 'early' immunocompetence. Broilers of the third and fourth generations (S3 and S4) of the selected lines (HC and LC) and a control, unselected line (CT) were vaccinated at 10 days of age with E. coli vaccine, Newcastle virus vaccine (NDV), sheep erythrocytes (SRBC) or bovine serum albumin (BSA). Line-HC chicks exhibited higher antibody titers to E. coli, NDV and SRBC than CT or LC chicks. At 20 days of age HC chicks demonstrated a higher total protein and a higher beta- and gamma-globulin levels in their serum. At 21 days of age, HC chicks cleared carbon particles faster than LC chicks. Peripheral blood lymphocytes (PBL) from HC chicks vaccinated with E. coli vaccine, proliferated in vitro more actively in the presence of the stimulating antigen than the PBL of LC chicks. Peripheral blood lymphocytes (PBL) obtained from HC-line chicks exhibited a higher proliferative response to concanavalin A (Con A)-, phytohemagglutinin (PHA)- or pokeweed mitogen (PWM)-stimulation than LC PBL. These results demonstrate that the selection for high or low antibody response to E. coli at a young age resulted also in a significant change in the response of other parameters of the immune system. The high response to E. coli was found to be associated with a high antibody response to other antigens (NDV and SRBC), increased phagocytic activity and increased proliferative response to antigen or mitogens. The selection most probably affected early immunocompetence.
Aging↗
Exophytic syrinx, an extreme form of syringomyelia: CT, myelographic, and MR imaging features.
Magnetic resonance (MR) imaging and computed tomography (CT) were used to study severe syringomyelia, in which the syrinx was so eccentric relative to the center of the spinal cord that at initial examination it appeared to be an exophytic extramedullary mass, in five of six patients with type 2 Arnold-Chiari malformation and one patient with an intramedullary tumor. Sagittal and axial images were routinely obtained at 1.5 T; CT was performed after intrathecal injection of contrast material. On sagittal MR images, the exophytic component of the syrinx typically displaced the spinal cord peripherally and mimicked an extramedullary intradural lesion such as an arachnoid cyst or meningioma. On axial MR images, the gradual appearance and disappearance of this component could be traced as it compressed the spinal cord, which had a signet-ring appearance at the equator of the syrinx. It is concluded that both MR imaging and postmyelographic CT can reveal the characteristics of this lesion on axial images, but MR imaging is superior because it enables direct sagittal imaging.
Adolescent↗
Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy.
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Acquired Immunodeficiency Syndrome↗
Induction of immune response to protein antigens by subcutaneous co-injection with water-miscible vitamin A derivatives.
Subunit vaccines require potent adjuvants to induce effective immunity. Currently, most known adjuvants have not been approved for human and veterinary use, mainly because of adverse effects resulting from local injections. A material with adjuvant properties proven to be safe for the host would be of importance, particularly if it had a constructive physiological role. A possible candidate is vitamin A and its analogues. The objectives herein were to re-evaluate adjuvant properties of vitamin A by employing water-miscible vitamin A (WMVA) derivatives (retinol palmitate and retinoic acid), and to determine their ability to induce effective immune responses to protein antigens. Injection of WMVA in an aqueous solution prevented adverse effects of local injection, hypervitaminosis and oil depot damage. Other results show that WMVA derivatives behave as extrinsic adjuvants, and increase immune responses to protein antigens without causing hypervitaminosis or significant elevation of liver vitamin A. Primary immune responses were of short duration, but were increased and maintained by booster immunizations. The responses induced by WMVA derivatives were of similar magnitude to those induced by water soluble murmyl-dipeptide and Salmonella typhimurium mitogen. Hence, WMVA derivatives have potential as both efficient and safe adjuvants.
Adjuvants, Immunologic↗
Gastrin releasing peptide antagonists with improved potency and stability.
Gastrin releasing peptide (GRP) is a 27 amino acid peptide hormone which is homologous to the amphibian peptide bombesin. Two series of novel GRP antagonists were developed by C-terminal modification of N-acetyl-GRP-20-27 amide. Peptide derivatives within each series resist enzymatic degradation in serum and exhibit strong affinity for the GRP receptor. The first series of compounds replaces the Leu26-Met27 region of GRP with an alkyl ether N-acetyl-GRP-20-25-NH-[(S)-1-ethoxy-4-methyl-2-pentane], specifically blocked radiolabeled GRP binding with an IC50 of 6 nM. In the second series of antagonists the oxygen of the ether moiety is replaced with a methylene group, resulting in GRP antagonists which are equipotent to native GRP in receptor binding assays (IC50 = 2 nM) and are also resistant to proteolytic degradation in vitro. All of the C-terminally modified peptides tested blocked GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts. Representative compounds also blocked GRP-induced elevation of [Ca2+]i in human SCLC cells, and inhibited GRP-independent release of gastrin in vivo.
Animals↗
Implantation of chicken embryonic tissue and cells into unfertilised eggs.
1. Chick embryo cells and halved embryos were successfully implanted into unfertilised eggs. Yolks containing implants were placed in recipient eggshells, covered by transparent vacuum-formed plastic cones and incubated for 72 h. 2. Dispersed cells were obtained from eggs expelled from the uterus or from eggs that had been laid. Implantation of these cells often resulted in aggregation and epithelial growth, in several cases with axial development. 3. Growth of implanted halved embryos of different ages was often observed, including one 10-somite embryo. Non-axial epithelia, sometimes with a central hole, a central fluid-filled cellular vesicle or a vesicle only, were also observed. 4. In another culture system, whole and halved embryos obtained from laid eggs were cultured on a vitelline membrane stretched across semi-solid egg albumen. During the 72 h incubation, axial development was observed only in whole embryos, while halved embryos grew either into epithelia containing fluid-filled cellular vesicles or into vesicles only. 5. It was found that daily drainage of the accumulating fluid from the embryo compartment encouraged axial development in halved embryos, and almost abolished vesicle formation. Holes were formed in half the embryos cultured on a vitelline membrane. 6. It appeared that physical and biological conditions could inflict serious malformations on the implants.
Animals↗
Decreased resistance and immune response to Escherichia coli infection in chicks with low or high intakes of vitamin A.
The effects of vitamin A excess of insufficiency on resistance to Escherichia coli infection and subsequent anti-E. coli immune response were examined in chicks. Chicks receiving depleted (0 microgram/kg), sufficient (0.85 mg/kg) or excess (1000 mg/kg) levels of vitamin A in their feed were inoculated by a subcutaneous injection of pathogenic E. coli (1 x 10(9) and 2 x 10(9) cfu per chick). Susceptibility to E. coli was determined by mortality, morbidity and immune responses (antibody production and T lymphocyte proliferation). Excess of insufficient vitamin A led to increased susceptibility of chicks of E. coli infection; this was accompanied by depressed immune responses. Chicks receiving excess vitamin A were more sensitive to E. coli than vitamin A-depleted chicks. This was reflected in higher mortality and morbidity rates and in severely depressed immune responses. In contrast to chicks receiving excess vitamin A, T lymphocyte responses (though not antibody responses) of vitamin A-depleted chicks achieved levels similar to those of vitamin A-sufficient birds with a lag period of 6 to 10 d. Therefore, reduction in resistance to E. coli infection, resulting from vitamin A excess or deficiency, probably was compounded by a delayed immune response.
Animals↗
Human papilloma virus in uterine cervix: a comparison of detection by morphology and by dot-blot hybridization.
Colposcopically directed cervical biopsies, smears, and swabs obtained from 210 women with a previous abnormal cervical cytology were evaluated for the presence of human papilloma virus (HPV) using morphology and dot-blot hybridization. The diagnosis of HPV infection in biopsies and smears examined morphologically was rendered using established criteria for condyloma/cervical intraepithelial neoplasia (CIN). In hybridization studies, DNA was isolated from cells obtained from cervical swabs and annealed with probes that detected HPV types 6/11, 16/18, and 31/33/35 using a dot-blot procedure. Ninety-five cases demonstrated morphologic evidence of condyloma/CIN; 51 of these (54%) were positive for HPV DNA (five cases 6/11, 21 cases 6/18, 20 cases 31/33/35, and five cases two different probes). HPV DNA was also detected in 6 of the 115 cases (5.2%) that were morphologically negative (three cases 16/18, three cases 31/33/35). The results demonstrated that morphology was more sensitive than dot-blot hybridization for detection of HPV-related lesions. The dot-blot hybridization did detect HPV DNA in a small percentage of the cases that showed no morphologic abnormality and was useful for typing of the HPV. At this juncture, however, the clinical significance of the latter findings is unclear.
Cervix Uteri↗
Psychotic complications of long-term levodopa treatment of Parkinson's disease.
The prevalence of psychotic complications of levodopa treatment was assessed in 198 Parkinson patients. The symptoms were seen in 44 (22.2%). Those who developed complications were significantly older at disease onset (63.3 +/- 9.2 vs 57.6 +/- 11.6). The observed psychiatric symptoms were classified into two categories: simple, including incidents of confusion alone or hallucinations with preserved insight, and complex, including delusions or chronic confusion without preserved insight. Patients with complex symptoms were significantly younger at the onset of the disease, and the duration of the disease prior to these psychiatric symptoms was longer than in the group of patients with simple symptomatology. Patients with complex symptoms were more susceptible to another central side-effect of the treatment: dyskinesias, than those with simple.
Adult↗
Clinical evaluation of a scintigraphic method for diagnosing inflammations/infections using indium-111-labeled nonspecific human IgG.
This study was undertaken as part of a Phase II study to assess the sensitivity and safety of 111In-DTPA-human IgG, an imaging agent for the detection of inflammations and/or infections. Forty patients with infection/inflammation on the basis of clinical findings, microbiologic results, and/or the basis of results from other imaging modalities were studied. For evaluation of sensitivity, whole-body images were obtained at 6-12 hr (early) and 20-28 hr (delayed) postinjection and occasionally at 48 hr. No adverse reactions were recorded in any of the 40 patients studied. Positive results were obtained in 37 of 37 evaluable subjects (100%). The test appears to be a promising method for the detection of inflammation and/or infection.
Adult↗
[New molecular technology in prenatal genetic diagnosis].
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Female↗
An NMDA-mediated component of excitatory synaptic input to dentate granule cells in 'epileptic' human hippocampus studied in vitro.
Recordings were made from human hippocampal tissue surgically removed for treatment of epilepsy. In 70% of cases, an N-methyl-D-aspartate (NMDA) receptor-mediated component was present in excitatory synaptic input to gyrus dentatus. NMDA receptors are normally present, but do not participate in low-frequency synaptic transmission, in this region of the mammalian brain. These findings suggest that recruitment of normally dormant excitatory amino acid receptors may be a feature of the epileptic brain.
2-Amino-5-phosphonovalerate↗
High-density functional gastrin releasing peptide receptors on primate cells.
Gastrin releasing peptide (GRP) is a 27 amino acid hormone that elicits a variety of biological effects. Receptor-binding antagonists of GRP may have therapeutic use in several pathologic conditions including cancer. The identification and characterization of GRP receptor antagonists have been aided by the use of murine 3T3 cells that possess functional GRP receptors. However, no human or primate cell lines that possess high-density GRP receptors and exhibit a biochemical or biological response to GRP have been described. To address this problem, we examined a series of cell lines and found that GRP specifically binds to Cos-7 monkey cells and stimulates elevation of intracellular calcium in these cells. Cos-7 cells exhibit a single class of high-affinity (dissociation constant = 0.13 nM) GRP binding sites (35,000/cell). Cross-linking experiments that use radiolabeled GRP identified two species of putative GRP receptor proteins (relative molecular mass, 90,000 and 22,000). Competitive binding inhibition studies indicate that Cos-7 cells tightly bind GRP-specific receptor antagonists. These antagonists block the binding of radiolabeled GRP to Cos-7 cells and inhibit GRP-stimulated elevation of intracellular calcium. These properties make Cos-7 cells a useful reagent for the study of GRP receptor antagonists.
Animals↗
The frequency of the delta F508 mutation on cystic fibrosis chromosomes in Israeli families: correlation to CF haplotypes in Jewish communities and Arabs.
We have analysed the distribution of the delta F508 mutation and the haplotypes of cystic fibrosis (CF) bearing chromosomes among the Israeli CF population. The population was classified according to its ethnic origin and included 3 groups, Ashkenazi Jews, Sephardic/Oriental Jews and Arabs. Haplotype B (KM19 allele 2, XV2c allele 1) was found to be the predominant haplotype in all groups but in each of them the haplotype distribution was different. The delta F508 mutation was present in all groups and accounts for 32% of the CF mutations. It was mainly associated with the B haplotype but only one third of the CF chromosomes with this haplotype carry the delta F508 mutation.
Chromosome Deletion↗
Ritodrine treatment for uterine hyperactivity during the active phase of labor.
Forty consecutive patients with uterine hyperactivity, defined as either tachysystole and/or hypertonus during the active phase of vertex delivery, were treated with intravenous ritodrine (50 up to 300 micrograms/min, in 50 micrograms increments/5 min). Thirty-four patients (85%) responded within 20 min with termination of the uterine dysfunction and all (21, 52%) concomitant fetal heart rate distress signs disappeared. The treatment did not prolong labor, as this was significantly correlated to parity and cervical dilation when treatment was initiated (P less than 0.0006 and P less than 0.008, respectively). Fifteen patients were delivered by cesarean section (37.5%) mainly for cephalopelvic disproportion. Multiparas were older and had shorter ritodrine initiation-delivery intervals, but these were the only significant differences when compared to primiparas. Ritodrine is therefore suggested as an effective treatment of uterine hypercontractility dysfunction.
Adult↗