[The role of the private-practice pediatrician].
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Family Health↗
Biomedical subjects
B Sandler
Publications and source records attributed to B Sandler.
[Neonatal lupus erythematosus and neurologic involvement: an incidental association?].
UNLABELLED: Neonatal lupus erythematosus is a rare disorder characterized by cutaneous lesions of the face and/or congenital heart block. The transplacental transfer of maternal anti-Ro/SSA, anti-La/SSB, or anti-U1RNP antibodies is responsible for the development of the disease. Few cases of neonatal lupus erythematosus with neurological involvement were reported in the medical literature. CASE REPORT: A 36-week GA female infant presented with neonatal lupus erythematosus comprising cutaneous, hematologic and hepatic disorders with a favorable outcome. However, cutaneous atrophy and hyperpigmentation persisted. Spastic paraparesis was diagnosed at the age of six months. CONCLUSION: The neurological lesions in neonatal lupus erythematosus could either be related to the presence of anti-Ro/SSA antibodies of maternal origin, or of anticardiolipin antibodies.
Antibodies, Anticardiolipin↗
Social paediatrics and child public health--a European perspective.
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Child↗
Peptide T blocks GP120/CCR5 chemokine receptor-mediated chemotaxis.
We previously reported that certain short gp120 V2 region peptides homologous to vasaoactive intestinal peptide (VIP), such as "peptide T," were potent inhibitors of gp120 binding, infectivity, and neurotoxicity. The present study shows that synthetic V2-region-derived peptides have potent intrinsic chemotaxis agonist activity for human monocytes and also act as antagonists of high-affinity (0.1 pM) gp120-mediated monocyte chemotaxis. Selectivity is shown in that peptide T is more potent at suppressing M-tropic than T-tropic gp120 chemotaxis. Peptide T was also able to suppress monocyte chemotaxis to MIP-1beta, a chemokine with selectivity for CCR5 chemokine receptors, while chemotaxis of the more promiscuous ligand RANTES was not inhibited, nor was chemotaxis mediated by SDF-1alpha. In order to determine if peptide T mediated its gp120 antagonistic effects via modulation of CCR5 receptors, RANTES chemotaxis was studied using a CCR5 receptor-transfected HOS cell line. In this case, RANTES chemotaxis was potently inhibited by V2-region-derived short peptides. Peptide T also partially suppressed (125)I-MIP1-beta binding to human monocytes, suggesting action at a subset of MIP1-beta receptors. The V2 region of gp120 thus contains a potent receptor binding domain and synthetic peptides derived from this region modulate CCR5 chemokine receptor chemotactic signaling caused by either gp120 or chemokine ligands. The results have therapeutic implications and may explain recent clinical improvements, in that HIV/gp120 actions at CCR5 receptors, such as occur in the brain or early infection, would be susceptible to peptide T inhibition.
CCR5 Receptor Antagonists↗
Agrobacterium radiobacter as a cause of pseudobacteremia.
Agrobacterium radiobacter was isolated from 15 blood cultures collected from 15 newborns. Contamination of blood cultures was suspected because, in most cases, the babies' illnesses seemed incompatible with infection. A radiobacter was isolated from citrated tubes used for clotting-factor studies. Review of venipuncture technique revealed that occasionally the coagulation study tubes were being inoculated before the blood-culture bottles. This investigation demonstrated how an environmental source coupled with faulty technique caused a cluster of false-positive blood cultures.
Bacteremia↗
Morphological and morphometric studies of the splenic antitumor immune response, elicited by liposome-covered soluble p53 kDa antigen, in chemically-induced rat colon cancer.
We evaluated the splenic morphometric changes in rats treated with carcinogen to study development of anti-cancer immune response. When liposome-covered soluble 53 kDa antigen (s53) was injected into these rats, significant tumor-suppression was seen and the percentage of tumor-free animals rose from 15.4% in non-vaccinated rats to 53.8%. In the spleens of carcinogen treated rats that did not develop tumors, activity of B lymphocytes increased significantly. This was manifested by the expansion of the germinal centers to 50.9% of the follicular area reflecting depletion of B cells, and the decrease of the mantle layer to 48.9% of the follicles. A similar picture was seen with T lymphocytes: the area of the marginal zone decreased to 55.2% of the T zone of the white pulp, and that of the periarterial lymph sheaths (PALS) to 33.6%. In tumor-bearing rats features of the immune decompensation were seen: the germinal centers increased to 96.5% of the follicular area, and the mantle layer and PALS decreased significantly. Vaccination prevented these effects, especially in tumor-bearing rats: the PALS occupies 30.4% of the white pulp and the marginal zone 56.1%, and the mantle layer occupied 58.1% of the follicular zone. Similar changes were found in vaccinated rats without tumors reflecting the compensatory character of the immune reaction in vaccinated rats. In conclusion, we found that treatment with carcinogen followed by vaccination with the s53-liposomes complex stimulated the activity of the splenic B, and to a lesser degree the T systems.
Animals↗
Usefulness of serological determinations of soluble 53 kDa protein in follow-up of melanoma patients.
The role of the soluble 53 kDa antigen (s53) determinations in follow-up of melanoma patient was studied. high performance liquid chromatography (HPLC) was used to measure serum levels of s53 antigen after its partial isolation on gel fiberglass (GFG) affinity chromatography columns. Two main proteins were isolated from these columns as representatives of soluble tumor-associated antigens (TAA) with molecular masses of 64 and 53 kDa. In a Western immunoblot analysis, the 53 kDa protein exhibited a strong positive reaction to the commercial p53 antibody. HPLC isolated both antigens with individual variations and significant differences in their concentrations in patients from different groups. The presence of metastases was manifested by a significant increase in the serum levels of both isolated TAA. This finding is in accordance with our previous observations on the role of the soluble 53 kDa protein in the development of colon and uterine cancers. We conclude that the determination of the serum level of the s53 antigen is of diagnostic significance in the monitoring of melanoma patients.
Antigens, Neoplasm↗
Effects of low doses of carcinogen and different antibodies on the splenic lymphoid system of p53 transgenic mice: morphometric and immunohistochemical studies.
The role of the splenic immune system in the development of high sensitivity of p53 transgenic mice to low doses of carcinogen and vaccination was investigated immunohistochemically and morphometrically. Spleens were obtained from human p53 promoter-chloramphenicol acetyl transferase transgenic mice, grouped as follows: 1, untreated controls; 2, exposed to dimethylhydrazine (DMH); 3, and 4, vaccinated with polyclonal antibodies to soluble-53 kDa protein (s53); 5, vaccinated with monoclonal PAb DO1; 6, vaccinated with monoclonal PAb 421; 7, vaccinated with polyclonal alphaH-p53 antibody. Mice in groups 4-7 were treated with DMH after the course of vaccination. Six months later all the mice were tumor-free, but effects of the low dose carcinogen were distinct in the splenic immune system. They were mainly manifested in blast transformation: the total number of lymphocytes and lymphoblasts decreased to 56.5% of the controls. The total of lymphoid cells in the follicles (B zone) and periarterial lymph sheath (T zone) declined, reflecting moderate insufficiency of the spleen's lymphoid system. Vaccination of transgenic mice with antibodies to soluble-p53 elicited mainly a B system response, with lesser T system involvement. Only few signs of B system insufficiency were found in these mice. Vaccination of mice with different antibodies, with subsequent carcinogen treatment, caused changes in the spleen that were similar to those described for DMH alone, but varied with different anti-p53 antibodies. Vaccination with polyclonal antibodies to soluble-p53, or with monoclonal antibodies PAb DO1 or PAb 421, stimulated the splenic activity of T system, and therefore can decrease the tumorigenic effect of carcinogens.
1,2-Dimethylhydrazine↗
Recurrent plantar keloid.
Keloids of the plantar foot present a unique challenge to the surgical dermatologist. Many of the established regimens often fall short of their desired goals. Some of the obstacles to overcome include the repetitive nature of ambulation, the inability to primarily close the plantar foot, and the exquisite tendency for even fine suturing of skin grafts to form keloids. The use of excision, postoperative electron beam therapy, and secondary intention healing provides a useful approach in the management of plantar keloids.
Adult↗
Transplacental effects of IgG generated against soluble 53 kDa protein on the splenic lymph system of rat progeny exposed to carcinogen: rate of apoptosis, proliferation of lymphocytes and expression of Fas and Fas ligand proteins.
BACKGROUND: We have previously shown that vaccination with IgG generated against the soluble 53 kDa (s53) protein modified the splenic response to carcinogens. Here we studied whether such immunization could affect the splenic lymphatic system of the offspring. METHODS: Offspring of normal female rats or of rats immunized with anti-s53 IgG were exposed to a carcinogen (dimethyl-benz(a)antracene). After 4 months, their spleens were resected and evaluated immunohistochemically for lymphocyte proliferation, apoptosis and apoptosis-related proteins (Fas and Fas ligand), in tumor-free and tumor-bearing animals. RESULTS: Spleens of progeny of unvaccinated rats had a significant decrease in the areas of follicles, germinal centers and the mantle layer after exposure to carcinogens, while maternal vaccination resulted in a significant expansion of the progeny's splenic follicles and germinal centers, the zones of B cell proliferation. The area of periarterial lymph sheaths (PALS) expanded in these offspring, reflecting activation of the T-zone. Maternal vaccination also resulted in a significant rise of Fas ligand-positive lymphocytes in the follicles and PALS of their tumor-free offspring. Tumorigenesis stimulated the Fas activity of B and T cells in the spleens, and this was much enhanced by maternal vaccination. CONCLUSIONS: Maternal vaccination before pregnancy results in altered morphological and functional attributes of the splenic immune system of the offspring. This increased immunoreactivity could reduce the risk of tumors in progeny of vaccinated mothers.
9,10-Dimethyl-1,2-benzanthracene↗
Congenital cutaneous defects as complications in surviving co-twins. Aplasia cutis congenita and neonatal volkmann ischemic contracture of the forearm.
BACKGROUND: During twin pregnancies, several complications may result in the death of a co-twin depending on the date of death. We describe herein 2 infant survivors of monozygotic twin pairs with 2 distinct possible complications: a aplasia cutis congenita and Volkmann ischemic contracture. OBSERVATIONS: One infant had extensive aplasia cutis congenita with an associated monozygotic co-twin who died at 3 months of gestation, and the other child had a localized arm defect due to Volkmann ischemic contracture and brain damage, with a co-twin who died at approximately 6 weeks of gestation. CONCLUSIONS: Congenital cutaneous defects may result in the death of a co-twin. The most common of these defects is aplasia cutis congenita associated with a fetus papyraceus or a dead fetus related to ischemic/thrombotic events in the placenta and fetus. Volkmann ischemic contracture is rare in the newborn but can cause neonatal cutaneous defects. The cause of Volkmann ischemic contracture in newborns is unknown; however, our second observation suggests the possible role of a dead fetus.
Compartment Syndromes↗
Collodion baby and lamellar ichthyosis.
It is important to differentiate the collodion baby from harlequin ichthyosis as the latter rarely survives past the first few days of life. Occasionally, babies share features of both disorders and defy a clinical diagnosis. We recently encountered such a baby who initially presented with harlequin-like features, but evolved into lamellar ichthyosis once the keratin cast was shed. Since the routine histology of all these ichthyoses is similar, we used electron microscopy to study serial biopsy specimens from the affected infant on days 7, 14, and 150, and compared them to our own other cases of harlequin ichthyosis and lamellar ichthyosis. Electron microscopic studies of our case revealed that the marginal band of cornified cells of the stratum corneum was absent when the baby exhibited collodion/harlequin ichthyosis features. Another biopsy taken when the clinical picture evolved into lamellar-like ichthyosis, showed a well-formed marginal band in the cornified cells. In harlequin ichthyosis, the marginal band is present at birth. It is suggested that electron microscopy can differentiate severe collodion baby from harlequin ichthyosis at birth using the absence of the marginal band. Previously reported features of harlequin ichthyosis, such as the presence of giant mitochondria and an abnormal formation of the marginal band in luminal villi of acrosyringeal eccrine duct, were absent in our case.
Abnormalities, Multiple↗
The role of the soluble p53 antigen and its autoantibodies as markers for diagnosis of colon cancer: a comparative study.
The role of various serological tumor markers, p53 soluble antigen and its autoantibodies, was evaluated for the detection of colon cancer in humans. An HPLC technique was used to measure serum levels of both forms of p53 protein after their partial isolation on gel fiberglass affinity chromatography columns. Tumor-associated proteins (TAP) in the form of either antigens or autoantibodies were about 4% of the total protein isolated from the serum of colon cancer patients. The absolute amount of each of the two types of TAP was also similar: 14.69 2.88 and 18.29 3.85 mg ml-1, respectively. The amount of p53 autoantibodies was higher than those of p53 antigen, but the difference was not significant: 9.35 3.48 and 6. 19 3.87 mg/ml, respectively (p>0.05). A good correlation was found between the total amount of tumor-associated antigens (TAA) and the amount of p53 antigen (r=0.69), total amount of IgG and the amount of p53 autoantibodies (r=0.46), and between both forms of p53 protein (r=0.46). A high coefficient of regression was found between the total amount of TAA and the amount of p53 antigen (b=2.4). Relationships between Duke's stage in colon cancer and the serum levels of p53 protein were weak: 0.33 and -0.32 for p53 antigen and its autoantibodies, respectively. Serum determination of p53 autoantibodies has no advantage over the determination of p53 antigen. Both forms of p53 protein can be isolated with extremely high accuracy for the pathological diagnosis of cancer (87-93%). Specificity of the method was proved using of commercial p53 PAb OD1: the GFG columns with this antibody were able to isolate the same proteins which were isolated by GFG columns with anti-p53 IgG. Moreover, the isolation of p53 protein was performed with higher effectiveness using the GFG columns with entrapped anti-p53 IgG than those columns with commercial DO1 PAb.
Autoantibodies↗
Specificity of polyclonal anti-p53 IgG for isolation of the soluble p53 antigen from human serum.
The possibility to use anti-p53 IgG for isolation of the soluble p53 antigen as a serological tumor marker has been shown in our previous studies. In order to prove the specificity of such IgG, we compared the effectiveness of columns with anti-p53 IgG and IgG isolated from non-treated rabbits (regular IgG). The gel fiberglass (GFG) columns for affinity chromatography were prepared separately with both types of IgG. The same serum was percolated simultaneously through both columns and the results of elution were compared. The total concentration of tumor-associated antigens (TAA) eluted from the serum of cancer patients was similar in both TAA mixtures isolated either with anti-p53 IgG or with the regular IgG. Differences are manifest in the content of total proteins and amount of each eluted protein: a mixture eluted with the regular IgG contains several proteins whereas the anti-p53 IgG isolated only two proteins, p64 and p53. The amount of the soluble p53 antigen isolated from the cancer serum was significantly higher when it was isolated with anti-p53 IgG. The method developed in our laboratory was shown to be highly specific both to isolate proteins related to cancer (p53) and non-cancer disorders (p64). Data presented in this report show that such specificity can be achieved only if the anti-p53 IgG is used: the regular IgG obtained from non-treated animals isolate many proteins among which the concentration of specific p53 protein is lost.
Animals↗
Expression of p53 protein in rat colon cancer cell lines transfected with Rous sarcoma virus-33.
Expression of the cytoplasmic soluble form of p53 protein in the different rat colon cancer cell lines transfected and non-transfected with Rous sarcoma virus-33 was studied. Concentrations of the p53 protein were detected by commonly used immunochemical methods after its isolation by affinity chromatography columns with the gel fiberglass membranes. The main component of tumor-associated antigens (TAA) eluted from virus-transfected cells was the 53 kDa protein in its cytoplasmic soluble fraction. The non-virogenic colon cancer cells contain a few proteins and concentration of 53 kDa protein was low. Western immunoblotting revealed that the 53 kDa protein isolated from the cell lyzates studied was distinctly recognized by the p53 MAb. ELISA showed that its concentration was markedly higher in the lyzate obtained from the highly virogenic and tumorigenic R9 cell line compared with the non-virogenic cell line RT1. We concluded that the expression of the p53 protein is related to the viral transfection of cancerous cells. The possible role of this phenomenon in the etiology of cancer is discussed.
Animals↗
Serological and immunohistochemical determinations of p53 protein in diagnosis of endometrial cancer: a comparative study.
BACKGROUND: The role of different methods for the determination of p53 protein was evaluated for the detection of endometrial cancer in humans. METHODS: p53 antigen was detected immunohistochemically in the cell nuclei of endometrial tumors and serologically in the serum of the same patients. The high performance liquid chromatography (HPLC) technique was used to measure serum levels of p53 protein after its partial purification on gel fiberglass affinity chromatography columns. RESULTS: Image analysis of cellular concentrations of p53 protein revealed an increase from 12% in hyperplastic endometrium to 74% in adenocarcinomas. Image analysis has also revealed a strong correlation between cellular concentrations of p53 antigen and tumor grade (r = 0.54). Visual cell determination of p53 antigen was effective mainly among patients with benign lesions (r = 0.61). There was a positive correlation between cellular concentration of p53 protein in tumor tissue and its serum level in cancer patients (r = 0.44). The serum level of the cytoplasmic form of p53 antigen significantly increased in cancer patients (3 mg/ml) compared to the concentration in patients with benign disorders (0.7 mg/ml); a consequence of its higher concentration in tumor cells. Serum level of p53 antigen was highly active both in patients with non-cancerous lesions (r = 0.42) and in patients with cancer (r = 0.51). Diagnostic significance of tissue concentrations of estrogen and progesterone applies only to cancer patients: coefficients of correlation between these parameters and tumor gradation were 0.58 and 0.89, respectively. CONCLUSIONS: Serum determination of cytoplasmic p53 antigen can reveal this oncoprotein in the early stages of cancer, or even foretell its development.
Adenocarcinoma↗
[Materno-fetal infection and Pseudomonas aeruginosa meningitis].
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Female↗
An elevated day three follicle-stimulating hormone:luteinizing hormone ratio (FSH:LH) in the presence of a normal day 3 FSH predicts a poor response to controlled ovarian hyperstimulation.
OBJECTIVE: To determine if an elevated FSH:LH ratio predicts response in infertile patients undergoing controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN: Retrospective study. SETTING: The Division of Reproductive Endocrinology at the Mount Sinai Medical Center, New York, New York. PARTICIPANTS: Seventy-four patients undergoing IVF-ET using similar protocols for COH with day 3 FSH, LH, and E2 testing available for analysis. All patients were < 41 years of age and had day 3 serum FSH < 15 mIU/mL (conversion to SI unit, 1.00). MAIN OUTCOME MEASURES: Follicle-stimulating hormone:LH ratio, day 8 serum E2, peak serum E2, cancellation rate, pregnancy rate, and number and size of follicles. RESULTS: An FSH:LH ratio > or = 3.6 (group I) predicted a poor response to COH (sensitivity 85.7% and specificity 95%). There were no significant differences regarding day 3 serum FSH and ampules of gonadotropins used for COH. Group I (ratio > or = 3.6) patients responded to COH with lower day 8 E2 (97 +/- 18 versus 319 +/- 36 pg/mL; conversion factor to SI unit, 3.671), peak E2 (422 +/- 115 versus 2,368 +/- 183 pg/mL), and fewer follicles > 15 mm (1.3 +/- 0.5 versus 17.1 +/- 1.0). In group I the cycle cancellation rate (12/14) was significantly higher than the group II cycle cancellation rate (2/60) and pregnancy rate in group II (ratio < 3.6) was 25%. CONCLUSIONS: The FSH:LH ratio may increase before a dramatic increase in serum FSH is observed and appears to be a useful marker of ovarian reserve.
Adult↗