Biomedical subjects
Publications and source records attributed to M Schwartz.
The evaluation and management of fertility problems in Jewish Orthodox patients who strictly follow the Biblical teachings post special problems to the physician. Understanding of the religious, social, and cultural background is of paramount importance in the management of these patients. In this paper some of these problems are discussed.
Congenital lymphedema of the genitalia has profound physical and psychological consequences for the growing child. Extensive resection of this tissue and reconstruction by skin grafting offers a less than satisfactory cosmetic result. Over the past year we have employed a method of total excision of the lymphedematous tissue of the penile shaft with cosmetic reconstruction without skin grafting. A circumferential incision was made 5-10 mm from the coronal sulcus and deepened to the level of Buck's fascia. The skin and subcutaneous tissue were then completely dissected away from the penis. The skin was everted and all of the abnormal lymphedematous tissue excised up to the dermal skin margin. The skin was then tailored to the size of the penile shaft and reapproximated. This method has been employed in two patients with the advantages of (1) shorter hospitalization, (2) lack of morbidity associated with the skin donor site, and (3) satisfactory cosmetic results.
HLA-A, B, C and Bf antigens were studied in 153 blood donors who developped a titre of greater than or equal to 25 i.u./ml antitetanus antibodies following tetanus anti-toxin vaccination. Antigen frequency was compared with that of 412-464 normal blood donors living in the same area. Few significant differences were demonstrated: absence of Bw21 antigen and slight increase of Bf F antigen were observed in "good responders".
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Among 69 ColE3 mutant plasmids selected on the basis of their inability to produce an active colicin, seven (cop-1 to cop-7) were found to bear a mutation affecting the structural gene for colicin. Three of these (cop-1, cop-2 and cop-3) lead to the production of an inactive colicin molecule which has the same molecular weight as wild-type colicin E3 (67,000). These three inactive colicins are still able to interact with the outer membrane receptor. The cop-1 protein retained the ability to inhibit protein synthesis in vitro and therefore seems specifically affected in it ability to penetrate the cell envelope. The cop-2 and cop-3 proteins lost the ability to inhibit protein synthesis in vitro, and activity which is normally associated with the C-terminal part of the colicin molecule. On the basis of this and further evidence, it is suggested that the cop-2 and cop-3 mutations affect the structure of the C-terminal part of the colicin molecule. The other four mutations (cop-4 to cop-7) lead to the production of colicin-related polypeptides of lower molecular weight (29,000 to 45,000) which display a reaction of partial immunological identity with wild-type colicin. These four polypeptides are unable to interact with the cell surface receptor. Three of these mutants are shown to carry a nonsense mutation.
A series of plaque-forming lambda h80 transducing phages carrying various portions of the malA region were isolated. A 5,800-base pair HindIII-EcoRI DNA fragment from one of these phages was cloned into pBR322 and shown to contain malT, which is the positive regulator gene of the maltose regulon, and most of malP, the structural gene for maltodextrin phosphorylase. A restriction map of the HindIII-EcoRI fragment was established, and it was correlated with the genetic map of the malA region (i) by mapping deletions which had been generated in vitro on the plasmid and (ii) by locating on the restriction map a DNA insertion of known genetic position. A 600-base pair HincII-HaeII segment was shown to contain all or part of the promoters for malT and malP, which are known to be transcribed in opposite directions. Strains carrying gene malT on a plasmid synthesized a 94,000-dalton polypeptide which was not produced by identical strains carrying similar plasmids in which malT was partially deleted. Estimates of the size of the malT gene support the conclusion that the 94,000-dalton polypeptide is the malT product.
tpo mutations, located at 74 min on the genetic map, rendered Escherichia coli K-12 resistant to TP1, a phage which can use either the OmpF protein or the LamB protein as its receptor. tpo mutants synthesized decreased amounts of OmpF and LamB proteins but increased amounts of the OmpC product, another outer membrane protein. The effect of the tpo mutations in lam B gene expression was transcriptional. It is one facet of the following effect on the maltose regulon: strong decreases in the syntheses of the LamB protein and the periplasmic MalE protein occurred when the regulon was uninduced; a lesser decrease occurred in the syntheses of the LamB protein the MalE protein, and the cytoplasmic MalQ protein (amylomaltase) when the regulon was induced. The tpo mutants were found to be phenotypically identical to the perA mutant recently described by Wanner et al. (J. Bacteriol. 140:229--239, 1979) and to some of the ompB mutants described by Verhoef et al. (Mol. Gen. Genet. 169:137--146, 1979). Mapping and complementation analysis suggested that these three types of mutations belong to the same cistron. Our results bring to at least four the number of clearly distinct phenotypes which can result from mutations at, or close to, ompB, a locus which appears increasingly complex.
Experimental autoimmune myasthenia gravis (EAMG) is an appropriate model for studying the molecular origin, immunological mechanism and regulation of myasthenia gravis. Several approaches are being utilised for the regulation of the immune response to AChR and for immunosuppression of EAMG: Corticosteriods and azathioprine can suppress EAMG concomitantly with suppression of immune responses to AChR. High dose cyclophosphamide treatment in mice facilitates the onset of EAMG and results in a selective suppression of the humoral response to AChR whereas the cellular response is enhanced. Specific immunosuppression of EAMG is achieved by using a nonmyasthenic, denatured AChR preparation which cross reacts with the intact receptor. Various degradations and modifications of AChR are being performed in order to identify the smallest molecular entity responsible for the myasthenic activity of AChR. Studies on specific monoclonal antibodies, anti-idiotypes, and on the effect of measles virus on EAMG are being described and their possible significance in regulating myasthenia are being discussed.
Administrative records of the Title XIX (Medicaid) Program of New York City were reviewed to determine the impact of a surveillance system introduced to monitor physician billing. Billing patterns of the physicians subject to program sanctions, as well as the larger universe of all participating New York City physicians, showed changes coincident with the introduction of the surveillance program: utilization of x-rays, lab tests, injections, and first visit billing decreased.
Mice possessing the H-2b haplotype are high responders to the cross-reactive antigens (T,G)-A--L and (Phe,G)-A--L whereas mice with the H-2k haplotype respond only to (Phe,G)-A--L. On the level of cross-immunization we have demonstrated that either (Phe,G)-A--L or (T,G)-A--L primed high responder C3H.SW (H-2b) mice could be boosted with both antigens. On the other hand, low responder C3H/DiSn (H-2k) mice which were primed to (Phe,G)-A--L and thus possess (T,G)-A--L specific antibodies, could not be boosted with (T,G)-A--L to mount a secondary response. Only (Phe,G)-A--L primed and boosted H-2k mice produced high levels of (T,G)-A--L reactive antibodies. Furthermore, the binding of the anti-(Phe,G)-A--L antibodies of either C3H/DiSn or C3H.SW mice to 125I-(T,G)-A--L was better inhibited by guinea-pig anti-idiotypes than the binding of C3H.SW anti-(T,G)-A--L antibodies which are the homologous idiotypes (T,G)-A--L was found to be an equally efficient tolerogen in both high and low responder mice. Thus, when C3H.SW and C3H/DiSn mice were injected with a tolerogenic dose of (T,G)-A--L and then immunized with (Phe,G)-A--L, they were found to be tolerant to (T,G)-A--L antigenic determinants, since they produced only the unique antibodies to (Phe,G)-A--L. These results suggest that the H-2 linked Ir genes controlling antibody response to (T,G)-A--L are not involved in the induction of tolerance to (T,G)-A--L.
A report of a doubly heterozygous case for both haemoglobins: Hb Stanleyville II (alpha 78 replaced by Lys) and Hb S (beta 6 Glu replaced by Val) with Hb hybrid S/St II. A 29-year-old woman from Zaïre was found to have four haemoglobins: Hb A, Hb Stanleyville II, Hb S and Hb hybrid S/St II. The clinical and hematological effects of this combination were similar to those of heterozygous sickle cell anaemia. Substitution of Lysin for Asparagin at residue alpha 78 reduced the tendency to polymerization and increased mechanical stability. These findings demonstrated involvement of this site in intermolecular interactions and explained the moderate severity of the sickle cell anaemia syndrome.
This report describes a patient with simultaneous Crohn's disease of the terminal ileum and ulcerative colitis of the left colon and rectum. Well documented cases of "mixed" ileocolitis are quite rare.
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A series of deletions, Mu insertions and point mutations affecting the malK-lamB operon have been isolated. They were used to establish a deletion map of this operon, which could be divided in 27 intervals, with 16 in malK and 11 in lamB. One interesting feature of this map is the lack of randomness in the distribution of Mu insertions in the lamB gene; by using data published elsewhere on the physical length of the deletion intervals it can be concluded that about 25% of these Mu insertions are clustered in a segment representing 2 to 8% of the gene. This map is presently being used to study the biosynthesis, structure, and function of the lamB product, which is an outer membrane protein involved in the transport of maltose and maltodextrin, and which in addition constitutes the receptor for phage lambda.
Starting with a strain containing a malK-lacZ fusion, a series of lambda plaque-forming phages which carry varying amounts of the malE,F operon have been isolated. We have used these phages to construct a deletion map of the malE,F operon. The construction of this deletion map has led to the identification of a new gene, malG. The malG gene is located distal to malF. The malG gene product is a protein required for the active transport of maltose and maltodextrins.
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