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Biomedical subjects

S S Clark

Publications and source records attributed to S S Clark.

At least 37 records · Page 2Linked to original sources

Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL.

In the Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML), the c-abl gene on chromosome 9 is translocated to bcr on chromosome 22. This results in the expression of a chimeric bcr-abl message that encodes the P210bcr-abl tyrosine kinase. The cells of 10% of acute lymphocytic leukemia patients (ALL) carry a cytogenetically similar Ph1 translocation. We report that Ph1-positive ALL cells express unique abl-derived tyrosine kinases of 185 and 180 kilodaltons that are distinct from the bcr-abl-derived P210 protein of CML. The appearance of the 185/180-kilodalton proteins correlates with the expression of a novel 6.5-kilobase messenger RNA. Thus, similar genetic translocations in two different leukemias result in the expression of distinct c-abl-derived products.

DNA, Neoplasm↗

Liquid chromatographic determination of guanethidine salts and hydrochlorothiazide using electrochemical detection and ion-pair techniques.

A high-performance liquid chromatographic method with amperometric detection utilizing oxidation at the glassy carbon electrode is reported for the quantitative determination of a guanethidine (1)-hydrochlorothiazide (2) mixture. The drug mix is difficult to analyze by a single assay procedure due to large differences in the chemistry and chemical structure of the compounds. The drugs are best separated on an octadecylsilane column using 30:70 acetonitrile:0.05 M aqueous sodium dihydrogen phosphate containing 0.02 M sodium pentanesulfonate (pH 2.5) as the mobile phase at a 1.0 mL/min flow rate. Using a cell potential of +1300 mV versus Ag/AgCl and procaine hydrochloride as the internal standard, calibration curves were established for 1 monosulfate or sulfate and 2 in the 0.5-10 and 1.25-25 micrograms/mL range, respectively. Accuracy and precision of the assay are in the 1.7-6% range. The procedure is shown applicable to the analysis of a combination dosage form and is also useful for either drug in a single component dosage form.

Chromatography, High Pressure Liquid↗

Expression and function of transplantation antigens with altered or deleted cytoplasmic domains.

Two mutants of the class I gene encoding the H-2Ld transplantation antigen have been constructed. In one mutant the cytoplasmic domain of the class I molecule has been altered by deletion of 24 of the 31 C-terminal residues, and in the second the C-terminal 25 residues of the cytoplasmic domain have been replaced with a unique sequence of 19 amino acids. These mutant class I genes have been transferred into mouse L cells by DNA-mediated gene transfer. Both mutant genes are expressed at normal levels on the cell surface, and they have charge properties and sizes consistent with the introduced alterations. These mutant Ld molecules can serve as target antigens for allogeneic cytotoxic T cells and as restricting elements for virus-specific cytotoxic T cells. These results show that the 24 residues replaced or deleted from the carboxy terminus of the class I molecule are not required for its transport to or integration in the plasma membrane, nor for its function as a target antigen or a restricting element during T-cell-mediated cytotoxicity.

Amino Acid Sequence↗

Allogeneic and associative recognition determinants of H-2 molecules.

Data presented here describe recent attempts to understand the structural basis for H-2 function. Inbred strains differing only by point mutation in different regions of H-2Kb have proven valuable in the analysis of H-2 domain function. Evidence for the interaction between the N and C1 domains in forming allorecognition determinants and antigen interaction sites is shown. The functional role of C2 is not yet known, since no mutations have been found there, but DNA-mediated gene transfer and exon shuffling techniques should prove invaluable in addressing this issue. Ir gene-type functions of class I molecules were demonstrated. The inability of low responder mutant strains to cross-react with H-2Kb-restricted CTL suggests that these phenomena reflect the failure of virus antigen to interact with low responder H-2Kbm molecules. Thus, the mutant strains provide a valuable system for investigating class I Ir genes.

Animals↗

Attrition of schistosomes in an irradiation-attenuated cercarial immunization model of Schistosoma mansoni.

The attrition of Schistosoma mansoni challenge worms was studied in irradiation-attenuated cercaria-immunized mice as a function of site and time. The peak recovery of schistosomula from the lungs of immunized mice was delayed 2 days in comparison with non-immunized controls. The difference between the peak recoveries of control and immunized mice accounted for about half of the final attrition observed at the 7-week adult worm stge. Hepatic-mesenteric vein worm recoveries obtained 10 to 42 days after challenge were reduced in most cases at least as much as the 49-day counts. Somewhat higher reductions were observed at 14 to 28 days than at 49 days, confirming the evidence of delayed migration obtained at the lung phase. These findings, coupled with histologic observations, indicate that at least half of the worm elimination attributable to immunization occurs 8 or more days after the challenge infection.

Animals↗

Attempts to transfer the resistance of Schistosoma mansoni-infected and irradiated cercaria-immunized mice by means of parabiosis.

Acquired resistance to Schistosoma mansoni infection was measured in S. mansoni-infected or irradiated cercaria-immunized mice, and in normal mice to which the former had been surgically joined. Such parabiotic partners were shown to freely exchange humoral and cellular blood constituents. There was no detectable transfer of resistance from mice infected for 8, 12, or 28 weeks to their uninfected partners, even if parabiosis was established before the initial infection and maintained to autopsy. In comparison with parabiosed controls, the number of adult worms surviving from a challenge infection was reduced by 51-96% in the previously infected mice but was not significantly reduced in their uninfected partners. In contrast, mice immunized with irradiated cercariae and their nonimmunized parabiotic partners showed similar levels of resistance. These data indicate that the resistance induced in mice by irradiated cercariae can be transferred, confirm that at least under some experimental conditions the resistance induced in mice by a previous S. mansoni infection is not readily transferred, and provide additional evidence that the resistance induced by normal infection and irradiated cercarial immunization differ in some fundamental way.

Animals↗

Fibroma of tunica albuginea.

A case of fibroma of the tunica albuginea is presented with a review of the literature on previously reported cases of this rare entity. The characteristics of this lesion, its pathogenesis, and its treatment are considered.

Adult↗

An unusual solution to complicated prostatic urethral stricture: modified pull-through urethroplasty-urethroneocystostomy.

A modified transpubic pull-through procedure was used in a failed Solovov-Badenoch pull-through repair of a traumatic prostatomembranous urethral stricture. The modification consisted of an incision of the intracrural septum through which the mobilized bulbous urethra was then passed and anastomosed to the most available dependent portion of the anterior bladder wall. The outcome was an unexpectedly good result that has persisted for more than 30 months. A review of the literature revealed no absolutely similar procedure.

Abdominal Injuries↗

Cell-mediated immune competence in patients with prostatic carcinoma.

The immune competence of 65 patients with prostatic cancer was evaluated by 2 in vivo and 2 in vitro tests to study the contribution of host factors to the progress of the disease. Patients with benign prostatic hypertrophy served as controls. Our results indicate that the delayed skin hypersensitivity response to common microbial recall antigens (streptokinase/streptodornase, purified protein derivative, dermatophytin 0 and dermatophytin) is unaltered in advanced stages of malignancy. The ability to be sensitized by dinitrochlorobenzene declines significantly in patients with metastatic disease. Blastogenic response of peripheral blood lymphocytes to phytohemagglutinin stimulation is not depressed in late stages of malignancy, although in the circulating T cells per cent and absolute values are somewhat lower in patients with metastases. Herein we show that immune competence (measured by the 4 tests) of patients with prostatic carcinoma does not decrease markedly even in the late stages of the disease. Primary sensitization to dinitrochlorobenzene is the only test showing a decline in responsiveness related to the tumor stage.

Carcinoma↗