Search PubMed⌕ Search

Biomedical subjects

M M Jones

Publications and source records attributed to M M Jones.

At least 145 records · Page 8Linked to original sources
PubMed1989

Antipseudomonal effects of selected dithiocarbamates alone and in combination with gentamicin or aztreonam.

The antipseudomonal effects conferred by combinations of substituted dithiocarbamates, gentamicin or aztreonam (Azactam) were measured and compared to those produced by single agents alone in female BALB/C mice bearing overwhelming Pseudomonas aeruginosa infections. Dimethyldithiocarbamate (DMDTC), diethyldithiocarbamate (DEDTC), and sodium N-methyl-D-glucamine dithiocarbamate (NMGDTC) were chosen as representative substituted dithiocarbamates. All three dithiocarbamates rescued some cisplatin-immunosuppressed mice from pseudomonal infections but DMDTC and NMGDTC produced better results than DEDTC. Single daily injections of DMDTC at doses of 5 mg/kg/day or higher for a total of 7 days rescued 14 of 18 mice given 10(6) viable Pseudomonas aeruginosa by tail vein inoculation. Similar dose regimens of 10 mg/kg/day or higher NMGDTC for a total of 7 days rescued 15 of 18 mice. DEDTC at doses of 5 mg/kg/day or higher for 7 days rescued 7 of 18 mice. Combinations of DMDTC or NMGDTC with gentamicin failed to produce better results than each agent alone in mice immunosuppressed with methyl-prednisolone (Solumedrol) at the dose range evaluated in mice inoculated with 10(6) viable organisms via tail veins. Combinations of DMDTC and aztreonam were effective in mice immunosuppressed with methylprednisolone and given overwhelming numbers of viable Pseudomonas aeruginosa (10(7) or more, ip). Combinations of 6 mg/kg/day or higher of each agent with multiple daily injections rescued 11 of 18 mice. The results yielded by either agent alone were not impressive. Similar results were obtained when mice immunosuppressed with cisplatin were given ip injections of 10(8) or more viable bacteria. No mice were rescued by the use of DMDTC, NMGDTC, aztreonam or gentamicin only. Combinations of DMDTC (6 mg/kg) and aztreonam (6 mg/kg) with multiple daily injections for seven days rescued 11 of 20 infected mice while combinations of NMGDTC with aztreonam were less effective (3 of 20 rescued). The concurrent administration of DMDTC and aztreonam offers considerable promise in the treatment of overwhelming pseudomonal infections in mice and may prove to be of value in human patients as well.

Animals↗
PubMed1988

Comparative mobilization of lead by chelating agents.

The relative abilities of approximately 20 chelating agents to act as antagonists for acute and chronic lead poisoning have been examined in the mouse. The acute LD50 for lead acetate trihydrate was determined and found to be 135.3 mg Pb/kg for i.p. injection with a 95% confidence interval of 87.1-210.3 mg Pb/kg. The relative efficacy of chelating agents to reduce liver, kidney, spleen, bone and brain levels of lead was determined. The movement of lead from the liver to the bone was followed during the first 7 days post injection and was found to result in appreciable changes in the lead levels of these organs from day to day during this entire period. Of the compounds examined, the ones which were most effective in mobilizing lead under various conditions included meso-2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane-1-sulfonate (DPMS), disodium calcium ethylene-diaminetetraacetate (Na2CaEDTA), trisodium zinc triethylenetetraminehexa-acetate, dicalcium ethylenediaminetetra(methylenephosphonate) (Ca2EDTPO) and diethyl dimercaptosuccinate (DEMSA) and 2,3-dimercapto-1-propanol (BAL).

Animals↗
PubMed1988

Dependence on chelating agent properties of nephrotoxicity and testicular damage in male mice during cadmium decorporation.

An examination of the histopathological appearance of the kidneys of mice treated with cadmium chloride (s.c.) and simultaneously given 1 of 3 chelating agents (i.p.) reveals that the extent of nephrotoxicity is greatest when L-cysteine is the chelating agent. When either of 2 dithiocarbamates capable of mobilizing cadmium from its intracellular deposits, i.e. sodium N-methyl-D-glucamine dithiocarbamate (NaG) or sodium N-benzyl-D-glucamine dithiocarbamate (NaB) is used as the chelating agent, no morphological renal damage was evident. Under these same conditions the testes of the mice were protected to the extent of 95% by both of the dithiocarbamates, whereas the protection afforded by the L-cysteine was only about 50%. One factor governing the extent of nephrotoxicity appears to be the stability of the cadmium complexes which are formed and the manner in which this affects their behavior in vivo. Complexes which are preferentially excreted in the bile, cause little or no renal damage.

Acute Kidney Injury↗
PubMed1988

Esters of meso-dimercaptosuccinic acid as cadmium-mobilizing agents.

The dimethyl, diethyl, di-n-propyl, diisopropyl (Di-PDMS), and di-n-butyl esters of meso-2,3-dimercaptosuccinic acid were prepared by esterification of the parent acid and were subsequently purified and characterized. Their relative ability to mobilize cadmium from its aged (greater than 30 days) deposits was evaluated in mice in comparison with 2,3-dimercapto-1-propanol (BAL). All but the dimethyl ester were superior to BAL in reducing the hepatic cadmium levels, though none was superior in reducing renal cadmium levels. Their efficacy in reducing hepatic cadmium levels had the result that all except the dimethyl ester were significantly more effective than BAL in reducing total cadmium body burdens in mice. The most effective of these compounds, Di-PDMS, caused a reduction of whole body cadmium of 59% (i.e., to 41% of control values) under conditions where the corresponding reduction found for BAL was only 18% (i.e., to 82% of control value). The predominant route of excretion of cadmium subsequent to administration of these compounds is via the fecal route (greater than 99%). A synergistic effect was found in the reduction of whole body and kidney cadmium burdens when Di-PDMS was used in combination with trisodium calcium diethylenethriaminepentaacetate.

Animals↗
PubMed1988

N-alkyl-N-dithiocarboxy-D-glucamine analogs as cadmium antagonists: synthesis and evaluation of the n-propyl, n-butyl, and n-amyl derivatives.

N-(n-Propyl)-, N-(n-butyl)-, and N-(n-amyl)-N-dithiocarboxy-D-glucamine were newly synthesized by (a) addition of each n-alkylamine to glucose, (b) high-pressure catalytic reduction of each glucosamine thus formed to the corresponding glucamine, and (c) reaction of the resultant secondary amines with CS2 to form the dithiocarboxy derivatives. Each compound was evaluated as an antagonist of acute cadmium (Cd) toxicity and as a complexing agent for intracellular metallothionein-bound Cd (Cd-MT) in mice. N-Benzyl-N-dithiocarboxy-D-glucamine (BDCG) was used as a positive control compound. Each congener afforded partial or complete protection against the lethal effects of 10.0 mg/kg CdCl2.2.5 H2O, and retarded accumulation of Cd in livers and kidneys when given 2 h after the acutely toxic dose of Cd. Each derivative was also effective in mobilizing Cd from MT-bound sites in livers and kidneys of mice which had received a sub-lethal dose of CdCl2 along with 109CdCl2 2 weeks earlier. Excretion of mobilized Cd was almost exclusively by the fecal route. Potency of the analogs, as well as the octanol/aqueous partition coefficients, increased with the overall length of the N-(n-alkyl) carbon chain. Each compound readily complexed Cd from partially purified Cd-MT in vitro. Serum Cd from mice treated with BDCG was associated principally with proteins of high molecular weight.

Animals↗
PubMed1988

Meso-2,3-dimercaptosuccinic acid and sodium N-benzyl-N-dithiocarboxy-D-glucamine as antagonists for cadmium intoxication.

Orally administered meso-2,3-dimercaptosuccinic acid (DMSA) is an effective antagonist for acute oral cadmium chloride (1 mmol/kg) intoxication in mice when administered up to 8 h after cadmium ingestion. Administration of sodium N-benzyl-N-dithiocarboxy-D-glucamine (NaB) i.p. along with DMSA p.o. resulted in kidney and liver cadmium levels only marginally smaller than those obtained with DMSA alone. Both chelation treatment regimens permitted survival of 80% or more of the animals, in comparison to a survival rate of 40-50% in untreated animals. Intraperitoneally administered NaB by itself is a very effective antagonist for cadmium chloride administered intraperitoneally in either acute or chronic cadmium intoxication. A dose-response study was made of the mobilization of cadmium from the liver and kidney of cadmium-loaded mice by NaB; this showed that NaB is one of the most effective cadmium mobilizing agents developed to date. We have also confirmed the earlier report of Kojima and his co-workers of the ability of NaB to remove cadmium from animals which have been treated with cadmium over an extended period of time. NaB causes a very large increase in the biliary excretion of cadmium. Nuclear magnetic resonance (NMR) spectra of 113Cd in bile from treated animals and model solutions indicates that such cadmium is undergoing rapid ligand exchange.

Administration, Oral↗
PubMed1988

Radionuclide bone/joint imaging in children with rheumatic complaints.

We reviewed the medical records and technetium bone/joint scans of 160 children presenting to the inpatient Pediatric Rheumatology service over a 3-year period. When the scan result (normal versus abnormal) was considered for each patient as a whole, scan sensitivity and specificity were both approximately 75%. However, when each joint was considered individually, sensitivity decreased to 37%, while specificity rose to more than 95% when compared to clinical examination. Reasons for these variations and their clinical correlation are discussed. Overall, radionuclide bone/joint scanning was found to be very useful in the evaluation of monoarticular and nonrheumatic disorders, but it did not alter therapy in children with known connective tissue disorders or other polyarticular diseases.

Adolescent↗
PubMed1988

Optimal dithiocarbamate structure for immunomodulator action.

While the commercially available sodium diethyldithiocarbamate (DEDTC) has been used by several groups in the treatment of AIDS patients, chemical evidence suggests that other dithiocarbamates which are more stable at pH 7.4 might prove to be quite superior for this purpose. Of these other compounds, sodium pyrrolidinedithiocarbamate (PDTC) and sodium di-n-propyldithiocarbamate (DPDTC) which have much longer half lives at pH 7.4, are expected to exhibit similar lipophilicity to DEDTC but superior stability towards hydrolysis. They can be expected to be superior to DEDTC, especially for oral administration.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Mobilization of aged in vivo cadmium deposits by diethyl dimercaptosuccinate.

Diethyl dimercaptosuccinate (DEDMS) was prepared and found to be capable of mobilizing cadmium from mice one month after they had been given an injection (i.p.) of 0.03 mg CdCl2.2.5H2O containing 1.0 microCi of 109 CdCl2. When pure, DEDMS is a waxy solid with a melting point of 61-62 degrees C which is soluble in warm peanut oil. Its LD50 value (i.p.) in mice is approximately 2.6 mmol/kg, a value which allows it to be given at a higher dosage than other known lipid-soluble dithiols. This compound is especially effective in reducing hepatic and whole body levels of cadmium; it is not as effective as 2,3-dimercaptopropanol (BAL) in reducing renal cadmium levels.

Animals↗
PubMed1988

Synergistic enhancement of the biliary excretion of cadmium by the simultaneous administration of two dithiocarbamates.

The simultaneous i.p. administration of the two chelating agents bis(2-hydroxyethyl)dithiocarbamate (DEDTC) and 4-carboxamidopiperidinedithiocarbamate (INADTC) to rats given cadmium in their drinking water at a level of 50 mg cadmium/liter for 39 days led to a large synergistic effect on the biliary excretion of cadmium. A much smaller synergistic effect on the urinary excretion of cadmium was also noted. When treated with a similar mixture of chelating agents after a similar cadmium-drinking water exposure of 180 days, rats showed significant decreases in both renal and brain cadmium levels.

Animals↗
PubMed1988

Dithiocarbamate treatment of chronic cadmium intoxication in mice.

The dithiocarbamate analogs, N-benzyl-N-dithiocarboxy-D-glucamine (BDCG) and N-cyclohexyl-N-(2-hydroxy-3-sulfonatopropyl)dithiocarbamate (CAPSO-DTC), were evaluated as cadmium (Cd) antagonists in mice which had received repetitive injections of Cd to effect accumulation of substantial levels of metallothionein-bound Cd in kidneys and livers. BDCG was highly effective in lowering whole body Cd stores and renal Cd concentrations. While the percent of renal Cd mobilized decreased with increasing Cd concentrations, the total amount of Cd mobilized increased. CAPSO-DTC was also effective in reducing whole body Cd levels, but appeared to have less affinity for renal Cd than did BDCG. Treatment of Cd-laden mice with BDCG provoked only a modest elevation of serum creatinine levels, suggesting that the complex of Cd with BDCG may be less nephrotoxic than the complex of Cd with EDTA or dimercaprol. The log of the percent reduction of renal Cd by BDCG was found to be a linear function of the pretreatment renal Cd concentration, and reductions of whole body Cd burdens correlated closely with reductions of liver and kidney Cd concentrations. It was suggested that a Cd complexing agent of the dithiocarbamate class may have ultimate application in a provocative methodology to estimate body or organ Cd stores based upon the amount of Cd excreted following a standard dose of the chelator.

Animals↗
PubMed1988

Transient myeloproliferative disorder and acute nonlymphoblastic leukemia in Down syndrome.

Two infants with Down syndrome had transient myeloproliferative disorder (TMD) during the neonatal period and subsequently acute nonlymphoblastic leukemia (ANLL). Histochemically, the blast cells in TMD were indistinguishable from those in ANLL. Only the constitutional chromosome (trisomy 21) was found in TMD, whereas new cytogenetic abnormalities emerged in ANLL. A mixed growth pattern in stem cell cultures during TMD suggested the existence of an abnormal clone that might be responsible for the evolution into ANLL at a later date. Serial cytogenetic studies and culture studies of peripheral blood cells may help to understand the pathophysiology and risk of ANLL in patients with TMD.

Acute Disease↗
PubMed1988

Antagonists for acute oral cadmium chloride intoxication.

An examination has been carried out on the relative efficacy of a number of chelating agents when acting as antagonists for oral cadmium chloride intoxication in mice. The compounds were administered orally after the oral administration of cadmium chloride at 1 mmol/kg. Of the compounds examined, several were useful in terms of enhancing survival, but by far the most effective in both enhancing survival and leaving minimal residual levels of cadmium in the liver and the kidney, was meso-2,3-dimercaptosuccinic acid (DMSA). Several polyaminocarboxylic acids also enhanced survival. The most effective of these in reducing liver and kidney levels of cadmium were diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetic acid (CDTA), and triethylenetetraminehexaacetic acid (TTHA). D-Penicillamine (DPA) was found to promote survival but also led to kidney cadmium levels higher than those found in the controls. Sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was as effective in promoting survival as DMSA but left levels of cadmium in the kidney and liver that were approximately four times greater than those found with DMSA.

Administration, Oral↗
PubMed1988

The effect of zinc on the dithiocarbamate-induced mobilization of cadmium deposits in mice.

In comparison with similar experiments in which no zinc acetate was used, the addition of small amounts of zinc acetate to sodium N-methyl-N-dithiocarboxyglucamine produces a significant increase in the amount of cadmium mobilized from the liver and kidneys of mice loaded ip with 10 mg CdCl2.2.5H2O/kg 2 wk prior to the initiation of treatment. Neither treatment results in the transport of significant amounts of cadmium to the brain. The injection of zinc acetate alone did not produce this effect. Experiments in which zinc acetate in drinking water was administered to cadmium-loaded animals showed that the liver and kidney cadmium levels were significantly increased, presumably via zinc-mediated processes in which cadmium from other organs was mobilized to the liver and kidneys.

Acetates↗
PubMed1988

The interior of the flexor tendon sheath of the finger. The functional significance of its structure.

We examined the structure of the digital flexor sheath by dissection and histology. The inner aspect of the sheath was found not to be a continuous smooth surface, as depicted in anatomical and surgical texts. The thin parts of the sheath often overlapped the pulleys before attaching to their superficial aspects, so that the pulleys possessed free edges within the sheath. The frequency of occurrence and sizes of these overlaps were studied in 48 cadaveric fingers; the largest and most frequent overlap was at the distal end of the A2 pulley. Functional studies showed an intricate mechanism of pulley approximation and sheath bulging during flexion. Sutured or partly cut tendons triggered on the free edges; this could be a major contributor to the failures of tendon repairs in "no man's land".

Female↗
PubMed1988

Structure of the crypt epithelium in human palatine tonsils.

Material from human palatine tonsils from a group of 18 tonsillectomised patients aged 22 months to 8 years was studied by LM, TEM and SEM. Special attention was focused on the structure of the epithelium lining the tonsillar crypts. This is of a dynamic nature in the living organism. In contrast to the stratified squamous epithelium covering the oropharyngeal surface of the tonsil it was often reticulated and invaded by non-epithelial cells. However, it was not uniform throughout. When studied by LM and TEM, adjacent patches of epithelium varied in degree of reticularity. The reticulated epithelium was either covered by a thin layer of squamous cells, or this was disrupted in places where non-epithelial cells passed through. Hence the intact surface, as seen on the SEM, is not a reliable indication of the nature of the underlying structure of the epithelium. Small blood vessels were frequently observed in association with the reticulated epithelium. They formed numerous finger-like projections surrounded by a sleeve of subepithelial connective tissue, and also a fine capillary network within the epithelial thickness. It is proposed that such an organisation of the crypt epithelium offers favourable means for the capturing and processing of antigens by the palatine tonsils.

Blood Vessels↗
PubMed1988

Mobilization of cadmium in mice by combined treatment with N-benzyl-N-dithiocarboxy-D-glucamine and diesters of meso-2, 3-dimercaptosuccinic acid.

Mice which had received a non-lethal injection of cadmium (Cd) as CdCl2 nine days prior to therapy were treated with N-benzyl-N-dithiocarboxy-D-glucamine (BDCG) alone or in combination with either di(iso-butyl)dimercaptosuccinate (DiBDMS) or di(iso-amyl)-dimercaptosuccinate (DiADMS). Seven injections of BDCG (1.0 mmole/kg), DiBDMS (0.4 mmole/kg), and DiADMS (0.4 mmol/kg) reduced whole body Cd burdens 50%, 54% and 37%, respectively; coadministration of BDCG + DiBDMS and BDCG + DiADMS produced respective reductions of 65% and 61%. Seven injections of BDCG lowered renal Cd concentrations an average of 82%, but reduced hepatic Cd concentrations only 53%. The DMSA diesters were more effective in lowering hepatic Cd than in reducing the levels of Cd in the kidneys. The respective hepatic and renal Cd reductions were 50% and 20% after treatment with DiADMS, and were 73% and 30% after treatment with DiBDMS. Coadministration of BDCG with DiADMS reduced hepatic and renal Cd concentrations 74% and 82%, respectively, while BDCG co-administered with DiBDMS yielded respective reductions of 80% and 82%. It is suggested that combined use of these newer Cd complexing agents in studies of experimental Cd poisoning may now permit resolution of the issue of reversibility of Cd-induced nephrotoxicity.

Animals↗