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Biomedical subjects

M M Jones

Publications and source records attributed to M M Jones.

At least 181 records · Page 10Linked to original sources

Effects of the mobilization of aged tissue cadmium by chelating agents.

An examination of the kidney and liver subsequent to the mobilization of aged cadmium deposits from them by the use of both dithiocarbamates and 1,2-dimercapto-1-propranolol (BAL) was carried out. No striking permanent effects due to cadmium mobilization were noted in the kidneys or livers for most of the chelating agents used. After the mobilization of part of the cadmium burden, the remaining cadmium gives evidence of undergoing a redistribution, leading to a renewed increase in both the kidney and liver levels of this element.

Animals↗

Comparative antidotal effects of diethyldithiocarbamate, dimercaptosuccinate, and diethylenetriaminepentaacetate against cadmium-induced testicular toxicity in mice.

The compounds diethyldithiocarbamate (DDTC, Dithiocarb), 2,3-dimercaptosuccinic acid (DMSA), and diethylenetriaminepentaacetic acid (DTPA) were evaluated for effectiveness in protecting mouse testes following administration of an LD100 dose of CdCl2 X 2.5 H2O (Cd). Toxicologic responses were assessed by light microscopic techniques. DTPA gave the most effective testicular protection of the three compounds when given within 30 minutes prior to Cd, but only DDTC was effective when given 30 minutes or longer after Cd. Degenerative changes were minimal when DDTC was given as late as three hours after Cd, and were mild following a four-hour interval. However, the changes were marked, but less severe than in mice receiving Cd only, when DDTC was administered five hours after Cd.

Animals↗

Effects of diethyldithiocarbamate and selected analogs on lead metabolism in mice.

Diethyldithiocarbamate (DDTC) and certain of its N,N-disubstituted analogs were evaluated for effectiveness in reducing organ concentrations and whole body burdens of lead (Pb) in mice which had received 0.06 mg of Pb(II) acetate along with 2.0 microCi of 210Pb 9 days earlier. CaNa2EDTA was used as a positive control for studies in which the compounds were administered ip, and meso-2,3-dimercaptosuccinic acid (DMSA) was used as a positive control for po studies. DDTC was more effective than EDTA in lowering the whole body Pb burdens after 5 ip injections, while N-methyl-N-dithiocarboxyglucamine (MDCG) was less active than EDTA. The other 4 analogs tested were inactive. When DDTC (1.5 mmoles/kg) was coadministered with EDTA (1.5 mmoles/kg), the reduction of total body Pb burdens was significantly greater than that attained with either compound alone at 3.0 mmoles/kg. DDTC was particularly effective in reducing hepatic and splenic Pb concentrations, but was less active than EDTA in lowering the Pb content of bone, kidneys, and brain. Excretion of Pb following ip treatment with EDTA, DDTC, or MDCG was predominantly by the fecal route. DDTC was significantly more effective than DMSA at an equimolar dose in reducing whole body Pb burdens when each was given po. However, po administration of DDTC caused a substantial increase in brain Pb levels.

Animals↗

Comparative effects of parenteral and oral administration of selected dithiocarbamates on body burdens and organ distribution of cadmium in mice.

Diethyldithiocarbamate (DDTC), N-methyl-N-dithiocarboxyglucamine (MDCG), and 4-carboxamidopiperidine-N-dithiocarboxylate (CAP-N-DTC) were compared at equimolar doses administered by the ip and po routes for effectiveness in mobilizing metallothionein (MT)-bound cadmium (Cd) using 109Cd in mice. DDTC was highly effective by both routes in lowering hepatic, renal, and splenic Cd levels, but enhanced redistribution of Cd to testes and brain. While MDCG and CAP-N-DTC were much less active by the oral route, each effected a significant reduction of renal Cd levels, and MDCG reduced the testicular Cd burden. Neither analog lowered hepatic Cd levels impressively when given po.

Administration, Oral↗

Maternal cortical vein thrombosis and the obstetric anesthesiologist.

Maternal cortical vein thrombosis is a potentially fatal complication of pregnancy and the puerperium. Patients may present with focal neurologic deficits, seizures, or symptoms indicating increased intracranial pressure. Associated conditions include maternal dehydration and preeclampsia or frank eclampsia. Parturients may require anesthesia for various types of delivery. Safe administration of appropriate anesthesia must take into account the possible presence of a coagulopathy or reduced intracranial compliance. Case presentations, a literature review, possible pathogenetic mechanisms, and specific anesthetic considerations are discussed to enable the obstetric anesthesiologist to develop a rational plan of management.

Adolescent↗

Influence of crystalloid versus colloid infusion on peripartum colloid osmotic pressure changes.

Plasma colloid osmotic pressure acts to retain fluid in the intravascular space. Intravenous crystalloids have been identified as one of the major factors contributing to the consistent peripartum decline in colloid osmotic pressure. This study was undertaken to compare the effect of two crystalloid infusions (1000 and 2000 mL Plasma-Lyte A) and a colloid infusion (1000 mL 5% albumin) on the peripartum colloid osmotic pressure. Before elective cesarean section, 45 parturients received one of the three infusions. The lowest mean maternal colloid osmotic pressure (16.6 +/- 1.1 mmHg, P less than .05 compared with baseline) occurred in the 2000-mL crystalloid infusion group eight to 16 hours postpartum. Although the colloid osmotic pressure fell in all groups postpartum, this reduction was significantly (P less than .05) less during the first 24 hours in the colloid infusion group. Minimizing this disruption of the colloid osmotic pressure to pulmonary capillary wedge pressure gradient may be clinically important in selected patients.

Cesarean Section↗

Immunologic, morphologic and chromosomal characterization of a cell line (TC78) established from a child with acute lymphoblastic leukemia.

We characterized a cell line established from bone marrow cells from a child with acute lymphoblastic leukemia. This cell line, TC78, had lymphoblastic morphology and was cytoplasmic peroxidase and esterase negative. The cells did not have T- or B-cell properties such as E- or EAC-rosette forming ability, reactivity with monoclonal T-cell or B2 antibodies, or immunoglobulin synthesis. We concluded that TC78 was a pre-pre B-cell line based on the following monoclonal antibody staining pattern: BA-1+, BA-2+, cALLa+, Ia+, 2H7+ and OKB2+. Growth in 'Dickie' culture and reactivity with 1G10 myeloid antibody suggested coexpression of lymphoid and myeloid characteristics. However, 1G10 expression proved dependent on culture conditions, illustrating one caveat in application of monoclonal antibodies in lineage determination.

Antigens, Neoplasm↗

Effects of oral ethinyl oestradiol and norethisterone on plasma copper and zinc complexes in post-menopausal women.

Orally administered ethinyl oestradiol increased the plasma total copper concentration and reduced the albumin concentration in post-menopausal women. Approximately 80% of the increase in copper was due to a rise in caeruloplasmin-bound copper and 20% to an increase in the amount of copper bound per gram of albumin. The plasma total zinc concentration was reduced, due partly to the decrease in albumin concentration and partly to a reduction in the amount of zinc bound per gram of albumin. Norethisterone had no significant effect on plasma copper but it reduced plasma zinc and albumin, though to a lesser extent than ethinyl oestradiol. When administered sequentially with ethinyl oestradiol, norethisterone diminished the effects of the former on plasma copper, zinc and albumin.

Administration, Oral↗

Effects of diethyldithiocarbamate and selected analogs on cadmium metabolism following chronic cadmium ingestion.

Effects of ip treatment with diethyldithiocarbamate (DDTC), 4-carboxamidopiperidine-N-dithiocarboxylate (CAP-N-DTC), and N-methyl-N-dithiocarboxyglucamine (MDCG) on cadmium (Cd) levels in selected mouse organs and tissues were assessed after mice were offered deionized water containing 0.05 mg/ml of CdCl2 X 2.5 H2O, 10 mg/ml of sucrose, and 0.125 microCi/ml of carrier-free 109-CdCl2 as the sole drinking fluid for 15 days. Only 0.31 +/- 0.01 % of the ingested Cd was absorbed. Data obtained following treatment were compared with those obtained earlier in similar studies following ip Cd injection. In contrast to its action when administered after ip Cd injection, DDTC enhanced hepatic Cd burdens in mice which received Cd po. DDTC did, however, reduce renal Cd levels markedly after Cd ingestion, while enhancing brain Cd levels. CAP-N-DTC and MDCG, which were shown earlier to have no effect on Cd levels in striated muscle following ip Cd administration, effected significant reduction of muscle Cd concentrations after Cd administration po, while also reducing hepatic and renal Cd levels significantly. It was concluded that certain dithiocarbamates effectively mobilize and promote excretion of Cd which has been absorbed from one of the natural portals of entry.

Administration, Oral↗

Effects of substituted dithiocarbamates on distribution and excretion of inorganic mercury in mice.

Diethyldithiocarbamate (DDTC) and six of its N,N-disubstituted congeners were evaluated for their relative efficacies in mobilizing and promoting excretion of mercury (Hg++) using mice which had been given 203Hg++; D-penicillamine (PEN) was used as a positive control compound. While none was as effective as PEN when compared on a molar dose basis, significant activity as assessed by reduction of whole body 203Hg burden, was observed following treatment with three of the analogs. The order of effectiveness was PEN greater than N-methyl-N-dithiocarboxyglucamine (MDCG) greater than di(carboxymethyl)dithiocarbamate (DCDC) greater than di(hydroxyethyl)dithiocarbamate (DHDC).

Animals↗

Antidotes for gold (sodium bis[thiosulfato]gold[I]) intoxication in mice.

Eight compounds were examined to determine their relative efficacy as antidotes in acute gold intoxication in mice after the intraperitoneal injection of 200 mg/kg of Na3 [Au(S2O3)2] X 2H2O. Of the compounds examined, 2,3 dimercaptosuccinic acid was the most effective antidote. It was noted that with D-penicillamine those animals which did not survive died sooner (in a matter of hours) than the corresponding control animals which had received no antidote (about 3 days). In subsequent experiments in which Na3 [Au(S2O3)2] X 2H2O was administered at the lower level of 140 mg/kg, 2,3 dimercaptosuccinic acid showed itself to be capable of reducing kidney gold levels by a factor of about 5 and liver gold levels by a factor of approximately 2.

Animals↗

Effects of diethyldithiocarbamate and N-methyl-N-dithiocarboxyglucamine on murine hepatic cadmium-metallothionein in vitro.

A study was made of the effects of diethyldithiocarbamate (DDTC) and N-methyl-N-dithiocarboxyglucamine (MDCG) on partially purified cadmium-metallothionein (Cd-MT) in vitro obtained from livers of mice previously injected with CdCl2 containing 109CdCl2. Analytical Sephadex G-75 gel filtration showed that MDCG effected a time-dependent removal of Cd from MT, and 99% of the Cd was recovered as the soluble Cd(MDCG)2 complex after 24 hr of incubation. Only a portion of Cd of Cd-MT was complexed by DDTC after 24 hr of incubation; 44% remained as Cd-MT, and the net loss following centrifugation prior to application of the samples to the column corresponded to 56% of the Cd originally present. It was proposed that MDCG complexes the 4 g-atoms of Cd in cluster A of MT as well as the 3 g-atoms in cluster B, while DDTC complexes only the 4 g-atoms of Cd in cluster A.

Animals↗

Spontaneous remission of presumed congenital acute nonlymphoblastic leukemia (ANLL) in a karyotypically normal neonate.

A 3-hour-old phenotypically normal girl was transferred to Children's Hospital Medical Center because of skin nodules, hepatosplenomegaly, and marked leukocytosis. The predominant cells in the blood, bone marrow, and dermis were monoblasts consistent with congenital leukemia. Known causes of leukemoid reactions were excluded. The infant received two double-volume exchange transfusions but no chemotherapy. As the white blood cell counts decreased, the monocytic cells became more mature, suggesting that the monoblasts had the ability to differentiate. The proliferative capacity of the marrow appeared to be normal as determined by the ability of marrow cells to form colonies in soft agar. Chromosomal analysis of bone marrow blasts including trypsin--Giemsa banding was normal. Three weeks after birth the patient's CBC and physical examination were normal, and the bone marrow was normal by 4 months of age. The patient has remained in remission for over 3 years.

Age Factors↗

Effects of sodium N-methyl-N-dithiocarboxyglucamine on cadmium distribution and excretion.

Sodium N-methyl-N-dithiocarboxyglucamine (MDCG) was evaluated for its efficacy in mobilizing and promoting excretion of metallothionein-bound 109Cd using mice which had received 0.03 mg of CdCl2 . 2 . 5H2O along with 1.0 muCi of 109CdCl2 three weeks earlier. The MDCG-induced change in the fecal excretion of Cd ranged from a 15-fold increase over the control rate at the lowest dose level used (2.2 mmol/kg; 684 mg/kg) up to a 72-fold increase at the highest dose (8.8 mmol/kg; 2736 mg/kg) following three daily injections. The latter treatment regimen resulted in a fecal excretion of almost 30% of the administered Cd over a 3-day period of observation. Urinary Cd excretion was insignificant in both the control and treated groups. The whole body burden of Cd was reduced by over 50% following seven thrice-weekly i.p. injections of MDCG at 8.8 mmol/kg. There was a 60-65% reduction in both the liver and kidney Cd levels following the same treatment regimen. Radioassay of ten other organs and tissues revealed only modest changes. Testicular Cd was decreased slightly at the highest dose level, and heart tissue from each treated group contained slightly more Cd than controls. Results indicated a rather marked specificity of MDCG in lowering the Cd content of two organs most susceptible to Cd-induced toxicity.

Animals↗

Increase in plasma lactate at the menopause and its relation to the "anion gap".

The mean plasma anion gap (Na + K + Ca + Mg)--(Cl + HCO3(-) + HPO4(2-) + protein), was significantly higher in post-menopausal women compared with pre-menopausal women (8.04 mEq/l compared with 7.03 mEq/l). This change was due, in part, to an increase in the plasma lactate concentration and to smaller increases in citrate and pyruvate concentrations. There were also changes in bicarbonate and chloride concentrations which suggested an increase pH of approximately 0.02 U. Together, these changes accounted for 46% of the increase in the "anion gap", leaving 54% unexplained. It is suggested that the rise in plasma lactate concentration may be due to mild alkalosis and that this change may account for the rise in plasma urate concentration which also occurs at the menopause.

Acid-Base Equilibrium↗

Sodium N-methyl-D-glucamine dithiocarbamate and cadmium intoxication.

The sodium and ammonium salts of N-methyl-D-glucamine dithiocarbamate were prepared and their usefulness as antidotes for cadmium intoxication investigated. This chelating agent was found to be effective in both acute and repeated exposure cadmium poisoning. A single intraperitoneal injection of sodium N-methyl-D-glucamine dithiocarbamate (NaNMG-DTC), administered at a level greater than 1.1 mmol/kg body weight, protects against a normally lethal (greater than 95%) dose of cadmium chloride (10 mg CdCl2/kg body weight) and results in a subsequent dose-dependent decrease in the liver and kidney burdens of cadmium ion. In repeated exposure cadmium intoxication, repeated administration of NaNMG-DTC can result in substantial reductions in both the kidney (71%) and the liver (40%) levels of cadmium. The LD50 of the compound was not determined, but single injections of 26.6 mmol/kg body weight (injectate volume 1.0 ml) are well tolerated in mice.

Animals↗

Contrast enhancement of magnetic resonance images by chromium EDTA: an experimental study.

Chromium EDTA was evaluated as an intravenous contrast agent for magnetic resonance (MR) imaging in vitro and in vivo in rabbits and rats. The effect of Cr EDTA on T1 and T2 values in vitro was first quantitated by spectroscopy at 2.5 MHz, followed by animal trials in which the effects of intravenous injection of Cr EDTA on calculated T1 MR images (obtained by the spin- warp technique at 1.7 MHz) were determined. Following administration of chromium EDTA, differences in T1 values between normal and abnormal kidneys were noted, renal hydronephrosis and renal ischemia were readily identified by the pattern of change in T1, and changes were observed in the normal rabbit brain and in tumors implanted in rats. It is concluded that the use of stable paramagnetic metal ion chelates, such as Cr EDTA, as intravenous contrast agents in MR imaging is feasible and that such agents would make possible the observation of tissue vascularity, breakdown of the blood-brain barrier, and renal function.

Animals↗

Structure-activity relationships among dithiocarbamate antidotes for acute cadmium chloride intoxication.

Eight sodium dithiocarbamates (NaS2CNR1R2) have been examined as antidotes for acute cadmium intoxication. While all of them possess an ability to increase survival when given to mice 2 hr after a lethal (greater than 99%) intraperitoneal injection of 10 mg/kg of CdCl2 X 2.5H2O, their effects on the organ distribution of cadmium vary considerably. It has been possible to show that the accumulation of cadmium in the brain and kidney as well as the survival rates can be correlated with a numerical measure of the polarity of the groups R1 and R2. Each factor has a different dependence on the polarity, but it is possible to construct a composite factor for antidotal efficacy which incorporates survival rate, brain cadmium levels and kidney cadmium levels. The factor constructed here exhibits an optimal value approximately in the middle of the polarity range studied. Compounds which have R1 = -CH2CH1OH and R2 = -CH2CH2OH, or -CH3 or -C2H5 appear to be the most effective antidotes of the compounds examined.

Acute Disease↗