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Biomedical subjects

D C Martin

Publications and source records attributed to D C Martin.

At least 127 records · Page 7Linked to original sources
PubMed1990

Partial tolerance in rat renal allograft recipients following multiple blood transfusions and concomitant cyclosporine.

Multiple prior administrations of donor-strain blood while under limited cyclosporine cover, consistently induce extensive rat renal allograft survival and transplantation tolerance. Yet it was hypothesized that some chronic rejection mechanisms were nevertheless operative since consistent but nonprogressive minor renal dysfunction was observed long-term. A histopathologic study on these putative tolerant rats was undertaken to test this hypothesis. Twenty long-term LEW recipients of BN renal allografts receiving the blood-CsA regimen were examined histopathologically at day 100 post-transplant. Sixteen control LEW recipients receiving only a BN renal allograft were studied acutely at day 7 posttransplant. The control recipients demonstrated a range of lesions consistent with previous studies on acute renal allograft rejection in the rat. However, tolerant recipients demonstrated mild-to-moderate lesions consistent with chronic mechanisms of rejection including the following: moderate focal interstitial mononuclear inflammatory cellular infiltration, with periglomerular and perivascular accumulation; occasional arteriolar luminal obliteration and glomerular atrophy; focal areas of moderate interstitial fibrosis; mild interstitial hemorrhage; mild-to-moderate tubular atrophy; and focal tubular necrosis. Previously our laboratory has documented that tissue-specific renal basement membrane antigens may be responsible for inciting this pattern of focal chronic interstitial inflammation. However, from the present histopathologic studies, it would appear likely that chronic rejection mechanisms in these recipients, which were defined as tolerant by immunologic criteria, involve both tissue-specific and MHC determinants. Therefore, induction of transplantation tolerance in these indefinite survivors is partial or incomplete.

Animals↗
PubMed1990

Phenotypic characterization of the Ath-1 gene controlling high density lipoprotein levels and susceptibility to atherosclerosis.

The Ath-1 gene determines the levels of high density lipoprotein (HDL) lipid in response to a high fat diet challenge as well as susceptibility to diet-induced atherosclerosis in mice (Paigen et al. 1987. Proc. Natl. Acad. Sci. USA. 84: 3763-3767). As yet, the identity of the Ath-1 gene and how it acts to affect HDL levels are completely unknown. In an effort to clarify the nature of the gene, we have examined HDL phenotypes in strains carrying either the susceptible or resistant alleles. When challenged with a high fat diet, the susceptible strain C57BL/6 exhibited a marked decrease in the levels of HDL cholesterol and apolipoprotein A-I (apoA-I), the major protein of HDL, whereas the resistant strains C3H and BALB/c maintained high levels of both. Separation of HDL subfractions by polyacrylamide gradient gel electrophoresis revealed that the decrease was particularly striking among the larger HDL species. The rates of synthesis of apoA-I in liver and intestine were similar in the strains and were unaffected by the high fat diet. Although the rates of synthesis of apoA-II and the levels of apoA-II mRNA were decreased in response to the high fat diet, similar decreases were observed in both the susceptible and resistant strains. We conclude that the Ath-1 gene results in a rapid decrease in both HDL lipid and HDL apolipoprotein levels in the susceptible strain in response to the high fat diet and that this is mediated primarily at the level of HDL catabolism.

Alleles↗
PubMed1989

Laparoscopic appearances of peritoneal endometriosis.

This article studies endometriosis diagnosed in patients undergoing laparoscopy for infertility and/or pain from 1982 to 1988. The diagnosis of endometriosis at laparoscopy increased from 42% in 1982 to 72% in 1988. The greatest change is in "subtle" lesions, which increased from 15% in 1986 to 65% in 1988. An increased awareness and histologic confirmation of the protean presentation of endometriosis is associated with a significant increase in the diagnosis of endometriosis at laparoscopy.

Cicatrix↗
PubMed1989

Effects of ketamine and fentanyl on lung metabolism in perfused rat lungs.

The effects of ketamine and fentanyl on serotonin (5-hydroxytryptamine; 5-HT) metabolism, angiotensin-converting enzyme (ACE), and protein synthesis (PS) were investigated in an isolated lung model. Rat lungs were perfused in situ with a blood-free physiological salt solution. The pulmonary vasculature was exposed to ketamine (0.005-2.1 mM) or fentanyl (1.8-4.5 microM) for up to 2 h. After 1 h, accumulation of 5-[14C]hydroxyindoleacetic acid (5-HIAA) by the lung was monitored as an index of 5-HT metabolism. ACE activity was estimated from hydrolysis of [3H]benzoylphenylalanyl-alanyl-proline, a synthetic substrate for the enzyme. [3H]phenylalanine was added to the perfusate after 1 h, and its incorporation into acid-precipitable lung protein was measured over the subsequent hour. Ketamine inhibited 5-HT uptake in a concentration-related manner. The inhibition was characterized as competitive and reversible. Fentanyl had no effect on lung 5-HIAA accumulation. Neither drug altered ACE activity or protein synthesis over the concentration ranges tested. The results indicate an action by ketamine that inhibits the 5-HT membrane-transport process. The different effects observed by ketamine and fentanyl on this process could contribute to the diverse pharmacological properties of these two drugs.

Animals↗
PubMed1989

Luminal hypertonic solutions stimulate concentration-dependent duodenal serotonin release.

The serotonin (5-HT) response to varying concentrations and types of luminal hyperosmolar solutions was examined in rabbit duodenum to define the mechanisms and direction (luminal or vascular) of release. Segments of duodenum were studied in either the Ussing chamber or an isolated, vascularly perfused model. Adjacent mucosal sheets devoid of muscularis were studied in parallel Ussing chambers with exposure of the mucosal surface to 0 to 50 gm/dl dextrose or 0 to 20 gm/dl mannitol. The 5-HT response to hyperosmolar dextrose was measured in the presence of autonomic receptor blockers and tetrodotoxin. In the isolated, perfused duodenum, venous and luminal drainage were sampled during basal, dextrose-infusion, and recovery periods. 5-HT content was measured by high-performance liquid chromatography. In chambered mucosal sheets the percentage of change in mucosal 5-HT release was a linear function of luminal dextrose (r = 0.96; p less than 0.05) or mannitol (r = 0.98; p less than 0.02) concentrations. A significant 65.8 +/- 19% inhibition of 5-HT release was observed for tetrodotoxin but not for atropine, hexamethonium, phentolamine, or propranolol. In the isolated, perfused duodenum, 50 gm/dl dextrose caused an integrated 5-HT venous response of 3.0 +/- 0.7 micrograms/100 gm (p less than 0.05 vs luminal or control venous release). It was therefore concluded that duodenal 5-HT release is concentration dependent for intraluminal glucose and mannitol, is partially neurally mediated by a nonadrenergic, noncholinergic pathway, and is predominantly into the venous drainage.

Animals↗
PubMed1989

Serologic properties of the triple antibody-sandwich-lymphocyte-agglutination assay (TASLA).

Detailed studies concerning the serologic properties of the triple antibody-sandwich-lymphocyte-agglutination (TASLA) assay are described herin. The technique is a sensitive one based on sandwiching three layers of antibody onto the target cell. Two different test systems were utilized which included xeno- and allogeneic models. In the xenogeneic test system, rabbit-anti-DA lymphocyte xenosera served as the primary antibody sandwich layer. Goat-anti-rabbit and swine-anti-goat IgG served as the secondary and tertiary antibody sandwich layers, respectively. In the rat allogeneic test system, LEW-anti-BN rat lymphocyte allosera served as the primary antibody layer. Rabbit-anti-rat and goat-anti-rabbit IgG served as the secondary and tertiary antibody sandwich layers, respectively. Several different experiments were run with varying numbers of antibody sandwich layers, and differing concentrations within each layer. The lymphocyte agglutination reaction was then evaluated by regression analysis. Regardless of the number or concentration of antibody sandwich layers, it was found that the reaction could be functionally defined mathematically, by regression analysis. A secondary or tertiary antibody sandwich layer increased assay sensitivity. The level of lymphocyte agglutination was found to be both a linear function of the number of antibody sandwich layers and the concentration of each utilized. In addition, the serological properties of the TASLA assay were extended to the rat allogeneic test system and was again functionally defined mathematically by regression analysis.

Agglutination↗
PubMed1988

Anesthetic effects on 5-hydroxytryptamine uptake by rat brain synaptosomes.

As a neurotransmitter involved in modulating central nervous system nociception and awareness, 5-hydroxytryptamine (5-HT) may play an important role in the clinical sequelae of certain anesthetic compounds. Anesthetic agents are known to affect peripheral, non-neuronal 5-HT uptake but little is known about their effects on 5-HT metabolism in the central nervous system. The effects of several anesthetic compounds on 5-HT uptake were examined in synaptosomes isolated from rat brain cortex. Inhibition of this uptake process was observed by exposure to clinically relevant concentrations of the volatile anesthetics halothane, isoflurane, and enflurane. The non-volatile agent, ketamine also inhibited uptake while the narcotic fentanyl had an effect only at the highest concentrations tested. Non-volatile agents which had neither a consistent nor significant effect on synaptosomal 5-HT uptake included pentobarbital, sufentanil, and etomidate. These alterations of 5-HT metabolism could represent a mechanism that contributes to anesthetic action.

Anesthetics↗
PubMed1988

Subtle appearance of pelvic endometriosis.

This retrospective study demonstrates an increased documentation of subtle appearances of endometriosis. This documentation was associated with an increased emphasis on excising these lesions for histologic examination. Endometriosis was documented in pink, clear, red, white, and puckered black lesions in 106 (97%) of 109 patients. This included 22 (100%) of 22 patients undergoing laparotomy and 84 (97%) of 87 patients undergoing laparoscopy. Subtle lesions were documented at laparoscopy in 32% of patients in the first 5 months and in 72% of patients in the last 5 months of the study. The increased documentation of these subtle lesions appeared to be related to an increased awareness and anticipation of subtle lesions. The ability to detect such lesions increased with experience and was reinforced by histologic confirmation.

Endometriosis↗
PubMed1988

The medical evaluation of elderly patients with major depression.

Elderly patients hospitalized for management of major depression frequently have an extensive medical evaluation to determine if physical illness is masquerading as, or serving as the precipitating event for, the depression. The purpose of this study was to determine the incidence of newly discovered medical problems and the yield of various diagnostic modalities in such elderly depressed patients. Of 100 depressed geropsychiatric inpatients, the most frequent new diagnoses included: electrolyte abnormalities (6 patients), bacteriuria (13), medication reactions (7), exacerbation of previous thyroid disease (6), new thyroid function abnormalities (3), and renal failure, Parkinson's Disease, and chronic obstructive lung disease (2 each). One patient had a cerebellar hemangioblastoma, and 4 had acute illnesses. A workup including CBC, blood chemistries, urinalysis, and thyroid function tests frequently yielded abnormal results. When used as screening tests, head CT scanning, electroencephalography, and chest radiography did not affect management. We conclude that elderly depressed patients have a high prevalence of undiscovered physical illnesses, but that history, physical examination, and simple laboratory evaluation may be sufficient to guide their workups.

Acute Disease↗
PubMed1988

Progression of lower-extremity arterial occlusive disease in type II diabetes mellitus.

The prevalence of lower-extremity arterial occlusive disease (LEAOD), the progression of LEAOD, and the incidence of new LEAOD were determined by noninvasive method in 410 volunteers between the ages of 50 and 70 yr; 252 individuals had type II (non-insulin-dependent) diabetes, 158 were control subjects. LEAOD was monitored with the ankle/arm systolic blood pressure index in combination with Doppler arterial velocity waveform analysis. LEAOD was much more prevalent in the type II patients (22%, 55 of 252) than in the control subjects (3%, 4 of 158) (P less than .00001). The prevalence of risk factors for LEAOD was much higher in the type II patients, including elevated triglyceride, depressed high-density lipoprotein (HDL) cholesterol, hypertension, smoking, and elevated systolic blood pressure. In type II diabetic patients the incidence of new LEAOD over a 2-yr period (14%, 28 of 197) was lower than the incidence of LEAOD progression (87%, 45 of 52). Type II patients with LEAOD also had a high incidence of mortality (22%, 12 of 55) compared with those without LEAOD (4%, 8 of 197) (P less than .0005). A risk score including smoking history, duration of diabetes, depressed HDL cholesterol, total cholesterol, elevated systolic blood pressure, and low obesity index is related to LEAOD. After accounting for the effect of all of the risk factors, we suggest that type II diabetes contributes additional risk for LEAOD.

Aged↗
PubMed1988

The development of humoral immunity to tissue-specific tubular basement membrane alloantigens after renal transplantation across the major histocompatibility barrier in rats immunomodulated with blood transfusions and cyclosporin.

The development of a humoral immune response to the tubular basement membrane (TBM) alloantigen of Brown-Norway (BN) rat kidneys was studied after transplantation of BN rat kidneys into bilaterally nephrectomized Lewis (LEW) rats. The LEW rat recipients consisted of four groups receiving no form of immunosuppression, pretransplantation cyclosporin alone, or pretransplantation donor-specific or donor-nonspecific transfusions combined with cyclosporin. The latter two regimens induce indefinite allograft survival in the majority of recipients. Circulating antibody to collagenase-solubilized BN rat renal basement membrane (CS-BN-RBM) was present in all four groups of transplant recipients within 1 week after transplantation, and no significant differences in antibody levels were noted between rats receiving no immunosuppression (survival of 1-2 weeks) and the groups of rats who received various immunosuppressive regimens and survived longer. Circulating antibody to BN-CS-RBM continued to increase in quantity in the cyclosporin-treated group until the time of death (2-10 weeks post-transplantation). In the much longer lived combined transfusion and cyclosporin-treated groups, circulating antibody to BN-CS-RBM generally attained a maximum at approximately 2 to 4 months post-transplantation and then plateaued or decreased somewhat before the time of death (3-16 months post-transplantation). No correlation was found between quantity of circulating anti-BN-CS-RBM antibody and post-transplantation survival. Comparative study of the quantity of circulating antibody to BN-CS-RBM (the presumed nephritogenic antigen of experimental tubulointerstitial nephritis in the BN rat) in serum from transplant recipients as compared to serum from BN rats with severe experimental tubulointerstitial nephritis (TIN) (as induced by immunization with heterologous TBM antigens) demonstrated a greater quantity of potentially nephritogenic antibody circulating in transplant recipients than in BN rats with experimental TIN. Histologically, the transplanted kidneys in immunomodulated recipients demonstrated focal chronic interstitial inflammatory infiltrates with tubular atrophy and relative sparing of the glomeruli. The development of immune responses to tissue-specific alloantigens may become of clinical significance as graft-survival times are increased.

Animals↗
PubMed1988

Laparoscopic and vaginal colpotomy for the excision of infiltrating cul-de-sac endometriosis.

Palpable endometriotic nodules deep in the cul-de-sac and vagina represent the extension of intraperitoneal disease. Although such nodules used to be excised with vaginal colpotomy and by tracing the endometriosis to the peritoneum, the dissection of these lesions under laparoscopic visualization had aided in their removal. Of seven patients who were approached with a plan for combined laparoscopic and vaginal excision, five underwent the procedure. The last two required laparotomy due to bowel muscularis involvement.

Douglas' Pouch↗
PubMed1988

B12 and folate deficiency dementia.

Both B12 and folate deficiency have been linked to a dementia syndrome. In the case of B12, the neurologic sequelae may precede the hematologic by months to years. Treating a B12 deficient patient with folate or conversely a folate deficient patient with B12 may exacerbate the neurologic consequences of either deficiency. Iron deficiency is a frequent concomitant of both B12 and folate deficiency, often developing during replacement therapy. Patients with borderline B12 deficiency states have shown biochemical evidence of megaloblastosis and B12 replacement is recommended for those patients.

Aged↗
PubMed1988

Inhibition of synaptosomal serotonin uptake by Ketalar.

The effects of the clinical preparation of ketamine, Ketalar and its preservative, benzethonium chloride on [3H]5-hydroxytryptamine uptake were studied using rat brain synaptosomes. Ketalar caused a concentration-dependent inhibition of substrate uptake by the high affinity transport site (I50 = 20.2 +/- 2.75 microM) while benzethonium chloride had no effect. Kinetic analysis indicated the inhibition to be competitive with serotonin; the apparent km (54 nM) was increased nearly two-fold at 10 microM ketamine. This action may represent a mechanism involved in ketamine anesthesia.

Animals↗