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Biomedical subjects

R A Martin

Publications and source records attributed to R A Martin.

At least 55 records · Page 3Linked to original sources
PubMed1993

Dipeptidyl peptidase IV (DPP-IV) from pig kidney cleaves analogs of bovine growth hormone-releasing factor (bGRF) modified at position 2 with Ser, Thr or Val. Extended DPP-IV substrate specificity?

The literature reported DPP-IV substrate specificity includes oligopeptides with a penultimate Pro, Hyp or Ala residue. Bovine GRF is a substrate for DPP-IV and is rapidly degraded by the enzyme via removal of its N-terminal Tyr-Ala. Incubation of selected GRF analogs from the [X2,Ala15,Leu27]bGRF(1-29)NH2 series with a porcine-kidney-derived DPP-IV in PBS (pH 7.4) resulted in cleavage at the X2-Asp3 bond. The extent of enzymatic hydrolysis varied with X2 as reflected in the following relative cleavage rates: Ala2 (100%), Ser2 (4%), Thr2 (2.5%), Val2 (0.53%), Ile2 (0%). These cleavages were sequestered when similar experiments were performed in the presence of the DPP-IV-specific inhibitor N-epsilon-(p-NO2-benzyloxycarbonyl)-Lys-Pro-OH. A side reaction, buffer-induced deamidation of Asn8, contributed less than 5% of the total substrate degradation. Although our finding qualitatively extends the DPP-IV substrate specificity to also include N-terminal X-Ser, X-Thr and X-Val sequences, quantitatively, relatively fast cleavages of the GRFs with Ala2 make the latter preferred substrates for DPP-IV. The data presented here indicates that the observed GRF(3-29) fragment formation upon incubation of Ser2- and Thr2-substituted bGRF analogs in bovine plasma could have been DPP-IV-related.

Animals↗
PubMed1993

Effect of anti-TNF-alpha treatment in an antibiotic treated murine model of shock due to Streptococcus pyogenes.

Experimentally, Gram-negative septic shock can be prevented by the prophylactic use of an anti-TNF-alpha monoclonal antibody. The clinical similarity between Gram-negative and Gram-positive septic shock suggested that anti-TNF-alpha therapy might have a wide application. Increased levels of TNF-alpha were seen in a murine model of septic shock due to Streptococcus pyogenes but administration of an anti-TNF-alpha monoclonal antibody had no beneficial effect on the outcome.

Animals↗
PubMed1993

Position 2 and position 2/Ala15-substituted analogs of bovine growth hormone-releasing factor (bGRF) with enhanced metabolic stability and improved in vivo bioactivity.

In order to prepare GRF analogs with high activity in vivo, a strategy was undertaken to stabilize the peptide to dipeptidylpeptidase IV (DPP-IV), a protease found in plasma which inactivates native human and bovine GRF by cleavage of the Ala2-Asp3 bond. Replacement of the Ala2 residue with Ser, Thr, or Gly in [Leu27]bGRF(1-29)NH2 resulted in peptides greatly stabilized against proteolysis in plasma, but having low inherent GH-releasing activity when tested in bovine pituitary cell cultures. Replacement of Gly15 with Ala15 was marginally effective in improving the in vitro bioactivity of this group of peptides. When tested for GH-hormone release in steers, however, the Thr2,Ala15 analog was four times more potent than bGRF(1-44)NH2. Eleven additional analogs from the [X2,Ala15,Leu27]bGRF(1-29)NH2 series were synthesized and evaluated for metabolic stability in bovine plasma and for GH releasing activity in steers in vivo and in rat pituitary cells in vitro. Two compounds, [Val2,Ala15,Leu27]dGRF(1-29)NH2 and [Ile2,Ala15,Leu27]-bGRF(1-29)NH2, had increased GH-releasing activity in steers over that of [Thr2,Ala15,Leu27]-bGRF(1-29)NH2 and over a previously reported super-potent analog, [desNH2Tyr1,D-Ala2,Ala15]-hGRF(1-29)NH2.

Alanine↗
PubMed1993

Tympanic bulla osteotomy for treatment of middle-ear disease in cats: 19 cases (1984-1991).

Twenty-two tympanic bulla osteotomies were performed in 19 cats for the treatment of bacterial otitis media (n = 11), inflammatory polyps (n = 7), or middle-ear neoplasia (n = 4). Inflammatory polyps mostly affected young adult cats (mean age, 1.5 years), whereas otitis media affected middle-aged cats (mean age, 5.5 years) and neoplasia affected older cats (mean age, 10.25 years). Although not specific for the underlying disease process, fluid density within the tympanic bulla or thickening of the bulla was observed radiographically in 100% of cats with middle-ear disease. In cats for which results were available, bacterial culturing revealed pathogens in 6 cats diagnosed with otitis media and in 7 cats with benign or malignant tumors within the bulla. The ventral approach to the bulla was the most common surgical procedure (18 osteotomies), followed by the lateral approach combined with ablation of the vertical and horizontal parts of the external acoustic meatus (4 osteotomies). Immediate postoperative complications were common but short-term, and included Horner's syndrome (11 cats), facial nerve paralysis (5 cats), and otitis interna (2 cats). Bulla osteotomy resulted in resolution of clinical signs without recurrence in cats with middle-ear polyps. Drainage of the infected tympanic cavity aided in resolution of the clinical signs of bacterial otitis media, but the long-term clinical course was characterized by persistent neurologic deficits (5 cats) and recurrence of disease (2 cats). Neoplastic infiltration of the tympanic bulla was associated with a poor prognosis, and although surgery helped to establish a diagnosis, it did not alter the clinical course of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1993

Lunotriquetral arthrodesis.

Lunotriquetral arthrodesis has been recommended for the treatment of disabling pain at the lunotriquetral joint after more conservative measures have failed. We retrospectively analyzed a series of 22 patients treated with a lunotriquetral arthrodesis for presence of fusion, method of fixation, duration of immobilization, carpal alignment, pain relief, and ability to return to work. Fixation with a Herbert screw supplemented with a Kirschner wire (K-wire) was superior to fixation with K-wires alone. Immobilization longer than 6 weeks was superior to immobilization less than 6 weeks. Combined use of a Herbert screw supplemented with a K-wire and immobilization longer than 6 weeks resulted in union in all patients, even when performed for nonunion after a prior attempted arthrodesis. Pain was improved in all patients; all patients who previously were working returned to work. Routine posteroanterior and lateral x-ray films often failed to adequately profile the arthrodesis site. We recommend using a Herbert screw supplemented with a K-wire for lunotriquetral arthrodesis and keeping the patient in a cast until fusion is documented, usually at least 8 weeks. Fluoroscopic spot views or tomograms are recommended to demonstrate bone fusion.

Adult↗
PubMed1993

Congenital portosystemic shunts in the dog and cat.

Congenital portosystemic shunts were not reported as a clinical entity until the 1970s. Historical and clinical findings and surgical data were detailed in the 1980s. The methods of surgical management learned in the last decade offer challenges of redefinition to surgical management in the 1990s.

Animals↗
PubMed1992

Pentalogy of Cantrell and ectopia cordis, a familial developmental field complex.

The association of sternal fusion defects with various cardiac, diaphragmatic, and anterior body wall defects represents a developmental field complex that includes the Pentalogy of Cantrell and ectopia cordis. No familial cases have been reported previously. We present 3 consecutively born brothers with extensive diaphragmatic defects, 2 who had the Pentalogy of Cantrell. One of the 2 also had ectopia cordis.

Adult↗
PubMed1992

Congenital absence of the vas deferens: recurrence in a family.

We report on 2 brothers with congenital absence of the vas deferens discovered in childhood during inguinal hernia repairs. The vas is absent unilaterally in one sib and bilaterally in the other. The unusual presentation of inguinal hernias in these children is discussed as well as mechanisms of inheritance and associated risk of renal anomalies.

Child, Preschool↗
PubMed1992

Differential analysis of animal bone marrow by flow cytometry.

A simple procedure was developed for rapid analysis of animal bone marrow by flow cytometry using the lipophilic cationic dye 3,3'-dihexyloxacarbocyanine iodide [DiOC6(3)]. The batch process allows differentiation of bone marrow cells into lymphoid, erythroid, and myeloid populations and enables classification of erythroid and myeloid cells into proliferating and maturing subpopulations. From these data, myeloid:erythroid (M:E) ratios and maturation indices for erythroid and myeloid cells (EMI and MMI, respectively) can be derived. This procedure provides the opportunity to analyze bone marrow quantitatively and offers distinct advantages to current manual methods in terms of simplicity, throughput, and reproducibility. The method has been tested successfully using marrow from Wistar rats, B6C3F1 mice, beagle dogs, and cynomolgus monkeys. This technique facilitates the evaluation of bone marrow samples taken from preclinical safety studies or from animal colonies of large size.

Animals↗
PubMed1992

Effect of ACE inhibition on the fetal kidney: decreased renal blood flow.

The kidneys of nine fetuses whose mothers were chronically hypertensive were examined microscopically. Three of these mothers used antihypertensive agents throughout pregnancy including one who used an angiotensin-converting enzyme (ACE) inhibitor. The tubular defects found in these kidneys were compared to the kidneys of 20 normal controls, 13 fetuses with various multiple malformation syndromes and six cases of the twin to twin transfusion syndrome. Evidence from these cases as well as the literature suggest that the primary mechanism by which ACE inhibitors affect development of the fetal kidney is through decreased renal blood flow.

Abnormalities, Drug-Induced↗
PubMed1992

Chronic toxicity and carcinogenicity studies with the beta-adrenoceptor antagonist levobunolol.

The chronic toxicity and carcinogenicity of levobunolol, a nonselective beta-adrenoceptor antagonist, was evaluated in Swiss mice and Wistar rats. The drug was administered in the diet to mice at 0, 12, 50, and 200 mg/kg/day for 80 weeks and to rats at 0, 0.5, 2, 5, 30, and 180 mg/kg/day for 2 years. In mice, uterine leiomyomas were present in 4 of 50 females at 200 mg/kg but not in any other group. The incidences of other tumor types, as well as pathologic findings, were comparable among groups. In rats, significant body weight gain suppression occurred at 5, 30, and 180 mg/kg. Brown discoloration of perianal fur and steel-gray discoloration of hairless skin were evident in high-dose rats. A generalized steel-gray discoloration of internal organs and tissues occurred in the 30 and 180 mg/kg groups. No other differences between treated and control groups were evident. The clinical relevance of the increased incidence of uterine leiomyoma in mice is questionable because it occurred only in one species at more than 200 times the projected therapeutic dose.

Adrenergic beta-Antagonists↗
PubMed1992

Functional, radiographic, and histologic assessment of healing of autogenous osteochondral grafts and full-thickness cartilage defects in the talus of dogs.

A circular (5.5 mm diameter) full-thickness cartilage defect was created on the medial ridge of the talus in 12 skeletally mature dogs. In 6 dogs, the articular surface of the lesion was repaired, using an osteochondral graft obtained from the ipsilateral manus. The graft (digit I, first phalanx, distal articular surface and diaphysis) was contoured to obtain a press fit in the drilled talar recipient site. In 6 dogs, the lesion was not treated and healed by fibrous tissue replacement. Functional assessment (lameness, hock range of motion, joint stability, joint crepitus, and mid-femoral muscle circumference) was completed before surgery and at postoperative weeks 2 through 20. Radiographic assessment (periarticular soft tissue width, joint space width, osteophyte formation, and graft incorporation) was completed before surgery and at postoperative weeks 0, 6, 12, and 20. To facilitate histologic assessment, tissues were stained with toluidine blue and H&E. Histologic assessment of the articular surface on the surgically treated talus, ipsilateral tibia, and contralateral talus was completed, using a modification of the Mankin grading system. Subchondral bone was examined to assess graft viability and incorporation. Analysis of the ordinal data was completed, using a Mann-Whitney rank sum test. All dogs were fully weight bearing by postoperative week 7. Dogs without grafts had significantly (P = 0.036) better clinical function at postoperative week 6. Significant difference in functional assessment was not evident at postoperative week 20. Immediate postoperative radiographic assessment revealed significant (P = 0.005) difference between nongrafted and grafted groups. Significant difference was not observed at postoperative week 6, 12, or 20. All grafts appeared radiographically incorporated by postoperative week 12. All grafts restored joint surface congruity, whereas 3 of 6 nongrafted lesions had poor articular congruity. Of 6 grafts, 4 partially retained normal hyaline cartilage, resulting in significantly (P = 0.014) lower Mankin grades. Significant histologic differences between groups were not apparent when the apposing tibia and control talus were examined. Talar reconstruction by use of a phalangeal osteochondral graft is a viable surgical procedure. These data indicate that normal articular and subchondral architecture are more closely approximated by osteochondral reconstruction than by fibrous tissue repair.

Animals↗
PubMed1992

Investigation of glomerular lesions in dogs with acute experimentally induced Ehrlichia canis infection.

Six male Beagles were inoculated with Ehrlichia canis. Transient proteinuria was confirmed during the acute phase of infection by serial determination of urinary protein-to-creatinine ratio. Peak urine protein loss, consisting principally of albumin, was observed 2.5 to 3.5 weeks after inoculation. Renal biopsy specimens were obtained before inoculation, during peak proteinuria, and 10 weeks after inoculation when proteinuria had resolved. Renal tissue was evaluated by use of light, immunofluorescent, and electron microscopy to correlate specific glomerular lesions with development of proteinuria. Histologic examination revealed perivenular and interstitial infiltrates of lymphocytes and plasma cells localized principally to the renal cortex. Glomerular lesions were minimal to absent. Immunofluorescent staining revealed moderate to marked deposition of anti-canine IgG and IgM in the glomerular tufts and mesangium. Depositions of anti-canine complement factor C3 were not observed. Immunofluorescent staining persisted 10 weeks after inoculation, despite resolution of proteinuria, and probably represented passive trapping of immunoglobulins. Ultrastructural examination revealed fusion of podocyte processes that coincided with development of proteinuria. Electron-dense deposits or changes in the basement membrane were not observed. Morphometric measurements of average podocyte process length and percentage of coverage of basement membrane by podocyte processes were used to quantify the degree of process fusion. Both measurements increased significantly (P < 0.05) during peak proteinuria, and returned to preinoculation values when proteinuria had resolved 10 weeks after E canis inoculation. These findings indicated possible minimal-change glomerulopathy, rather than immune-complex glomerulonephritis, during acute E canis infection and could explain transient proteinuria without histologic evidence of glomerular disease.

Animals↗
PubMed1992

Rectovaginal fistula with atresia ani in three kittens.

Rectovaginal fistula with atresia ani was diagnosed in 3 kittens. Physical abnormalities included abdominal distension, bulging of the perineum, and lack of an anal opening. Vaginography was helpful in determining the type of malformation present in 2 cases. In each kitten attempts were made to surgically correct the anatomic malformations. Various post-operative complications such as fecal incontinence, would dehiscence, constipation, and excessive scar tissue formation occurred and are discussed.

Anal Canal↗
PubMed1991

Delineation of the Costello syndrome.

We present a 15-year-old girl with mental retardation, short stature, coarse face, unusually thick, loose skin of the hands and feet, deep plantar and palmar creases, and nasal papillomata. Her history and physical findings are compared to those of 2 children initially reported by Costello and to 1 child recently reported by Der Kaloustian et al.

Adolescent↗
PubMed1991

In vitro regulation of B cell differentiation by interleukin-6 and soluble CD23 in systemic lupus erythematosus B cell subpopulations and antigen-induced normal B cells.

Polyreactive systemic lupus erythematosus (SLE) B cells were compared with antigen-induced SLE and normal B cells for their interleukin-6 (IL-6) and soluble CD23 requirements. Unlike normal B cells, secretion of antibody by SLE B cells in serum-free medium was not enhanced by exogenous IL-6. Anti-IL-6 antibodies inhibited immunoglobulin production in cultures of normal and SLE B cells, which suggests that IL-6 is required for B cell differentiation. SLE culture supernatants had elevated levels of IL-6, which explains the poor response of the SLE cells to exogenous IL-6. Soluble CD23 enhanced the responses of cells from normal subjects and SLE patients.

Adult↗