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Biomedical subjects

T Martin

Publications and source records attributed to T Martin.

At least 217 records · Page 12Linked to original sources

Comparative cross-linking study on the 50S ribosomal subunit from Escherichia coli.

We have carried out an extensive protein-protein cross-linking study on the 50S ribosomal subunit of Escherichia coli using four different cross-linking reagents of varying length and specificity. For the unambiguous identification of the members of the cross-linked protein complexes, immunoblotting techniques using antisera specific for each individual ribosomal protein have been used, and for each cross-link, the cross-linking yield has been determined. With the smallest cross-linking reagent diepoxybutane (4 A), four cross-links have been identified, namely, L3-L19, L10-L11, L13-L21, and L14-L19. With the sulfhydryl-specific cross-linking reagent o-phenylenedimaleimide (5.2 A) and p-phenylenedimaleimide (12 A), the cross-links L2-L9, L3-L13, L3-L19, L9-L28, L13-L20, L14-L19, L16-L27, L17-L32, and L20-L21 were formed; in addition, the cross-link L23-L29 was exclusively found with the shorter o-phenylenedimaleimide. The cross-links obtained with dithiobis(succinimidyl propionate) (12 A) were L1-L33, L2-L9, L2-L9-L28, L3-L19, L9-L28, L13-L21, L14-L19, L16-L27, L17-L32, L19-L25, L20-L21, and L23-L34. The good agreement of the cross-links obtained with the different cross-linking reagents used in this study demonstrates the reliability of our cross-linking approach. Incorporation of our cross-linking results into the three-dimensional model of the 50S ribosomal subunit derived from immunoelectron microscopy yields the locations for 29 of the 33 proteins within the larger ribosomal subunit.

Computer Graphics↗

Acute systemic organ injury in term infants after asphyxia.

The systemic manifestations of "asphyxia" were evaluated prospectively in 35 consecutively intubated term newborn infants. The following systemic organ injuries were identified most often: (1) renal, ie, oliguria less than 1 mL/kg per hour for at lest 24 hours (40%), an elevated urinary beta-2-microglobulin concentration (57%), azotemia (11%), and an elevated serum creatinine level (17%); (2) central nervous system, ie, hypoxic-ischemic encephalopathy (including seizures) (31%) or an abnormal cranial ultrasound scan, ie, diffuse parenchymal echogenicity, slitlike ventricles, and poor visualization of the sulci, and/or intracranial hemorrhage (26%); (3) cardiovascular, ie, an abnormal echocardiogram (25%) or abnormal electrocardiogram (11%); (4) pulmonary complications, including persistent pulmonary hypertension (23%); and (5) gastrointestinal complications, which were rare. Traditional markers of fetal distress were not related to the frequency and/or distribution of systemic organ injury. An important implication of this study relates to the recognition of the extent and distribution of organ injury in the "asphyxiated" infant.

Apgar Score↗

Allergic reaction with immune hemolytic anemia resulting from chlorambucil.

In a 73-year-old female with chronic lymphocytic leukemia we observed an acute illness with shivering, high fever, and hemolytic anemia following chlorambucil administration. Reexposure in a controlled clinical situation suggested an allergic drug reaction. In an in vitro assay, we were able to demonstrate chlorambucil as the causative agent of immune hemolysis.

Aged↗

Accidental overdose of mitoxantrone in three patients.

Mitoxantrone is a new effective antineoplastic agent with activity against a wide range of tumors. Compared with the anthracycline drugs doxo- and daunorubicin, it exhibits a clearly lower toxicity and, most importantly, a reduced cardiotoxicity. The analysis of the side-effects recorded after accidental overdosage of the drug gives additional insight into its tolerability. Here we describe our observations in three patients who inadvertently received 100 mg m-2 (two pts) and 183 mg m-2 (one pt) as single slow bolus injections. The main side-effects were moderate nausea and vomiting, shaking chills, and profound but reversible neutro- and thrombocytopenia. There was no immediate cardiac toxicity. One patient with extensive previous daunomycin exposure developed congestive heart failure after 4 months. Two patients were not evaluable for late cardiac complications because of early death due to tumor progression.

Adult↗

Broth culture: the modern 'guinea-pig' for isolation of mycobacteria.

Three cases of mycobacterial infection were confirmed in our laboratory by exclusive isolation of the pathogen in Middlebrook 7H9 broth medium. The mycobacteria failed to grow in all three cases on three different solid media. In one patient Mycobacterium tuberculosis was isolated from a pleural biopsy; a lymph node biopsy from another patient also yielded M. tuberculosis and M. avium-intracellulare was isolated from the spinal fluid of a patient with acquired immunodeficiency syndrome (AIDS). Only the broth culture was positive in all three cases. We suggest these findings emphasise the need for laboratories to use a liquid medium in addition to egg-based or agar media, especially for isolation of mycobacteria from specimens with small numbers of bacilli.

Acquired Immunodeficiency Syndrome↗

Prospective monitoring trial for carcinoma of colon and rectum after surgical resection.

In 1978, a prospective program was initiated to evaluate postoperative monitoring of patients after resection of carcinoma of the colon and rectum. The program included clinical examination, interval endoscopy, measurement of carcinoembryonic antigen (CEA), selected liver function tests (alkaline phosphatase and gamma glutamyl transferase) and roentgenologic testing: roentgenograms of the chest, barium enema, intravenous pyelogram (IVP) and computerized axial tomographic (CAT) scan. Of the initial 226 patients enrolled, 179 had at least one abnormal elevation of the CEA level, and in 70 (39 per cent), recurrence developed. Of the 70 with recurrence, 62 (89 per cent) had elevated CEA levels (greater than 3.0 nanograms per milliliter) prior to detection of recurrence by other means. Eight patients had normal levels (two were false-negative and the other six were tested at inappropriate times). Although other test results often complemented CEA, they were generally less sensitive for early detection. Selective use of these tests frequently documented site and extent of recurrence. The detection sensitivity of these other tests was highest with CAT scan (83 per cent), followed by barium enema and endoscopy (56 and 46 per cent). Forty-five patients underwent re-exploration. Recurrence was found in 42, of whom 23 had resectable disease (five of 11, liver; 17 of 24, local or pelvis, and one of one, lung). In three patients, nothing abnormal was found at exploration; two of these patients ultimately had metastases develop. The median survival time was 43 months and the estimated five year survival rate was 38 per cent. CEA is the best over-all indicator of early recurrence and frequent testing at short intervals is most important. Periodic clinical examination and selected other studies are also essential for early documentation of recurrence. Second-look surgical procedures appear beneficial for survival time in selected patients.

Carcinoembryonic Antigen↗

Superficial mycobacterial lymphadenitis in Saskatchewan.

A total of 43 bacteriologically verified cases of superficial mycobacterial lymphadenitis were reported in Saskatchewan between 1981 and 1986; 35 (81%) were due to Mycobacterium tuberculosis. Among the eight cases (19%) due to nontuberculous mycobacteria the agent most frequently isolated was M. avium-intracellulare. Five additional cases were smear-positive and culture-negative. Direct smears of node tissue or aspirate were positive for acid-fast bacilli in 7 (88%) of the 8 cases of nontuberculous mycobacterial lymphadenitis but in only 16 (46%) of the 35 cases due to M. tuberculosis. Superficial tuberculous lymphadenitis was most frequent in female North American Indian or Asian-born adults and most commonly involved the cervical nodes. Nontuberculous mycobacterial lymphadenitis was most frequent in female white children, and most commonly involved the submandibular nodes. The cases of both tuberculous and nontuberculous mycobacterial lymphadenitis were spread throughout the province. There was an urban concentration of cases of tuberculous lymphadenitis in those of Asian origin. It is important to distinguish between superficial mycobacterial lymphadenitis due to M. tuberculosis and that due to nontuberculous mycobacteria for treatment and management purposes.

Adolescent↗

The double reactivity of a human monoclonal rheumatoid factor to IgG and histones is related to distinct binding sites.

The structural basis of the double reactivity of a human monoclonal rheumatoid factor (RF) with both human IgG and histones H1 and H3 was investigated by means of competitive inhibition experiments. The monoclonal RF binding to solid-phase histones was inhibited by increasing concentrations of heat-aggregated IgG. However, increasing concentrations of purified histones were almost unable to reduce the RF binding to solid-phase IgG. Inhibition of antigen binding with two murine monoclonal anti-idiotopes reacting with distinct idiotopes on the monoclonal RF indicated that the fixation to the different antigens was mediated by distinct binding sites. This result was confirmed by showing the selective sensitivity to mild acid treatment of the histone binding site but not of the IgG binding site. This report provides a structural basis for the existence of polyfunctional combining regions on a human autoantibody.

Antibodies, Monoclonal↗

Hyperphosphorylation of N-60, a protein structurally and immunologically related to nucleolin after tumour-promoter treatment.

Okadaic acid, a non-TPA-type tumour promoter, induces hyperphosphorylation of a 60-kd protein in primary human fibroblasts. Treatment with TPA-type tumour promoters (e.g. TPA and teleocidin) did not cause this hyperphosphorylation. Phosphorylation of this protein was not seen at times earlier than 90 min after the addition of 75 ng/ml okadaic acid to the proliferating cell cultures. The presence of inhibitors such as actinomycin D and cycloheximide, did not significantly influence the level of hyperphosphorylation induced by okadaic acid treatment. By immunoblotting using an antibody anti-nucleolin, the 60-kd protein was identified as a fragment of nucleolar protein, nucleolin. Similarly, antibodies against the 60-kd protein cross-reacted with nucleolin. Furthermore peptide mapping, using staphylococcal V8 protease, showed that the 60-kd protein phosphorylated by casein kinase II in vitro and the okadaic-acid-induced hyperphosphorylated 60-kd protein exhibited identical phosphopeptide maps, indicating that there is also structural relatedness between N-60 and nucleolin. Hyperphosphorylation of the nucleolin fragment (N-60) was suppressed by anti-tumour promoter retinoic acid.

Carcinogens↗

Antacid maintenance therapy in the prevention of duodenal ulcer relapse.

The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p less than 0.01) and bedtime Maalox TC (p less than 0.04). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo.

Adult↗

A peptide from alveolar macrophages that releases neutrophil enzymes into the lungs in patients with the adult respiratory distress syndrome.

A monoclonal antibody has been made to a peptide that is released by human alveolar macrophages. This enzyme-releasing peptide (ERP) causes neutrophils to secrete azurophilic granule enzymes. Normal subjects, patients with pulmonary fibrosis, and patients with sarcoidosis had similar concentrations of this peptide in their bronchoalveolar lavage fluids. However, patients with the adult respiratory distress syndrome (ARDS) had about 2.7 times higher concentrations in their lavage fluids. The enzyme-releasing activity in the lavage fluids was significantly correlated with 2 indices of the severity of the clinical illness in patients with ARDS, the APACHE score, and the chest radiograph score. The correlation was diminished or ablated by removing the peptide with the monoclonal antibody bound to staphylococcal Sepharose 4B. This peptide accounted for 62.08% (SD = 15.88%) of the enzyme-releasing activity in fluids from lungs of patients with ARDS and 86.39% (SD = 24.46%) of the activity in fluids from lungs of normal control subjects. Therefore, ERP is the major neutrophil enzyme-releasing agent in the bronchoalveolar lavage fluid from patients with ARDS and from normal persons. There was a significant correlation between the neutrophil enzyme-releasing activity and the ERP concentrations in BAL of patients with ARDS. These observations suggest that modulation of neutrophil function by ERP significantly controls the protease and peroxidase loads in the lungs of patients with ARDS.

Adolescent↗