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Biomedical subjects

L Harrison

Publications and source records attributed to L Harrison.

At least 19 recordsLinked to original sources
PubMed1992

Uroporphyrinogen decarboxylase in Saccharomyces cerevisiae. HEM12 gene sequence and evidence for two conserved glycines essential for enzymatic activity.

The HEM12 gene from Saccharomyces cerevisiae encodes uroporphyrinogen decarboxylase which catalyzes the sequential decarboxylation of the four acetyl side chains of uroporphyrinogen to yield coproporphyrinogen, an intermediate in protoheme biosynthesis. The gene was isolated by functional complementation of a hem12 mutant. Sequencing revealed that the HEM12 gene encodes a protein of 362 amino acids with a calculated molecular mass of 41,348 Da. The amino acid sequence shares 50% identity with human and rat uroporphyrinogen decarboxylase and shows 40% identity with the N-terminus of an open reading frame described in Synechococcus sp. We determined the sequence of two hem12 mutations which lead to a totally inactive enzyme. They correspond to the amino acid changes Gly33----Asp and Gly300----Asp, located in two evolutionarily conserved regions. Each of these substitutions impairs binding of substrates without affecting the overall conformation of the protein. These results argue that a single active center exists in uroporphyrinogen decarboxylase.

Amino Acid Sequence↗
PubMed1992

Extrahepatic portal vein aneurysm: report of a case treated by thrombectomy and aneurysmorrhaphy.

Extrahepatic portal vein aneurysm is a rare condition with only 15 cases before ours being reported in the English literature. The etiology is thought to be congenital, secondary to portal hypertension or associated with abnormal weakness of the vein wall. It often presents in conjunction with major gastrointestinal bleeding, but may occur with minimal or no symptoms. Diagnosis is made with color duplex ultrasound, computed tomographic scan, venous phase mesenteric angiography, magnetic resonance imaging, or splenoportography. Thrombosis, rupture, and pressure effects are the major complications of portal vein aneurysm. Shunting procedures are recommended in cases with portal hypertension secondary to liver disease. We report the first case treated by thrombectomy and aneurysmorrhaphy with a successful 10 year follow-up. This procedure should be considered to preserve portal vein flow when portal hypertension is absent or is secondary to the aneurysm itself.

Adult↗
PubMed1992

A reappraisal of the role of prophylactic cranial irradiation in limited small cell lung cancer.

The use of prophylactic cranial irradiation in limited stage small cell lung cancer remains controversial. Prospective trials have demonstrated that PCI can reduce central nervous system relapse rates, but the impact on survival remains questionable except for the possible evidence of a beneficial effect for long term survivors. With higher rates of thoracic control now obtainable with hyperfractionated radiation and concomitant chemotherapy, it becomes important to analyze the benefit of PCI in that setting. Before 1982, we included PCI in the management of all patients with limited stage small cell lung cancer; thereafter, we discontinued its use. This report compares the outcome of the two treatment approaches and addresses the role of PCI among patients who achieve durable local control. There were 36 limited stage small cell lung cancer patients treated with PCI from 1979-1982 and 26 patients treated without PCI from 1985-1989. Induction chemotherapy was followed in both groups by thoracic irradiation (45 Gy). The PCI patients received 30 Gy to the whole brain in 10 fractions. Both groups received maintenance chemotherapy. Of complete responders, brain failure was the first failure in 18% (4/22) of PCI (+) versus 45% (10/22) of PCI (-) (p = .04). Survival at 2 years was 42% for PCI (+) versus 13% for PCI (-) (p less than .05). When the analysis was limited to those patients permanently controlled in the thorax; there were 25% (4/16) brain failures PCI (+) versus 70% (7/10) PCI (-) (p = .03). For this same subset the 2-year survival was 56% PCI (+) versus 14% PCI (-) (p less than .05). There were no 5 year survivors without PCI compared to 38% (6/16) with PCI. These data suggest that PCI appears to be effective in enhancing survival of patients who achieve durable thoracic control. Prospective trials are necessary to evaluate the use of PCI combined with therapeutic regimens with a documented ability to achieve high rates of sustained control of thoracic disease.

Brain↗
PubMed1992

Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12).

Abasic (AP) sites in DNA are produced spontaneously and by many genotoxic agents. The repair of such damages is initiated by AP endonucleases, which are evidently ubiquitous. We employed the recently cloned cDNA, APE, that encodes the major human AP endonuclease, to isolate large genomic fragments that contain the intact APE gene. The sequence of 3 kb encompassing APE was determined (GenBank Accession No. M99703). The APE gene contains four small introns (ranging 130 to 566 bp) and five exons, the first of which is untranslated. The 0.5 kb of DNA sequence upstream of APE did revealed only a possible CCAAT box, but no other regulatory sites or a TATA box, consistent with the constitutive expression of AP endonuclease activity observed in other studies. The location of APE in the human genome was mapped to chromosome 14, bands q11.2-12, by fluorescence in situ hybridization of metaphase cells with DNA from the genomic clones and subclones. Although this locus has not been associated causally with genetic diseases of DNA repair, some translocations that affect 14q11.2-12 could compromise APE and lead to genetic instability.

Base Sequence↗
PubMed1992

Herpes simplex virus type 2 infection, syphilis, and hepatitis B virus infection in Haitian women with human immunodeficiency virus type 1 and human T lymphotropic virus type I infections. The Johns Hopkins University (JHU)/Centre pour le Developpement et la Santé (CDS) HIV Study Group.

Antibodies to herpes simplex virus type 2 (HSV-2), antibodies to hepatitis B virus (HBV) core antigen (anti-HBc), and VDRL antibodies (serologic evidence of syphilis) were evaluated in women known to be infected with human immunodeficiency virus type 1 (HIV-1) (n = 95) or human T lymphotropic virus type I (HTLV-I) (n = 45) and controls (n = 89). HIV-1-seropositive women were more likely than controls to have antibodies to HSV-2 (88% vs. 54%; P less than .001), anti-HBc (67% vs. 43%; P = .008), and VDRL antibodies (21% vs. 8%; P = .02). Similarly, HTLV-I-seropositive women were more likely than controls to have antibodies to HSV-2 (82% vs. 54%; P = .003) and anti-HBc (67% vs. 43%; P = .008). There was no evidence that HIV-1 or HTLV-I predisposed to chronic hepatitis B virus infection. The stronger associations between HIV-1 and HTLV-I with HSV-2 than the associations with syphilis or HBV are consistent with the hypothesis that recurrent disruptions of mucous membranes caused by HSV-2 infections predispose to sexual transmission of HIV-1 and HTLV-I.

Adolescent↗
PubMed1992

Substance misuse and social work qualifying training in the British Isles: a survey of CQSW courses.

In 1989, all Certificate of Qualification in Social Work (CQSW) courses in the British Isles were included in a survey of the training offered social work students on responding to psychoactive substance misuse. There was a 74% response rate. Eleven per cent of the courses that responded provided no formal substance misuse training. Those that offered training provided a median of 8 hours, with over 70% of students receiving less than 11 hours, indicating that many students were being given the briefest of overviews. Outside of four or five 'centres of excellence', social workers and probation officers training in 1988-89 received less than adequate preparation to work with people with alcohol- and drug-related problems, despite evidence that they account for a large and growing proportion of their caseloads.

Adult↗
PubMed1992

Transfection of the Escherichia coli nth gene into radiosensitive Chinese hamster cells: effects on sensitivity to radiation, hydrogen peroxide, and bleomycin sulfate.

The Escherichia coli nth gene encodes endonuclease III, which catalyses the glycolytic removal of various oxidized thymine residues from DNA. A truncated version of nth, with the prokaryotic regulatory sequences removed, was ligated into the retrovirus-based vector pZipneoSV(X)1 and transfected into the radiosensitive Chinese hamster ovary cell line, xrs7. Following selection with G418, two clones (x7nth1 and x7nth6) were shown by Southern analysis to contain the nth gene. No substantial difference in gamma-ray sensitivity was detected between xrs7, clones x7nth1 and x7nth6, and the parent vector transfected clone (x7neo1). However, clones containing the nth gene were more resistant to hydrogen peroxide cytotoxicity [D0's for x7nth1 and x7nth6 were 0.072 microgram/ml (4 microM) and 0.046 microgram/ml, respectively, compared with D0's of 0.034 and 0.027 microgram/ml for xrs7 and x7neo1, respectively] but markedly more sensitive to bleomycin sulfate cytotoxicity than xrs7 and x7neo1 (e.g., 1D0's for x7nth6 and xrs7 were 0.05 and 0.12 microgram/ml, while 2D0's for x7nth1 and xrs7 were 0.35 and 0.48 microgram/ml, respectively). Alterations in sensitivity to hydrogen peroxide and bleomycin sulfate could not be explained by differences in the distribution of the cell-cycle phases and growth rate of nth-containing clones and control cell lines. These results are consistent with the hypothesis that modified thymine lesions are potentially cytotoxic. Hence, when cells incur a high level of endonuclease III-repairable damage relative to strand breakage, such as after treatment with hydrogen peroxide, increased repair capacity increases survival. Gamma radiation produces a lower level of endonuclease III-repairable damage relative to all the other types of lesions produced; hence increased repair capacity has no measurable effect on cell survival. The increased sensitivity of x7nth1 and x7nth6 to bleomycin sulfate toxicity may indicate that, when thymine damage and single-strand breaks are in close proximity on opposite strands of the DNA, endonuclease III, which incises DNA at the site of damaged residues, can increase the number of double-strand breaks and hence decrease the level of cell survival.

Animals↗
PubMed1991

Intraoperative brachytherapy alone for incomplete resected recurrent rectal cancer.

In order to determine the impact of intraoperative brachytherapy alone in patients with recurrent rectal cancer who, due to prior pelvic radiation therapy, were ineligible to receive further external beam pelvic radiation, we retrospectively reviewed the records of 36 patients with recurrent rectal cancer who had gross residual disease remaining in the pelvis following biopsy alone or subtotal resection. The median follow-up was 24 months (6-81 months). The median survival was 27 months and the 4 year actuarial survival was 25%. There was a suggestion of lower survival in patients who underwent biopsy alone compared with those who underwent a subtotal resection (21% vs. 34%). The local failure (LF) rate was 22% as the only site of failure and 44% as a component of failure. There was a lower but non-significant LF rate in patients who underwent subtotal resection vs. biopsy alone (33% vs. 66%) and those with an 125I implant volume of less than 40 cm3 vs. greater than or equal to 40 cm3 (39% vs. 100%). Four patients (11%) developed treatment-related severe complications (without evidence of LF). Our data suggest that, although it is not clear that intraoperative brachytherapy impacts on the ultimate survival rate in this group of patients, it does offer reasonable local control with acceptable morbidity. Since local control, in and of itself is an important endpoint in the treatment of rectal cancer, we continue to recommend brachytherapy as part of an overall aggressive approach in patients who are unable to receive pelvic radiation therapy.

Adenocarcinoma↗
PubMed1991

Pseudomycins, a family of novel peptides from Pseudomonas syringae possessing broad-spectrum antifungal activity.

A family of peptide antimycotics, termed pseudomycins, has been isolated from liquid cultures of Pseudomonas syringae, a plant-associated bacterium. These compounds were purified using Amberlite XAD-2 and reverse-phase liquid chromatography. Pseudomycin A, the predominant peptide in a family of four, showed selective phytotoxicity, and had impressive activity against the human pathogen Candida albicans. Amino acid, mass spectroscopic, and comparative electrophoretic and chromatographic analyses revealed that the pseudomycins are different from previously described antimycotics from P. syringae, including syringomycin, syringotoxin and syringostatins. Pseudomycins A-C contain hydroxyaspartic acid, aspartic acid, serine, arginine, lysine and diaminobutyric acid. The molecular masses of pseudomycins A-C, as determined by plasma desorption mass spectrometry, are 1224, 1208 and 1252 Da, respectively. Pseudomycin D, on the other hand, has a molecular mass of 2401 Da and is more complex than pseudomycins A-C.

Amino Acids↗
PubMed1991

Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer.

Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists.

Adult↗
PubMed1991

An interactive computer graphics system for the design of molded and orthopedic shoe lasts.

The Department of Computer Science at North Carolina State University, with support from the Department of Veterans Affairs and National Aeronautics and Space Administration (NASA) Langley Research Center, has developed an interactive graphics program for the development of shoe lasts from digitized images of feet or digitized images of commercial shoe lasts. The program runs on a Sun 3/260 computer with a TAAC-1 graphics accelerator. The program contains operations for region addition and deletion, techniques for narrowing the ankle area, methods for toe extension, operations to allow for shoe inserts, etc. Once the operations by the user are complete, the program will resample the resulting last in a 512 x 512 array. The user is then allowed to select an error tolerance which will guide a data reduction program to represent the last as Coons patches. These patches are then transmitted to a milling machine which will cut the last.

Computer Graphics↗
PubMed1991

Addison's disease.

Addison's disease is an uncommon endocrine condition manifested by a variety of nonspecific symptoms, such as malaise, anorexia and nausea. Symptoms usually do not occur until most of the adrenal gland has been destroyed. Autoimmune disease has surpassed tuberculosis as the primary cause of Addison's disease. Nevertheless, tuberculosis still accounts for a significant proportion of cases. The rapid adrenocorticotropic hormone (ACTH) stimulation test is useful for identifying adrenal insufficiency. Maintenance therapy consists of hydrocortisone and fludrocortisone.

Addison Disease↗
PubMed1990

Anti-sperm antibodies in homosexual men: prevalence and correlation with sexual behaviour.

The sera of 60 homosexual males were examined for the presence of antibodies to sperm using an indirect immunobead test (IBT). Six of 60 (10%) had antibodies of IgG isotype; in addition two of the six had antibodies of IgA isotype. The presence of antibodies was associated with the practice of unprotected receptive anal intercourse in the previous six months. Antibodies were not found in homosexual men who were celibate, or who practised only oral intercourse during the same period. There was no correlation between the presence of anti-sperm antibodies and antibodies to human immunodeficiency virus (HIV), or numbers of T lymphocytes. These preliminary results lend support to the hypothesis that antigen presentation in the lower gut may be a source of sensitisation against sperm. The possibility that anti-sperm antibodies may be a marker of receptive anal intercourse merits further investigation.

Adult↗
PubMed1990

Norfloxacin use in urinary tract infection by urologists and infectious disease specialists.

One hundred thirty-one patients of urologists and infectious disease specialists were entered into an open trial of norfloxacin in the therapy of urinary tract infections (UTIs). All patients were evaluable for tolerability and 98 were evaluable for efficacy. The patient population in this study was older (mean age 53 years) and had more underlying urogenital disorders (30%) or recent invasive urologic procedures (20%) than the typical patient population with UTIs. Over 50% of the patients had infections due to organisms other than Escherichia coli, including Pseudomonas aeruginosa (14), Klebsiella pneumoniae (5), Enterobacter spp (3) and Group D streptococcus (6). Clinical and bacteriologic cure rates were 90 and 91%, respectively. Side effects occurred in 5 patients and were generally mild.

Administration, Oral↗
PubMed1990

Norfloxacin versus trimethoprim-sulfamethoxazole in the treatment of urinary tract infections.

In a controlled, randomized trial of 133 patients with proven urinary tract infections (UTIs), significantly more pathogens were found to be susceptible to norfloxacin than to trimethoprim-sulfamethoxazole (TMP-SMZ) (p less than 0.01). Among patients with pathogens susceptible to both drugs, more of those treated with norfloxacin were cured or improved (p = 0.06). When at least one patient variable, i.e., prior history of therapy, was corrected for, this difference became significant (p = 0.03). Norfloxacin eradicated 11 of 13 infections due to Pseudomonas aeruginosa and 6 of 7 due to enterococci. Five patients treated with norfloxacin and two treated with TMP-SMZ had relapses within 6 weeks. Significantly fewer adverse experiences occurred in patients receiving norfloxacin (p less than 0.01).

Adult↗