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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1998

Effect of salmeterol on Haemophilus influenzae infection of respiratory mucosa in vitro.

Haemophilus influenzae is a common bacterial pathogen causing human respiratory tract infections. We have previously shown that the beta2-agonist salmeterol reduces damage to the respiratory mucosa caused by Pseudomonas aeruginosa in vitro. We have now investigated the effect of salmeterol on H. influenzae infection of adenoid tissue in an organ culture by scanning electron microscopy. Tissue was preincubated with or without salmeterol (4x10(-7)M), prior to infection with H. influenzae and incubated for 12 or 24 h. Infected organ cultures had increased epithelial damage and decreased numbers of both ciliated and unciliated cells at 12h, which were significantly different (p < or = 0.01) from the controls at 24 h. Salmeterol (4x10(-7)M) significantly (p < or = 0.03) reduced damage and loss of ciliated cells in infected organ cultures at both 12 and 24, and significantly (p < or = 0.03) reduced loss of unciliated cells at 24 h. Salmeterol had no effect on the density of bacteria adhering to each individual mucosal feature or the total number of bacteria adhering to the organ culture. These results suggest that salmeterol protects the respiratory epithelium against Haemophilus influenzae-induced damage. The mechanism of salmeterol cytoprotection and its potential clinical relevance remain to be investigated.

Adenoids↗
PubMed1998

Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer.

PURPOSE: This phase I study was performed to evaluate the safety and pharmacokinetics of escalating doses of Marimastat (British Biotech, Inc, Oxford, United Kingdom) in patients with advanced malignancies and to determine the phase II recommended dose to be used in subsequent studies. PATIENTS AND METHODS: A standard phase I design was used in this study, in which consecutive groups of three patients were treated with escalating doses of the study drug. Marimastat was administered orally at 25, 50, or 100 mg twice daily to consecutive groups of patients with advanced lung cancer. An additional three patients were added at the highest dose studied (100 mg orally twice daily) to assess whether the inflammatory polyarthitis observed at that dose level can be prevented by a concurrent administration of nonsteroidal antiinflammatory drugs (NSAIDS) and/or low-dose corticosteroids. Blood was drawn for safety monitoring, pharmacokinetic analysis, and plasma levels of metalloproteinase (MMP)-2 and MMP-9 (determined by zymography). A total of 12 patients were studied. RESULTS: The most significant toxicity at the highest dose studied (100 mg orally twice daily) was a symptomatic inflammatory polyarthritis that persisted for up to 8 weeks after discontinuation of the study drug and was dose-limiting. The estimated plasma elimination half-life of Marimastat was 4 to 5 hours. The mean maximum concentration (Cmax) at a reasonably well-tolerated dose (50 mg orally twice daily) was 196 ng/mL and was reached within 1 to 2 hours (Tmax) after administration. Areas under the curve (AUC) tended to correlate with the dose of Marimastat. Zymographic analysis of peripheral-blood ratios of activated proenzymatic forms of MMP-2 and -9 did not show any consistent patterns of change in MMP levels or in a degree of their activation during the course of treatment. CONCLUSION: Marimastat was well absorbed from the gastrointestinal tract, with high levels of the study drug detected in plasma within hours after drug administration. Plasma concentrations of Marimastat achieved at dose levels 2 and 3 (50 mg and 100 mg orally twice daily) were substantially higher than those required for MMP inhibition in vitro. The dose-limiting toxicity (DLT) was severe inflammatory polyarthritis, which seemed to be a cumulative toxicity.

Administration, Oral↗
PubMed1998

DNA sequence analysis of the genes for the fowl adenovirus serotype 10 putative 33K and pVIII.

The nucleotide sequence and genomic location of the fowl adenovirus serotype 10 (FAV-10) putative 33K and precursor protein VIII (pVIII) genes have been determined. The total genomic region sequenced was 1814 base pairs (bp) in length with the 33K coding region occupying the sequence from nucleotides 44 to 634 and the pVIII coding region nucleotides 949 to 1689. The location of both the 33K and pVIII genes have the same positional organization as their human adenovirus (HAV) counterparts which is 3 prime (3') to the 100K gene. Along with the 100K the 33K and pVIII form the late transcription unit 4 (L4). The FAV-10 putative 33K coding region could encode a polypeptide of 196 amino acids in length with a relative molecular mass of 21.9 kilodaltons (kDa) while the pVIII produces a polypeptide of 246 amino acids with a calculated relative mass of 26.7 kDa. Two possible splice acceptor sites were identified one 5' to the 33K and one 5' to the pVIII coding regions. A putative poly A recognition sequence of AATAAA was identified 3' to the pVIII, signaling the end of the L4 transcription unit.

Amino Acid Sequence↗
PubMed1998

AIDS in older people. A literature review for clinical nursing research and practice.

Older Americans, 50 years of age and older, account for 10% of the 400,000 reported cases of AIDS nationwide (Centers for Disease Control and Prevention, 1994). the integrated literature review format in this article examines the published literature on HIV/AIDS in older adults. Most articles are case studies and reports, with only 17% having a research basis. The information reviewed indicates that older adults have different risk factors than younger populations for contracting HIV disease and a different pattern of disease progression. These differences create a need for knowledge of HIV infection and AIDS and its parameters in aging populations so nurses may provide both timely and appropriate care.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Laparoscopic staging of gastric cancer is safe and affects treatment strategy.

The accuracy of laparoscopic staging has been documented, but its safety and impact on clinical decision making are less clear. In a prospective series of 64 patients referred to a single consultant, laparoscopy was performed in 49, after exclusion of patients unlikely to derive benefit from laparoscopic staging. The prelaparoscopy treatment plan was altered in 17 (34%). Laparoscopy detected 11 cases of peritoneal and four cases of liver metastasis, of which nine and two, respectively, were not detected by CT scan. Laparoscopy was useful in assessing fitness for major surgery, the planned extent of which was reduced in five cases as a result. Port site metastasis occurred in one case of stage IVB cancer, in conjunction with widespread progressive disease. Laparoscopic staging is recommended in gastric cancer, since it causes important changes to the management plan in one-third of cases, and the risks of port site metastasis appear low.

Adenocarcinoma↗
PubMed1998

Functional laboratory assessment after oncologic shoulder joint resections.

A laboratory evaluation was undertaken to assess the shoulder range of motion and distal strength after oncologic resection and reconstruction involving the shoulder joint and to compare these functional parameters based on potentially important variables. Inclusion in the study was limited to 32 patients with bone tumors of the proximal humerus or scapula treated surgically by resection of the shoulder joint including the proximal humerus from 1976 through 1992. Active shoulder range of motion and isometric elbow extension and forearm supination strength are significantly less after surgery in patients with greater amounts of bony resection and with resection of the deltoid. Patients who had a modified Tikhoff-Linberg resection were able to achieve 10 degrees to 15 degrees greater shoulder motion in each direction than were patients who had the classic procedure including complete scapulectomy. However, elbow flexion and extension strength and forearm pronation strength were greater for the patients with the classic resection. Osteoarticular allografts as a reconstructive alternative provide as a group the best shoulder motion and overall distal upper extremity strength, but these reconstructions were performed only when the rotator cuff muscles and deltoid were able to be reconstructed. Diminishing elbow strength was seen with longer followup in the patients with osteoarticular reconstructions, corresponding temporally to subchondral collapse observed on radiographs. Range of shoulder motion except rotation was just as good for allograft vascularized fibular arthrodeses as for the osteoarticular allografts, but strength was significantly less with the arthrodeses.

Adolescent↗
PubMed1998

HIV.

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Family Practice↗
PubMed1998

Do women with HIV infection consult with their GPs?

In a cohort of 106 HIV-positive women, 86 (81%) were registered with a general practitioner (GP) and 71 (83%) had a GP who was aware of their HIV status. GPs were primarily consulted for perceived non-HIV-related problems and prescriptions. This is encouraging. However, primary and secondary care services should aim to increase the proportions of HIV-positive individuals with access to primary care.

Adult↗
PubMed1998

Hearing conservation. Community outreach program for high school students.

1. A community service project for a local constituency of the AAOHN involved teaching hearing conservation classes in junior high school shop classes. 2. Pre-test/post-test comparisons showed that students benefited from the 1 hour class, including indications they planned to use hearing protection devices in the presence of loud noise. 3. Occupational health nurses' expertise in the area of hearing conservation can enhance work-school partnerships that strengthen communities.

Adolescent↗
PubMed1998

Two pore types in the inner-wall endothelium of Schlemm's canal.

PURPOSE: It has been reported that fixation conditions significantly influence the apparent pore density in the inner-wall endothelium of Schlemm's canal. In the present study, the manner in which fixation conditions affect the two subtypes of inner-wall pores, intracellular pores and intercellular (or border) pores, was investigated. METHODS: Outflow facility was measured in enucleated human eyes. Eyes were fixed under constant flow" or constant pressure conditions, microdissected to expose the inner wall of Schlemm's canal, and prepared for scanning electron microscopy. The density and diameter of the two subtypes of pores in the inner wall were measured. RESULTS: Intracellular pore density decreased with increasing postmortem time (P < 0.001) and increased with increasing volume of fixative passed through the outflow pathway (P < 0.001), whereas border pore density showed no dependence on these parameters (P > 0.25 and P > 0.15, respectively). Border pore density increased with increasing fixation pressure (P < 0.005), even though intracellular pore density showed no such dependence (P > 0.4). No correlation was found between outflow facility and the predictions of Poiseuille's law, Sampson's law, or the funneling theory for the hydraulic conductivity of the intracellular pores (P > 0.35) or the border pores (P > 0.1). CONCLUSIONS: The intracellular and border pores form two morphologically and functionally distinct populations in the inner wall of Schlemm's canal. The dependence of intracellular pore density on postmortem time and on volume of fixative passed through the outflow pathway suggests that these pores are artifacts of tissue fixation or processing conditions. That border pores do not depend on such conditions and that their presence is correlative with perfusion pressure suggests that this population may be nonartifactual. New histologic techniques for examining the inner wall of Schlemm's canal are necessary to determine the in vivo state of inner-wall pores and how they influence outflow facility.

Aged↗
PubMed1998

Nocturnal enuresis.

Nocturnal enuresis (NE), the involuntary passing of urine during sleep after the age at which bladder control would normally be anticipated, is a widespread and potentially disabling disorder for children. The treatment of NE constitutes several approaches and its pathophysiology remains unsolved. Careful consideration should be given to the work-up of NE since there may be concurrent symptoms that require attention either before or in conjunction with the treatment. Patient/family education and a cooperative approach usually produce the most favorable results in treating NE.

Age Distribution↗
PubMed1997

Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis.

Members of the TGF-beta superfamily are important regulators of skeletal development. TGF-betas signal through heteromeric type I and type II receptor serine/threonine kinases. When over-expressed, a cytoplasmically truncated type II receptor can compete with the endogenous receptors for complex formation, thereby acting as a dominant-negative mutant (DNIIR). To determine the role of TGF-betas in the development and maintenance of the skeleton, we have generated transgenic mice (MT-DNIIR-4 and -27) that express the DNIIR in skeletal tissue. DNIIR mRNA expression was localized to the periosteum/perichondrium, syno-vium, and articular cartilage. Lower levels of DNIIR mRNA were detected in growth plate cartilage. Transgenic mice frequently showed bifurcation of the xiphoid process and sternum. They also developed progressive skeletal degeneration, resulting by 4 to 8 mo of age in kyphoscoliosis and stiff and torqued joints. The histology of affected joints strongly resembled human osteo-arthritis. The articular surface was replaced by bone or hypertrophic cartilage as judged by the expression of type X collagen, a marker of hypertrophic cartilage normally absent from articular cartilage. The synovium was hyperplastic, and cartilaginous metaplasia was observed in the joint space. We then tested the hypothesis that TGF-beta is required for normal differentiation of cartilage in vivo. By 4 and 8 wk of age, the level of type X collagen was increased in growth plate cartilage of transgenic mice relative to wild-type controls. Less proteoglycan staining was detected in the growth plate and articular cartilage matrix of transgenic mice. Mice that express DNIIR in skeletal tissue also demonstrated increased Indian hedgehog (IHH) expression. IHH is a secreted protein that is expressed in chondrocytes that are committed to becoming hypertrophic. It is thought to be involved in a feedback loop that signals through the periosteum/ perichondrium to inhibit cartilage differentiation. The data suggest that TGF-beta may be critical for multifaceted maintenance of synovial joints. Loss of responsiveness to TGF-beta promotes chondrocyte terminal differentiation and results in development of degenerative joint disease resembling osteoarthritis in humans.

Animals↗
PubMed1997

Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain.

The deposition of the beta amyloid peptide in neuritic plaques and cerebral blood vessels is a hallmark of Alzheimer's disease (AD) pathology. The major component of the amyloid deposit is a 4.2-kDa polypeptide termed amyloid beta-protein of 39-43 residues, which is derived from processing of a larger amyloid precursor protein (APP). It is hypothesized that a chymotrypsin-like enzyme is involved in the processing of APP. We have discovered a new serine protease from the AD brain by polymerase chain reaction amplification of DNA sequences representing active site homologous regions of chymotrypsin-like enzymes. A cDNA clone was identified as one out of one million that encodes Zyme, a serine protease. Messenger RNA encoding Zyme can be detected in some mammalian species but not in mice, rats, or hamster. Zyme is expressed predominantly in brain, kidney, and salivary gland. Zyme mRNA cannot be detected in fetal brain but is seen in adult brain. The Zyme gene maps to chromosome 19q13.3, a region which shows genetic linkage with late onset familial Alzheimer's disease. When Zyme cDNA is co-expressed with the APP cDNA in 293 (human embryonic kidney) cells, amyloidogenic fragments are detected using C-terminal antibody to APP. These co-transfected cells release an abundance of truncated amyloid beta-protein peptide and shows a reduction of residues 17-42 of Abeta (P3) peptide. Zyme is immunolocalized to perivascular cells in monkey cortex and the AD brain. In addition, Zyme is localized to microglial cells in our AD brain sample. The amyloidogenic potential and localization in brain may indicate a role for this protease in amyloid precursor processing and AD.

Adult↗