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J R Harris

Publications and source records attributed to J R Harris.

At least 199 records · Page 11Linked to original sources
PubMed1993

Reduced carbon monoxide transfer factor (TLCO) in human immunodeficiency virus type I (HIV-I) infection as a predictor for faster progression to AIDS.

BACKGROUND: In addition to the acute fall in carbon monoxide transfer factor (TLCO) associated with Pneumocystis carinii pneumonia (PCP) or other opportunistic lung infections, reduced TLCO occurs in HIV-I seropositive individuals without active pulmonary disease. Abnormal TLCO, in the absence of lung disease, may be a surrogate marker of HIV-I induced immunosuppression and, therefore, a predictor for a more rapid progression to AIDS. METHODS: Eighty four individuals with AIDS, who had regular pulmonary function tests before the diagnosis of AIDS was made, were identified from a cohort of patients with HIV-I infection. None had evidence of active pulmonary disease at the time of initial pulmonary function testing. The relation between the time taken to progress to AIDS and initial pulmonary function tests was examined with life table survival analysis. RESULTS: Patients with a TLCO value of < 80% of predicted normal (n = 46) progressed significantly faster to AIDS, with a median time of 8.0 months compared with 16.5 months for those with a TLCO value of > or = 80% (n = 38). When stratified by AIDS defining diagnosis (PCP or non-PCP), median time to PCP was also significantly related to initial TLCO values (TLCO of < 80% = 9.0 months, TLCO of > or = 80% = 19.0 months). Reductions in other measurements of lung function (FEV1, FVC, KCO) were not temporally associated with the development of AIDS. CONCLUSIONS: HIV-I seropositive individuals with TLCO values of < 80% predicted and no evidence of lung disease progress more rapidly to AIDS than those with TLCO values of > or = 80%.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Prognosis following salvage mastectomy for recurrence in the breast after conservative surgery and radiation therapy for early-stage breast cancer.

PURPOSE: The prognosis and factors that influence prognosis following salvage mastectomy in patients with recurrence in the treated breast after conservative surgery (CS) and radiation therapy (RT) were investigated. MATERIALS AND METHODS: A total of 1,593 patients with stage I or II invasive breast cancer were treated following gross total excision of the tumor at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1985. One hundred sixty-six of the 1,593 (10%) had subsequent recurrence in the breast. Of these, 123 had salvage mastectomy and constitute the study population. The recurrent tumor was predominantly invasive in 99 patients, noninvasive in 14, and focally invasive in 10. Following mastectomy, chemotherapy or hormonal therapy was administered to 29 patients. The median follow-up time was 39 months after salvage mastectomy. RESULTS: The 5-year actuarial rate of further local or distant relapse for the entire group was 41%. None of the 24 patients with focally invasive or noninvasive tumors had a subsequent relapse. In comparison, the 5-year actuarial rate of further relapse in the 99 patients with a predominantly invasive recurrence was 52% (P = .001). The method of detection of the recurrence, the age of the patient at initial diagnosis, the disease-free interval, and the location of the recurrence in the breast were not found to have a statistically significant association with the risk of further relapse. CONCLUSION: We conclude that the histology of the recurrent tumor is an important prognostic factor for the risk of further relapse. Patients with purely noninvasive or focally invasive tumors have an excellent prognosis following salvage mastectomy. In contrast, patients with predominantly invasive tumors are at substantial risk for further relapse.

Adult↗
PubMed1993

Contralateral breast cancer: clinical characteristics and impact on prognosis.

PURPOSE: To determine the characteristics of patients with unilateral breast cancer who subsequently develop contralateral breast cancer (CBC), to assess their prognosis relative to patients who do not develop a CBC, and to assess the feasibility of using conservative surgery (CS) and radiotherapy (RT) to treat CBC. MATERIALS AND METHODS: Of 1,624 women treated with CS and RT for unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy, 77 developed an invasive CBC. Sixty-two CBCs were treated with CS and RT. The median follow-up duration was 95 months from the time of initial breast cancer diagnosis, and 63 months from CBC diagnosis. RESULTS: The cumulative actuarial rate of CBC was 7.0% at 10 years, and the annual incidence rate for CBC was relatively constant. Young age predicted for CBC. When age was analyzed by decade the relative risk (RR) for older patients compared with younger patients was 0.79 (95% confidence interval [CI], 0.62 to 1.01). The presence of lobular carcinoma in situ (LCIS), higher tumor stage, and lack of adjuvant systemic therapy also predicted for CBC with borderline significance. Multivariate analyses showed that CBC was associated with a statistically significant greater likelihood of local recurrence (LR) or distant recurrence (RR, 1.68; 95% CI, 1.03 to 2.71), and distant-only recurrence (RR, 2.17; 95% CI, 1.28 to 3.69). Among assessable patients treated with bilateral RT, 28 of 31 ipsilateral and 11 of 11 contralateral breasts had an excellent or good overall cosmetic outcome at 5 years, and treatment-related complications were minimal. CONCLUSION: We conclude that (1) young age is associated with a greater likelihood of CBC, (2) patients who develop a CBC have a greater subsequent risk of distant relapse as compared with patients without CBC, and (3) it is feasible to deliver sequential nonoverlapping bilateral RT without compromising the cosmetic outcome or increasing complications.

Adult↗
PubMed1993

Serial pulmonary function tests in the diagnosis of P. carinii pneumonia.

The predictive value of serial versus isolated measurements of transfer factor for carbon monoxide (TLCO) in the diagnosis of pneumocystis carinii pneumonia (PCP) in a cohort of 474 HIV-1 seropositive patients, with all stages of HIV disease, was evaluated. Two groups of patients were studied, one group with serial lung function measurements (Group 1) and another with only a single set of measurements (Group 2). During the study period 118 patients performing serial tests developed a respiratory illness of which 58 were performing monthly and 60 three monthly measurements of lung function (Group 1). In 36 patients from Group 1, where PCP was diagnosed, monthly lung function tests showed a decrease in TLCO from 68% (+/- 3.2) (SEM), (8 weeks prior to illness), to 44% (+/- 2.5) predicted normal at presentation, whereas in 22 patients who did not have PCP, TLCO fell from 71% (+/- 4.5) to 57% (+/- 3.1). TLCO was thus reduced to lower values in these with PCP than in those without PCP (p < 0.05). A fall of TLCO of 5% from initial values when used as predictive for presence of PCP had a sensitivity of 75% and a specificty of 28% (positive predictive value 56%; negative predictive value 48%). TLCO was < 70% predicted in 72/78 patients with PCP who performed only single lung function tests (Group 2), which gave a sensitivity of 92% and a specificity of 71% as a diagnostic test for PCP when compared with the cohort as a whole. The positive predictive value was 34%, negative predictive value was 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Breast cancer (3).

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Antineoplastic Agents↗
PubMed1992

Breast cancer (1)

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Breast Neoplasms↗
PubMed1992

Nonparticipation as a determinant of adverse health outcomes in a field trial of oral cholera vaccines.

The authors estimated the incidence rates of cholera and death between 1985 and 1988 for 32,642 age- and sex-eligible persons who did not participate in a randomized, placebo-controlled field trial of killed oral cholera vaccines in rural Bangladesh. As compared with 20,744 placebo recipients, the relative risk of cholera for all nonparticipants, adjusted for potentially confounding demographic variables, was 1.20 (95% confidence interval (CI) 1.03-1.41); this adjusted relative risk reflected elevated adjusted relative risks in nonparticipants who were medically ineligible (RR = 1.65; 95% CI 1.22-2.22) or refused to participate (RR = 1.19; 95% CI 1.01-1.41), but not in persons absent at the time of vaccination (RR = 1.00; 95% CI 0.78-1.28). The adjusted relative risk of death was also elevated in nonparticipants as compared with placebo recipients (RR = 1.28; 95% CI 1.10-1.48), with the same pattern of adjusted relative risks for different categories of nonparticipants: for ineligible subjects, 2.64 (95% CI 2.12-3.29); for refusers, 1.20 (95% CI 1.02-1.41); and for absentees, 0.95 (95% CI 0.75-1.22). The authors concluded that nonparticipation was associated with clinically cogent adverse health outcomes, but that the magnitude of these associations varied according to the reason for nonparticipation. These findings underscore the caution required in assessing vaccine efficacy with controls who are not vaccinated because of choices made by patients or vaccinators.

Administration, Oral↗
PubMed1992

Ubiquitous soluble Mg(2+)-ATPase complex. A structural study.

We have performed a detailed structural analysis of the soluble Mg(2+)-ATPase complex purified from Xenopus laevis ovary, which is an abundant and ubiquitous homo-oligomeric protein complex located in the nucleus and in the cytoplasm, belonging to a novel multigene-family of putative Mg(2+)-ATPases. Enzyme activity staining after non-denaturing polyacrylamide gel electrophoresis revealed that Mg(2+)-ATPase activity of the native protein is dependent on oligomerization and could not be detected in dissociated subunits. For the native protein a sedimentation coefficient of 15.3 S and a corresponding relative molecular mass of 612,000 was determined by analytical ultracentrifugation and a relative molecular mass of 590,000 was estimated from scanning transmission electron microscopy, supporting our previous conclusion that the oligomer comprises six 97,000 Mr subunits. Conventional electron microscopy of negatively stained specimens revealed the Mg(2+)-ATPase complex to be a hexagonal molecule in its favoured "end-on" projection and a double-banded molecule in its "side-on" projection (approx. 12 nm diameter; approx. 9 nm height). In addition, dimerized complexes could be observed in negatively stained specimens, yielding pronounced hexameric images and four-banded images in their end-on and side-on orientations, respectively (approx. 12 nm diameter; approx. 18.5 nm height). Two-dimensional (2D = mono-molecular) crystals have been produced from the dimerized complexes by the negative staining carbon film technique. Hexagonal crystals with a p6 plane group symmetry were obtained from molecules in their end-on orientation and longitudinal arrays with a p2 symmetry from complexes in their side-on orientation. A low-resolution molecular model of the native protein, derived from averages of these two 2D crystals, is presented. From our results we propose oligomerization as an inherent structural principle of organization for this whole newly defined Mg(2+)-ATPase multigene-family, that includes such seemingly diverse functionally defined proteins as mammalian and yeast "vesicle fusion" and "peroxisome assembly" proteins and the product of the yeast cell cycle gene CDC48.

Animals↗
PubMed1992

Quaternary and subunit structure of Calliphora arylphorin as deduced from electron microscopy, electrophoresis, and sequence similarities with arthropod hemocyanin.

Arylphorin was purified from larvae of the blowfly Calliphora vicina and studied in its oligomeric form and after dissociation at pH 9.6 into native subunits. In accordance with earlier literature, it was electrophoretically shown to be a 500 kDa hexamer (1 x 6) consisting of 78 kDa polypeptides (= subunits). Electron micrographs of negatively stained hexamers show a characteristic curvilinear, equilateral triangle of 12 nm in diameter (top view) and a rectangle measuring 10 x 12 nm (side view). Alternatively, particles in the top view orientation exhibit a roughly circular shape 12 nm in diameter. Crossed immunoelectrophoresis revealed the presence of a major subunit type; the nature of a very minor and a third immunologically separated component remains unclear. A novel 2 x 6 arylphorin particle was detected and isolated. It comprises less than 10% of the total arylphorin material and shows a long, narrow interhexamer bridge in the electron microscope. An arylphorin dissociation intermediate identified as a trimer (1/2 x 6) was isolated; its possible quaternary structure is discussed on the basis of electron micrographs. The epitope of monoclonal antibody Ec-7 directed against tarantula (Eurypelma californicum) hemocyanin subunit d and also reactive to Calliphora arylphorin was traced to a highly conserved peptide of 27 amino acids localized in the center of the protein. The primary structure of Calliphora arylphorin as published in our preceding paper (Naumann and Scheller 1991) is compared in detail to the sequences of spider and spiny lobster hemocyanin. This revealed a basic framework of 103 strictly conserved amino acids. Isofunctional exchanges are proposed for another 76 positions. On the basis of these similarities, and the published three-dimensional model of spiny lobster hemocyanin, a detailed model of the quaternary structure of Calliphora arylphorin is presented. A second larval storage protein previously termed protein II was purified from Calliphora hemolymph. It was demonstrated to be a 500 kDa hexamer of 83 kDa subunits. In the electron microscope it shows a cubic view 9 nm in length with a large central hole and a rectangular view (9 x 10 nm) with a large central cavity. A morphologically very similar hemolymph protein was detected in Drosophila melanogaster larvae. From its structural appearance it is uncertain whether protein II belongs to the hemocyanin superfamily or not.

Amino Acid Sequence↗
PubMed1992

Electron microscopy of a double helical tubular filament in keyhole limpet (Megathura crenulata) hemolymph.

A approximately 25 nm hollow double helical filament has been detected ultrastructurally in the cell-free supernatant from hemolymph of the keyhole limpet Megathura crenulata (Gastropoda: Prosobranchia: Fissurellidae). Subsequently, much higher concentrations of this material were found in the cell pellet from hemolymph. Both negative staining and thin sectioning have been performed in an attempt to obtain a preliminary structural characterization of this new filament. It is proposed that the filaments are released or secreted from blood hemocytes in response to bleeding, but it has not been possible to define absolutely an intracellular organelle containing this material. It is shown that the hollow filaments, which have fine fibrillar surface extensions, are readily distinguishable from collagen fibrils and from tubular (multi-decameric) keyhole limpet hemocyanin (KLH).

Actin Cytoskeleton↗
PubMed1992

Increased gut parasympathetic activity and chronic diarrhoea in a patient with the acquired immunodeficiency syndrome.

A 25-year-old homosexual man with a 2-year history of watery diarrhoea and a 20 kg weight loss is described. He had been diagnosed HIV-1 antibody positive 6 years previously. Investigations excluded opportunist pathogens and other known causes of diarrhoea. A range of anti-diarrhoeal medication had been unsuccessful. Plasma levels of gastrointestinal and pancreatic peptides were normal and treatment with the somatostatin analogue, octreotide, which inhibits release of pancreatic/gut peptides, did not provide any benefit. Cardiovascular autonomic function tests revealed blunted pressor responses but no other abnormalities. Gastric emptying studies with a technetium labelled meal indicated rapid gastric emptying time. This was slowed by the anticholinergic drug, atropine. This suggested increased parasympathetic activity to the gut. He was, therefore, treated with the anti-cholinergic agent, propantheline bromide, which reduced the frequency and volume of stools. He put on weight and has remained well since. This case highlights the diagnostic challenge in HIV-associated chronic diarrhoea, the case for investigations of autonomic function, and the need for a therapeutic trial of anticholinergic drugs, when other measures have failed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Final report of the phase I trial of continuous infusion etanidazole (SR 2508): a Radiation Therapy Oncology Group study.

Seventy-eight patients have been treated on a Phase I trial using continuous infusion etanidazole while undergoing brachytherapy for locally advanced tumors. There were two sequential schemata, the first treated 63 patients with doses ranging from 8-23 g/m2 over 48 hr and the second treated 15 patients with doses ranging from 20-23 g/m2 over 96 hr. The tumor sites were: brain (n = 42), cervix (n = 22), and breast (n = 14). Patients received a loading dose of etanidazole of 2 g/m2 followed by a continuous infusion for a total of 48 or 96 hr while radioactive implants were in place. Of the 63 patients in the 48-hr study, 52 were entered at doses of less than or equal to 21 g/m2 and there were no definite neuropathies but two patients with the cramping/arthralgia syndrome. Of the 11 patients entered at 22-23 g/m2, 1 patient had symptoms of peripheral neuropathy (Grade II) and 6 had the cramping/arthralgia syndrome. This is a new syndrome, distinct from the peripheral neuropathy, characterized by transient alterations in sensations consisting of cramping, arthralgias, or tingling that resolved completely at intervals varying from a few hours to about 1 week post-treatment. The cramping/arthralgia syndrome limited dose escalation; therefore, the maximum tolerated dose over 48 hr was determined to be 20-21 g/m2. The 96-hr infusion was limited to patients with recurrent gliomas undergoing stereotactic implantation. To date, 15 patients have been treated with doses of 20-23 g/m2. No toxicity was encountered at doses less than or equal to 22 g/m2. At 23 g/m2, one patient developed Grade III neuropathy and three patients had mild cramping/arthralgia syndrome, for whom the drug was discontinued. Therefore, it appears the maximum tolerated dose at 96 hr will be approximately 23 g/m2, which is 10-15% higher than for the 48-hr infusion.

Brachytherapy↗