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Biomedical subjects

J F Morris

Publications and source records attributed to J F Morris.

At least 109 records · Page 6Linked to original sources
PubMed1991

Oral ofloxacin for the treatment of acute bacterial pneumonia: use of a nontraditional protocol to compare experimental therapy with "usual care" in a multicenter clinical trial.

PURPOSE: This multicenter study was designed to compare an exclusively oral regimen with "usual care" in patients hospitalized with acute bacterial pneumonia. PATIENTS AND METHODS: One hundred forty-seven patients were enrolled. All patients presented with a clinical picture consistent with pneumonia: (1) clinical symptoms of a lower respiratory tract infection, such as chest pain, cough, and production of purulent sputum; (2) roentgenographic infiltrate compatible with acute infection; and (3) Gram's stain of purulent sputum or other appropriate bronchopulmonary specimen containing gram-negative organisms, staphylococci, or pneumococci. All patients required hospitalization. The design was a parallel-group, open-label study with randomization in blocks of four. Ofloxacin, a new fluoroquinolone antimicrobial agent, was administered orally or by nasogastric tube, 400 mg every 12 hours. This was compared with the individual investigator's best selection of therapy that was administered parenterally, at least initially. RESULTS: One hundred thirty-three patients were evaluable after exclusions for deviation from protocol, early death due to unrelated causes, incorrect diagnosis, or early adverse drug reactions. All 69 patients treated with ofloxacin and 61 of 64 control patients had favorable clinical and microbiologic responses. There were no statistically significant differences between the groups in terms of demographics, therapeutic outcome, and duration of therapy. There were few side effects overall and rates were similar for the two groups. CONCLUSIONS: An exclusively oral regimen, in this case ofloxacin, may be substituted for parenteral therapy in selected patients with pneumonia. This might significantly reduce costs and risks to the patient.

Administration, Oral↗
PubMed1991

Technetium-99m monoclonal antibody fragment (Fab) scintigraphy in the evaluation of small cell lung cancer: a preliminary report.

Small cell lung cancer (SCC) has the most rapid growth rate of the four cell types and metastasizes early. Present imaging modalities for staging include chest x-ray, CT, MRI and bone scans. In this preliminary study, we assessed the clinical role of 99mTc-monoclonal antibody (MOAB) scintigraphy in five patients with histologically proven SCC. Each patient was infused with 20-30 mCi of 99mTc labeled Fab fragment of MOAB (NR-LU-10, NeoRx, Seattle, Wash.). Total body simultaneous anterior and posterior images were obtained 14-16 h post injection. SPECT images of the chest were obtained through a 360 degrees rotation of the gamma camera and recorded on a 62 x 64 x 16 matrix. Images (1.2 cm thick) were generated in transaxial, sagittal and coronal views. Fourteen of fifteen chest lesions detected by CT were confirmed by 99mTc MOAB scintigraphy. Scintigraphy detected one additional chest lesion not seen by CT. Scintigraphy failed to detect a brain lesion (2 cm), a chest lesion, and two adrenal lesions, all of which were seen by CT. In one patient with multiple (more than 10) lesions in the liver, both scintigraphy and CT detected all lesions. Three spine lesions seen on 99mTc MDP scan and positive for metastasis on MRI concentrated 99mTc MOAB, but two rib lesions seen on 99mTc MDP bone scan did not concentrate 99mTc MOAB. It is concluded from these preliminary results that the potential usefulness of 99mTc MOAB scintigraphy as a complementary imaging modality in the staging of small cell lung cancer should be investigated further.

Bone Marrow↗
PubMed1991

Alteration of HIV-1 infectivity and neutralization by a single amino acid replacement in the V3 loop domain.

The V3 loop (residues 303-338) of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope protein represents a principal neutralizing determinant for the virus. An HIV-1 proviral clone containing a mutation in the V3 loop was constructed in which the proline residue at position 313 was changed to an alanine (P313-A). This mutation alters the conserved GPGR sequence that is found in the V3 loop sequences of different HIV-1 isolates. The P313-A clone produced virus particles, which were infectious for a number of T-cell lines including MOLT-4, CEM, and SupT1, but demonstrated a relatively low infectivity on the AA5 B-cell line when compared with wild-type viruses, HTLV-IIIB, HXB2/10 (a chimeric molecular clone), and another mutant virus (Q290-T). V3 loop-specific neutralizing polyclonal sera and the 9284 monoclonal antibody, which recognizes the amino side of the V3 loop sequence, effectively blocked infectivity and syncytia formation of all viruses tested. In contrast, the 0.5 beta monoclonal antibody, which is biologically more potent than 9284 and recognizes a different V3 loop determinant, failed to neutralize the P313-A virus. These results suggest that the proline residue in the relatively conserved GPGR "turn" region of the V3 loop is crucial for recognition by the 0.5 beta antibody. The observed variation in sensitivity of the B-cell line to the P313-A virus may reflect the presence of cell-specific factors which could be important in establishing an HIV-1 infection.

Alanine↗
PubMed1991

Pulmonary vein thrombosis following bilobectomy.

Acute thrombosis of the pulmonary vein following lobectomy or bilobectomy is a rare complication with no standard guideline for diagnosis or management. In this report, we present a case of right upper lobe vein thrombosis following a middle and lower lobectomy. Diagnosis was confirmed by ventilation-perfusion lung scan, pulmonary angiogram, and bronchoscopy. The patient was treated conservatively with no further complications and had a partial recovery of the circulation to the right upper lobe. A review of the literature is also presented along with the experimental data demonstrating the mechanisms of recovery.

Aged↗
PubMed1991

Characterization of the zinc finger protein encoded by the WT1 Wilms' tumor locus.

We analysed the biochemical properties of the transcription factor encoded by the putative tumor-suppressor gene present at the WT1 Wilms' tumor locus. A gene containing the full-length amino acid coding sequence of human wt1 was reconstructed from synthetic oligonucleotides and cloned into expression vectors for in vitro and in vivo protein synthesis. Polyclonal rabbit antibodies specific for the WT1 protein were raised to an Escherichia coli-produced 91 amino acid N-terminal segment and to a 136 amino acid C-terminal segment, which contains the zinc finger domain. WT1 produced by in vitro translation migrated as a 52 kDa protein on sodium dodecylsulfate-polyacrylamide gels and bound to the EGR consensus sequence in gel-retardation assays. Expression of the wt1 gene via transient transfection in COS-1 cells revealed a 52 kDa protein which was immunoprecipitated by both the N-terminal- and C-terminal-specific antisera. Immunofluorescence studies of wt1-transfected COS-1 cells revealed that the WT1 protein was localized to the nucleus. Metabolic labeling with [32P]orthophosphate failed to reveal significant phosphorylation of the WT1 protein in COS-1 cells. Two immunoreactive WT polypeptides of 52 and 54 kDa were observed in murine embryonic stem cells and COS-1 kidney cells and may represent previously identified splicing variants of WT1. These antisera should be useful in characterizing the structure and function of the WT1 protein in human Wilms' tumor specimens.

Amino Acid Sequence↗
PubMed1991

Peptide accretions in the endoplasmic reticulum of magnocellular neurosecretory neurons in normal and experimentally manipulated rats.

Light microscopic observations using Nomarski interference contrast optics or darkfield optics on unstained aldehyde-fixed vibratome sections of hypothalami from normal young adult male and female Long Evans rats and from vasopressin-deficient Brattleboro rats, revealed the presence of cells in the supraoptic, paraventricular and periventricular nuclei which possessed yellow birefringent inclusions of globular or filamentous appearance in their somata. These inclusions were morphologically distinct from the large lipid droplets present in vasopressinergic magnocellular neurons of diabetes insipidus mice. Small portions of the vibratome sections containing the birefringent cells were excised and prepared for correlative electron microscopy. This revealed that the birefringent inclusions represented electron-dense material within cisterns of endoplasmic reticulum in magnocellular neurons. Antibodies to oxytocin or oxytocin-associated neurophysin immunolabelled the intracisternal electron-dense material and neurosecretory granules in resin-embedded ultrathin sections. Antibodies to vasopressin or vasopressin-associated neurophysin, and a panel of lectins did not label the intracisternal material. Quantitation revealed a small increase in the numbers of birefringent cells in aged rats and in rats drinking saline for 3 days. Subcutaneous injection of oestradiol benzoate for 7 days prior to fixation caused a large increase. After cessation of oestradiol administration the numbers of birefringent cells decreased; observations on the remaining cells showed that the endoplasmic reticulum cisterns were frequently fused with the plasmalemma, resulting in direct release of neurosecretory material into the extracellular spaces.

Animals↗
PubMed1990

Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence.

The Wilms' tumor locus (WTL) at 11p13 contains a gene that encodes a zinc finger-containing protein that has characteristics of a DNA-binding protein. However, binding of this protein to DNA in a sequence-specific manner has not been demonstrated. A synthetic gene was constructed that contained the zinc finger region, and the protein was expressed in Escherichia coli. The recombinant protein was used to identify a specific DNA binding site from a pool of degenerate oligonucleotides. The binding sites obtained were similar to the sequence recognized by the early growth response-1 (EGR-1) gene product, a zinc finger-containing protein that is induced by mitogenic stimuli. A mutation in the zinc finger region of the protein originally identified in a Wilms' tumor patient abolished its DNA-binding activity. These results suggest that the WTL protein may act at the DNA binding site of a growth factor-inducible gene and that loss of DNA-binding activity contributes to the tumorigenic process.

Amino Acid Sequence↗
PubMed1990

Evaluation of primary lung cancer with indium 111 anti-carcinoembryonic antigen (type ZCE-025) monoclonal antibody scintigraphy.

A study was undertaken to test whether indium 111 (111In)-labeled anti-carcinoembryonic antigen (CEA) (type ZCE 025) monoclonal intact antibody (MoAb) would concentrate in primary lung cancer enabling its detection and localization by scintigraphy. The scintigraphic results were correlated with chest radiograph, computed tomograph (CT), bronchoscopy, surgical resection, and tumor CEA analysis. Twenty adult male patients with clinical suspicion of primary lung cancer were studied. Each subject was infused with 4 to 5 mCi of 111In anti-CEA ZCE 025 MoAb, and planar and tomographic scintiphotos were obtained on days 3 and 6 or 7 postinfusion. The scintigraphy was true-positive in 12 of 16 patients with primary lung cancer, eight of nine patients with squamous cell carcinoma, and four of seven with adenocarcinoma; it was true-negative in three of four patients with benign lung disease with an overall accuracy of 75%. In seven patients with confirmed primary lung cancer, but with negative bronchoscopic findings, the scintigraphy was true-positive in four. In 11 patients with definitely positive or suspicious malignancy by bronchoscopy the monoclonal scintigraphy was positive in eight. In true-positive cases, the location and size of the lesion by 111In anti-CEA ZCE 025 MoAb imaging correlated well with CT findings and also tumor mass at surgery. Only one of 12 tumors stained positive for CEA had serum CEA levels greater than 10 ng/ml, indicating nonleakage of the tumor antigen into general circulation in early lung cancer. It is concluded that 111In anti-CEA ZCE 025 MoAb planar and tomographic imaging shows potential to serve as a noninvasive diagnostic test in the evaluation of primary lung cancer. The lung lesion is likely to be malignant if it concentrates 111In anti-CEA ZCE 025 MoAb and benign if it does not. Further studies in large number of patients with suspected primary lung cancer are needed to define the ultimate role for MoAb scintigraphy.

Adenocarcinoma↗
PubMed1990

Fiberoptic bronchoscopy without premedication. A retrospective study.

The objective of this study was to determine if flexible FOB could be performed safely without premedication other than topical anesthesia. A total of 281 procedures performed during a 12-month period at a VA medical center were reviewed. Ninety-one procedures performed without premedication were compared with 190 procedures performed with premedication. Complications occurred in 5 percent of patients in each group. Statistical analysis revealed no significant differences in age, spirometry, P(A-a)O2 or SaO2 between both groups. Despite the proven safety of outpatient FOB without sedation, many bronchoscopists administer complicated premedication regimens and employ ambulatory surgery beds or recovery rooms to monitor patients before and after procedures. These results support a simplified approach to routine FOB which would include no premedications and greater use of outpatient facilities resulting in decreased expenditures without compromising patient care, safety or comfort.

Adult↗
PubMed1990

Morphometric analysis of nerve endings isolated from bovine and rat neurohypophysis.

A simple two-step centrifugation procedure has been used to obtain a preparation of isolated nerve endings (neurosecretosomes) from homogenates of bovine and rat neural lobe. It is likely that during homogenisation and centrifugation the large axonal swellings observed in fixed neural lobes are preferentially disrupted, which explains the smaller mean diameter of these structures in the neurosecretosomal fraction. Although the rat neurosecretosomal fraction provided a better yield of axon-related structures (nerve endings and swellings), the morphological appearance of both swellings and nerve endings, respectively, was very similar in rat and bovine neurosecretosomal fractions. An important increase of the relative volume occupied by the axon-related structures, associated with decrease of contamination, can be achieved by density-gradient centrifugation; this procedure also separates two populations of endings which differ significantly in terms of their sizes. Extended incubation of neurosecretosomal fraction induces morphological damage, which affects mainly the population of nerve endings.

Animals↗
PubMed1989

Sézary cell morphology induced in peripheral blood lymphocytes: re-evaluation.

In this study we examined the effect of mitogens and epidermal cells in inducing a Sézary cell morphology in normal peripheral blood lymphocytes. Peripheral blood mononuclear cells from six healthy volunteers were stimulated with the mitogens phytohemaglutinin and concanavalin A, and also cocultivated with human epidermal cell cultures. Incubation times with mitogens and epidermal cells were four days and stimulation of the lymphocytes by mitogens was confirmed by standard 3H-thymidine uptake. Standard transmission electron microscopy showed that in the mitogen-driven system 20% to 60% (33 +/- 15%) and in the epidermal cell-driven system 5% to 15% (8 +/- 4%) of the lymphoid cells exhibited mild to moderate indentation of the nuclei with nuclear contour indices (NCI) of 4.6 to 6.5 but no Sézary cells were observed (cells with NCI greater than 6.5 and up to 19.2). In the mitogen-stimulated preparation 2% to 5% (3 +/- 1%) of the lymphoid cells showed nuclear multilobulation resembling the cells seen in adult T cell lymphoma/leukemia. Incubation of mononuclear cells for longer periods of up to 4 weeks with mitogens and exogenous IL-2 resulted in no further morphologic changes. Using an indirect immunogold technique at the electron microscopic level, the cells showing nuclear indentation or lobulation were shown to bear both T helper (CD4) and T suppressor (CD8) cell phenotypes in a similar ratio to the total numbers of T helper and T suppressor cells present. Mitogens and epidermal cells are thus not able to induce a morphologic change to Sézary cells in normal peripheral blood lymphocytes.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Localisation of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of type-2 diabetic subjects.

Islet amyloid peptide (or diabetes-associated peptide), the major component of pancreatic islet amyloid found in type-2 diabetes, has been identified by electron-microscopic immunocytochemistry in pancreatic B-cells from five non-diabetic human subjects, and in islets from five type-2 diabetic patients. The greatest density of immunoreactivity for islet amyloid peptide was found in electron-dense regions of some lysosomal or lipofuscin bodies. The peptide was also localised by quantification of immunogold in the secretory granules of B-cells, and was present in cytoplasmic lamellar bodies. Acid phosphatase activity was also demonstrated in these organelles. Immunoreactivity for insulin was found in some lysosomes. These results suggest that islet amyloid peptide is a constituent of normal pancreatic B-cells, and accumulates in lipofuscin bodies where it is presumably partially degraded. In islets from type-2 diabetic subjects, amyloid fibrils and lipofuscin bodies in B-cells showed immunoreactivity for the amyloid peptide. Abnormal processing of the peptide within B-cells could lead to the formation of islet amyloid in type-2 diabetes.

Adolescent↗
PubMed1989

Dendrites of hypothalamic magnocellular neurons release neurohypophysial peptides by exocytosis.

Exocytosis of neurosecretory granules from dendrites of magnocellular neurons can be visualized electron microscopically after incubation of hypothalamic brain slices in media containing 1.2 mM tannic acid, which stabilizes extracellular peptidergic granule cores, and permits their immunocytochemical identification. Morphometric analysis of stimulated slices demonstrates that exocytosis of neurosecretory granules from the dendrites of magnocellular neurons can account for the vasopressin and oxytocin known to be released into the hypothalamus. Exocytosis from cell bodies of magnocellular neurons was not observed in stimulated slices from normal rats but, when granules had been caused to accumulate in the neuronal somata by prior administration of colchicine, exocytosis of granules from the somata was unambiguously identified. These data demonstrate exocytosis from dendrites and cell bodies of a mammalian peptidergic neuron, and show that all parts of their plasmalemma are competent for exocytosis of granules.

Animals↗
PubMed1989

Differential distribution of acetylcholinesterase activity among vasopressin- and oxytocin-containing supraoptic magnocellular neurons.

Acetylcholinesterase activity was demonstrated histochemically at light- and electron-microscopic levels, in Vibratome sections of the supraoptic nucleus of fixed hypothalami derived from osmotically stimulated and unstimulated Long Evans rats, from homozygous Brattleboro rats with hypothalamic diabetes insipidus, from lactating rats, from normal adult male house mice (Mus musculus) and from mice with hereditary nephrogenic diabetes insipidus (di/di). Reaction product was located in supraoptic magnocellular neurons; in dorsal and rostral aspects of the supraoptic nuclei lightly stained cells predominate, whereas in ventral and caudal regions densely staining perikarya predominate. Pre- and post-embedding immunocytochemical detection of oxytocin-neurophysin or vasopressin-neurophysin, combined with acetylcholinesterase histochemistry, showed that the lightly staining cells are oxytocinergic, and the densely staining cells vasopressinergic. Osmotic stimulation of the animals, either by substitution of drinking water for 3 days with 2.5% saline or reason of genetic defects which result in diabetes insipidus, enhanced the acetylcholinesterase activity of the vasopressin neurons but had little effect on the weekly acetylcholinesterase-reactive oxytocin cells. Acetylcholinesterase activity was particularly marked in the hypertrophied abnormal magnocellular neurons of homozygous Brattleboro rats which do not release significant amounts of vasopressin. The increased acetylcholinesterase activity in osmotically stimulated animals cannot, therefore, be a function of vasopressin. Acetylcholinesterase activity was also detected in large multipolar neurons lying dorsolateral to the supraoptic nucleus, and in their fine axonal processes which project towards the supraoptic nucleus. A very few synaptic boutons surrounded by acetylcholinesterase reaction product were found in contact with magnocellular neuron basal dendrites. However, much of the punctate acetylcholinesterase reactivity observed at the light microscopic level and previously interpreted as representing the loci of cholinergic synaptic boutons was shown to be intracellular, and probably caused by acetylcholinesterase activity in some large, secondary lysosomes.

Acetylcholinesterase↗
PubMed1989

Microglia in the neurohypophysis associate with and endocytose terminal portions of neurosecretory neurons.

The rat neurohypophysis contains a population of microglial cells, the majority of which occupy a pericapillary position in the resting gland. The microglia are immunocytochemically identifiable by the presence of macrophage-associated antigens and resemble microglia of the CNS. Morphometry at light and electron microscopic levels reveals that such cells constitute approximately 19% of the intrinsic cell population, excluding the endothelial cells. Two other populations of neurohypophysial glial cells, parenchymatous pituicytes and fibrous pituicytes, do not express macrophage-associated antigens. The microglia have long processes which surround and, in some cases, engulf apparently viable portions of the magnocellular neurosecretory nerve terminals. A sequence of stages of selective endocytosis and degradation of the engulfed nerve terminals can be visualized within pericapillary microglia. Some phagosomes and secondary lysosomes contain morphologically intact neurosecretory granules; others contain partially destroyed neurosecretory granules or amorphous material all of which are identifiable as originating from the magnocellular neurosecretory terminals by their immunoreactivity for oxytocin- or vasopressin-neurophysin. This finding indicates a novel role for the microglial cells in remodelling terminal aborizations of neurosecretory neurons and in processing or degrading hormones and peptides they contain. Because of their close and selective associations with other cellular elements of the neurohypophysis, any substances produced by microglia also have the potential to influence hormone secretion, pituicyte proliferation and neurohypophysial vasculature.

Animals↗
PubMed1989

Serum digoxin-like substances in pregnancy-induced hypertension.

1. Endogenous digoxin-like immunoreactivity (EDLI) was measured in the serum of 85 normotensive pregnant (NTP) women and 77 women with pregnancy-induced hypertension (PIH) by a radioimmunoassay (New England Nuclear). All women were in the third trimester. 2. EDLI, which was undetectable in serum from non-pregnant women, was present in NTP and PIH and was significantly higher in PIH. EDLI correlated with gestational age in NTP, but not in PIH. 3. Ouabain-sensitive Na+ transport was estimated in normal peripheral blood leucocytes after incubation with sera from 50 NTP and 42 PIH women. Significant inhibition of active Na+ transport occurred only with the serum of hypertensive patients without proteinuria. 4. EDLI did not correlate with the effect of the sera on active Na+ transport. The radioimmunoassay therefore provides a poor index of Na+ transport inhibitory activity in PIH.

Biological Transport, Active↗
PubMed1989

Standard and double dose ipratropium bromide and combined ipratropium bromide and inhaled metaproterenol in COPD.

Inhaled ipratropium bromide (IPR) is effective in the management of COPD. The purpose of this study was to determine if doubling the standard dose of IPR resulted in greater bronchodilation and if the addition of an inhaled beta-agonist was superior to standard dose IPR alone. Twelve male patients with stable COPD completed a double blind, randomized trial. On each of three consecutive days, following baseline spirometry, all patients inhaled two puffs of IPR. This was followed by either two additional puffs of IPR, two puffs of metaproterenol (META), or two puffs of placebo. All inhalants were delivered by an InspirEase spacer. Spirometry was repeated at 30, 60, 120, and 180 minutes. The group mean percentage increases in the FEV1 and FVC from baseline were similar at all times tested for the three protocols. In conclusion, for the group, there was no objective benefit to doubling the standard dose of IPR or combining IPR with META. Two of 12 patients benefited from combining the two bronchodilators. A potential sequence for bronchodilator testing is suggested.

Administration, Inhalation↗