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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 397 records · Page 22Linked to original sources
PubMed1993

Prognostic value of tumor "budding" in patients with colorectal cancer.

From 1970 to 1985, 663 patients underwent curative resection of colon and rectal adenocarcinomas. All surgical specimens were examined for tumor "budding," defined as small clusters of undifferentiated cancer cells ahead of the invasive front of the lesion. Patients were divided into two groups according to degree of budding: none or mild (BD-1) and moderate or severe (BD-2). BD-1 occurred in 493 patients (74.4 percent), and BD-2 was found in 170 patients (25.6 percent). More severe budding was associated with worse outcome: 71.1 percent of BD-2 patients had recurrence, compared with 20.0 percent of BD-1 patients (P < 0.005). The five-year survival rate was worse in BD-2 than in BD-1 (22.2 percent vs. 70.7 percent; P < 0.001). The 10-year survival rate was also worse in BD-2 than in BD-1 (13.8 percent vs. 50.6 percent; P < 0.001). The incidence of BD-2 rose with the Dukes stage. However, the five-year survival rate of Dukes B patients with BD-2 lesions was worse than that of Dukes C patients with BD-1 cancers (29.1 percent vs. 66.2 percent; P < 0.001). Moreover, there was no difference in five-year survival among BD-1 patients with either Dukes B or C lesions (68.3 percent vs. 66.2 percent). The presence of more severe budding appears to indicate a vigorous biologic activity of colorectal cancer. Thus, meticulous follow-up--and possibly adjuvant chemotherapy--may be beneficial for patients with marked budding, regardless of their Dukes stage.

Actuarial Analysis↗
PubMed1993

Construction of primary and subtracted cDNA libraries from early embryos.

By modifying current cDNA cloning and electroporation methods, large and representative murine cDNA libraries were synthesized from 10 to 100 ng mRNA isolated from unfertilized egg and preimplantation mouse embryos. High cloning efficiency is essential for complete representation of genes expressed in egg and preimplantation embryos and for the isolation of stage-specific genes using subtractive hybridization. Because the mouse embryo contains no more than 50 pg of poly(A)+ mRNA at any stage of preimplantation development, approximately 5000-10,000 embryos are required to obtain enough mRNA to synthesize libraries using current methods. To obtain a representative library that also includes rare transcripts, the size of the library should be at least 10(6) clones. The average percent conversion of mRNA to single-stranded cDNA was 20-40%, so that a cloning efficiency of nearly 2 x 10(8) cfu/microgram cDNA is required for such a cDNA library. No previous methods have provided directional cloning of cDNA into plasmids with these high efficiencies. The advent of electroporation methods for the introduction of nucleic acids into bacteria has made possible the use of standard plasmid vectors for high-efficiency cDNA cloning. Plasmid vectors are currently available that can accommodate the directional cloning of cDNA such that T7 and T3 RNA polymerase promoter sequences can be used to generate sense and anti-sense transcripts for subtractive hybridization and riboprobe synthesis. The cDNA libraries we derived using this methodology are a reusable and abundant source of genetic information about the control of preimplantation development. Specialized subtractive cDNA libraries enriched for genes expressed exclusively at a predetermined time in development give access to genes expressed in a stage-specific manner. The ability to construct new cDNA libraries from limited amounts of starting material ensures the provision of new and important resources for the identification and study of novel genes or gene families, and it is an important new tool for understanding the molecular control of mammalian development.

Animals↗
PubMed1993

NG-monomethyl-L-arginine does not restore loss of hypoxic pulmonary vasoconstriction induced by TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) causes systemic hypotension, pulmonary vasodilation, and loss of hypoxic pulmonary vasoconstriction. NG-monomethyl-L-arginine (L-NMMA) inhibits nitric oxide (NO) production and prevents some systemic manifestations of TNF-alpha. We tested using an isolated perfused canine lobe whether NO also mediates the pulmonary vascular effects of TNF-alpha. Total resistance (RT) was measured during control and hypoxic ventilation over a 90-min period in six control lobes, five lobes treated with TNF-alpha (250 micrograms), six lobes treated with L-NMMA (200 mg), and five lobes treated with L-NMMA (200 mg) + TNF-alpha (250 micrograms). In the control lobes RT increased (P < 0.02) from 0.0474 +/- 0.0105 to 0.0677 +/- 0.0133 cmH2O.ml-1 x min during normoxic and hypoxic ventilation, respectively. RT decreased (P < 0.05) from a baseline of 0.0593 +/- 0.0133 to 0.0449 +/- 0.0176 cmH2O.ml-1 x min 30 min after TNF-alpha administration and did not further change during hypoxic ventilation (0.0475 +/- 0.0107 cmH2O.ml-1 x min). L-NMMA pretreatment did not prevent the TNF-alpha-induced loss of hypoxic pulmonary vasoconstriction, with values of RT unchanged from normoxic (0.0541 +/- 0.0067 cmH2O.ml-1 x min) to hypoxic (0.0545 +/- 0.0078 cmH2O.ml-1.min) ventilation (P > 0.10) in the L-NMMA + TNF-alpha group after TNF-alpha administration. We conclude that NO is not the mediator responsible for the acute pulmonary vascular effects of TNF-alpha.

Animals↗
PubMed1993

Mild hypothermia after cardiac arrest in dogs does not affect postarrest multifocal cerebral hypoperfusion.

BACKGROUND AND PURPOSE: Although mild resuscitative hypothermia (34 degrees C) immediately after cardiac arrest improves neurological outcome in dogs, its effects on cerebral blood flow and metabolism are unknown. METHODS: We used stable xenon-enhanced computed tomography to study local, regional, and global cerebral blood flow patterns up to 4 hours after cardiac arrest in dogs. We compared a normothermic (37.5 degrees C) control group (group I, n = 5) with a postarrest mild hypothermic group (group II, n = 5). After ventricular fibrillation of 12.5 minutes and reperfusion with brief cardiopulmonary bypass, the ventilation, normotension, normoxia, and mild hypocapnia were controlled to 4 hours after cardiac arrest. Group II received (minimal) head cooling during cardiac arrest, followed by systemic bypass cooling (to 34 degrees C) during the first hour of reperfusion after cardiac arrest. RESULTS: The postarrest homogeneous transient hyperemia was followed by global hypoperfusion from 1 to 4 hours after arrest, with increased "no-flow" and "trickle-flow" voxels (compared with baseline), without group differences. At 1 to 4 hours, mean global cerebral blood flow in computed tomographic slices was 55% of baseline in group I and 64% in group II (NS). No flow (local cerebral blood flow < 5 mL/100 cm3 per minute) occurred in 5 +/- 2% of the voxels in group I versus 9 +/- 5% in group II (NS). Trickle flow (5 to 10 mL/100 cm3 per minute) occurred in 10 +/- 3% voxels in group I versus 16 +/- 4% in group II (NS). Cerebral blood flow values in eight brain regions followed the same hyperemia-hypoperfusion sequence as global cerebral blood flow, with no significant difference in regional values between groups. The global cerebral metabolic rate of oxygen, which ranged between 2.7 and 4.5 mL/100 cm3 per minute before arrest in both groups, was at 1 hour after arrest 1.8 +/- 0.3 mL in normothermic group I (n = 3) and 1.9 +/- 0.4 mL is still-hypothermic group II (n = 5); at 2 and 4 hours after arrest, it ranged between 1.2 and 4.2 mL in group I and between 1.2 and 2.6 mL in group II. CONCLUSIONS: After cardiac arrest, mild resuscitative hypothermia lasting 1 hour does not significantly affect patterns of cerebral blood flow and oxygen uptake. This suggests that different mechanisms may explain its mitigating effect on brain damage.

Animals↗
PubMed1993

Systemic Pasteurella haemolytica infection as a rare sequel to avirulent live Pasteurella haemolytica vaccination in cattle.

Eleven cases of systemic Pasteurella haemolytica infection in cattle were identified from routine diagnostic laboratory submissions during the falls of 1988, 1989, and 1991. All cases came with a history of recent vaccination with an avirulent live culture P. haemolytica product. Nine of 11 cases involved cattle vaccinated between 2 and 18 days previously with this product. Ten of 11 cases involved 182-227-kg beef calves that were vaccinated between September and November during routine processing for entry into feedlots. The morbidity and mortality was generally low. The major pathologic findings included meningitis, injection site abscessation and/or cellulitis, and polyarthritis. Systemic infection was indicated in all cases by the isolation of P. haemolytica from 2 or more organs or distinct anatomical sites. In 6 cases, the vaccine injection site was cultured, and in all 6 cases, P. haemolytica was isolated. Three separate P. haemolytica isolates from 2 cases were further studied by restriction enzyme analysis (REA). These isolates were from tissues with suppurative inflammation, including the brain, joint, and injection site. The REA patterns of each of these 3 isolates were identical to the REA pattern of the vaccine masterseed, which strongly suggested that the organisms causing systemic infection were the same as the organism used to produce the vaccine. Because the overall incidence was quite low, other factors, such as stress, probably played a major role in the expression of this syndrome.

Animals↗
PubMed1993

Cool, warm, and heat-pain detection thresholds: testing methods and inferences about anatomic distribution of receptors.

We recently found that vibratory detection threshold is greatly influenced by the algorithm of testing. Here, we study the influence of stimulus characteristics and algorithm of testing and estimating threshold on cool (CDT), warm (WDT), and heat-pain (HPDT) detection thresholds. We show that continuously decreasing (for CDT) or increasing (for WDT) thermode temperature to the point at which cooling or warming is perceived and signaled by depressing a response key ("appearance" threshold) overestimates threshold with rapid rates of thermal change. The mean of the appearance and disappearance thresholds also does not perform well for insensitive sites and patients. Pyramidal (or flat-topped pyramidal) stimuli ranging in magnitude, in 25 steps, from near skin temperature to 9 degrees C for 10 seconds (for CDT), from near skin temperature to 45 degrees C for 10 seconds (for WDT), and from near skin temperature to 49 degrees C for 10 seconds (for HPDT) provide ideal stimuli for use in several algorithms of testing and estimating threshold. Near threshold, only the initial direction of thermal change from skin temperature is perceived, and not its return to baseline. Use of steps of stimulus intensity allows the subject or patient to take the needed time to decide whether the stimulus was felt or not (in 4, 2, and 1 stepping algorithms), or whether it occurred in stimulus interval 1 or 2 (in two-alternative forced-choice testing). Thermal thresholds were generally significantly lower with a large (10 cm2) than with a small (2.7 cm2) thermode.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1993

The lack of effect of routine magnesium administration on respiratory function in mechanically ventilated patients.

STUDY OBJECTIVE: We wished to determine if magnesium infusion would improve respiratory muscle function in long-term ventilated patients even in the absence of hypomagnesemia. DESIGN: Prospective study of mechanically ventilated patients using a double-blind crossover design. SETTING: A combined medical-surgical ICU of a university teaching hospital. PATIENTS: Twenty-one separate admissions to the ICU in 20 patients were studied. Patients who were selected had been intubated and mechanically ventilated for at least 6 days with the admitting diagnosis of respiratory failure. INTERVENTIONS: Twelve patients received 6 g MgSO4 intravenous (i.v.) infusion over 16 h on day 1 followed by placebo infusion on day 2. Nine patients received placebo on day 1 followed by MgSO4 (6 g i.v.) on day 2. MEASUREMENTS AND MAIN RESULTS: We measured vital capacity (VC), maximal inspiratory pressure (Pmax) and maximal expiratory pressure (Pemax) in all patients. There were no significant differences in Pimax (37 +/- 14 vs 42 +/- 20 cm H2O), Pemax (59 +/- 32 vs 61 +/- 38 cm H2O), and VC (850 +/- 460 vs 960 +/- 490 ml) comparing values before and after magnesium infusion. We could not find a subgroup of patients with a marked improvement in Pimax or Pemax. CONCLUSIONS: In patients requiring mechanical ventilation for respiratory failure, magnesium infusion is not associated with increased respiratory muscle strength. Although a trial of MgSO4 administration may be considered for patients with difficulty weaning from mechanical ventilation, it is unlikely to result in clinical improvement.

Adult↗
PubMed1993

Biochemical parameters of recovery in acute severe head injury.

Levels of urinary catecholamines (noradrenaline, adrenaline, dopamine), plasma acetylcholinesterase, serum serotonin and plasma 3-methoxy-4-hydroxyphenylglycol were recorded in 38 adult subjects during the first 21 days after severe head injury. Levels of acetylcholinesterase, serotonin and 3-methoxy-4-hydroxyphenylglycol differed significantly between survivors and those who died. For survivors, initially abnormal biochemical levels recovered toward the norm as time after injury progressed.

Acetylcholinesterase↗
PubMed1993

Somatostatin analogue phase I trials in neuroendocrine neoplasms.

To further investigate the antineoplastic efficacy and safety of somatostatin analogues, 2 trials were performed. Octreotide, SMS 201-995 (Sandostatin), was escalated in doses ranging from 1,500 micrograms to 6,000 micrograms daily in 14 patients with carcinoid. Somatuline, (BIM 23014C, Angiopeptin, Lanreotide) was given in doses ranging from 2,250 micrograms to 9,000 micrograms daily to 13 neuroendocrine patients (6 carcinoid, 2 atypical carcinoid, 3 pancreatic islet cell and 2 small cell lung cancer patients). All patients successfully completed dose escalations without significant adverse effects and were evaluable for toxicity. The dose limiting side-effect of octreotide was the injection volume. No dose limiting adverse effects have been observed with somatuline. Carcinoid syndrome symptoms were better controlled with higher octreotide doses. Thirteen patients were evaluable for octreotide's antitumor efficacy with a partial response observed in 4 (31%), stable disease in 2 and progressive disease in 7 patients. Radiographic changes of increased tumor necrosis occurred in 5 patients and was independent of response. Somatuline resulted in a partial response in 4 patients (2 carcinoids, 1 gastrinoma and 1 small cell lung cancer) (31%), stable disease in 1 atypical carcinoid, and progressive disease in 8 (4 carcinoid, 1 atypical carcinoid, 2 islet cell and 1 multi-drug resistant small cell lung cancer). Six of the 8 carcinoid patients had radiographic changes of increased necrosis. Dose escalation of somatostatin analogues is well tolerated and may be associated with antitumor activity in some neuroendocrine neoplasms.

Adult↗
PubMed1993

A frameless stereotactic approach to neurosurgical planning based on retrospective patient-image registration. Technical note.

A frameless stereotactic device interfacing an electromagnetic three-dimensional (3-D) digitizer to a computer workstation is described. The patient-image coordinate transformation was found by retrospectively registering a digitizer-derived model of the patient's scalp with a magnetic resonance (MR) imaging-derived model of the same surface. This procedure was performed with routine imaging data, eliminating the need to obtain special-purpose MR images with fiducial markers in place. After patient-image fusion was achieved, a hand-held digitizing stylus was moved over the scalp and tracked in real time on cross-sectional and 3-D brain images on the computer screen. This device was used for presurgical localization of lesions in 10 patients with meningeal and superficial brain tumors. The results suggest that the system is accurate enough (typical error range 3 to 8 mm) to enable the surgeon to reduce the craniotomy to one-half the size advisable with conventional qualitative presurgical planning.

Adult↗
PubMed1993

Structure-function relationships of the HIV-1 envelope V3 loop tropism determinant: evidence for two distinct conformations.

OBJECTIVE: The V3 loop of the HIV-1 envelope glycoprotein gp120 is an important determinant of HIV-1-specific cell tropism. Nine different purified envelope proteins were prepared in order to examine the association between the structure of the gp120 proteins and functional properties of HIV-1 virions differing in their tropism for T-cell lines and macrophages. RESULTS: Six monoclonal antibodies to the V3 loop reacted preferentially with T-cell line-tropic gp120 envelope proteins, and one monoclonal antibody reacted preferentially with macrophage-tropic gp120 envelope proteins. T-cell line-tropic gp120 envelope proteins were at least 10-fold more susceptible to V3 loop proteolytic cleavage by human thrombin, and 1000-fold more susceptible to V3 loop proteolytic cleavage by human mast cell tryptase than macrophage-tropic gp120 envelope proteins. CONCLUSIONS: These findings suggest that there are two distinct conformations for the V3 loop of T-cell line-tropic and macrophage-tropic gp120 envelope proteins.

Amino Acid Sequence↗
PubMed1993

Carcinoma of the anus treated with primary radiation therapy and chemotherapy.

Between 1983 to 1989, 24 patients with previously untreated carcinoma of the anal canal (less than 3 centimeters in five patients and more than 3 centimeters in 19 patients) were entered in a prospective nonrandomized protocol of primary radiotherapy (4,050-4,500 cGy days one to 28) and chemotherapy (10 milligrams per meter squared of mitomycin C, on day two and 1,000 milligrams of 5-fluorouracil per molar squared for days two to five and 28 to 32). Therapy was discontinued for two patients because of severe (grade 4) skin reactions. The remaining patients tolerated the regimen well, with the exception of two patients who had grade 3 hematologic toxicity and three patients with grade 3 to 4 complications of the gastrointestinal tract. All of the patients who completed the regimen had a complete clinical and pathologic response when restaged six weeks after completion of therapy. All patients with lesions of less than 3 centimeters and 13 of 19 patients with lesions greater than 3 centimeters have remained free of disease (median follow-up period of 41 months; median survival rate of 36 months). Before 1983, 19 patients underwent abdominal perineal resection as primary treatment for carcinoma of the anus. Only six of seven patients with lesions less than 3 centimeters and zero of the 12 patients with lesions equal or greater than 3 centimeters have remained alive and free of disease. Eighteen of 24 patients treated with chemotherapy and radiotherapy only have remained free of disease and have preserved anal function. These results are superior to those reported with primary surgical treatment and primary radiotherapy only.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Mast cells in human optic nerve.

PURPOSE: Mast cells are classically found in ocular tissues within the conjunctiva, choroid, and iris. The aim of this study was to examine their distribution in the optic nerve and its meninges. METHODS: Sixty-six human optic nerves were studied from normal subjects at autopsy, fetuses aborted for chromosomal abnormalities, and from enucleation specimens of patients with a variety of inflammatory, traumatic, neoplastic, and vascular disorders. Mast cells were identified using a stain for the enzyme chloroacetate esterase, and confirmed using toluidine blue, revealing metachromatic cytoplasmic granules. RESULTS: Mast cells were found scattered in the meninges of almost all optic nerves examined, frequently in perivascular locations, with densities up to 2325 mast cells/mm3 (mean 269.7 +/- 64.1 cells/mm3 in normal nerves). Mast cells were found in the optic nerve parenchyma in nerves from four eyes that had severe abnormality, often associated with neovascularization. Normal nerves, as well as nerves from fetuses aborted for congenital defects, had significantly fewer meningeal mast cells than those from eyes with inflammatory or vascular diseases. Degranulation of mast cells was observed more often in eyes with recent severe trauma. CONCLUSIONS: Based on their work and the work of others suggesting an association between mast cells and nervous system autoimmune disorders, the authors hypothesize a role for optic nerve mast cells in certain ocular inflammatory conditions.

Adult↗
PubMed1993

High-frequency radio wave electrosection of full-thickness eyelid tissues.

The Ellman Surgitron, commonly used in dermatology practice, is an electrosurgical instrument with a high-frequency waveform that is modified by filtering and undamping the current so that an almost pure cut is possible, yet with a small amount of coagulation. This device was used in six patients undergoing full-thickness eyelid resection (unilateral in three and bilateral in three) for involutional entropion or ectropion. Nine lid margins were cut with scissors, and nine with the electrosurgical instrument. The latter was found to cause minimal tissue damage and to modify the superficial epithelial cell layer very slightly, without causing it to slough. The tissue was cut cleanly, with less bleeding than occurred with scissors incision.

Cautery↗
PubMed1993

Libraries for each human chromosome, constructed from sorter-enriched chromosomes by using linker-adaptor PCR.

We describe here the production of complex libraries enriched in sequences from each human chromosome type, starting with only a few thousand sorter-purified chromosomes. In this procedure, DNA is extracted from the sorted chromosomes, digested to completion by using the frequently cutting restriction endonuclease Sau3A1, and ligated, on each end, to an adaptor oligonucleotide. These fragments are then amplified using PCR with a sequence homologous to the adaptor oligonucleotide as a primer. We have used this procedure to produce PCR libraries for each of the 24 human chromosomes. These libraries were characterized by gel electrophoresis and found to be composed of a continuum of sequences ranging in size from a few hundred to approximately 1,000 bp. The libraries, when used as probes for fluorescence in situ hybridization, stained the target chromosomes more or less continuously, even after PCR amplification for more than 200 cycles. These libraries are useful as hybridization probes to facilitate molecular cytogenetic studies and as sources of probes either for identification of polymorphic short tandemly repeated sequences or for development of sequence-tagged sites.

Base Sequence↗