Biomedical subjects

M T Johnson

Publications and source records attributed to M T Johnson.

At least 37 records · Page 2Linked to original sources

PubMed1999

A contractile activity that closes phagosomes in macrophages.

Studies of Fc-mediated phagocytosis by mouse macrophages identified a contractile activity at the distal margins of forming phagosomes. Time-lapse video microscopic analysis of macrophages containing rhodamine-labeled actin and fluorescein dextran showed that actin was concentrated at the distal margins of closing phagosomes. Phagocytosis-related contractile activities were observed when one IgG-opsonized erythrocyte was engaged by two macrophages. Both cells extended pseudopodia until they met midway around the erythrocyte. It was then constricted and pulled into two phagosomes, which remained interconnected by a string of erythrocyte membrane. Butanedione monoxime, an uncompetitive inhibitor of class II and perhaps other myosins, and wortmannin and LY294002, inhibitors of phosphoinositide 3-kinase, prevented the constrictions without inhibiting the initial pseudopod extension. Immunofluorescence microscopy showed the presence of myosins IC, II, V and IXb in phagosomes. Of these, only myosin IC was concentrated around the strings connecting shared erythrocytes, suggesting that myosin IC mediates the purse-string-like contraction that closes phagosomes. The sequential processes of pseudopod extension and contraction can explain how macropinosomes and spacious phagosomes form without guidance from a particle surface.

Actins↗

PubMed1999

Familiarity and pronounceability of nouns and names.

Ratings of familiarity and pronounceability were obtained from a random sample of 199 surnames (selected from over 80,000 entries in the Purdue University phone book) and 199 nouns (from the Kucera-Francis, 1967, word database). The distributions of ratings for nouns versus names are substantially different: Nouns were rated as more familiar and easier to pronounce than surnames. Frequency and familiarity were more closely related in the proper name pool than the word pool, although both correlations were modest. Ratings of familiarity and pronounceability were highly related for both groups. A production experiment showed that rated pronounceability was highly related to the time taken to produce a name. These data confirm the common belief that there are differences in the statistical and distributional properties of words as compared to proper names. The value of using frequency and the ratings of familiarity and pronounceability for predicting variations in actual pronunciations of words and names are discussed.

Adult↗

PubMed1998

Temporal profile of the directional tuning of the discharge of dorsal premotor cortical cells.

This study examined the directional modulation of dorsal premotor (PMd) cells as a function of time in an instructed delay, reaching task that systematically varied direction and accuracy constraints. In two monkeys, the activity of 150 PMd cells was recorded and the preferred direction (PD) of the firing as a function of time, the PD trajectory, was calculated. Forty-one cells had nearly continuous significant directional tuning of at least 1 s duration (mean duration 1694 +/- 754 ms) that began in the instructed delay period and continued into the movement period. The PD gradually changed in time (mean change of 47.7 +/- 40.8 degrees), a change best described as a rotation. The change in the directional tuning as a function of time is consistent with the hypothesis that the PMd plays a role in the non-standard mapping of sensory stimuli into motor commands.

Animals↗

PubMed1997

Targeted disruption of the murine dihydrolipoamide dehydrogenase gene (Dld) results in perigastrulation lethality.

The Dld gene product, known as dihydrolipoamide dehydrogenase or the E3 component, catalyzes the oxidation of dihydrolipoyl moieties of four mitochondrial multienzyme complexes: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, branched-chain alpha-ketoacid dehydrogenase, and the glycine cleavage system. Deficiency of E3 activity in humans results in various degrees of neurological dysfunction and organic acidosis caused by accumulation of branched-chain amino acids and lactic acid. In this study, we have introduced a null mutation into the murine Dld gene (Dldtm1mjp). The heterozygous animals are shown to have approximately half of wild-type activity levels for E3 and all affected multienzyme complexes but are phenotypically normal. In contrast, the Dld-/- class dies prenatally with apparent developmental delay at 7.5 days postcoitum followed by resorption by 9.5 days postcoitum. The Dld-/- embryos cease to develop at a time shortly after implantation into the uterine wall when most of the embryos have begun to gastrulate. This null phenotype provides in vivo evidence for the requirement of a mitochondrial oxidative pathway during the perigastrulation period. Furthermore, the early prenatal lethal condition of the complete deficiency state may explain the low incidence of detectable cases of E3 deficiency in humans.

Animals↗

PubMed1997

A comparison of intracavitary versus interstitial irradiation in the treatment of cervical cancer.

OBJECTIVE: Management of locally advanced cervical cancer consists primarily of combination external and internal radiation. In order to investigate the impact of intracavitary brachytherapy versus interstitial brachytherapy on local tumor control, survival, and complications, we retrospectively reviewed the concomitant experience of two institutions, each of which practice exclusively one of these radiotherapeutic techniques. METHODS: Between 1979 and 1989, 61 patients with bulky stage II, III, or IVA cervical cancer were treated using a combination of teletherapy and intracavitary brachytherapy at one institution, while 70 similar patients were treated with teletherapy and interstitial brachytherapy at another institution. Patients in both groups were similar with respect to age, FIGO stage, tumor size, surgical stage, and histologic subtype. Patients treated with intracavitary therapy received a mean cumulative dose of 7706 cGy to point A and 5523 cGy to point B using standard Fletcher-Suit techniques. Those who received interstitial irradiation were treated with a mean external dose of 5050 cGy and 2 interstitial implants using a transperineal Syed-Neblett template with a mean tumor dose of 2239 and 1,942 cGy with each application, respectively. Patients treated with chemoradiation were excluded from this review. RESULTS: Although initial rates of local control were not different, prolonged 5-year disease-free survival (50% vs 21%, P = 0.01) and improved 5-year local control (61% vs 32%, P = 0.01) were observed among patients with stage II disease treated with intracavitary irradiation. No statistical differences in survival could be detected among stage III and IVA patients. Women treated with intracavitary irradiation received a larger dose of brachytherapy than those treated with interstitial therapy (4608 vs 3504 radium milligram hours equivalent, P < 0.0001) because a tandem was only used in 17 (24%) interstitial implants. Major complications occurred in 21% of patients in each group. CONCLUSION: When a tandem is infrequently used during interstitial brachytherapy, the toxicity is similar to that of intracavitary techniques. However, more relapses are observed among patients with stage II lesions treated with interstitial irradiation.

Adult↗

PubMed1997

Treatment and prevention of varicose veins.

Many factors predispose human beings to venous disease of the lower extremities, and this condition affects approximately eighty million Americans. Its manifestations may appear to be little more than a cosmetic nuisance, yet may be an indication of a more serious underlying problem undetected by visual inspection. Venous disease is also capable of producing a plethora of uncomfortable symptoms, and left untreated, may progress to cutaneous pigmentation, dermatitis, ulceration, hemorrhage, or superficial thrombophlebitis. Although uncomplicated cases of the disease are more common, venous disease should not be taken lightly. Steps to retard disease expression and progression should be implemented whenever possible. The purpose of this article is to aid the nurse in providing accurate information to patients about the disease process, treatment options, and interventions for its prevention.

Humans↗

PubMed1996

A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages.

Phosphoinositide 3-kinase (PI 3-kinase) has been implicated in growth factor signal transduction and vesicular membrane traffic. It is thought to mediate the earliest steps leading from ligation of cell surface receptors to increased cell surface ruffling. We show here that inhibitors of PI 3-kinase inhibit endocytosis in macrophages, not by interfering with the initiation of the process but rather by preventing its completion. Consistent with earlier studies, the inhibitors wortmannin and LY294002 inhibited fluid-phase pinocytosis and Fc receptor-mediated phagocytosis, but they had little effect on the receptor-mediated endocytosis of diI-labeled, acetylated, low density lipoprotein. Large solute probes of endocytosis reported greater inhibition by wortmannin than smaller probes did, indicating that macropinocytosis was affected more than micropinocytosis. Since macropinocytosis and phagocytosis are actin-mediated processes, we expected that their inhibition by wortmannin resulted from deficient signaling from macrophage colony-stimulating factor (M-CSF) receptors or Fc receptors to the actin cytoskeleton. However, video microscopy showed cell surface ruffling in wortmannin-treated cells, and increased ruffling after addition of M-CSF or phorbol myristate acetate. Quantitative measurements of video data reported slightly diminished ruffling in wortmannin-treated cells. Remarkably, the ruffles that formed in wortmannin-treated macrophages all receded into the cytoplasm without closing into macropinosomes. Similarly, wortmannin and LY294002 did not inhibit the extension of actin-rich pseudopodia along IgG-opsonized sheep erythrocytes, but instead prevented them from closing into phagosomes. These findings indicate that PI 3-kinase is not necessary for receptor-mediated stimulation of pseudopod extension, but rather functions in the closure of macropinosomes and phagosomes into intracellular organelles.

Androstadienes↗

PubMed1996

Effects of levodopa and viscosity on the velocity and accuracy of visually guided tracking in Parkinson's disease.

Deficits in velocity generation and movement accuracy occur in Parkinson's disease and are postulated to contribute to the characteristic bradykinesia. In the present study, we attempted to clarify the relationship between the deficits in velocity generation and movement accuracy. Patients with Parkinson's disease and normal controls tracked visually displayed sinusoidal and step targets with the wrist. Performance was evaluated using measurements of velocity and error. Movement velocity was manipulated by two methods: (i) administration of levodopa; (ii) viscous loading. Dependencies of velocity and error on disease state, medication state and viscosity were examined. Visually guided pursuit tracking was characterized by intermittent and frequent velocity excursions in both the patients and controls. For sinusoidal tracking, levodopa significantly increased velocity in the severely affected parkinsonian patients. Prior to the administration of levodopa, step tracking velocity was significantly lower in all patients than in controls. The "on' state produced an increase in velocity to control levels. Error was significantly greater in the parkinsonian subjects than in controls, but was unchanged by levodopa for both tracking tasks. Manipulations of viscosity produced greater changes in velocity than did levodopa, yet a similar independence with respect to accuracy remained. Velocity significantly changed by 40-60% in the two tracking tasks from the viscous to antiviscous loads. Error did not change significantly in 12 out of 14 comparisons of subgroups based on disease and medication state. This contradicts the hypothesis that patients with Parkinson's disease primarily reduce velocity during tracking to maintain acceptable accuracy in the presence of a defective error correction system. Although parkinsonian subjects tracked with reduced accuracy, both normal and parkinsonian subjects were able to compensate for significant changes in velocity due to external loading. Thus a propulsion deficit exists in parkinsonism that may be alleviated with either antiviscosity or levodopa. An error correction deficit is also present in parkinsonism, but is not modified by antiviscosity or levodopa.

Adult↗

PubMed1995

IL-6 induces target cell resistance to HIV-specific cytotoxic lysis.

Interleukin-6 (IL-6) is a pleiotropic cytokine with multiple immunomodulatory functions. Although IL-6 enhances cytotoxic effector cell function in vitro, we report the paradoxical effect of IL-6-induced resistance of target cells to lysis by cytotoxic T lymphocytes (CTL). The CTL system employed autologous, Epstein-Barr virus-transformed B lymphoblastoid target cells infected with vaccinia virus vectors carrying the envelope gene from the human immunodeficiency virus (HIV). Effector cells were fresh peripheral blood mononuclear cells from HIV+ individuals. Resistance was induced by exposing B cell line targets to exogenous IL-6, or via an autocrine pathway in which IL-6 was secreted by the target cells themselves. The IL-6 effect was dose dependent and reversible by antibody to IL-6. A large proportion of B cell lines from HIV+ individuals produced IL-6, and the lysis of HIV envelope-expressing B cell targets was inversely proportional to the amounts of IL-6 produced by the cell lines. These findings have significance for the utility and interpretation of CTL assays as in vitro correlates of T cell competence and may be significant in vivo in situations such as HIV infection where IL-6 production is increased.

Adult↗

PubMed1994

Bullatacin--in vivo and in vitro experience in an ovarian cancer model.

The cytotoxicity and antitumor effects of the acetogenin Bullatacin were evaluated in vitro in multiple ovarian cancer cell lines and in vivo in a murine ovarian teratocarcinoma (MOT) model in C3HeB/FeJ mice. The in vitro cytotoxicity of Bullatacin against four human ovarian epithelial tumor cell lines (OC-194, OC-222, OVCAR-3, and A-2780) was assessed in 48- and 72-h tetrazolium-dye (MTT) cytotoxicity assays. The percentage of cytotoxicity was determined on the basis of the mean optical density of the respective untreated cells and the dose effective against 50% of the cells (ED50) was calculated for each cell line. In vivo experiments were performed on adult female C3HeB/FeJ mice, which were injected i.p. with 10(5) MOT cells and varying amounts of Bullatacin given either in a single dose or in 5 subsequent doses over 72 h. All mice were observed for survival relative to that of the control groups, which were injected either with 10(5) MOT cells with or without serial injections of vehicle or with vehicle only. All four epithelial ovarian cancer cell lines displayed sensitivity to Bullatacin. The relative cytotoxic effects were very heterogeneous, with the ED50 value ranging between 10(-7) micrograms/ml for OC-194 and 4 micrograms/ml for the cisplatin-resistant cell line OVCAR-3 in a 72-h MTT cytotoxicity assay. All mice that had been injected i.p. with 10(5) MOT cells and 1.4 mg/kg or more of Bullatacin died within the first 24 h after injection, whereas all mice that had received 600 micrograms/kg of Bullatacin or less survived equally as long as the controls that had been injected with MOT only (21.1 +/- 0.9 days). Mice that had received Bullatacin at a dose ranging from 600 micrograms/kg to 1.4 mg/kg either died during the 1st day postinjection or survived, but not longer than the MOT control group. Serial i.p. injections of Bullatacin again either led to death of the mice within 24-48 h of the last dose of Bullatacin or did not have any effect on the survival of the mice as compared with the respective control groups, which had been injected with the tumor and serial injections of vehicle (22.5 +/- 2.2 days). In summary, Bullatacin showed no effect on MOT-caused animal death in C3HeB/FeJ mice at nonlethal dose ranges, whether it was given as a single i.p. dose or serially over 72 h. In vitro, however, it proved to be a very potent cytotoxic agent in a variety of ovarian cancer cell lines.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Acute effects of levodopa on wrist movement in Parkinson's disease. Kinematics, volitional EMG modulation and reflex amplitude modulation.

Acute changes in motor performance due to levodopa were evaluated by a series of four motor tests unified by their focus on wrist flexion-extension movements. Subjects with idiopathic Parkinson's disease were evaluated with this battery of tests before (OFF) and after their usual morning dose of levodopa (ON). The test battery consisted of (i) repetitive self-paced movement in which velocity was to be maximized; (ii) visually guided tracking of a sinusoid and a square wave; and (iii) an assay of stretch reflex modulation during volitional sinusoidal tracking. The maximal wrist joint velocity of self-paced reciprocating flexion and extension movements increased after levodopa (ON), without significant changes in the movement period or amplitude. In the two tracking tasks, some subjects improved as evident by a lower root mean square (rms) error, but in similar numbers of subjects the rms error increased. Overall, the rms error, peak velocity or peak movement amplitude did not change after levodopa in either tracking task. Significant and consistent changes did occur after levodopa in an assay of reflex modulation during error-constrained tracking (Johnson et al., Brain 1991; 114: 443-60). The amplitude of volitional EMG increased after levodopa, with a concurrent reduction in reflex EMG. These changes are consistent with the noted increase in movement velocity. These results show that the effects of levodopa on movement velocity were not consistently translated into increased accuracy. The changes in the long latency reflex gain argue for a central control of this reflex, mediated by structures sensitive to levodopa. Finally, the results show that the quantitative evaluation of levodopa therapy cannot be unidimensional, but requires a battery of motor tests as undertaken in this study.

Aged↗

PubMed1993

Independent control of reflex and volitional EMG modulation during sinusoidal pursuit tracking in humans.

It is well known that during volitional sinusoidal tracking the long-latency reflex modulates in parallel with the volitional EMG activity. In this study, a series of experiments are reported demonstrating several conditions in which an uncoupling of reflex from volitional activity occurs. The paradigm consists of a visually guided task in which the subject tracked a sinusoid with the wrist. The movement was perturbed by constant torque or controlled velocity perturbations at 45 degrees intervals of the tracking phase. Volitional and reflex-evoked EMG and wrist displacement as functions of the tracking phase were recorded. The relationship of both short-latency (30-60 ms) and longer-latency (60-100 ms) reflex components to the volitional EMG was evaluated. In reflex tracking, the peak reflex amplitude occurs at phases of tracking which correspond to a maximum of wrist joint angular velocity in the direction of homonymous muscle shortening and a minimum of wrist compliance. Uncoupling of the reflex and volitional EMG was observed in three situations. First, during passive movement of the wrist through the sinusoidal tracking cycle perturbation-evoked long-latency stretch reflex peak is modulated as for normal, volitional tracking. However, with passive joint movement the volitional EMG modulation is undetectable. Second, a subset of subjects demonstrate a normally modulated and positioned long-latency reflex with a single peak. However, these subjects have distinct bimodal peaks of volitional EMG. Third, the imposition of an anti-elastic load (positive position feedback) shifts the volitional EMG envelope by as much as 180 degrees along the tracking phase when compared with conventional elastic loading. Yet the long-latency reflex peak remains at its usual phase in the tracking cycle, corresponding to the maximal velocity in the direction of muscle shortening. Furthermore, comparison of the results from elastic and anti-elastic loads reveals a dissociation of short- and long-latency reflex activity, with the short-latency reflex shifting with the volitional EMG envelope. Comparable results were also obtained for controlled velocity perturbations used to control for changes in joint compliance. The uncoupling of the reflex and volitional EMG activity in the present series of experiments points to a flexible relationship between reflex and volitional control systems, altered by peripheral input and external load.

Adult↗

PubMed1993

Radical hysterectomy after pelvic irradiation in patients with high risk cervical cancer or uterine sarcoma: morbidity and outcome.

BACKGROUND: The optimal treatment of patients with "high risk" cancer involving the uterine cervix has not been defined. These patients include those with "bulky" or barrel shaped cervical tumors, individuals with adenocarcinomas or sarcomas, and those who respond poorly to radiation. As these patients are at high risk of failure if treated with radiation, it has been proposed that radical hysterectomy be performed in combination with radiation to improve local control of disease. We review our recent experience with this combined modality approach. METHODS: We reviewed patients treated at UCLA Medical Center between 1982 and 1990. All patients had multiple risk factors for poor local control. Twenty patients underwent radical hysterectomy (12 (60%) class II, 5 (25%) class III, one (5%) class IV, 2 (10%) class V) after pelvic irradiation. Fifty percent had "bulky" (> 4 cm) Stage I cervical cancer, while 45% had Stage II and 5% Stage III. Fifty percent of the patients had an element of adenocarcinoma. Two patients (10%) had uterine sarcoma with cervical involvement. Thirty percent of the study group had a poor response to preoperative radiation. RESULTS: Seventy percent of patients had nodal metastasis. Post-operative morbidity included infections (50%), urinary retention (10%), and ileus (5%). Long term morbidity included ureteral obstruction (30%), small bowel obstruction (20%), chronic gastrointestinal dysfunction (10%), chronic pelvic pain (10%), urinary fistula (10%), and vault necrosis (5%). Morbidity was less if patients only received preoperative brachy or teletherapy alone. Sixty-five percent of subjects are alive without disease with a mean follow up of 26 months. CONCLUSION: Although limited by the number of patients, we conclude that radical hysterectomy after radiation is morbid but may be effective in treating patients with 1) large cervical tumors, 2) cervical cancer that responds poorly to radiation, 3) small recurrent cervical tumors, 4) patients unable to undergo brachytherapy for cervical cancer, and 5) uterine sarcomas involving the cervix.

Adult↗

PubMed1991

Modulation of the stretch reflex during volitional sinusoidal tracking in Parkinson's disease.

Sinusoidal visually-guided wrist tracking, in normal and parkinsonian subjects, was perturbed by torque transients every 90 degrees throughout the movement. Long-latency stretch reflex and volitional EMG amplitude modulations were assessed as functions of the tracking phase. Reflex modulation during tracking, both in wrist flexor and extensor muscles, was found to differ significantly between parkinsonian and normal subjects. In the parkinsonian group, the abnormality consisted of an increased reflex activity during tracking phases in which the muscle was lengthening. At these phases the reflex generated torque is opposite in direction to the volitionally generated torque and the tracking movement. No differences in the unperturbed volitional EMG modulation were observed between groups for this error constrained tracking paradigm. Significant correlations were found between ratings of bradykinesia and the amount of abnormal reflex modulation in the wrist flexor. These data suggest that a component of bradykinesia results from a defective coordination of supraspinal reflex and volitional control systems.

Aged↗

PubMed1991

Computer-based program for identifying medication orders requiring dosage modification based on renal function.

A computer-based program that enables staff pharmacists to quickly review medication orders written for renally impaired patients is described. Medication orders requiring dosage modification based on the renal function of the patients for whom they were written were being identified by a medical staff-approved pharmacist intervention program. However, staff pharmacists were unable to assess the orders easily and rapidly because of a lack of readily available patient data. In response, a computer-based intervention program was developed. Specific dosage guidelines for renally eliminated drugs in patients with renal dysfunction were entered into the pharmacy computer. An interface with the laboratory computer enables the pharmacy computer to access creatinine concentration or clearance values, perform calculations if necessary, and alert pharmacists to specific drug orders that may require modification. Such medication orders are flagged by the pharmacy computer during order entry. When a staff pharmacist judges that intervention is needed, he or she telephones the ordering physician or sends a note to the patient's nursing station. Over a two-month period, 1485 orders were identified as being potentially inappropriate. Physicians were contacted about 191 of the flagged orders, and they accepted the pharmacist's recommendation for 141 (74%) of these orders. The interventions resulted in a drug acquisition cost saving of $7082 over the two-month period. A computer-based program enabled staff pharmacists to easily and rapidly identify orders for renally eliminated agents that required modification, reduced the risk of adverse reactions, trimmed costs, and promoted the clinical dimension of pharmacy practice.

Clinical Pharmacy Information Systems↗

PubMed1990

Influence of glottic mechanism on pulmonary function after acute lung injury.

We measured arterial gas tensions, respiratory timing, and intratracheal pressure in 12 rabbits to investigate the consequences of translaryngeal intubation with normal and subsequently injured lungs. Data were collected before, during, and after intubation. Intubation in normal rabbits precipitated no untoward effects on gas exchange or respiratory phase timing. However, there was significant elevation of subglottic pressure during expiration following extubation. Central venous injection of oleic acid (0.08 ml/kg) induced an acute lung injury that after 24 h was characterized by reduced PaO2 and dynamic lung-thorax compliance and tachypnea. Intubation in animals with acute lung injury was associated with a significant decline in arterial oxygenation, tachypnea, and increased PCO2. Expiratory tracheal pressure and expiratory time were greater and PaCO2 and respiratory rate were lower following extubation. We conclude that translaryngeal intubation following acute lung injury exacerbates already compromised pulmonary function by preventing a compensatory expiratory braking maneuver by the glottic apparatus.

Animals↗

PubMed1978

Purification and properties of a nucleoside diphosphosugar: NAD+ 2-hexosyl oxidoreductase.

Penicillium charlesii contains a nucleoside diphosphosugar: NAD 2-hexosyl oxidoreductase that oxidizes UDPgalactose (UDP-Galp), ADPribose [1,2] and UDPglucose (UDP-Glc). Dithiothreitol, NAD and 0.25 M NaCl but not nucleoside diphosphates stabilize the enzyme activity. The enzyme was purified and separated on polyacrylamide disc gels by electrophoresis into one major and eight minor bands of protein. Oxidoreductase activity was located in the major and three of the minor bands of protein. Each of these proteins catalyze the oxidation of UDPGalp, ADPribose and UDP-Glc.

Carbohydrate Dehydrogenases↗

PubMed1978

Fixatives and methods of fixation in selected tissues of the laboratory rat.

The histologic appearances of tissues fixed by immersion and perfusion were compared, as well as the effects of these different fixatives: 10% neutral buffered formalin, Carnoy's fluid, and Bouin's fluid. Intravascular perfusion provided better tissue preservation than fixation by immersion. The quality of preservation by neutral buffered formalin was equal to that of Carnoy's fluid and Bouin's fluid, but the overall staining quality of the latter two was judged to be superior.

Animals↗