Search PubMed⌕ Search

Biomedical subjects

M J Johnson

Publications and source records attributed to M J Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Antisense ablation of type I metabotropic glutamate receptor mGluR1 inhibits spinal nociceptive transmission.

Electrophysiological and behavioral studies point to a role of group I metabotropic glutamate receptors (mGluR1 and mGluR5) in mediating spinal nociceptive responses in rats. However, antagonists with a high degree of specificity for each of these sites are not yet available. We, therefore, examined the effects of antisense deletion of spinal mGluR1 expression in assays of behavioral analgesia and of electrophysiological responses of dorsal horn neurons. Rats treated with an mGluR1 antisense oligonucleotide reagent, delivered continuously to the intrathecal space of the lumbar spinal cord, developed marked analgesia as measured by an increase in the latency to tail-flick (55 degreesC) over a period of 4-7 d. This correlated with a selective reduction in mGluR1, but not mGluR5, immunoreactivity in the superficial dorsal horn compared with untreated control rats, in parallel with a significant reduction in the proportion of neurons activated by the mGluR group I agonist 3, 5-dihydroxyphenylglycine (DHPG), whereas the proportion of cells excited by the mGluR5 agonist, trans-azetidine-2,4-dicarboxylic acid (t-ADA) remained unaffected. In contrast, rats treated with mGluR1 sense or mismatch probes showed none of these changes compared with untreated, control rats. Furthermore, multireceptive dorsal horn neurons in mGluR1 antisense-treated rats were strongly excited by innocuous stimuli to their peripheral receptive fields, but showed severe reductions in their sustained excitatory responses to the selective C-fiber activator mustard oil and in responses to DHPG.

Animals↗
PubMed1998

Symptomatic hypocalcemia with oral clodronate.

We present a patient with prostate cancer who developed symptomatic hypocalcemia while taking oral clodronate for painful bony metastases. He had a past history of a bowel resection for Crohn's disease, and, although he was normocalcemic prior to taking clodronate, it is likely that the surgery had caused mild hyperparathyroidism. The addition of clodronate prevented the chronic osteolysis of bony metastases, which would have helped maintain normocalcemia. The case was complicated by hypomagnesemia and hypokalemia resulting from diarrhea. Hypomagnesemia is a cause of refractory hypocalcemia and hypokalemia. This case illustrates two important points. First, care must be taken with bisphosphonates in patients with a previous bowel resection. Second, magnesium plays a key role in the metabolism of both calcium and potassium, and must be considered in the evaluation of the hypocalcemic patient.

Administration, Oral↗
PubMed1998

Differential ventricular expansion in hydrocephalus.

In the large canine model of acquired obstructive hydrocephalus that we have developed recently, computer-assisted 3-dimensional morphometry has been performed on T1-weighted Spin Echo MRI images from adult dogs before and after the induction of hydrocephalus. To date, 7 hydrocephalic animals have been analyzed that survived 7-83 days (median = 54) after receiving injections of cyanoacrylate glue into the anterior fourth ventricle. Measurements were obtained from lateral, 3rd, and 4th ventricles. The volumes of the left and right lateral ventricles were symmetrical before and after induction. Mean lateral ventricle volume increased 424% from a baseline of 0.63 cc to a post-induction value of 3.30 cc (p < 0.01 with unpaired t-test). In contrast, the 3rd ventricle expanded 187% from a mean of 0.15 cc to 0.43 cc (p < 0.05). The combined volume of the lateral and 3rd ventricles increased 369% from a mean of 0.78 cc to 3.69 cc (p < 0.01). Evans' ratios, which are used routinely in the clinical setting, were also obtained from linear measurements of the lateral ventricle width divided by brain width at the level of the foramen of Monro. These values exhibited only a 94% increase from mean baseline ratios of 0.17 to post-induction ratios of 0.33 (p < 0.05). These findings indicate that in mechanically-induced obstructive hydrocephalus the relative expansion of the lateral ventricles is greater than that of the 3rd ventricle. In addition, volumetric measurements of the lateral and 3rd ventricles suggest that the extent of ventriculomegaly is 3-4 times greater than estimated by Evans' ratios.

Animals↗
PubMed1998

The microglial response to progressive hydrocephalus in a model of inherited aqueductal stenosis.

Although gliosis has been reported to be a common and persistent feature in the white matter of hydrocephalic brains, no studies have identified the cell types that characterize this response. Therefore, the present study has employed histochemical methods to evaluate microglial cells in the brains of infant rats with inherited hydrocephalus. This strain of rats acquires hydrocephalus during late fetal stages due to aqueductal stenosis. Tissue from the sensorimotor and auditory cortices of 12- and 21-day-old hydrocephalic and normal H-Tx rats was processed and stained for the lectin microglial marker Griffonia simplicifolia (GSA-IB4). During the progression of hydrocephalus, GSA-positive cells exhibited three changes: (1) Cytologically, the cell bodies were enlarged, and their processes were thicker, longer and more numerous. These changes were most notable in the gray matter. (2) The packing density of GSA-positive cells was either increased or decreased, depending on the age of the animal and the severity of hydrocephalus. (3) Localized clusters of GSA-positive cells were conspicuous in the white matter of 12-day animals with mild hydrocephalus, and in the gray matter of 21-day animals with severe hydrocephalus. These results indicate that the microglial response is initiated during intermediate stages of hydrocephalus, and is not restricted to the periventricular white matter. These changes may signal other pathophysiologic events in the hydrocephalic brain, and demonstrate that microglia constitute one important element in the gliosis that accompanies hydrocephalus.

Animals↗
PubMed1998

The significance of family history status in relation to neuropsychological test performance and cerebral glucose metabolism studied with positron emission tomography in older alcoholic patients.

Patients with severe chronic alcoholism have decreased rates of glucose metabolism in the medial frontal lobe and correlated abnormalities of neuropsychological functioning. The potential influence of family history of alcoholism has not been examined in these patients. In a retrospective study, we used neuropsychological tests and neuroimaging employing [18F]fluorodeoxyglucose with positron emission tomography to study 48 older subjects who had histories of severe, chronic alcohol dependence. These patients were divided into two groups: 27 with a first-degree relative with chronic alcoholism and 21 patients without first-degree relative with chronic alcoholism. No differences were found between groups on either neuropsychological or neuroimaging tests. These results suggest that a family history of alcoholism does not moderate the damaging effects of severe chronic alcoholism on the functioning of the medial frontal lobe.

Adult↗
PubMed1997

Obstetric complications and rheumatic disease.

This article summarizes common fetal and maternal complications of pregnancy and emphasizes special problems in women who have systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis, polymyositis, and Sjögren's syndrome. Joint management of pregnancies in these women requires an understanding of the obstetric management of the complications. Pathophysiology and treatment options for preterm-labor, preterm premature rupture of membranes, abnormal fetal growth, and hypertensive disorders of pregnancy are reviewed.

Female↗
PubMed1997

Value of cervical spine radiographs as a screening tool.

A review of the reports of 848 cervical spine radiographs was done to assess the yield of useful and critical information in a group of patients without trauma. In 470 of these patients the clinical record also was reviewed; 54.2% of the radiographs were read as having degenerative change, 35% were read as normal, and 8.5% were read as being consistent with muscle spasm. The remaining 2.3% included diagnoses of anatomic or congenital variants, soft tissue calcification, or old compression fractures. There were no serious diagnoses such as acute fracture, dislocation, or neoplasm that, had they not been identified, would have put the patient in jeopardy. Thus, for most outpatients with nontraumatic symptoms of a nonspecific or nonlocalizing nature, the use of cervical spine radiographs as a screening tool is not justified.

Adolescent↗
PubMed1997

Is it cancer or not?

Two cases are reviewed in whom a positive bone scan led to a diagnosis of metastatic bone disease and hospice referral. One of these was subsequently shown on magnetic resonance image (MRI) scanning to have benign metabolic bone disease; in the other, a repeat bone scan 18 months later confirmed benign pathology. The potential impact on patient and family in these situations is considerable and the usefulness of MRI in distinguishing benign from malignant bone disease is discussed.

Aged↗
PubMed1997

Problems of anticoagulation within a palliative care setting: an audit of hospice patients taking warfarin.

Patients with cancer have an increased risk of venous thromboembolism (VTE) compared with a healthy population. The risk increases as cancer progresses and this is reflected in the number of hospice inpatients with VTE. These patients also have an increased risk of bleeding due to tumour site, complications of treatment, progressive liver involvement and concurrent medication such as nonsteroidal anti-inflammatory agents. Therefore anticoagulation of cancer patients with VTE is fraught with difficulty. This audit of hospice inpatients taking warfarin showed a high incidence of bleeding which was possibly improved with very stringent international normalized ratio (INR) monitoring: 15 episodes in 17 patients improved to 11 episodes in 18 patients. Patient numbers were small and the two groups heterogeneous, thus formal statistical analysis could not be applied. One patient in each group continued to thrombose despite over anticoagulation with warfarin. Monitoring of INR increased from an average of once every six days to once every 2.4 days. Such frequent monitoring is likely to be highly impractical in many hospice and general practice settings. Control of warfarin as measured by average percentage of INRs in, above or below the therapeutic range if anything appeared to be worse in the second group. Any bleeding in these patients was distressing. As a result of this audit, practice in Huntershill Marie Curie Centre has changed. Low molecular weight heparins are proven to be efficacious in the treatment of VTE, are renally excreted and therefore do not interact with many commonly used concurrent medications. They can be administered once daily and do not need monitoring of anticoagulant effect. Thus they will be used in patients for whom anticoagulation is indicated during a six-month period, after which practice will be again reviewed.

Anticoagulants↗
PubMed1997

How do palliative physicians manage venous thromboembolism?

This postal survey among 174 UK palliative physicians, aimed to assess current practice and perceived problems within the management of venous thromboembolism (VTE) in patients with advanced cancer. The questionnaire was returned by 131 out of 174 (74%) of the doctors surveyed. The most common estimated incidence of patients with VTE was 1-5%. The diagnosis of VTE is usually confirmed by further investigation and in general, outpatients are more likely to be anticoagulated than inpatients. Problems with anticoagulation include bleeding, international normalized ratio instability, appropriateness of anticoagulation, practical difficulties associated with monitoring, and recurrent VTE. Although probably less effective, 77 out of 128 (60%) of respondents use subtherapeutic regimes in order to minimize the risks. Patients with advanced malignancy and VTE are anticoagulated, if considered appropriate, by the vast majority of palliative physicians in the UK. Warfarin has been abandoned in favour of low-molecular-weight heparin (LMWH) by 26%. LMWH provides anticoagulation with no need for monitoring, has no significant drug interactions and is not affected by liver dysfunction. Theoretically, LMWH is more effective than warfarin in the secondary prevention of VTE with less risk of bleeding.

Anticoagulants↗
PubMed1996

Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface.

Human manganese superoxide dismutase (MnSOD) is a homotetrameric enzyme which protects mitochondria against oxygen-mediated free radical damage. Within each subunit, both the N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands to the catalytic manganese site. Two identical four-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form a novel tetrameric interface that stabilizes the active sites. The 2.5 A crystallographic structure of the naturally occurring polymorphic variant Ile58Thr MnSOD reveals that the helical hairpin mutation Thr58 causes two packing defects in each of the two four-helix bundles of the tetrameric interface. Similar mutations, expected to cause packing defects in the Cu,ZnSOD dimer interface, are associated with the degenerative disease amyotrophic lateral sclerosis. Ile58Thr MnSOD is primarily dimeric in solution and is significantly less thermostable than the normal enzyme, with decreases of 15 degrees C in the main melting temperature and 20 degrees C in the heat-inactivation temperature. Consequently, this mutant MnSOD is compromised at normal body temperatures: thermal inactivation, predicted from the decrease in thermal stability, occurs with a theoretical half-life of only 3.2 h at 37 degrees C (1.4 h at 41 degrees C), compared with 3.1 years for native MnSOD. This prediction is supported by direct measurements: incubation at 41.7 degrees C for 3 h has no effect on the activity of native MnSOD but completely inactivates mutant MnSOD. Rapid inactivation of Ile58Thr MnSOD at the elevated temperatures associated with fever and inflammation could provide an early advantage by killing infected cells, but also would increase superoxide-mediated oxidative damage and perhaps contribute to late-onset diseases.

Binding Sites↗
PubMed1996

Spermatogenesis in the endosymbiont-bearing bivalve Loripes lucinalis (Veneroida: Lucinidae).

In the endosymbiont-bearing bivalve Loripes lucinalis, spermatogenesis is similar to that described for numerous bivalve species and leads to the formation of an aquasperm. The head and midpiece measure 10.5 +/- 1.5 microns in length. The head is made up of a cylindrical nucleus slightly tapered apically and capped by a short conical acrosome. The nucleus lacks both an anterior and posterior nuclear invagination. The acrosome is 1.0 +/- 0.1 micron long and consists of an acrosomal cone containing a diffuse subacrosomal material and an apical electron-lucent vacuole. There is no axial rod. The midpiece is made up of four mitochondrial spheres that surround the distal and proximal centrioles. The base of the distal centriole is joined to the plasmic membrane by the pericentriolar complex made up of nine radial arms. A cytoplasmic collar is observed that sheaths the flagellum as it emerges from the distal centriole. The spermatozoa present in mature acini are grouped into characteristic rings, which may have a nutritive function, with the acrosome oriented toward the centre of these ring formations. Also present within the gonad are somatic cells that seem to play a nutritive role in relation to the germinal cells. These nutritive cells undergo a cycle of development and lysis that corresponds to the spermatogenic cycle of the bivalve. These cells are large and rich in glycogen and lipid inclusions. In-depth examination of nutritive cells and gametes reveals that the male gonad is devoid of microorganisms in either a vegetative or cryptic form, suggesting that a vertical transmission through paternal gonadal inheritance is a very unlikely means of symbiont transmission in L. lucinalis.

Animals↗
PubMed1996

Medical, psychosocial, and behavioral risk factors do not explain the increased risk for low birth weight among black women.

OBJECTIVE: Our purpose was to determine whether various demographic, behavioral, housing, psychosocial, or medical characteristics explain the difference in pregnancy outcome between black and white women. STUDY DESIGN: A sample of 1491 multiparous women with singleton pregnancies, 69% of whom were black and 31% of whom were white and who enrolled for care between Oct. 1, 1985, and March 30, 1988, participated in the study. The frequencies of various demographic, medical environmental, and psychosocial risk factors among black and white women were determined. The outcome measures were birth weight, gestational age, fetal growth restriction, preterm delivery and low birth weight. RESULTS: White infants were heavier and born later than black infants. The white women in this sample smoked more cigarettes, moved more frequently, and had worse psychosocial scores. The black women had lower incomes, were less likely to be married, and had more hypertension, anemia, and diabetes. Besides race, only maternal height, weight, blood pressure, diabetes, and smoking had a consistent impact on outcome and did not explain the difference in outcome between the two groups. CONCLUSION: In this low-income population, many of the risk factors for low birth weight were more common among white women than black women. Nevertheless, black women had more infants born preterm, with growth restriction, and with low birth weight than did white women. The various maternal characteristics studied did not explain these differences.

Black People↗
PubMed1996

Detection of gastrointestinal nematodes by a coproantigen capture ELISA.

An assay is described for the quantitative detection of excretory/secretory antigens liberated by the intestinal nematode Heligmosomoides polygyrus and voided in the host's faeces. A rabbit polyclonal antiserum to the antigens detected them in a dose-dependent manner and was sufficiently sensitive to recognise infection in mice carrying a mean worm burden of nine worms. The assay was specific, giving higher optical density readings with the faeces of mice infected with H polygyrus than with faeces from mice carrying patent infections with Trichuris muris, Hymenolepsis microstoma or the intestinal phase of Trichinella spiralis, or with faeces from rats carrying Hymenolepis diminuta or hamsters carrying Necator americanus or Ancylostoma ceylanicum. It detected the parasite antigens in faeces stored for eight weeks at -20, 4 or 20 degrees C and could detect prepatent infections. The assay has potential for the development of infection intensity-sensitive assays for gastrointestinal nematodes and for the detection of animals harbouring the arrested larvae of parasites.

Animals↗
PubMed1996

Cross-correlation analysis reveals laminar differences in thalamocortical interactions in the somatosensory system.

1. Spontaneous and stimulus-induced activity were recorded from corresponding somatotopic representations in the ventroposterolateral nucleus (VPL) of the thalamus and primary somatosensory (SI) cortex of intact, halothane-anesthetized cats. Thalamic and cortical neurons with overlapping receptive fields on the hairy skin of the forelimb were excited by a series of interleaved air jets aimed at multiple skin sites. 2. The laminar locations of 68% (240 of 355) of the neurons recorded in SI cortex were histologically reconstructed and responses of these 240 SI neurons were analyzed with respect to responses recorded from 118 thalamic neurons. Maximum responsiveness during the initial onset (1st 100 ms) of air jet stimulation was similar for neurons distributed throughout all layers of SI cortex (2-4 spikes per stimulus) and did not differ significantly from VPL responses. During the subsequent plateau phase of the stimulus, VPL neurons discharged at a mean rate of 19.0 spikes/ s and neurons in cortical layers II, IIIa, IIIb, and IV discharged at similar rates. Mean responsiveness during the plateau phase of the stimulus was significantly reduced among neurons in cortical layers V and VI and only averaged 7.1 and 3.9 spikes/s, respectively. 3. Responses recorded simultaneously from pairs of thalamic and cortical neurons were analyzed with cross-correlation analysis to determine differences in the incidence and strength of neuronal interactions as a function of cortical layer. Among 421 thalamocortical neuron pairs displaying stimulus-induced responses, 68 neuron pairs exhibited significant interactions during air jet stimulation. A laminar analysis revealed that 28% (45 of 163) of the neurons in the middle cortical layers displayed significant interactions with thalamic neurons, whereas only 14% (13 of 92) of superficial layer neurons and 6% (10 of 166) of deep layer neurons were synchronized with thalamic activity during air jet stimulation. When thalamocortical efficacy for different layers of cortex was plotted as a cumulative frequency distribution, the strongest interactions in the middle cortical layers were twice as strong as interactions involving the superficial or deep cortical layers. 4. More than 70% of stimulus-induced interactions involved thalamic discharges followed by subsequent cortical discharges and the majority of these interactions involved interspike intervals of < or = 3 ms. Nearly 75% (27 of 37) of interactions in the thalamocortical direction that involved cortical neurons in layers IIIb and IV transpired within a 3-ms interspike interval. For interactions with superficial or deep cortical layers, the proportion of thalamocortical interactions transpiring within 3 ms was only 58% (7 of 12) and 33% (2 of 6), respectively. 5. Cross-correlation analysis of spontaneous activity indicated that 124 pairs of thalamic and cortical neurons displayed synchronous activity in the absence of sensory stimulation. A laminar analysis indicated that similar proportions of cortical neurons in each layer were synchronized with thalamic activity in the absence of cutaneous stimulation. Thus 27% (44 of 163) of middle layer neurons, 30% (28 of 92) of superficial layer neurons, and 31% (51 of 166) of deep layer neurons displayed spontaneous interactions with thalamic neurons. The temporal pattern of spontaneous activity was examined with autocorrelation analysis to determine whether neuronal oscillations were essential for coordinating thalamic and cortical activity in the absence of peripheral stimulation. Only 18.5% (23 of 124) of spontaneous interactions between thalamic and cortical neurons were associated with periodic activity, which suggests that thalamocortical synchronization occurs before the constituent neurons begin to oscillate. 6. The influence of sensory stimulation on spontaneous interactions was examined in 31 pairs of thalamic and cortical neurons that exhibited interactions during prestimulus and stimulus in

Animals↗