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Biomedical subjects

J D Watson

Publications and source records attributed to J D Watson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Evidence for limbic system activation during CO2-stimulated breathing in man.

1. The role of supra-brainstem structures in the ventilatory response to inhaled CO2 is unknown. The present study uses positron emission tomography (PET), with infusion of H2(15)O, to measure changes in relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during CO2-stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans were performed during 'passive' isocapnic (elevated fraction of inspired CO2) positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all subjects reported dyspnoea. 3. The anatomical locations of the increases in relative rCBF (CO2-SB versus control) were obtained using magnetic resonance imaging. 4. Group analysis identified neuronal activation within the upper brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus, fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex and parietal cortex. No neuronal activation was seen within the primary motor cortex (at sites previously shown to be associated with volitional breathing). 5. These results suggest neuronal activation within the limbic system; this activation may be important in the sensory and/or motor respiratory responses to hypercapnia in awake man.

Adult↗
PubMed1995

Genomic sequence, structural organization and evolutionary conservation of the 13.2-kDa subunit of rat NADH:ubiquinone oxidoreductase.

The 13.2-kDa subunit of NADH:ubiquinone oxidoreductase has been shown to be an integral part of the bovine iron-sulfur (IP) part of the protein. This subunit has been shown to interact with at least two other protein subunits of the IP fragment. The amino acid (aa) sequence of this subunit, determined from an acid extract of rat heart was used to generate an oligodeoxyribonucleotide probe which allowed isolation of a cDNA coding for the rat homologue of 13.2-kDa IP. The cDNA was used as a probe of a rat genomic DNA library and two clones were isolated, one of which contained the entire coding region for 13.2-kDa IP. Southern analysis indicates that the IP13 sequence exists as a single copy gene. The sequence of the genomic clone contains one intron and promoter elements including a TATAAA region. The 5' flank region has several potential regulatory sites, most notably regions similar to the nuclear respiratory factor 1 (NRF-1) motif, found in other genes which code for mitochondrial proteins [Evans and Scarpulla, Genes Dev. 4 (1990) 1023-1034]. The core domain of the deduced rat aa sequence has a high degree of identity with the mouse and cow homologues of this protein. The high degree of conservation of this protein indicates that the protein is essential for the function of complex I.

Amino Acid Sequence↗
PubMed1995

The antidiuretic effect of pneumadin requires a functional arginine vasopressin system.

Pneumadin is an antidiuretic decapeptide, recently isolated from rat and human lung. Bolus intravenous injection of 5 nmol of pneumadin into water-loaded rats caused a rapid and significant antidiuresis and a reduction in Na+ and Cl- excretion. Pneumadin administration did not alter mean arterial pressure, right atrial pressure, heart rate or haematocrit. Bolus intravenous injection of 20 nmol of pneumadin into non-water-loaded rats caused a significant increase in arginine vasopressin (AVP) within 10 min. Pneumadin administration also increased circulating atrial natriuretic peptide (ANP) but did not alter aldosterone or plasma renin activity levels. Injection of pneumadin into water-loaded Brattleboro rats, which genetically lack circulating AVP, did not change urine flow, confirming that the pneumadin induced antidiuresis is AVP dependent. Radioactive pneumadin was cleared from the circulation with a t1/2 beta of 480.3 s. Radioactive pneumadin, isolated from plasma, eluted at an altered position on reverse phase HPLC, which indicated that the peptide was modified in vivo. This modification was also observed when synthetic pneumadin was incubated in rat plasma in vitro. Purification and sequencing of the modified synthetic peptide indicated that the modification is not a proteolytic cleavage. These results indicate that pneumadin injected into the rat caused an antidiuresis by altering circulating AVP levels.

Aldosterone↗
PubMed1995

Analysis of the intra-epithelial lymphocyte compartment in SCID mice that received co-isogenic CD4+ T cells. Evidence that mature post-thymic CD4+ T cells can be induced to express CD8 alpha in vivo.

Severe combined immunodeficient (SCID) mice injected with co-isogenic CD4+/CD45RBhigh lymph node T cells from normal donors develop a wasting disease that is caused by hyperplasia of the intestinal epithelium. SCID mice injected with purified lymph node CD4+ T cells or CD4+/CD45RBlow T cells do not develop the disease. The IEL compartment from SCID mice injected with highly purified CD4+/CD45RBhigh T cells or CD4+ T cells contained significant numbers of T cells that expressed both CD4 and CD8 alpha, but not CD8 beta. The CDr+/CD8 alpha + T cells were unique to the IEL compartment of the small intestine and were not observed in significant numbers in the lamina propria, mesenteric lymph node, nor IEL compartment of the large intestine. By using Ly-5 mismatched donors and recipients, we determined that the CD4+/CD8 alpha + T cells were derived from the donor T cells. The expression of CD8 alpha was stable in vitro, and CD8 alpha mRNA was detected in sorted CD4+/CD8 alpha + T cells by reverse transcriptase-PCR (RT-PCR). Recombinase-activating gene (RAG)-1 and -2 mRNA was not detected in the intra-epithelial lymphocyte CD4+/CD8 alpha + T cell population. Thus, it appears that under conditions unique to the epithelial layer of the small intestine, mature post-thymic CD4+ T cells can be induced to express CD8 alpha.

Animals↗
PubMed1995

Retinotopic maps in human prestriate visual cortex: the demarcation of areas V2 and V3.

We have used PET (positron emission tomography) to chart the mapping of the retina in human occipital visual cortex and hence to locate the secondary and tertiary visual areas, V2 and V3. A group of four non-selected male volunteers was presented with dynamic stimuli that were aligned with either the vertical or the right horizontal meridians (VM or HM) from 0 degree to 29 degrees eccentricity; the vertical stimuli were restricted to either the inferior or the superior hemifields. PET scans were performed using intravenous infusion of H215O and a Siemens-CTI 953B PET scanner with 3D data acquisition. Subjects received 18 scans, divided equally among the right HM, the superior VM, and the inferior VM. Data were analyzed with SPM software. The group average result confirmed our experimental hypothesis that human occipital visual cortex has retinotopic maps similar to those of the macaque monkey. Thus human areas V2 and V3 can be defined on the basis that the border between them is formed by the HM and that the outer border of V3 is demarcated by a second representation of the VM that runs approximately parallel to the primary representation of the VM at the V1/V2 border. Furthermore, as in many mammals, the extrastriate representation of the HM is "split", such that the superior contralateral quadrant is mapped in lower V2 and V3, occupying the ventral surface of human cortex, and the inferior contralateral quadrant is mapped in upper V2 and V3, which extend over the lateral and medial surfaces of each hemisphere. After stereotaxic normalization, the position of V3 defined by retinal topography was found to correspond to that surmised from our previous PET studies employing moving stimuli.

Adult↗
PubMed1995

Amylase secretion by cultured porcine parotid cells.

The similarity of porcine and human physiology and the availability of slaughterhouse tissues suggests the use of porcine parotid cells as a model for amylase secretion. A procedure is described for the isolation of porcine parotid cells by collagenase-P/dispase digestion of the tissue. The preparation consisted of individual cells and small aggregates that were maintained in primary culture, during which the cells formed aggregates that firmly attached to the plastic substrate. The amylase content of the cultured cells remained adequate for assay of secretory activity during culture for one week after isolation. Depending upon variations in experimental treatments, the cultured cells secreted approx. 35-65% of cellular amylase in response to a carbachol challenge. The cells were slightly responsive to long exposures to isoproterenol, and were unresponsive to nicotine, elevated extracellular K+ or substance P. Secretion induced by carbachol required extracellular Ca2+, was inhibited by atropine and occurred with a nearly linear response over a 30-min period. The Ca2+ ionophore A23187 was also a potent secretagogue for amylase secretion, producing levels of secretion equal to that induced by carbachol. The ease of preparation and the retention of amylase during primary culture suggests that the preparation will be useful in studies on muscarinic receptor-mediated control of amylase secretion.

Amylases↗
PubMed1995

Postpartum hysterectomy.

OBJECTIVES: To review cases of postpartum hysterectomy regarding indications, risk factors and complications and compare them with cases of emergency cesarean section. METHODS: We conducted a retrospective chart review study of 20 cases of postpartum hysterectomy and 20 cases of emergency cesarean section performed at Sinai Samaritan Medical Center, Milwaukee, Wisconsin, between January 1984 and January 1994. Emergency postpartum hysterectomies were compared with emergency cesarean sections regarding obstetric history, placental location, operative time, blood loss, blood transfusion, intra- and postoperative complications and length of hospitalization. Emergency hysterectomies were reviewed according to their indications for the incidence of complications and length of hospitalization. Pathological diagnoses of the hysterectomy specimens were reviewed. Statistical analyses were performed using the two-tailed Student's t-test and Fisher's exact test. RESULTS: Placenta accreta was the most common indication for emergency postpartum hysterectomy. Prior cesarean section and/or placenta previa were risk factors. Emergency hysterectomies were associated with longer operating times (P < 0.0001), greater blood loss (P < 0.0001), more transfusions (P < 0.001), postoperative complications (P < 0.01), secondary surgeries (P < 0.01) and longer hospitalizations (P < 0.0001) than cases of emergency cesarean section. CONCLUSIONS: Emergency postpartum hysterectomy is associated with significant blood loss, need for transfusion, postoperative complications and longer hospitalization partly because of its indications. The combination of prior cesarean section and current placenta previa should alert the obstetrician that an emergency postpartum hysterectomy may be needed.

Adult↗
PubMed1995

Burns in the elderly in the south east of Scotland: review of 176 patients treated in the Bangour Burns Unit (1982-91) and burn inpatients in the region (1975-91).

One hundred and seventy-six patients aged 65 years and above, treated in Bangour Burns Unit during a 10-year period between 1982 and 1991 were studied in detail. Annual number of burn cases treated as inpatients in the South East of Scotland, within or outwith the Bangour burns unit, and all deaths due to burns, during the period from 1975 to 1991, among the estimated population were analysed to assess the trend in incidence and rates of burns in elderly persons in the community.

Aged↗
PubMed1995

Treatment of angina pectoris in the community: is medical therapy given a chance?

OBJECTIVE: To describe the routine management of patients with chronic stable angina by GPs in Northern Ireland and the factors which they perceived affected the success of medical therapy. DESIGN: A questionnaire survey of all general practitioners in Northern Ireland (n = 962). SETTING: A survey conducted collaboratively by the Departments of Public Health Medicine in each of the four Health Boards in the province. Total population served, 1.5 million. MAIN OUTCOME MEASURES: The relationship between the perceived reasons for medical treatment failure and the stated referral and prescribing practice of the GPs. RESULTS: A total of 541 GPs replied; the response rate was 56%. The two most important reasons given for the perceived failure of medical therapy were (i) underlying disease progression and (ii) an adverse patient lifestyle such as smoking or obesity (cited as of primary importance by (i) 264 and (ii) 225 doctors respectively). The ranking differed significantly according to the doctor's propensity to prescribe triple therapy, with those doctors in the highest tertile of this distribution being less likely to cite the patient's lifestyle as a primary reason for treatment failure (chi-squared = 6.7, d.f. = 2, P = 0.035) and more likely to cite underlying disease progression as a primary reason (chi-square = 7.0, d.f. = 2, p = 0.031). The overall ranking of the primary reasons for referral differed significantly according to the proportion of patients given a trial of triple therapy and to the doctor's propensity to refer. Doctors who had given a greater proportion of their patients at least a trial of triple therapy (in the highest tertile of the distribution) were more likely to cite the need for revascularisation assessment as the primary reason (chi-square = 12.5, d.f. = 2, P = 0.0019). On the other hand, the need for further advice on medical therapy was generally ranked higher by those doctors who had given fewer of their patients at least a trial of triple therapy (chi-square = 7.3, d.f. = 2, P = 0.027). GPs who had referred fewer of their new patients to hospital were more likely to be those doctors with fewer patients given at least a trial of triple therapy. Doctors with a greater percentage of their patients managed primarily by a hospital specialist tended to have more who had had a trial of triple therapy for their symptoms. CONCLUSIONS: The results suggest the need for clearer definition for GPs of the place of revascularisation and of medical therapy for patients with stable angina.

Angina Pectoris↗
PubMed1995

Cytokine mRNA expressed in tuberculin skin test biopsies from BCG-vaccinated and Mycobacterium bovis inoculated cattle.

To obtain a better understanding of the delayed-type hypersensitivity reaction to Mycobacterium bovis, we measured the expression of cytokine mRNA from tuberculin skin test biopsies of cattle. Non-vaccinated and BCG-vaccinated cattle were inoculated intratracheally with a low dose of virulent M. bovis or sham-inoculated and 20 weeks later were skin tested with tuberculin. At necropsy 1-2 weeks later, tuberculous lesions were found in six of the nine non-vaccinated and three of the nine BCG-vaccinated animals. All of the lesioned and the majority of the non-lesioned M. bovis inoculated cattle showed a distinct skin swelling response to tuberculin, irrespective of vaccination. However, cattle with tuberculous lesions displayed larger skin swelling responses than non-lesioned cattle. Tuberculin-induced expression of IFN-gamma, IL2, IL4, IL10 and TNF-alpha mRNA occurred in the skin biopsies of all of the lesioned, M. bovis inoculated animals except for an absence of tuberculin-induced TNF-alpha mRNA expression in two animals. A lower proportion of the non-lesioned M. bovis inoculated cattle displayed tuberculin-induced expression of the five cytokine mRNA. There was no evidence of a unique pattern of cytokine expression which could be used to distinguish between diseased and protected animals. By 28 weeks after vaccination, the three BCG-vaccinated, sham-inoculated cattle displayed minimal skin swelling response to tuberculin, but tuberculin-induced expression of IFN-gamma, IL2, IL4, IL10 and TNF-alpha mRNA was observed in skin biopsies of all of these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Dendritic cell presentation of PPD and 19 kDa protein of Mycobacterium tuberculosis and emergent T helper cell phenotype.

Protection against infection with Mycobacterium tuberculosis is preferentially associated with the development of the T helper 1 subset, IFN-gamma production and a cell-mediated response, rather than with T helper 2 cells, 4 (IL-4) and antibody production. The type of APC interacting with T cells responsive to mycobacterial peptides may influence which of these responses predominates. This investigation focuses on the role of dendritic cells (DC) because they are the most potent APC in both primary and recall immune responses. Our results show that splenic DC-enriched suspensions prepared from C57BL/6 mice and pulsed with either purified protein derivative (PPD) or the immunodominant 19 kDa protein from M. tuberculosis, can activate antigen-primed T cells in vitro, whereas spleen cell suspensions depleted of DC cannot. DC pulsed with PPD or 19 kDa antigen are able to prime naive T cells in vivo. Supernatants collected from cultures containing T cells from mice injected with PPD-pulsed DC and then challenged in vitro with PPD-pulsed DC were found to contain more IL-2 and IFN-gamma than those from control mice which received either DC or PPD alone. No such antigen-specific IFN-gamma response occurred if DC pulsed with 19 kDa were used in place of PPD-pulsed DC. IL-4 was not detected in any of the culture supernatants. We conclude that DC can induce production of cytokines associated with a protective immune response when presenting peptides derived from heterogeneous mycobacterial antigens but not when exposed to the single 19 kDa immunodominant protein.

Animals↗
PubMed1995

The physiology of coloured hearing. A PET activation study of colour-word synaesthesia.

In a small proportion of the normal population, stimulation in one modality can lead to perceptual experience in another, a phenomenon known as synaesthesia. In the most common form of synaesthesia, hearing a word can result in the experience of colour. We have used the technique of PET, which detects brain activity as changes of regional cerebral blood flow (rCBF), to study the physiology of colour-word synaesthesia in a group of six synaesthete women. During rCBF measurements synaesthetes and six controls were blindfolded and were presented with spoken words or pure tones. Auditory word, but not tone, stimulation triggered synaesthesia in synaesthetes. In both groups word stimulation compared with tone stimulation activated the classical language areas of the perisylvian regions. In synaesthetes, a number of additional visual associative areas, including the posterior inferior temporal cortex and the parieto-occipital junctions, were activated. The former has been implicated in the integration of colour with shape and in verbal tasks which require attention to visual features of objects to which words refer. Synaesthetes also showed activations in the right prefrontal cortex, insula and superior temporal gyrus. By contrast, no significant activity was detected in relatively lower visual areas, including areas V1, V2 and V4. These results suggest that colour-word synaesthesia may result from the activity of brain areas concerned with language and visual feature integration. In the case of colour-word synaesthesia, conscious visual experience appears to occur without activation of the primary visual cortex.

Adult↗
PubMed1995

Adrenaline administered via a nebulizer in adult patients with upper airway obstruction.

Racemic adrenaline administered via a nebulizer has been used successfully in children with upper airway obstruction resulting from croup and postintubation oedema. We report four adult cases of upper airway obstruction of differing aetiologies successfully managed with the administration of adrenaline via a nebulizer (1 mg in 5 ml of normal saline and repeated as necessary). This appears to be safe and effective in selected cases of upper airway obstruction with immediate benefits and few cardiovascular sequelae.

Administration, Intranasal↗
PubMed1995

Antigen-pulsed, interleukin-4-treated B cells activate primed T cells in vitro but not naive T cells in vivo.

The ability of B cells to act as effective antigen-presenting cells is a source of debate which centres on the degree of activation of either B cells or T cells. We have investigated whether B cells treated with interleukin 4 (IL-4) can express the two signals required to activate T cells: MHC Class 2/antigenic peptide complexes(signal 1) and the costimulatory molecules B7-1 and B7-2 (signal 2). We have also determined whether these cells could activate antigen-experienced T cells in vitro and whether they could prime naive T cells in vivo. We found that B cells expressed abundant MHC Class 2 molecules and moderate levels of B7-2 after 24 h culture in IL-4 with or without purified protein derivative (PPD) but B7-1 was not detectable. PPD-pulsed, IL-4 treated B cells induced antigen-experienced T cells to proliferate in vitro but these cells failed to prime naive T cells in vivo when injected into mice. We conclude that signals, in addition to those induced with IL-4, are required for B cells to initiate an immune response to antigen.

Animals↗
PubMed1995

Gene expression of A- and B-type natriuretic peptides in response to acute ethanol ingestion.

Given that ethanol ingestion is associated with a disruption of water and electrolyte balance in addition to being a significant risk factor for cardiovascular disease, we have investigated the gene expression of ANP and BNP in response to acute doses of ethanol. Wistar rats were administered either a 5 g/kg dose of ethanol or an equivalent volume of water, and atrial and ventricular tissue samples were removed at 30, 60, and 120 min for analyses. Although no differences in ANP mRNA were observed between ethanol and water-treated rats during the time course, BNP mRNA levels in ethanol-treated rats were 43% of those present in water-treated animals in atrial tissue at 120 min. In ventricular tissue, BNP mRNA levels were reduced similarly to 38% of control. These results suggest a possible differential regulation of A- and B-type natriuretic peptides under the influence of ethanol ingestion.

Alcoholic Intoxication↗