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Summary Obesity is a complex, chronic disease, frequently associated with multiple comorbidities. Its management is hampered by a lack of translation of evidence on chronicity and pathophysiology into clinical practice. Also, it is not well understood how to support effective provider–patient communication that adequately addresses patients’ personal root causes and barriers and helps them feel capable to take action for their health. This study examined interpersonal processes during clinical consultations, their impacts, and outcomes with the aim to develop an approach to personalized obesity assessment and care planning. We used a qualitative, explorative design with 20 participants with obesity, sampling for maximum variation, to examine video‐recorded consultations, patient interviews at three time points, provider interviews and patient journals. Analysis was grounded in a dialogic interactional perspective and found eight key processes that supported patients in making changes to improve health: compassion and listening; making sense of root causes and contextual factors in the patient's story; recognizing strengths; reframing misconceptions about obesity; focusing on whole‐person health; action planning; fostering reflection and experimenting. Patient outcomes include activation, improved physical and psychological health. The proposed approach fosters emphatic care relationships and sensible care plans that support patients in making manageable changes to improve health.

Results are reported on the sensitivity of various gynaecological tumour cell lines to 5-aminolaevulinic acid-induced protoporphyrin IX-sensitised photodynamic therapy (ALA-PDT) in vitro. All cell lines tested accumulated ALA-induced protoporphyrin IX (PpIX) and demonstrated good sensitivity to ALA-PDT. Localisation of PpIX in the mitochondria was demonstrated by fluorescence microscopy. Subcellular damage following ALA-PDT was observed using transmission electron microscopy. This damage was localised initially to the mitochondria, with damage to membranes and the nucleus and complete loss of intracytoplasmic organisation being observed subsequently. There was no apparent difference in ALA-PDT response between a multidrug-resistant ovarian carcinoma cell line and its parent line. These results indicate that ALA-PDT has potential for application to therapy of gynaecological malignancies. Images Figure 5 Figure 6 Figure 7

FK1, a ferret ventricular full-length cDNA clone, encodes a 654-amino acid protein with 98% identity to human K+ transient outward current (Ito)-like HK1 (Tamkun et al. FASEB J.5: 331-337, 1991). FK1 is detectable in ferret brain, atrium, left and right ventricle, and kidney but not in skeletal muscle, endothelial cells, aorta, and liver. In Xenopus oocytes, FK1 cRNA gives rise to a rapidly activating and inactivating Ito-like current, which is highly K+ selective (Na(+)-to-K+ permeability ratio = 0.003). Activation occurs over an approximately 50-mV range (-40 to +10 mV) and displays a sigmoid delay in onset with potential-dependent time constants that decrease with depolarization. Steady-state activation can be described with either a simple Boltzmann relationship [half-activation potential (V1/2) = -25 mV, slope (k) = 10 mV] or a Boltzmann relationship raised to either the third or fourth power (alpha 3: V1/2 = -43 mV, kappa = 13.1 mV; alpha 4: V1/2 = -48 mV, kappa = 13.6 mV, where alpha is the activation variable). Inactivation kinetics are biexponential, with the main fast time constant becoming independent of membrane potential depolarized to 0 mV. Steady-state inactivation can be described with a single Boltzmann relationship (V1/2 = -57 mV, kappa = 5.0 mV). Fast inactivation is removed by NH2-terminal deletions. Recovery from inactivation (-90 mV) is quite slow (half-time = 4.8 +/- 2.5 s). In 2 mM extracellular K+ concentration ([K+]o), FK1 tail currents display conventional deactivation behavior; however, in 98 mM [K+]o the tail currents display "reopening" behavior. These results suggest a molecular basis for the electrophysiological similarities between ferret and human ventricular Ito (Campbell et al. J. Gen. Physiol. 101: 571-601, 1993; Nabauer et al. Circ. Res. 73: 386-394, 1993).

A simple flow cytometric technique for rapid measurement of multilog cytotoxic responses to photosensitization of cellular systems is described. This technique is particularly useful for cell lines with a low colony-forming efficiency, for which a nonclonogenic assay is required. The assay separates cell-sized objects from cellular debris by gating on forward scatter versus side scatter, identifies viable cells by positive calcein AM and negative ethidium homodimer-1 staining and measures cell concentration relative to an internal standard of polystyrene beads. Large numbers of cells can be analyzed rapidly. Two patient-derived small cell lung cancer cell lines, NCI-H209 and SV-E, were used to test the technique. Photordiation survival curves of the response of these cell lines to 5-aminolevulinic acid-induced protoprophyrin IX photosensitization correlated with the extent of photosensitizer accumulation. There was good agreement between the results obtained using the tritiated thymidine incorporation assay and the flow cytometric cytotoxicity assay. The technique can be used to measure cytotoxic responses to photosensitization of cell lines regardless of their plating efficiencies.

A putative mitogen-activated protein kinase (MAPK) has recently been identified, which potentially phosphorylates the human epidermal growth factor (EGF) receptor at a physiological site (Thr-669) and is distinguished from other MAPKs/extracellular signal-regulated protein kinases (ERKs) on the basis of chromatographic, immunological, and kinetic data. Here we report that this newly discovered MAPK is physically associated with the EGF receptor in A431 cells and with the related receptor/tyrosine kinase HER2 (encoded by c-neu) in enzyme preparations obtained from Wilm's tumors. This human EGF receptor-associated kinase is characterized as a 40-kDa Thr-669 kinase that exists in a high molecular mass complex with the respective growth factor receptor. EGF treatment of A431 cells stimulates the tyrosine phosphorylation of p40 and increases Thr-669 kinase activity in p40-containing fractions. The 40-kDa kinase is recognized by affinity-purified polyclonal antibodies directed against the sea star p44mpk and a Pan-ERK antibody directed against the conserved subdomain VIII of MAPKs/ERKs, but is not recognized by antibodies selective for the rat p44erk1 and/or the p42mapk/erk2 isoforms, thus identifying the EGF receptor-associated kinase as a novel MAPK that may regulate receptor function in vivo.

During 1984 to 1988, the U.S. Occupational Safety and Health Administration (OSHA) investigated 10 incidents, with 11 fatalities, involving the inadvertent connection of air-line respirators to inert gas supplies. Seven deaths resulted from connecting an air-line respirator supply hose to a line which normally carried inert gas. Four deaths were caused by leakage or backfill of inert gas into a line which normally carried breathable air. Ten of the deaths were from nitrogen and one from argon. The circumstances of the 11 deaths indicated that coupling compatibility and supervisory oversight were major factors in the inappropriate supply of irrespirable gas to the respirators worn by these workers. Conscientiousness among safety personnel to the hazards of asphyxiation by inert gas, and compliance with current OSHA regulations, the ANSI Z88.2 standard, and NIOSH respirator certification approval regulations would have prevented these fatalities.

Smooth muscle caldesmon was phosphorylated in vitro by sea star p44mpk up to 2.0 mol of phosphate/mol of protein at both Ser and Thr residues. The phosphorylation sites were contained mainly in the COOH-terminal 10-kDa cyanogen bromide fragment which houses the binding sites for calmodulin, tropomyosin, and F-actin. Tryptic peptide maps of 32P-labeled caldesmon by p44mpk and p34cdc2 showed that while both enzymes recognized similar sites of phosphorylation, they have different preferred sites. Phosphorylation of caldesmon attenuated slightly its interaction with actin and had no effect on its binding to calmodulin and tropomyosin. Smooth muscle cell extracts from chicken gizzard and rat aorta contained 42- and 44-kDa proteins, respectively, which were cross-reactive with an antibody to sea star p44mpk. Immunoprecipitates from gizzard and aorta cell extracts, generated with the p44mpk antibody, possessed kinase activities toward myelin basic protein as well as caldesmon. These results suggest that MAP kinase may have functions in the differentiated smooth muscle cells distinct from those involved in the cell cycle.

Previous studies of stretch reflexes in patients with spastic hypertonia have emphasized the dynamic character of stretch reflex output. In contrast, our own studies of stretch reflex dynamics in spastic elbow flexor muscles of 14 hemiparetic human subjects have shown that stretch-evoked torque displays a relatively weak dependence on stretch velocity, and there is generally no preferential enhancement of dynamic as compared with static reflex output. Moreover, stretch reflex dynamics are broadly similar in voluntarily activated spastic and normal elbow flexor muscles. These findings support our hypothesis that spastic hypertonia results primarily from a decrease in stretch reflex threshold. The strong velocity dependence of stretch-evoked electromyographic activity in initially inactive spastic muscles could be due to a decrease in reflex threshold with increasing stretch velocity, rather than an abnormal velocity-dependent increase in stretch reflex responsiveness.