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Biomedical subjects

L Porter

Publications and source records attributed to L Porter.

At least 37 records · Page 2Linked to original sources

Identification of a second human nm23 gene, nm23-H2.

Reduced RNA and/or protein levels corresponding to the murine nm23-1 and human nm23-H1 complementary DNA clones have been correlated with high tumor metastatic potential in several rodent model systems and human breast carcinomas. We report the identification of a second human nm23 gene, designated nm23-H2. The pNM23-H2S complementary DNA clone predicted a Mr 17,000 protein 88% identical to nm23-H1. nm23-H2 also shared a significant homology with nucleoside diphosphate kinases and a Drosophila developmental gene. Southern blots containing BglII-restricted genomic DNA, which exhibited an allelic restriction fragment length polymorphism for nm23-H1, contained nonallelic bands upon rehybridization to the nm23-H2 probe. Thus, nm23-H1 and nm23-H2 are distinct genes. Northern blot hybridization of nm23-H1- and nm23-H2-specific probes to breast tumors and cell lines indicated that nm23-H1 expression was reduced in high metastatic potential tumor cells to a greater extent than nm23-H2. The data indicate the existence of a family of independently regulated nm23 genes.

Amino Acid Sequence

Dying pattern in volume-controlled hemorrhagic shock in awake rats.

We previously determined that in awake, unmonitored Sprague-Dawley rats, bleeding of 2.5 ml/100 g over 20 min resulted in hemorrhagic shock (HS) with about a 75% survival rate over 24 h, and bleeding of 3.0 ml/100 g in about 25% survival to 24 h. In the present study, we monitored systolic and mean arterial pressure (MAP), central venous pressure (CVP), breathing movements, electroencephalogram (EEG), and arterial blood gases to 3 h in order to study dying patterns. After cannulation under light anesthesia and awakening for 2 h, the rats were bled over 20 min. Ten rats in each of four groups were studied. Shed blood volume (SBV) in group I was 2.0 ml/100 g; in group II, 2.5 ml; in group III, 3.0 ml; and in group IV, 3.5 ml. Three hour survival rates were 100% for group I, 80% for group II (survival time 149 +/- 65 [106-180] min), 40% for group III (survival time 116 +/- 72 [93-180] min), and 0% for group IV (survival time 32 +/- 38 [5-69] min). MAP decreased at end of bleeding, increased transiently to moderately hypotensive levels (attempted self-resuscitation), and then either recovered to normotension or declined to cardiac arrest (death), which was defined as simultaneous apnea, systolic arterial pressure less than or equal to 30 mmHg without pulsations, and isoelectric EEG. EEG depression began with hypotension to MAP less than or equal to 50 mmHg. During HS, PaO2 increased, and PaCO2, pHa, and Hct all decreased. The results suggest that this model with SBV of 3.25 ml/100 g would give a low, but not zero 3 h survival, and therefore would be suitable for the study of responses to field resuscitation potentials.

Animals

Improved survival of hemorrhagic shock with oxygen and hypothermia in rats.

A previously established model in awake rats of hemorrhagic shock (HS) with 25% spontaneous survival rate (without resuscitation) was used to evaluate the effects of 4 novel life-supporting first aid (LSFA) measures on survival time and rate. After shed blood volume (SBV) of 3.25 ml/100 g, withdrawn over 20 min, hemodynamic and respiratory responses were recorded to 3 h and survival to 24 h. The 5 groups of 20 rats each (total n = 100) were as follows: group I, controls without treatment; II, oxygen 100% inhalation; III, external cooling to rectal temperature 30 degrees C; IV, Ringer's solution 5 ml/100 g rectally; and V, acoustic and surface stimuli for arousal. Survival rates were: control group I, 35% at 3 h and 15% at 24 h; oxygen group II, 75% (P less than 0.05 compared with group I) at 3 h and 60% (P less than 0.05 compared with group I) at 24 h; hypothermia group III, 65% at 3 h and 45% (P less than 0.05 compared with group I) at 24 h; rectal fluid group IV, 50% at 3 h and 40% at 24 h; stimulated group V, 15% at 3 h and 15% at 24 h. Compared with group I, median survival times during HS 0-3 h were longer in groups II and III; and self-resuscitation attempts were longer in groups II, III and IV. We conclude that in untreated severe hemorrhagic shock, chances of survival to delayed arrival of advanced life support with i.v. fluid resuscitation might be increased with O2 inhalation and/or moderate external cooling.

Animals

Bovine IgG1, but not IgG2, binds to human B cells and inhibits antibody secretion.

We previously observed that milk-derived bovine IgG, but not serum-derived bovine IgG, strongly inhibits antibody secretion by pokeweed mitogen (PWM)-stimulated human peripheral blood mononuclear cells (PBMC). Bovine milk contains a greater percentage of IgG1 (90%) than does bovine serum (53%). To determine whether bovine IgG subclasses have different functional capabilities, we have examined the effects of bovine IgG1 and IgG2 subclasses upon not only antibody secretion but also mitogenesis by human PBMC. Both bovine IgG subclasses markedly inhibited PWM-stimulated mitogenesis. However, only bovine IgG1, and not IgG2, inhibited antibody secretion during a 14-day in vitro culture period. Also, antibody secretion was inhibited following a 24-hr preincubation of human PBMC with bovine IgG1, but not with IgG2. To determine whether these differences corresponded to specificities of human Fc gamma receptors on subsets of mononuclear cells, fluorescence-activated cell sorter (FACS) analyses were performed. Both bovine IgG subclasses bound to human monocytes. However, only bovine IgG1 bound to human B cells, and bovine IgG1 bound more avidly to human B cells than did human IgG. One model to explain these findings is that inhibition of mitogenesis may be due to the binding of both bovine IgG1 and IgG2 subclasses to monocytes; whereas subclass-specific inhibition of antibody secretion may result from the selective binding of bovine IgG1, but not bovine IgG2, to B cells. The observation that bovine IgG1 has a greater avidity for human B lymphocyte Fc receptors than human IgG may have important implications for future studies of Fc gamma receptors on human leucocytes.

Animals

Heterogeneous expression of erbB-2 messenger RNA in human breast cancer.

Amplification and mRNA expression of the erbB-2 gene was analyzed in 61 samples of primary human breast carcinoma. In the 57 samples where RNA could be isolated four different expression level groups were identified. Comparison of hybridization signal with that for beta-actin revealed that erbB-2 mRNA could not be detected in 6 of 57 samples (11%), was detected at normal levels in 32 of 57 samples (56%), showed 4- to 8-fold overexpression in 8 of 57 samples (14%), and showed 16- to 128-fold overexpression in 11 of 57 samples (19%). Examination of the DNA of the same set of samples revealed 6 of 61 samples (10%) with distinct gene amplification and 6 of 61 samples (10%) with possible gene amplification. The highest levels of erbB-2 overexpression were associated with gene amplification. Samples with 4- to 16-fold overexpression of the erbB-2 mRNA occurred without evident gene abnormalities. There was no association of erbB-2 expression or gene amplification with clinical stage of breast carcinoma or axillary lymph node involvement. The clear amplification of the erbB-2 gene may be associated with a significantly shorter time to treatment failure.

Actins

Antenatal urinary screening for drugs of addiction: usefulness of sideroom testing?

Based on a pilot study of 400 samples at our Antenatal Clinic (which yielded 3.5% positives when assessed for amphetamines, cannabinoids and opiates) 600 consecutive patients attending Antenatal Booking Clinic had urine samples tested in the sideroom for amphetamines, barbiturates, cocaine metabolites, methadone and opiates using the Syva EMIT ETS apparatus. Positive samples were checked in the West Midlands Regional Laboratory for Toxicology, initially by EMIT-dau on a second ETS instrument and then by thin layer and gas chromatography. Two per cent produced a total of 14 positive EMIT results. Cocaine metabolites and methandone were not detected. Four specimens could not be confirmed as positive. In one sample, amphetamine-like compounds were isolated but not identified. Positive identification was made in the remaining seven specimens (two cannabinoid, two pseudoephedrine, one pseudoephedrine plus dihydrocodeine and two dihydrocodeine). There was a serious problem of false positive results observed in the initial sideroom testing. The value of sideroom testing for drugs of abuse was assessed in relation to the technical problems and to the small rate of drug positive samples.

Adult

Ligand-independent tyrosine phosphorylation of EGF receptor and the erbB-2/neu proto-oncogene product is induced by hyperosmotic shock.

Treatment of intact cells with media containing high concentrations of ionic and non-ionic solutes induced increased tyrosine phosphorylation of the epidermal growth factor (EGF) receptor and the protein product of the erbB-2/neu proto-oncogene. This self phosphorylation occurred in the absence of EGF or other growth factors. High concentrations of solutes did not activate phosphorylation of either isolated EGF receptor or EGF receptor solubilized by non-ionic detergents. No evidence for receptor dimerization was found in response to hyperosmotic shock. Since receptor dimers have been implicated in the EGF-induced activation of EGF receptor, hyperosmotic shock may activate EGF receptor by a different mechanism.

Cell Line

Conditioned circling in rats: bilateral involvement of the mesotelencephalic dopamine system demonstrated following unilateral 6-hydroxydopamine lesions.

High rates of conditioned circling have previously been associated with a bilateral augmentation of striatal dopamine metabolism. These results suggest that both striata subserve this response. The present experiment further assessed this possibility by determining the effects of unilateral 6-hydroxydopamine lesions of the mesotelencephalic dopamine system on conditioned circling. Rats were initially trained to circle in their preferred direction for water reinforcement. Upon establishment of this response, they received unilateral lesions at the level of the lateral hypothalamus either contralateral or ipsilateral to the reinforced direction of circling. Reinforced responding was virtually abolished in rats with contralateral lesions. In contrast, rats lesioned ipsilateral to the direction of reinforced circling exhibited only a 50% decrease in rate of reinforced responding. Non-reinforced responding was increased only in rats with contralaterally placed lesions. Following 5 postoperative test sessions, the experimental contingencies were reversed. 'Ipsilaterally lesioned' rats were now required to circle away from their lesion whereas 'contralaterally lesioned' rats had to turn towards their lesion. The 'Contralateral' group acquired the reversal, such that reinforced responding occurred more frequently than non-reinforced responding. However, reinforced rates of responding did not reach preoperative rates. Conversely, 'ipsilaterally lesioned' rats could not learn to turn contraversively and now made more non-reinforced than reinforced responses. These findings suggest that conditioned circling is mediated by a bilateral involvement of the mesotelencephalic dopaminergic systems. However, the specific role of each side appears to be dependent upon its relationship with the direction of circling emitted.

Animals

The development of an observation schedule for measuring nurse-patient touch, using an ergonomic approach.

An observation schedule for recording nurse-patient touch was developed, using an ergonomic approach to design. A preliminary study using video-tape analysis and a ward survey indicated that 'instrumental touch' was more frequently employed by nursing staff than 'expressive touch'. Three levels of relevant information relating to touch were recorded: General circumstances (the type of hospital, etc.); Demographic variables (relating to participants in the touch episode); Events specifically relating to the touch episode. The third section of the schedule was tested in an acute geriatric ward, using inter-observer reliability techniques. Reliability was found to be acceptable for those where the criteria for categorization were reasonably objective. It was concluded that an instrument for recording nurse-patient touch has useful applications for both ergonomic and nursing research.

Adult

Sonography of arcuate uterine blood vessels.

Five sonographic cases are presented with images that demonstrate normal arcuate arteries and peripheral uterine blood vessels. These vascular structures are shown in both the longitudinal and transverse sections, and should not be confused with pathology such as Nabothian cysts, hydrosalpinx, pelvic inflammatory disease, hydatid cysts of Morgagni, endometriosis, or abnormal pelvic varices.

Adult

Mental health centers and the criminal justice system.

Through questionnaires, interviews, and site visits, the authors undertook to ascertain to what extent the 26 community mental health centers in Kansas were contributing to the resolution of problems that concern the criminal justice system. They found that in all large communities some reciprocal programs have developed between the two systems, but meaningful collaboration is rare in small communities. Juvenile courts, urban law enforcement agencies, and county probation officers are most receptive to collaborative programs. An evaluation of several effective programs revealed three basic conditions that attribute to their success: an urban community setting, individual initiative by staff from each system, and location of the program within the criminal justice system.

Adolescent

Cell-mediated destruction of human leukemic cells by MHC identical lymphocytes: requirement for a proliferative trigger in vitro.

These experiments have investigated cellular mechanisms involved in the generation of cellular immune responses to human acute leukemic blasts. Because normal human lymphocytes are not able to recognize immunologically, in vitro, lymphocytes from MHC identical siblings, the present studies have examined the in vitro proliferative and cytotoxic responses of normal lymphocytes to MHC identical AML and ALL blasts. In those cases where acute leukemic cells were unable to induce a proliferative response by MHC identical lymphocytes, the generation of effective anti-leukemic cytotoxicity required the addition of unrelated stimulating cells to the sensitization culture. In contrast, leukemic blasts that induced a proliferative response by MHC identical lymphocytes were also able to stimulate anti-leukemic cytotoxicity. This could be augmented by the addition of unrelated stimulating cells to the sensitization culture. The specificity of anti-leukemic cell cytotoxicity was demonstrated in all instances by simultaneous testing of putative killer cells on 51Cr leukemic blasts as well as 51Cr-labeled MHC identical phytohemagglutinin blasts or normal lymphocytes. Simultaneous sensitization to MHC identical leukemic blasts and unrelated stimulating lymphocytes did not invariably generate anti-leukemic cytotoxicity even when allogeneic cytotoxicity was observed; the absence of demonstrable suppressor activity in these nonreactive combinations suggested that some individuals may be specifically immunoincompetent, and thereby unable to generate effective anti-leukemic CML.

Cell Transformation, Neoplastic