On the presence of NK2 receptor subtypes in peripheral and central tissues.
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Animals↗
Biomedical subjects
R Franks
Publications and source records attributed to R Franks.
[125I]neurokinin A labels pharmacologically distinct populations of NK2 binding sites in hamster and rabbit urinary bladder.
The pharmacological profile of NK2 binding sites has been characterised in homogenates of rabbit urinary bladder and compared with that present in homogenates of hamster bladder. In both species, [125I]neurokinin A-specific binding to urinary bladder membranes was displaced by neurokinin A and the NK2 agonist [beta-Ala8]neurokinin A-(4-10) whilst the NK1 ligands [Sar9,Met(O2)11]substance P and (+/-)-CP-96,345, and the NK3 agonist, senktide, were only weak displacers or ineffective. At rabbit NK2 sites, the rank order of affinity of NK2 receptor-selective antagonists was; MEN 10,376 > MEN 10,207 > L-659,877 >> R 396. In contrast, the rank order of displacement of [125I]neurokinin A-specific binding to hamster bladder membranes was: L-659,877 > R 396 > MEN 10,376 > MEN 10,207. These data demonstrate that [125I]neurokinin A binds to pharmacologically distinct NK2 binding sites in hamster and rabbit urinary bladder.
Amino Acid Sequence↗
Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma.
PURPOSE: To evaluate the activity and the toxicity of the combination of cisplatin (CDDP)/recombinant interleukin-2 (rIL-2) and interferon alfa-2a (IFN alpha) in disseminated malignant melanoma (DMM). PATIENTS AND METHODS: Between December 1990 and March 1992, 39 patients with biopsy-proven metastatic malignant melanoma (MM), bidimensionally measurable lesions and an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2 entered this protocol. Seventy-nine percent had received previous chemotherapy including platinum complex (15%) and alpha interferon (44%). They received CDDP (100 mg/m2 on day 0) followed by IL-2 18.10(6) IU/m2/d continuous intravenous (IV) infusion from day 3 to day 6 and from day 17 to day 21. The cycle was repeated on day 28. Subcutaneous IFN alpha 9.10(6) IU three times weekly was administered throughout the treatment period. From day 66 or 94, patients were administered a maintenance cycle with CDDP 100 mg/m2, subcutaneous IL-2 5.10(6) IU/m2/d from day 15 to day 19 and from day 22 to day 26 and IFN alpha 9.10(6) IU three times weekly repeated every 5 weeks (maximum four cycles). RESULTS: Among 39 assessable patients, five patients achieved complete responses (CRs). Sixteen patients had partial responses (PRs). The overall objective response rate was 53.8%. The number of metastatic sites was the only response-predictive factor. Toxicity was manageable in a routine patient setting and there was no life-threatening toxicity. CONCLUSION: These results seem to indicate a possible synergy between CDDP/rIL-2 and IFN alpha in MM.
Adult↗
Drosophila single-minded gene and the molecular genetics of CNS midline development.
Our goal is to understand the molecular mechanisms that govern the formation of the central nervous system. In particular, we have focused on the development of a small group of neurons and glia that lie along the midline of the Drosophila CNS. These midline cells possess a number of unique attributes which make them particularly amenable to molecular, cellular, and genetic examinations of nervous system formation and function. In addition, the midline cells exhibit distinctive ontogeny, morphology, anatomical position, and patterns of gene expression which suggest that they may provide unique functions to the developing CNS. The single-minded gene encodes a nuclear protein which is specifically expressed in the midline cells and has been shown to play a crucial role in midline cell development and CNS formation. Genetic experiments reveal that sim is required for the expression of many CNS midline genes which are thought to be involved in the proper differentiation of these cells. In order to identify additional genes which are expressed in some or all of the midline cells at different developmental stages, a technique known as enhancer trap screening was employed. This screen led to the identification of a large number of potential genes which exhibit various midline expression patterns and may be involved in discrete aspects of midline cell development. Further molecular, genetic, and biochemical analyses of sim and several of the enhancer trap lines are being pursued. This should permit elucidation of the genetic hierarchy which acts in the specification, differentiation, and function of these CNS midline cells.
Animals↗
Balloon dilatation of the arterial duct in congenital heart disease.
The systemic circulation of newborn infants with congenital left-heart obstruction is supplied from the right ventricle via a patent arterial duct between the pulmonary artery and descending aorta. The duct closes during the first few days of life, but infusion of prostaglandin E2 can prevent closure in some cases. We report four newborn infants (aged 3-8 days) with intractable heart failure due to severe obstruction of the left heart in the presence of a closing arterial duct. Infusion of prostaglandin E2 did not improve their clinical condition. Cardiac catheterisation and balloon dilatation of their arterial ducts resulted in a dramatic improvement in the babies' clinical condition; during subsequent surgical repair of the infants' hearts, the arterial ducts were found to be widely patent. Balloon dilatation gives immediate and sustained wide patency of the arterial duct in infants who do not respond adequately to prostaglandin E2.
Catheterization↗
Aortico-left ventricular tunnel: long-term outcome after surgical repair.
Over a 14 year period, four children (three male, one female) underwent surgical correction of an aortico-left ventricular tunnel. All presented in infancy (age range 5 days to 9 months). The presenting feature was a systolic and diastolic murmur in all, one of whom developed heart failure within 2 weeks of presentation. In the first two patients, the echocardiographic findings were inconclusive and the diagnosis was confirmed at cardiac catheterization (at 10 and 23 months of age, respectively); the other two were diagnosed echocardiographically by two-dimensional and Doppler color flow imaging. All four patients underwent surgery by patch closure of the aortic end of the tunnel (three patients) or direct suture closure (one patient) and there were no deaths. The mean age at operation was 11 months. During a mean follow-up period of 71 months (range 2 to 157), three patients have clinical and echocardiographic evidence of trivial aortic valve regurgitation, which was noted in the immediate postoperative period in one and at early (less than 6 months) follow-up study in the other two. All are symptom-free, are taking no medications and are growing and developing normally. Aortico-left ventricular tunnel can be accurately diagnosed by echocardiography. In patients presenting in infancy, echocardiography also provides the necessary morphologic information to enable surgical correction without angiography. Early operation is associated with an excellent outcome, whereas repair at a later age is associated with a high incidence of residual aortic regurgitation requiring further surgery.
Aorta↗
Diaphragmatic hernia with extrathoracic heart.
We report the cross sectional ultrasonic diagnosis of a rare form of central diaphragmatic hernia. The inferior portion of the parietal pericardium was also absent, with herniation of the heart through the defect. Surgical repair was successfully undertaken based on the ultrasonic findings.
Echocardiography, Doppler↗
Aortic-ventricular tunnel in a neonate: diagnosis and management based on cross sectional and colour Doppler ultrasonography.
A five day old symptom free neonate was referred for assessment of a to and fro murmur associated with large volume pulses. Cross sectional echocardiography and colour flow mapping confirmed the diagnosis of an aortic-ventricular tunnel with forward flow into the aorta and regurgitant flow into the ventricle through both the tunnel and the dilated aortic valve ring. Surgical correction by patch closure of the aortic end of the tunnel was successfully undertaken two weeks later without any additional investigations. Postoperative echocardiography and colour flow imaging showed no aortic regurgitation and normal left ventricular dimensions and function.
Aorta↗
Sensory physiology and catecholamines in schizophrenia and mania.
Hypersensitivity to sensory stimulation is a prominent characteristic of both schizophrenia and mania. Neurophysiological recordings suggest a common deficit in a central neuronal sensory gating mechanism which regulates sensitivity to repeated auditory stimuli. Dopamine and norepinephrine are hypothesized to have major roles in these illnesses, but their role in aberrant sensory processing has not yet been proved. Presumptive evidence for effects of catecholamines on sensory processing comes from psychophysiological studies of normal subjects challenged with stimulants who show decreased sensory gating, and studies of psychotic patients treated with neuroleptics who show improved function. Studies of similar phenomena in animals show comparable effects of catecholamines on sensory processing, both behaviorally and at the single neuron level. In this study, gating of auditory evoked potentials (EPs) during treatment of both illnesses was compared with plasma dopamine and norepinephrine metabolites. Comparisons of medicated and unmedicated states showed that schizophrenic patients have a fixed deficit in sensory gating, which is a familial trait, unchanged by medication. During acute illness, they have an additional transient hypersensitivity to stimuli, manifested as smaller EPs, which seems to be mediated by dopamine. Manic patients have only the deficit in sensory gating, which is transient and seems to be mediated by norepinephrine. Thus, similar neurophysiological deficits in the two psychoses are associated with different biochemical abnormalities, which may explain similarities in acute symptoms and differences in other aspects of the illnesses, such as their response to treatment.
Adult↗
Cardiopulmonary bypass for resection of low tracheal haemangioma.
A 3 month old girl, weighing 4000 g, presented with a capillary haemangioma obstructing the lower trachea and left main bronchus; it was not responsive to steroids. Using cardiopulmonary bypass to maintain oxygenation the tumour was excised. We are not aware that this technique has been used before for the resection of such an obstructive haemangioma.
Cardiopulmonary Bypass↗
Comparison of the identifiability of the low intensity ABR and MLR in the mentally handicapped patient.
The auditory brain stem response and the middle latency response were recorded from low intensity click stimuli in 48 patients with mental handicaps. In the 23 patients (45 ears) with normal hearing thresholds, the ABR was found to have a lower test-retest variability than the MLR. This lower variability will correspond to higher identifiability at threshold. In the 25 patients with a hearing loss, four had MLRs recorded in ears with absent ABRs. In five of these ears no auditory response would have been detected if ABRs alone were recorded. Based on the above findings, the following recommendations can be made. Recording the ABR with open filters is the desired method for threshold detection in most subjects. If no response is obtained it is desirable to record a MLR. The recording of a MLR is probably more important in laboratories recording responses with steep filter slopes, since a greater portion of the slow wave activity, P phi (V) complex, will be phase shifted into the later portion of the time base.
Adolescent↗
Analog and digital filtering of the brain stem auditory evoked response.
This study compared the filtering effects on the auditory evoked potential of zero and standard phase shift digital filters (the former was a mathematical approximation of a standard Butterworth filter). Conventional filters were found to decrease the height of the evoked response in the majority of waveforms compared to zero phase shift filters. A 36-dB/octave zero phase shift high pass filter with a cutoff frequency of 100 Hz produced a 16% reduction in wave amplitude compared to the unfiltered control. A 36-dB/octave, 100-Hz standard phase shift high pass filter produced a 41% reduction, and a 12-dB/octave, 150-Hz standard phase shift high pass filter produced a 38% reduction in wave amplitude compared to the unfiltered control. A decrease in the mean along with an increase in the variability of wave IV/V latency was also noted with conventional compared to zero phase shift filters. The increase in the variability of the latency measurement was due to the difficulty in waveform identification caused by the phase shift distortion of the conventional filter along with the variable decrease in wave latency caused by phase shifting responses with different spectral content. Our results indicated that a zero phase shift high pass filter of 100 Hz was the most desirable filter studied for the mitigation of spontaneous brain activity and random muscle artifact.
Brain Stem↗
Digital filtering and spectral analysis of the low intensity ABR.
Spectral analysis along with zero and standard-phase shift digital filtering were performed on evoked potentials recorded from 12 normal hearing subjects. The results indicated a progressive shifting of the mean spectral content of the ABR toward the low frequencies as the stimulus intensity was lowered. Despite this, the effects of zero-phase shift high-pass digital filtering at 100 Hz (36 dB/oct) did not significantly differ between waveforms elicited by a 75 dB nHL, 55 dB nHL, and 35 dB nHL stimulus. The major response frequency of the ABR is related to the distance between the peak (IV/V) and the following major trough (approximates one-half the response period). In waveforms where the major trough occurred before 10 msec, the use of 100 Hz, 36 dB/oct, zero-phase shift high-pass filters produced only a small reduction in response amplitude, even at low stimulus intensity levels. Waveforms which had a major trough (Na1) between 10 to 15 msec were reduced in amplitude by 100 Hz, 36 dB/oct, zero-phase shift high-pass filters (the longer period of the response energy in these waveforms corresponds to a lower energy frequency). However, this trough has a latency that prevents it from being recorded on a 10 msec time base or defined as an ABR. Based on these results, the use of zero-phase shift high-pass filters with a high-pass cutoff frequency that is equal to or less than the resolution of the time base (1/time base) appears to be a desirable method of reducing muscle artifact and other electrical contamination of the ABR.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Neurobiological studies of sensory gating in schizophrenia.
The sensory disturbance in schizophrenia is often described as an inability to filter out extraneous noise from meaningful sensory inputs. The neurobiological basis of this inability to filter has been examined using auditory evoked potentials, which are computerized averages of the brain's electrical response to sound. The sounds are presented in pairs to test the ability of the brain to inhibit, or gate, its response to a repeated stimulus. Schizophrenic patients lack the ability to gate the neuronal response shown by a particular wave, the P50 wave. The measurement of this deficit in human subjects and the exploration of its neurobiology in animals has produced evidence about several issues in the pathophysiology of schizophrenia: (1) the role of dopamine in improvement of sensory function in schizophrenic patients treated with neuroleptic drugs, (2) the interaction between familial or genetic deficits in sensory functioning in schizophrenic patients and possible abnormalities in dopamine metabolism, and (3) a mechanism by which noradrenergic hyperactivity in mania and other psychiatric illnesses might mimic some pathophysiological deficits in schizophrenia.
Antipsychotic Agents↗
Difference between inactive renins in amniotic fluid and in control or pregnancy plasma.
Phenylethylamine-agarose column chromatography has been used to compare inactive renins in amniotic fluid, in control plasma during estrogen treatment and in maternal plasma during normal pregnancy. Inactive renin in all three was retained by the column and separated from renin substrate. Inactive renin in control and maternal plasma desorbed similarly and was different than that in amniotic fluid. The results suggest that during normal pregnancy the elevated concentrations of inactive renin in maternal plasma are more likely of renal than placental origin.
Amniotic Fluid↗
An unusual traumatic cause of cardiac tamponade and mitral regurgitation.
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Adult↗
Experience with the modified Blalock-Taussig operation using polytetrafluoroethylene (Impra) grafts.
Between June 1978 and January 1982, 115 patients underwent 122 subclavian artery-pulmonary artery shunts using polytetrafluoroethylene (PTFE Impra) grafts. Forty-six of the patients had a ductus dependent pulmonary circulation, the patency of which was maintained by an infusion of prostaglandin E2 in 29 cases. There were nine hospital deaths, four of which were related to shunt failure. Five patients underwent a second shunt procedure within one week of the first. There were two cases of late graft occlusion. Twelve shunts were considered to have failed. The actuarial estimate of shunt patency was 90% (+/- 3%) at two years for all patients and 74% (+/- 10%) for neonates. There was no statistically significant difference in two year shunt patency between 4 mm grafts (88 +/- 5%) and 6 mm grafts (96 +/- 3%). The modified Blalock shunt using a PTFE graft is an effective pulmonary-systemic shunt with a good short term patency.
Adolescent↗
Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes.
Terminal deoxynucleotidyl transferase (TdT) and purine metabolic enzymes were examined in subsets of human infant thymocytes (defined by surface cell antigens) and normal peripheral T lymphocytes. Putative prothymocytes (RFB-1+, HTA-1+/- large blast-like cells), medium and high density cortical thymocytes (RFB-1+, HTA-1+), and medullary thymocytes (RFB-1-, HTA-1-, OKT3+) were isolated by density gradient centrifugation, monoclonal antibody and complement-mediated cytolysis, and cell-antibody affinity chromatography. Peripheral T lymphocytes were isolated from normal adult mononuclear cells using nylon fiber technique. Adenosine deaminase (ADA) and TdT were highest in prothymocytes 48.8 +/- 14.7 mumol/hr/10(8) cells (mean +/- SE) and 22.9 +/- 1.4 U/10(8) cells, respectively. Both enzymes decreased progressively down the maturation pathway. In peripheral T lymphocytes, ADA was 3.9 +/- 1.5 mumol/hr/10(8) cells, and TdT was undetectable. Purine nucleoside phosphorylase (PNP) and ecto-5'nucleotidase (5'NT) were lowest in cortical thymocytes (27.5 +/- 11.0 nmol/hr/10(6) cells and 2.8 +/- 1.3 nmol/hr/10(6) cells, respectively) and increased with T cell maturation. The PNP level was 124.9 +/- 17.2 nmol/hr/10(6) cells and 5'NT was 30.1 +/- 3.9 nmol/hr/10(6) cells in peripheral T lymphocytes. The deoxynucleoside kinases (deoxyguanosine, deoxyadenosine, and deoxycytidine kinases) paralleled the changes in ADA and TdT activity among the different T subsets. The proliferative activity (labeling index) was highest in the prothymocyte fraction and lowest in peripheral T cells. Variation in the distribution of these enzymes in T cell subsets may explain their different sensitivities to deoxyadenosine and deoxyguanosine toxicity and the different effects on T cell development of ADA or PNP deficiency.
Adenosine Deaminase↗