Genetic influences on ultrasonic vocalizations in young mice.
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Biomedical subjects
Publications and source records attributed to M Adams.
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Serum CA125 concentrations are elevated in 60% (49/86) of patients, with histologically proven residual adenocarcinoma of the ovary, before chemotherapy. The frequency of elevated levels correlates with stage of disease and tumour size but not histological tumour type. Serial antigen determinations in 44 patients receiving monthly i.v. infusions of platinum therapy suggest that an elevated serum CA125 concentration after chemotherapy may identify the presence of residual tumour but a serum antigen level falling into the normal range does not always indicate the complete eradication of tumour. The role of this serum marker is limited by lack of sensitivity for small tumour masses.
Peptide E is a 25 amino acid opioid peptide which, if cleaved at the sole double basic (Lys-Arg) typical processing site, would generate two opioid fragments, the amino-terminal fragment BAM 18 and the carboxy-terminal fragment Leu-enkephalin. We have analysed extracts of bovine adrenal medulla in order to quantify these three opioid peptides (peptide E, BAM 18, and Leu-enkephalin). Here we present evidence that BAM 18 and Leu-enkephalin were present in similar amounts, whereas peptide E was present at a higher concentration. This is consistent with previous observations showing a preferential accumulation of larger peptides in the bovine adrenal, and also with the Lys-Arg bond being the principal site of cleavage of peptide E. However, when bovine adrenal chromaffin cells were maintained in culture for several days, Leu-enkephalin was found to be present in much greater amounts than was BAM 18-like immunoreactivity. The molar amounts of peptide E still exceeded the estimated levels of BAM 18 and Leu-enkephalin. We provide evidence that under conditions of basal release BAM 18 and peptide E were released, whereas Leu-enkephalin was released in much smaller amounts, if at all. On stimulation with nicotine results were consistent with an increased release of all three peptides with a preferential stimulation of Leu-enkephalin release. Under all conditions, the molar amounts of peptide E released apparently exceeded that of the other peptides. The results are discussed in terms of the regulation of partial proteolysis and the fate of peptide E.
Investigations into the effects of culturing bovine adrenal chromaffin cells in the presence (72 h) of dibutyryl cyclic AMP, forskolin, and reserpine on the level and release of [Met]enkephalyl-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline are reported. The assay for [Met]enkephalyl-Arg6-Phe7 immunoreactivity recognises both peptide B, the 31-amino acid carboxy-terminal segment of proenkephalin, and its heptapeptide fragment, [Met]enkephalyl-Arg6-Phe7. Treatments that elevate cyclic AMP increase the amount of peptide immunoreactivity in these cells; this is predominantly peptide B-like immunoreactivity in both control cells and cyclic AMP-elevated cells. Treatment with reserpine gives no change in total immunoreactivity levels, but does not result in increased accumulation of the heptapeptide [Met]enkephalyl-Arg6-Phe7 at the expense of immunoreactivity that elutes with its immediate precursor, peptide B. Cyclic AMP treatment causes either no change or a decrease in levels of accumulated noradrenaline and adrenaline. However, the release of [Met]enkephalin-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline is increased by 72-h pretreatment with forskolin or dibutyryl cyclic AMP, whether release is stimulated by nicotine or elevated potassium. In each case the molecular form of [Met]enkephalyl-Arg6-Phe7 immunoreactivity that is released approximately reflects the cell content. Pretreatment with reserpine has no effect on the total [Met]enkephalyl-Arg6-Phe7 immunoreactivity released, but does result in an increased release of the heptapeptide and a decrease in release of peptide B-like immunoreactivity. The studies suggest that the levels of [Met]enkephalyl-Arg6-Phe7 and peptide B available for release are controlled both at the level of proenkephalin synthesis and at the level of double-basic residue proteolysis.
The present review considers evidence that in chronic hypertension, hypertrophy of the muscles of the resistance vessels and left ventricle (LV) accounts for their intrinsic properties as haemodynamic amplifiers. In spontaneously hypertensive rats (SHR) there is early hypertrophy of both vessels and LV, suggesting that they may initiate hypertension; slow development of alpha-adrenoceptors may contribute to the early preponderance of the LV amplifier. In human hypertension LV hypertrophy occurs in most patients, including a high proportion of mild hypertensives. In Goldblatt one-kidney hypertension the stenosis resistance, which is the initiating cause, accounts for 25% of the rise in blood pressure throughout, with 75% initially due to systemic constrictor action of angiotensin II and later due to the amplifier properties of the hypertrophied heart and vessels. The cardiovascular amplifiers must be important in all chronic hypertension, so that if hypertrophy can be reversed, detection of the initiating mechanism should be easier. Studies in patients indicate that drug therapy can reverse hypertrophy and that subsequent redevelopment of hypertension is markedly slowed. We postulate an intrinsic disturbance of muscle performance in all primary hypertension, which may be triggered through the sympathetic nervous system in some patients and through altered cation transport in others.
A simulation model of the walk-in emergency psychiatric service of a large metropolitan public hospital has been developed using Dynamo simulation language on an IBM-PC microcomputer. The model reveals the basis of equilibrium in the system, despite the rising demand for service.
Plasma beta-endorphin-like radioimmunoreactivity (BEND) was measured in opiate addicts and controls with an antisera which cross reacted with lipotropin but not with other endogenous opiate peptides. 43 stable male methadone maintained patients had mean BEND of 18 +/- 11 pg/ml. No relationship was found between BEND, and time of day, dose or time since last methadone. Controls had 22 +/- 8pg/ml. 9 hospitalized freshly detoxified male opiate addicts, 7-23 days after last opioid, had BEND of 32 +/- 11 pg/ml. These same took 7 days of 50 mg oral naltrexone (NTX) daily, and repeat BEND was 41 +/- 13 pg/ml, rising in all instances compared to baseline. Ex-addicts after detoxification had high BEND which rose further during a short course of NTX. Methadone maintained patients had normal BEND. These data are consistent with previous animal and human reports of high plasma BEND level with NTX or detoxification.
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Only two types of pepsinogens, which are products of the Pg-1 locus, are present in rat urine. In gastric mucosa, however, additional pepsinogen isozymes are expressed. We have found a polymorphism for rat gastric mucosa pepsinogen using agarose gel electrophoresis. Some inbred rat strains expressed a pepsinogen band, while others did not. The trait was found to be controlled by a single autosomal locus. We tentatively designated the locus as Pg-2 with two alleles, Pg-2a for the one controlling presence of the band and Pg-2o for the one controlling absence. Linkage analysis using BN and TM strains revealed that Pg-2 was closely linked to Pg-1 (3.7 +/- 1.8 cM), and that it did not belong to LG I (Hbb and p), LG II (Acon-1 and Mup-1), LG IV (Hao-1 and Svp-1), LG V (Es-1 and Es-3), LG VI (Gc and h), LG IX (RT1), LG X (Fh and Pep-3), nor a LG containing Ahd-2 (as yet undetermined).
The carboxy terminal part of the proenkephalin A sequence is the 31 amino acid peptide B, which has as its final seven amino acids the sequence of the opioid peptide Met-enkephalyl-Arg6-Phe7. Using a radioimmunoassay which recognises both these peptides we have investigated the relative amounts of peptide B and Met-enkephalyl-Arg6-Phe7 in a human neuroblastoma cell line. We show that these cells contain peptide B-like immunoreactivity but not its heptapeptide fragment. This may be due to lack of proteolytic activity cleaving Met-enkephalyl-Arg6-Phe7 from its precursor, peptide B. On treatment with dibutyryl cyclic AMP the level of immunoreactivity approximately doubles, due to increased amounts of peptide B-like immunoreactivity. Treatment with reserpine, which increases conversion of peptide B to the heptapeptide in bovine chromaffin cells in culture does not stimulate the accumulation of Met-enkephalyl-Arg6-Phe7 in the human neuroblastoma cells. The results are discussed with respect to peptide processing.
In the anaesthetised rat, human and rat CGRP (calcitonin gene-related peptide) which differ by 4 out of 37 amino acids, when given intravenously, lowered blood pressure and increased heart rate. The effects of human CGRP were unaltered by either propranolol or by mepyramine plus cimetidine. In the rat isolated perfused heart the peptides decreased coronary perfusion pressure and evoked a tachycardia. The latter effect was not seen in the rabbit isolated heart, although human CGRP increased coronary flow. The two peptides were equipotent at increasing the rate and force of contraction in the rat isolated right atrium, effects unaltered by propranolol. In the guinea-pig isolated atrium, rat CGRP was 10 times as potent as a chronotropic agent than as an inotrope, unlike human CGRP which was equipotent. In conclusion, human and rat CGRP probably acted directly on the cardiovascular system to produce their qualitatively similar effects.
We have examined the linkage relationships between five biochemical markers, Acon-1, Ahd-2, Ahd-c, Akp-1, and Hao-1, and 19 other genetic loci in five breeding combinations. The genetic locus that codes for a recently described aldehyde dehydrogenase in the liver (Ahd-c) has been assigned to linkage group X (LG X). Hydroxyacid oxidase is coded for by a locus (Hao-1) that is linked to genes that encode agouti coat color and seminal vesicle proteins in linkage group IV. Alkaline phosphatase (Akp-1) was linked to the locus that encodes the C6 component of complement and this association provisionally defines a new linkage group (LG XI) in the rat. The locus Acon-1 could not be positively assigned to a specific linkage group but the results from one breeding combination suggest that this locus may be included in linkage group II. No linkage relationship could be detected for the aldehyde dehydrogenase coded for by Ahd-2.
In this 7 year review of the operative records of a single city's teaching hospitals, we found 28 patients with aortoenteric fistulas. Among 25 patients with secondary aortoenteric fistulas, 80 percent presented with a herald bleed. Sepsis was rare. Most diagnostic maneuvers, with the possible exception of upper gastrointestinal tract endoscopy, computerized axial tomography, or ultrasonography, were unhelpful. As noted by others, graft excision, aortic ligature, and extraanatomic bypass is the only predictably useful operative therapy. Initial hospital survival was 60 percent, but this decreased to 36 percent because recurrent aortic complications developed in more than half the initial survivors, 75 percent of whom died. Although the pathogenesis of aortoenteric fistulas remains obscure, our study demonstrates that patients who have previously undergone complicated, repeated, or emergency aortic operations, including previous repair of an aortoenteric fistula, are at high risk for the development of another aortoenteric fistula. Serial screening by noninvasive imaging techniques, such as ultrasonography or computerized axial tomography, may be warranted in these patients.
Isoenzyme electrophoretic techniques were applied to the characterization of seven Sarcocystis spp. that had been identified by conventional morphological studies. Cystozoites were harvested from macroscopic cysts from sheep, cattle, and mice and from microscopic cysts from sheep, cattle, and goats. Soluble cystozoite extracts were subjected to cellulose acetate gel electrophoresis and characterized at 15 of the 39 enzyme loci examined. Genetic relationships among isolates were examined by simple phenetic clustering. Two different morphological types of macroscopic cysts from sheep, identified as S. gigantea (syn. S. ovifelis) and S. medusiformis, consistently differed at 40% of the loci examined. Such genetic divergence confirms their separate morphotypic classification. Both differed from microscopic cyst isolates from sheep at 87% of the loci examined; however, two different morphotypes of microscopic cysts were found in the sheep sampled (thick-walled and thin-walled cysts). Until sufficient numbers of each type can be isolated and examined separately, both were regarded as belonging to the species S. tenella (syn. S. ovicanis). Macroscopic and microscopic cysts from cattle consistently differed at 80% of the loci thereby supporting their separate classification as S. hirsuta (syn. S. bovifelis) and S. cruzi (syn. S. bovicanis), respectively. Isolates from goats (microscopic cysts identified as S. capracanis) differed from S. tenella and S. cruzi at 20% and 47% of the loci, respectively. All macroscopic cyst isolates from the various host animal species (including S. muris from mice) differed from each other at nearly all loci. Isoenzyme electrophoretic techniques therefore provided genetic evidence supporting the classification of these various Sarcocystis spp. by their morphological characteristics.
In a [(BN X TM) X TM] backcross progeny of rats, nine significant linkage associations were found among 105 pairwise combinations of 15 loci. After comparing this with other published data and data of personal communications, we considered that the d gene we tentatively designated may be identical to the gene for pink-eyed dilution (p), and that the associations of Gc-Hbb, RT1-h, and Gc-Fh were due to chance rather than real linkage. The linkages obtained in this study, therefore, were Hbb-p (26.5 +/- 5.5) in LG I, Mup-1-Acon-1 (12.5 +/- 4.1) in LG II, Hao-1-Svp-1 (23.8 +/- 6.6) in LG IV, Es-1-Es-3 (17.2 +/- 4.7) in LG V, h-Gc (10.9 +/- 3.3) in LG VI, and Fh-Pep-3 (32.3 +/- 5.9) in LG X.
This study compared the stress response in patients with coronary artery disease undergoing myocardial revascularization anesthetized with either sufentanil and oxygen or enflurane-nitrous oxide and oxygen. Throughout induction and maintenance of anesthesia, and while the patients were in the intensive care unit, hemodynamics plus plasma catecholamine, sufentanil, and enflurane concentrations were recorded and compared. Three groups were studied: sufentanil, 15 micrograms/kg at induction; sufentanil, 15 micrograms/kg at induction plus 10 micrograms/kg on initiation of cardiopulmonary bypass (CPB); and enflurane anesthesia. Hemodynamics were remarkably stable in all groups but required considerable fine tuning when enflurane was administered. The "stress" of CPB was blunted by the additional dose of sufentanil, as well as by enflurane. This was reflected in those patients receiving the extra sufentanil or enflurane by less severe increases in their epinephrine or norepinephrine concentrations and by less frequent use of sodium nitroprusside to control mean arterial pressure compared to the group of patients given the lower-dose sufentanil. This study suggests that higher blood levels of sufentanil can attenuate, but not eliminate, the stress response to CPB, as can enflurane, and that both the narcotic and inhalation anesthetic techniques for patients with coronary artery disease were quite satisfactory.
The function of the entero-insular axis and abnormalities of circulating gastric inhibitory polypeptide (GIP) were examined in mice for 40 days after induction of streptozotocin diabetes. Compared with untreated controls, streptozotocin diabetic mice exhibited marked hyperglycaemia and hypoinsulinaemia, with impaired body weight gain, lipoatrophy, hyperphagia, intestinal hypertrophy, polydipsia and renal hypertrophy. Plasma GIP concentrations were elevated in fed but not fasted streptozotocin diabetic mice, and oral fat evoked a greater GIP response than control mice. In spite of marked hyperglycaemia, fat-stimulated GIP release did not raise plasma insulin in streptozotocin diabetic mice. Neither oral nor intraperitoneal glucose produced a significant insulin response in streptozotocin diabetic mice, although oral glucose resulted in a smaller change in glycaemia. The results indicate that streptozotocin diabetes in mice is associated with ineffectiveness of the entero-insular axis, despite elevated GIP concentrations, which are probably mediated through hyperphagia and defective feedback inhibition by insulin on intestinal K cells.
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