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Biomedical subjects

K R Olson

Publications and source records attributed to K R Olson.

At least 19 recordsLinked to original sources

Microcirculation of gills and accessory respiratory organs of the walking catfish Clarias batrachus.

BACKGROUND: An ability to extract oxygen directly from the atmosphere enables air-breathing fish to survive otherwise debilitating hypoxic environments. Addition of accessory respiratory organs (ARO) necessitates changes in both the general circulatory system and the microcirculation of the respiratory epithelia. Understanding these modifications provides information on the efficiency of gas exchange organs as well as an indication of the evolutionary processes associated with adaptation to terrestrial habitats. METHODS: Vascular organization and structure of gills and ARO of the facultative air-breathing walking catfish Clarias batrachus were examined by scanning electron microscopy of vascular replicas and fixed tissue. RESULTS: Well-developed filaments are present on all four pairs of gill arches and they possess three vascular pathways: respiratory (arterioarterial), nutrient (arteriovenous), and interlamellar (arteriovenous), typical of teleosts. ARO, consisting of gill fans, dendritic organs on the second and fourth gill arch, and the suprabranchial epithelium are derived from gill tissue and retain structural features and arterioarterial vessels similar to gill filaments. Gill and ARO vessels are in parallel with each other, and together they are in series with the systemic circulation. Nutrients and interlamellar vessels are reduced in ARO. CONCLUSIONS: Other than the presence of multiple ventral aortas, and an additional vessel connecting the suprabranchial epithelium to the dorsal aorta, there are no vascular shunts or anatomical modifications that indicate spatial separation of flow through the heart or between gills and ARO. However, a mechanism is proposed that would prevent unsaturation of dorsal aortic blood by local myogenic vasoconstriction of gill vessels when the fish is in hypoxic water. Despite considerable differences in the gross features of ARO in Clarias and Heteropneustes fossilis (Olson et al. 1990 J. Morphol., 203:165), there are striking similarities in vascular organization and respiratory islet structure that suggest these ARO evolved in a common silurid ancestor and were later modified into an everted arborescent organ or inverted air sac, respectively.

Animals

Isolation and biological activity of [Trp5]bradykinin from the plasma of the phylogenetically ancient fish, the bowfin and the longnosed gar.

The holostean fish occupy an important position in vertebrate phylogeny as extant representatives of a ancient group of ray-finned fish with evolutionary connections to present-day teleosts. Incubation of heat-denatured plasma from the bowfin Amia calva with trypsin generated bradykinin-like immunoreactivity. The primary structure of bowfin bradykinin was established as Ala-Pro-Pro-Gly-Trp-Ser-Pro-Phe-Arg. This amino acid sequence contains one amino acid substitution (Phe5 --> Trp) compared with mammalian bradykinin. The same peptide was generated in heat-denatured plasma from the longnosed gar Lepisosteus osseus. Treatment of plasma from either the bowfin or gar with glass beads under conditions previously shown to activate Factor XII in the plasma of mammals and reptiles did not generate bradykinin. Bolus injections of synthetic bowfin bradykinin (0.1, 0.3, and 1.0 nmol/kg) into the bulbus arteriosus of unanesthetized bowfin resulted in an immediate fall in arterial blood pressure of 5-10 min duration that was followed by a dose-dependent rise in pressure that was sustained for 30-60 min. There was no change in heart rate following bradykinin administration. The data suggest that the kallikrein-kinin system may predate the appearance of teleosts and may play a role in cardiovascular regulation in holosteans.

Amino Acid Sequence

Analysis of MAP 4 function in living cells using green fluorescent protein (GFP) chimeras.

MAP 4 is a ubiquitous microtubule-associated protein thought to play a role in the polymerization and stability of microtubules in interphase and mitotic cells. We have analyzed the behavior of protein domains of MAP 4 in vivo using chimeras constructed from these polypeptides and the green fluorescent protein (GFP). GFP-MAP 4 localizes to microtubules; this is confirmed by colocalization of GFP-MAP 4 with microtubules that have incorporated microinjected rhodamine-tubulin, and by loss of localized fluorescence after treatment of cells with anti-microtubule agents. Different subdomains of MAP 4 have distinct effects on microtubule organization and dynamics. The entire basic domain of MAP 4 reorganizes microtubules into bundles and stabilizes these arrays against depolymerization with nocodazole. Within the basic domain, the PGGG repeats, which are conserved with MAP 2 and tau, have a weak affinity for microtubules and are dispensable for microtubule binding, whereas the MAP 4-unique PSP region can function independently in binding. The projection domain shows no microtubule localization, but does modulate the association of various binding subdomains with microtubules. The acidic carboxy terminus of MAP 4 strongly affects the microtubule binding characteristics of the other domains, despite constituting less than 6% of the protein. These data show that MAP 4 association with microtubules is modulated by sequences both within and outside the basic domain. Further, our work demonstrates that GFP chimeras will allow an in vivo analysis of the effects of MAPs and their variants on microtubule dynamics in real time.

Animals

Vascular compliance and mean circulatory filling pressure in trout: effects of ACE inhibition.

Mean circulatory filling pressure (MCFP), whole body vascular compliance (C), and unstressed blood volume (USV) are important indexes of cardiovascular function in mammals, but they have not been measured in fish. In the present experiments, dorsal aortic (PDA) and sinus venosus (PSV) pressures were measured in unanesthetized trout before and during electrical cardiac fibrillation, while blood volume (BV) was manipulated between 50 and 150% of normal. Measurements were repeated after angiotensin-converting enzyme (ACE) inhibition with lisinopril. Cardiac fibrillation (zero-flow condition) rapidly (approximately 5 s) dropped PDA and increased PSV (equals MCFP). MCFP in normovolemic trout (4.8 +/- 0.3 mmHg) varied directly with BV. C determined from in vivo capacitance curves was similar to that obtained gravimetrically, in vitro (3.4 and 3.5 ml.mmHg-1.kg body wt-1, respectively). USV was 13.3 ml/kg body wt (approximately 45% of BV). ACE inhibition reduced PDA in unfibrillated trout at all BV and reduced PDA in fibrillated fish at BV > or = 80%. ACE inhibition did not affect PSV, MCFP, C, or USV. The systemic arteriovenous pressure gradient at zero flow (delta PF0) was greatest at 100% BV (8.2 +/- 0.5 mmHg) and was reduced by ACE inhibition at 80-120% BV. These results show that key indexes of venous function are readily measured in fish and that the trout venous system is not an effector of angiotensin-mediated regulation of arterial blood pressure. Thus angiotensin acts solely on arterial resistance vessels. Furthermore, the drop in delta PF0 during ACE inhibition is due to a decrease in arteriolar resistance.

Angiotensin-Converting Enzyme Inhibitors

Isolation, localization, and cardiovascular activity of tachykinins from the stomach of the bowfin Amia calva.

The bowfin is an extant representative of an ancient group of ray-finned fish with evolutionary connections to modern teleosts. A peptide with substance P-like immunoreactivity was isolated from an extract of bowfin stomach and its primary structure was established as Ser-Lys-Ser-His-Gln-Phe-Tyr-Gly-Leu-Met-NH2. This amino acid sequence resembles mammalian substance P only in the COOH-terminal region of the peptide. A second tachykinin with neurokinin A-like immunoreactivity isolated from the extract comprises 23 amino acid residues and shows limited structural similarity to mammalian neuropeptide-gamma. A randomly distributed population of cells in the gastric glands of the bowfin were immunostained with an antiserum raised against substance P, but no immunopositive structures were identified in the surface epithelium, lamina propria, or the nerve plexuses of the submucosa. Bolus injections of synthetic bowfin substance P (0.1-10 nmol/kg) into the bulbus arteriosus of unanesthetized bowfin resulted in a significant and dose-dependent rise in vascular resistance and arterial blood pressure (P < 0.01) and a fall in cardiac output (P < 0.05) without change in heart rate. After 5-10 min, arterial pressure and vascular resistance returned to preinjection levels, but cardiac output significantly (P < 0.05) increased over baseline values. The response to the peptide was unaffected by pretreatment of the animals with phentolamine. The study has shown that the stomach of the bowfin synthesizes tachykinins with novel structural features that display cardiovascular activity in this species.

Animals

Health care cost effects of public use of a regional poison control center.

Poison control centers in the United States are threatened with closure, and attempts at a cost-benefit analysis of these services have been indeterminate. The purpose of this study was to compare the operating costs of a regional poison control center resulting from public use of its telephone hotline services with those of hypothetical alternative sources of advice and care. We conducted a follow-up telephone survey among 589 public callers to the San Francisco Bay Area Regional Poison Control Center who had been managed at home without medical referral after an unintentional poisoning. All survey respondents were asked what alternative action they would have taken had the poison control center not been available to assist them by telephone consultation. We then surveyed emergency departments and physicians' offices cited as alternatives by the callers to determine their response and charges for evaluating a suspected poisoning case. A total of 464 (79%) of the callers surveyed would have sought assistance from their local emergency health care system had the poison control center not been available. We conservatively estimated that the total charges for such evaluations would be +71,900. Comparatively, the total actual operating cost of services provided by the poison control center for all 589 poisoning cases was +13,547. Most of the study subjects (429 [73%]) had private insurance coverage. Direct public access to these services probably reduces the use of emergency health care resources, thus lowering health care costs.

Emergency Service, Hospital

Underreporting of fatal cases to a regional poison control center.

We assessed fatal drug overdose and poisoning case surveillance by a regional poison control center, comparing it with medical examiner determinations of death by poisoning over the same 2-year period and from the same catchment area. We studied 358 fatal cases of poisoning or drug overdose reported by a medical examiner and 10 fatal cases of poisoning or drug overdose reported by a poison control center, analyzing demographics and other case-associated factors with with possible successful poison control center case surveillance. Of the medical examiner cases, 245 (68%) were prehospital deaths. Of the remaining 113 emergency department or hospital cases, only 5 (4.4%) were also reported to the poison control center. Compared with cases involving illicit drugs, other narcotics, and sedative drugs, those that involved other prescription drugs (relative odds, 30.6; 95% confidence interval, 2.7 to 351) and over-the-counter products and other substances (odds ratio, 18.9; 95% confidence interval, 1.4 to 257) were significantly more likely to be reported to the poison control center. Most fatal cases of poisoning and drug overdose are not detected through poison control center surveillance. For prevention and treatment, health planners and policy makers should recognize the implications of case underreporting.

Adult

Occupational factors in work-related inhalations: inferences for prevention strategy.

As part of a larger investigation of inhalational toxic exposures, we studied occupationally related cases in order to examine possible preventive strategies. We analyzed data from 224 structured interviews. Of the interviewed subjects, 48 (21%) reported closed space exposures and 44 (20%) concomitant skin exposure at the time of inhalation. Chlorine gas and bleach mixtures were the most common single reported exposure type, occurring in 54 (24%) of cases. The most common occupational groups represented were crafts workers, operatives, and laborers (n = 84, 38%), and service workers (n = 64, 29%). Adjusting for occupational group in a multiple logistic regression analysis that also included length of hire and access to personal respiratory protective equipment, report of prior specific chemical safety training was significantly protective against closed space inhalation (odds ratio (OR) = 0.2; 95% confidence interval (CI) 0.1-0.4) and concomitant skin exposure (OR = 0.3, 95% CI = 0.1-0.7). These data suggest that chemical safety training may be an effective preventive strategy for potentially high-risk inhalational exposure scenarios.

Adult

Cephalic circulation in the air-breathing snakehead fish, Channa punctata, C. gachua, and C. marulius (Ophiocephalidae, Ophiocephaliformes).

The macrocirculation in the head of three air-breathing species of Channa was examined with the aid of vascular corrosion replicas and a scanning electron microscopic study was conducted on the pseudobranch, choroid gland and lentiform body. Two facultative air-breathing murrels, C. punctata and C. gachua, and one obligate air-breather, C. marulius were examined. In all three, the air-breathing organs (ABO) and systemic circulations were in-parallel, and both were in-series with the branchial circulation. Efferent branchial arteries from the first and second gill arches formed the arterial supply to the ABO, whereas the third and fourth arch efferents perfused systemic tissues. Postbranchial blood from the second gill arch also entered the systemic circulation directly via a shunt from the efferent branchial artery to the lateral aorta and via hypobranchial arteries. Vascular specialization to prevent mixing of oxygenated ABO venous and deoxygenated systemic venous blood was evident in arterial, but not venous circuits. Pseudobranchs of C. gachua and C. punctata are tri-lobed, in C. marulius they have numerous lobules. Pseudobranch lamellae are wider and shorter along the axis of blood flow than gill lamellae and folded perpendicular to this axis. Pseudobranch lamellae appear to be modified to minimize their epithelial surface while retaining an extensive vascular endothelial-pillar cell surface area, counter-current amplification is also possible. The choroid gland is an extensive planar counter-current capillary rete. The lentiform body of the eye is a globular capillary rete but there is no evidence of a counter-current circulation. The choroid and lentiform rete may have distinct physiological functions.

Air

Microcirculation of gills and accessory respiratory organs from the air-breathing snakehead fish, Channa punctata, C. gachua, and C. marulius.

Snakehead fish of the genus Channa have well-developed air-breathing organs (ABO) yet retain their gill arches for respiratory and non-respiratory functions. Alterations in the macrocirculation accompany inclusion of the ABO and appear to enhance gas exchange efficiency (Munshi et al., 1994. Anat. Rec. 238:77-91). In the present study, the microcirculatory anatomy of gill and ABO from two facultative air-breathing Channa, C. punctata and C. gachua, and one obligate air-breather, C. marulius, were examined in detail using scanning electron microscopy (SEM) of vascular corrosion replicas and fixed whole-sectioned tissue. The results show that the circulation in the filaments from the first, second, and third gill arches is similar to that found in water-breathing teleosts. Fourth gill arch microcirculation of C. punctata is not different from the other three, whereas in C. marulius, it has been greatly modified into a network of low-resistance vascular shunts, although remnants of an intralamellar filamental microcirculation remain. The vascular shunts are formed from extensions of afferent and efferent lamellar arterioles and the complete, or nearly complete, loss of a lamellar sinus. The vasculature of the ABO has been highly modified in all species into a coiled-spiral capillary network with a constricted aperture guarding a dilated capillary dome at the epithelial surface. Microvilli are found congregated on the aperture endothelium of C. punctata but they are virtually absent from C. marulius endothelium. Less than 15% of the ABO capillary surface appears to face the epithelium and thereby contributes directly to gas exchange. These findings suggest that the microvascular modifications observed in Channa entail more than a simple increase in the contact surface between ABO vessels and air and they may serve other unknown physiological functions.

Air

Rainbow trout ventricular natriuretic peptide: isolation, sequencing, and determination of biological activity.

Ventricular natriuretic peptide (VNP) is a new type of cardiac natriuretic peptide initially isolated from the eel ventricle. VNP has been isolated from cardiac ventricles of the rainbow trout, Oncorhynchus mykiss, and found to consist of 35 amino acid residues carrying a C-terminal tail sequence with 14 amino acid residues. Thus, the long C-terminal sequence characteristic of VNP was also conserved in the trout VNP. A VNP with 4 amino acid residues truncated from the C-terminus was also isolated from trout ventricles and sequenced. Sequence identity of trout VNP to eel VNP was 77%; while it was 56% to eel A-type natriuretic peptide (ANP). Trout VNP caused characteristic biphasic vasopressor/depressor effects in the trout similar to those produced by rat and eel ANP. Trout VNP and human ANP were almost equipotent in their vasopressor and depressor activity in trout. Unlike eel VNP, therefore, homologous VNP did not exhibit greater activity in the trout. In the rat, however, trout VNP was more potent than eel peptide and was almost equipotent to human ANP for both vasodepressor and natriuretic effects. The high potency of trout VNP appears to be due in part to its longer-lasting effect compared to human ANP.

Amino Acid Sequence

Seizures associated with poisoning and drug overdose.

A retrospective review of cases consulted by the San Francisco Bay Area Regional Poison Control Center during a 2-year period was performed to determine the causes and consequences of seizures associated with poisoning and drug intoxication. Of 233 charts coded as involving seizures, 191 occurred in humans and were available for analysis. The leading causes of seizures reported to the Poison Control Center were cyclic antidepressants (55 cases, 29%); cocaine and other stimulants (55 cases, 29%); diphenhydramine and other antihistamines (14 cases, 7%); theophylline (10 cases, 5%); and isoniazid (10 cases, 5%). Stimulants and diphenhydramine were more likely than other drugs to produce brief, self-limited seizures. In contrast, poisoning by cyclic antidepressants, cardiodepressant antiarrhythmic agents, or theophylline was more likely to be associated with death. Seizures in elderly patients were more likely to result in complications and death. The frequency of seizure-related cases by substance type was also compared with the results of an earlier survey performed in 1981, and found a striking increase in the proportion of seizures caused by cocaine and (23% in 1988 to 1989 compared with 4% in 1981). Poison Control Center data can provide valuable information about the causes and consequences of drug-related medical complications, as well as highlight changing trends in drug-related injury.

Adolescent

Angiotensin II relaxation of rainbow trout vessels in vitro.

The effects of salmonid angiotensin II ([Asn1,Val5]ANG II) were examined in isolated trout arteries [celiacomesenteric (CMA), coronary (COA), 3rd or 4th gill arch epibranchial (EBA), ventral aorta (VA)] and veins [anterior cardinal (ACV) and ductus Cuvier strips (DOC)]. ANG II (10(-10)-10(-6) M) produced modest (< 50% other agonists) transient contractions in otherwise unstimulated COA but was a poor agonist in other vessels. In precontracted vessels, ANG II responses were triphasic; transient contraction (P1), relaxation (P2), and partial recovery (P3) and vessel specific. P1 was similar to uncontracted vessels. With 10(-6) MANG II, %P2 was: EBA, 60.3 +/- 8.3% (n = 22); CMA, 48.8 +/- 8.8% (n = 4); ACV, 38.8 +/- 5.3% (n = 29); VA, 29.4 +/- 4.9% (n = 8); DOC, 25.5 +/- 2.4% (n = 14); COA, 13.2 +/- 6.7% (n = 4). P2 in EBA and ACV was dose dependent [EBA vs. ACV: mean effective concentration (EC50) = 3.6 x 10(-9) +/- 8.1 x 10(-10) M, n = 7 vs. 6.2 x 10(-8) +/- 2.3 x 10(-8) M, n = 8, respectively; P < or = 0.05] and inhibited by indomethacin but unaffected by propranolol, NG-monomethyl-L-arginine, saralasin, PD-123177, or DuP-753. Removal of EBA endothelium also inhibited relaxation. By comparison, ANG II did not relax bullfrog arteries (dorsal aorta, systemic arch, CMA) or femoral veins. These results show that, in large vessels of trout, the predominant effect of ANG II is an endothelium-dependent, prostanoid-mediated relaxation that is unaffected by classical ANG II-receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II

Osmolar gap with minimal acidosis in combined methanol and methyl ethyl ketone ingestion.

Methyl ethyl ketone is a common solvent but data on overdose in humans are scarce. We report a case of co-ingestion of methyl ethyl ketone together with methanol associated with a hyperosmolar coma without anion gap metabolic acidosis. Blood levels of methyl ethyl ketone and its metabolite, 2-butanol, indicated that this solvent did contribute approximately 20 mosm/L to an observed osmolar gap of 99 mosm/L. At the levels detected, methyl ethyl ketone may have inhibited methanol metabolism, contributing to the low serum formate (1.3 mmol/L) and normal anion gap despite a blood methanol of 67 mmol/L.

Acidosis

Drug detection and trauma cause--a case control study of fatal injuries.

Although drugs are frequently detected when studied in trauma series, the association between specific trauma types (such as gun shot wound) and drug use complicates interpretation of such reports. We carried out a case control study of trauma deaths with drug detection matched by cause with non-drug detection trauma fatality controls. We studied 117 case and control pairs identified from medical examiner's records. By multiple logistic regression analysis, younger adult age (OR 3.1; 95% CI 1.5 to 6.1) and black race (OR 2.3; 95% CI 1.1 to 5.0) were both strongly associated with drug detection. In contrast, neither gender, intent (homicide, suicide or unintentional), primary trauma site, nor ethanol detection were significantly associated with drug detection. Our findings suggest that case mix variables should be considered when interpreting the drug use rates in trauma.

Adolescent

Purification of a vasoactive peptide related to lysyl-bradykinin from trout plasma.

Incubation of plasma from the steelhead trout, Oncorhynchus mykiss with porcine pancreatic glandular kallikrein generated bradykinin-like immunoreactivity. The primary structure of the immunoreactive peptide was established as: Lys-Arg-Pro-Pro-Gly-Trp-Ser-Pro-Leu-Arg. This sequence shows two amino acid substitutions (Phe6-->Trp and Phe9-->Leu) compared with mammalian lysyl-bradykinin (kallidin). Bolus intraarterial injection of the purified peptide produced a strong and sustained vasopressor response in the unanaesthetized trout. The data demonstrate that the kallikrein-kinin system predates the appearance of tetrapods and suggest a role for this system in cardiovascular regulation in fish.

Amino Acid Sequence

Evidence for multiple adrenoceptor sites in rainbow trout vasculature.

The importance of neuronal and lumenal vascular adrenoceptors in the regulation of vascular reactivity was examined in rainbow trout (Oncorhynchus mykiss), in vivo and in vitro. In vivo, ganglionic blockade with hexamethonium or alpha-adrenoceptor blockade, with either phentolamine or prazosin, produced similar (7mmHg) decreases in dorsal aortic blood pressure. The drop in dorsal aortic pressure produced by phentolamine or prazosin was due to reduced systemic vascular resistance. Neither the alpha-adrenoceptor antagonist, phenoxybenzamine nor chemical sympathectomy with 6-hydroxy-dopamine affected dorsal aortic pressure. However, after chemical sympathectomy, phenoxybenzamine lowered dorsal aortic pressure to levels similar to that produced by either phentolamine or prazosin. Plasma epinephrine and norepinephrine concentrations increased four- and twofold, respectively, in sympathectomized fish. Sympathectomy also produced a leftward shift in the epinephrine dose/response curve of the in vitro perfused splanchnic vasculature, placing the effective catecholamine concentration well within the in vivo plasma levels. These results indicate that following chemical sympathectomy arterial blood pressure is stabilized by circulating catecholamines through the combined effect of increased plasma catecholamine concentrations and increased sensitivity of vascular adrenoceptors. Phenoxybenzamine is incapable of blocking neuronal vascular adrenoceptors but is a potent antagonist of the up-regulated adrenoceptors, suggesting that the latter are localized on the lumenal side of the vessel.

Animals