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Biomedical subjects

S K Hong

Publications and source records attributed to S K Hong.

At least 19 recordsLinked to original sources

Mechanical allodynia is more strongly manifested in older rats in an experimental model of peripheral neuropathy.

Partial peripheral nerve injury often leads to chronic neuropathic pain characterized by symptoms such as allodynia. In the present study, employing a rat model of experimental neuropathy produced by partial denervation of the tail, we examined whether peripheral nerve injury-induced mechanical and thermal allodynia were affected by the animal's age at the time of the injury. The motive of this study was the demonstration in other neuropathy models of the age effects on the manifestation of neuropathic pain symptoms following partial peripheral nerve injury. We compared two groups of young (n = 23, 7-8 weeks old, 150-200 g) and old rats (n = 14, 16-18 months old, 550-800 g). We found that the older rats exhibited more vigorously the behavioral signs of mechanical allodynia during the first week after the nerve injury. With respect to thermal (cold or warm) allodynia, however, we detected no significant difference between young and old rat groups. The results of the present study, as those of previous studies, support the idea that the age at the time of partial peripheral nerve injury affects the severity of certain neuropathic pain symptoms appearing after the injury. However, the present results argue against the suggestion from previous studies that younger subjects are more vulnerable to partial peripheral nerve injury-induced neuropathic pain symptoms.

Aging

Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression in the locus coeruleus.

The mechanisms by which stress and anti-depressants exert opposite effects on the course of clinical depression are not known. However, potential candidates might include neurotrophic factors that regulate the development, plasticity, and survival of neurons. To explore this hypothesis, we examined the effects of stress and antidepressants on neurotrophin expression in the locus coeruleus (LC), which modulates many of the behavioral and physiological responses to stress and has been implicated in mood disorders. Using in situ hybridization, we demonstrate that neurotrophin 3 (NT-3) is expressed in noradrenergic neurons of the LC. Recurrent, but not acute, immobilization stress increased NT-3 mRNA levels in the LC. In contrast, chronic treatment with antidepressants decreased NT-3 mRNA levels. The effect occurred in response to antidepressants that blocked norepinephrine uptake, whereas serotonin-specific reuptake inhibitors did not alter NT-3 levels. Electroconvulsive seizures also decreased NT-3 expression in the LC as well as the hippocampus. Ntrk3 (neurotrophic tyrosine kinase receptor type 3; formerly TrkC), the receptor for NT-3, is expressed in the LC, but its mRNA levels did not change with stress or antidepressant treatments. Because, NT-3 is known to be trophic for LC neurons, our results raise the possibility that some of the effects of stress and antidepressants on LC function and plasticity could be mediated through NT-3. Moreover, the coexpression of NT-3 and its receptor in the LC suggests the potential for autocrine mechanisms of action.

Animals

Infarction of the territory supplied by the contralateral superior cerebellar artery in a case of descending transtentorial herniation.

Infarction of the territory supplied by the contralateral superior cerebellar artery in cases of descending transtentorial herniation has not been reported. The authors experienced a primitive neuroectodermal tumor in a patient whose consciousness deteriorated transiently due to descending transtentorial herniation. On the magnetic resonance imaging taken 8 days after the herniation, lesions thought to be infarction of territories supplied by the ipsilateral posterior cerebral artery and the contralateral superior cerebellar artery were noted. The possible mechanism of this peculiar pattern of infarction is discussed.

Arteries

Glomerular hyperfiltration in Koreans with non-insulin-dependent diabetes mellitus.

Glomerular hyperfiltration (GHF) may play an important role in the pathogenesis of diabetic nephropathy. The prevalence of GHF in non-insulin-dependent diabetes mellitus (NIDDM) is reported to vary in different populations, ranging from 35% in black Americans with new-onset diabetes to less than 5% in whites. We measured glomerular filtration rate (GFR) by 51Cr-EDTA clearance methods in 284 Korean NIDDM patients without overt nephropathy. Glomerular hyperfiltration (defined as GFR > 140 mL/min/1.73 m2) was found in 25% (71 of 284) of the patients. Thirty percent and 15% of the patients with known duration of diabetes less than 5 years and more than 10 years, respectively, showed GHF. Microalbuminuria (defined as urinary albumin excretion rate 20 to 200 micrograms/min) was found in 23% (64 of 284) of the patients. The mean GFR of the microalbuminuric patients was not significantly different from that of the normoalbuminuric patients (121.5 +/- 30.1 mL/min/1.73 m2 v 124.9 +/- 26.4 mL/min/1.73 m2; P = NS). However, when the patients with microalbuminuria were divided according to the presence or absence of retinopathy, the microalbuminuric patients with retinopathy had a lower GFR compared with the microalbuminuric patients without retinopathy (109.6 +/- 35.5 mL/min/1.73 m2 v 130.0 +/- 26.3 mL/min/1.73 m2; P < 0.01). These results show that the prevalence of GHF in Korean NIDDM patients without overt nephropathy is higher than that reported in whites and that it is similar to that in black Americans. The high prevalence of GHF in Korean NIDDM patients may contribute to the relatively higher prevalence of clinical diabetic nephropathy in this population.

Adult

Role of chloride groups in the nephrotoxic potential of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide, an oxidative metabolite of N-(3,5-dichlorophenyl)succinimide.

Although the addition of chloride groups to the phenyl ring of N-phenylsuccinimide (NPS) is known to enhance the nephrotoxic potential of NPS, the mechanism of this enhancement is unknown. One chlorinated NPS derivative, N-(3,5-dichlorophenyl)succinimide (NDPS), is a potent nephrotoxicant which induces marked proximal tubular necrosis at i.p. doses of 0.4 mmol/kg or greater. The purpose of this study was to compare the nephrotoxic potential of 2-hydroxy-N-phenylsuccinimide (HNPS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS), an oxidative and nephrotoxicant metabolite of NDPS, to determine the importance of the chloride groups for the nephrotoxic potential of NDHS. Male Fischer 344 rats (4/group) were administered a single i.p. injection of HNPS (1.0 or 1.5 mmol/kg), NDHS (0.1 mmol/kg) or vehicle (25% dimethyl sulfoxide in sesame oil), and renal function measured at 24 and 48 h. HNPS was a nonnephrotoxicant at both doses tested, while NDHS induced marked nephrotoxicity characterized by diuresis, increased proteinuria, glucosuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, decreased organic ion accumulation by renal cortical slices and proximal tubular necrosis. In vitro, HNPS reduced p-aminohippurate (PAH) and tetraethylammonium (TEA) accumulation beginning at HNPS bath concentrations of 0.05 and 0.5 mM, respectively. The results of this study indicate that although HNPS has direct effects on renal function in vitro, HNPS is not a nephrotoxicant in vivo at doses up to 15 times the minimal nephrotoxicant dose of NDHS. Therefore, the chloro groups present on NDHS play an essential role in the nephrotoxic potential of NDHS and contribute to aspects of the nephrotoxic mechanism of NDPS beyond NDPS oxidation to form NDHS.

Analysis of Variance

Expression of Streptomyces peucetius genes for doxorubicin resistance and aklavinone 11-hydroxylase in Streptomyces galilaeus ATCC 31133 and production of a hybrid aclacinomycin.

The aklavinone 11-hydroxylase gene and two doxorubicin resistance genes cloned from Streptomyces peucetius subsp. caesius ATCC 27952 were introduced into doxorubicin-sensitive Streptomyces galilaeus ATCC 31133, an aclacinomycin producer. The doxorubicin resistance genes drrA and drrB endowed S. galilaeus with high-level resistance to doxorubicin, indicating that the resistance mechanism for doxorubicin might be different from that for aclacinomycin A. Transformation of S. galilaeus ATCC 31133 with plasmid pMC213 containing the aklavinone 11-hydroxylase gene (dnrF) resulted in the production of many red pigments. A new metabolite was purified, and the position of the newly introduced hydroxyl group was determined. This result indicated that the aklavinone 11-hydroxylase gene was stably expressed in S. galilaeus ATCC 31133 and that it gave rise to a hybrid aclacinomycin A which showed highly specific in vitro cytotoxicity against leukemia and melanoma cell lines.

Aclarubicin

Diving patterns of ama divers of Hegura Island, Japan.

Daily diving patterns, especially depth-time profiles, were continuously recorded during the entire work shift in four cachido and four funado divers of Hegura Island, Japan. All Hegura divers (cachido and funado alike) were female and habitually wore wet suits. Cachidos dive free and unassisted from a boat or float, whereas funado divers are assisted by weighted descent and during the ascent by being pulled by a partner into a boat on the water surface. Both funado and cachido divers spent 250-280 min/day on the sea at their diving locations; the actual diving time was 100-120 min. The divers made 90-120 dives/day to a depth of 13-22 m, each dive lasting approximately 60 s, considerably longer and deeper than those observed and recorded previously in ama divers in the Chiba and Miura regions. These dive profiles are similar to those reported by Paulev in which he observed apparent signs of decompression sickness when the subject dived to a depth of 15-20 m 100 times in 5 h. The average bottom time for each dive of Hegura funados was 23.6 s which is approximately 10 s longer than that of Korean female ama. The rate of ascent in the funado divers was 1.5 m/s, which is nearly twice that of the cachido divers (0.8 m/s). The dive frequency of Hegura funados (109 dives/day) was greater than the Chiba male funados (23 dives/day). Accordingly, cumulative bottom time of Hegura funado was 48 min/day, whereas that of Chiba funado was 17 min/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Diurnal renal responses in man to water loading at sea level and 31 atm abs.

The hyperbaric environment causes a sustained diuresis accompanied by normal water intake and a decrease in insensible water loss. The maintained water intake may be necessary for the maintenance of water balance because of a reduced ability of the kidney to retain water, or may be causal in the diuresis. This problem was studied in four male subjects. Each ingested 1 liter of water (15 degrees C) at 0800 and 2000 h on different days, at 1 atm abs during a predive control, at 31 atm abs, and at 1 atm abs during the postdive control period. Urine was collected 30 min before and 3 h after the drink. Plasma vasopressin (VP) showed a circadian rhythm only at 1 atm abs, higher during the daytime. Because of this, and slightly lower VP levels at hyperbaria, a decrease in VP in response to the water load was significantly detectable only at 1 atm abs during the daytime. At 60 min after all water loads, there were no differences in plasma VP or plasma or urinary osmolality. Variability in the length of time of similarly reduced urine osmolality and increased free water excretion accounted for the increased urine flow during day compared to night (P < 0.05) at 120 and 150 min after the water load. The ability to excrete a water load both day (free water clear-ance, P < 0.05 at 60 min post-drink) and night (free water clearance, P < 0.05 at 60, 90, and 120 min post-drink) at 31 atm abs was enhanced. It is concluded that maintained water intake at hyperbaria is necessary to maintain water balance because there is a reduced ability of the body through renal mechanisms to retain a water load.

Adult

Critical role of the capsaicin-sensitive nerve fibers in the development of the causalgic symptoms produced by transecting some but not all of the nerves innervating the rat tail.

We investigated the role of capsaicin-sensitive small diameter fibers in the development of the thermal and mechanical allodynia in a new rat model for neuropathic pain, produced by transecting some but not all of the nerves innervating the tail. Capsaicin (50 mg/kg, s.c.) injected neonatally prior to the nerve injury produced thermal hypoalgesia in the tail the degree of which was variable across individual rats, presumably as a result of variable degeneration of the small diameter fibers. When subjected to the nerve injury, the animals with moderate thermal hypoalgesia exhibited signs of pain (e.g., tail flick) to normally innocuous mechanical stimuli applied to the tail with von Frey hairs (4.9 mN or 19.6 mN bending force), but not to thermal stimuli given by immersion of the tail into cold (4 degrees C) or warm (40 degrees C) water. The animals with marked thermal hypoalgesia, on the other hand, exhibited no signs of pain either to the mechanical or to the thermal stimuli. These results suggest that the capsaicin-sensitive fibers are critical in the development of both the mechanical and thermal allodynia. It is hypothesized that the destruction of A delta- and C-nociceptive fibers by capsaicin prevented activities induced in these fibers by the nerve injury from producing a central sensitization and thus allodynia.

Animals

Phosphorylation of the AfsR protein involved in secondary metabolism in Streptomyces species by a eukaryotic-type protein kinase.

A global regulatory protein, AfsR, involved in secondary metabolism, was found to be phosphorylated by a membrane-associated phosphokinase, named AfsK, of Streptomyces coelicolor A3(2) and S. lividans. The N-terminal portion of AfsK, deduced from the nucleotide (nt) sequence of the afsK gene, which was located downstream from the afsR gene, showed significant sequence similarity to the catalytic domain of eukaryotic Ser/Thr protein kinases (PKs). Consistent with this, experiments with AfsK produced by use of an Escherichia coli host-vector system revealed a self-catalyzed phosphate incorporation into both Ser and Tyr residues of AfsK. The recombinant AfsK phosphorylated the purified AfsR at both Ser and Thr residues. Disruption of the chromosomal afsK gene with the phage vector KC515 resulted in significant, but not complete, loss of actinorhodin production. This result implies the involvement of afsK in the regulation of secondary metabolism. The presence of an additional PK able to phosphorylate AfsR is predicted, because the afsK-disrupted strain still contained an activity able to phosphorylate Ser and Thr residues of AfsR. Southern hybridization experiments showed that nt sequences homologous to afsK, as well as afsR, were distributed among many Streptomyces spp. It is thus concluded that a signal transduction system similar to that found in higher organisms is involved in the regulation of secondary metabolism in the bacterial genus Streptomyces.

Amino Acid Sequence

A behavioral model for peripheral neuropathy produced in rat's tail by inferior caudal trunk injury.

We attempted to develop an experimental animal model using rat's tail for understanding the mechanisms involving peripheral neuropathic pain. Under sodium pentobarbital anesthesia, the left inferior caudal trunk of the rat was resected between the S3 and S4 spinal nerves. Latencies of tail-flick induced by the stimulus such as warm (40 degrees C) and cold (4 degrees C) water to the tail were measured for the following 30 weeks. In addition, sensitivity of the tail to mechanical stimulation was tested with von Frey hairs on these rats. Operated rats showed abnormal sensitivity of the tail to normally innocuous mechanical and thermal (warm and cold) stimuli. We interpreted these results as signs of neuropathic pain following nerve injury. The present model offers several advantages in performing behavioral tests; (1) it is easy to apply thermal stimulation to the rat's tail using a water bottle; (2) it is easy to apply the mechanical stimulation with von Frey hairs and to localize sensitive areas in the tail; and (3) blind behavioral studies are possible due to the lack of deformity in the tail after surgery.

Animals

Molecular cloning and characterization of the aklavinone 11-hydroxylase gene of Streptomyces peucetius subsp. caesius ATCC 27952.

The gene encoding aklavinone 11-hydroxylase of Streptomyces peucetius subsp. caesius ATCC 27952 was cloned and sequenced. The deduced amino acid sequence of the gene contains at least two common motifs of well-conserved amino acid sequences of several flavin-type bacterial hydroxylases. The hydroxylase gene is apparently transcribed from a single transcriptional start point. The phenotype of a dnrF mutant generated by gene disruption supports the idea that the dnrF gene encodes aklavinone 11-hydroxylase.

Amino Acid Sequence

Effect of water temperature on diuresis-natriuresis: AVP, ANP, and urodilatin during immersion in men.

Effects of water temperature on diuresis, natriuresis, and associated endocrine responses during head-out immersion were studied in eight men (23.4 +/- 0.3 yr) during four 5-h experimental conditions: air control at 28 degrees C and immersion at 34.5 degrees C [thermoneutral (Tnt)], 36 degrees C [above Tnt (aTnt)], and 32 degrees C [below Tnt (bTnt)]. Esophageal temperature decreased by approximately 0.4 degrees C in bTnt and increased by approximately 0.5 degrees C in aTnt. Cardiac output increased by approximately 80% in aTnt and approximately 40% in bTnt while thoracic impedance, an index of central blood pooling, decreased by 7.5 omega in bTnt (NS vs. Tnt) and 8.8 omega in aTnt (P < 0.05 vs. Tnt and bTnt). Total peripheral resistance decreased at all temperatures (50% in aTnt, 20% in bTnt). Urine flow and Na+ excretion increased by sixfold in bTnt and Tnt but by only threefold in aTnt. Creatinine clearance was unchanged while osmolal clearance (but not free water clearance) increased two-fold with all immersions. Plasma atrial natriuretic peptide (ANP), urinary urodilatin, and urinary guanosine 3',5'-cyclic monophosphate increased while plasma renin activity, aldosterone, and arginine vasopressin (AVP) decreased similarly at all temperatures. bTnt did not potentiate diuresis by selective attenuation of AVP. The overall natriuretic response exhibited a higher correlation with urodilatin (r = 0.45, P < 0.001) than with ANP (r = 0.26, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Diving pattern of fishermen in the Pescadores.

Professional diving fishermen in the Pescadores Archipelago (119.30 degrees W, 23.30 degrees N) dive with a simple hookah system. Although they use modern equipment, such as wet suit, face mask, mouth piece with demand valve, spear gun, weight belt, and fins, their lack of knowledge of diving medicine is apparent. On the average, 180 cases of decompression sickness (DCS) per year were reported to occur in the Pescadores. We conducted studies in 1990 and 1992 on three islands of the Archipelago. At the time of our study, an estimated 140 diving fishermen resided on these three islands. Of the 62 fishermen interviewed, 14 volunteered for the recording of dive profiles using a diver-carried data logger. In the summer of 1990, a group of eight fishermen dived, on the average, to a depth of 17.8 +/- 5.3 m (mean +/- SD; range, 8-27 m) for 26.9 +/- 19.7 min (5-66 min). Although the diving depth was similar to that of the average recollections of 43 divers, 20.1 +/- 4.4 m (15-30 m), the actual diving time was far shorter than that of their recollections, 426 +/- 138 min (240-630 min). The post-typhoon sea floor conditions may have shortened their diving time. In the summer of 1992, a group of six fishermen dived to 20.5 +/- 3.8 m (15-26 m) for 56.4 +/- 21.2 min (18-84 min). Again, the diving depth matched that of their recollection well, 22.2 +/- 2.5 m (20-26 m), but their bottom time was far shorter than they believed, 270 +/- 108 min (120-480 min). They used no decompression procedures, regardless of the bottom time and diving depth. In the 1990 group, 5 out of 10 equivalent single dive bottom times (ESDBT) exceeded U.S. Navy no-decompression (No-D) air dive limits; whereas in the 1992 group, 7 out of 9 ESDBTs exceeded No-D limits. Eight of the 38 discrete dives exceeded the No-D limits, even if we underestimate their decompression stress by disregarding their repetitive dive history. However, no symptoms of DCS were observed in either the 1990 or 1992 groups of 14 divers, despite 63% of the ESDBTs and 21% of discrete dives having exceeded the No-D limits. Adaptation to diving work may have allowed them to exceed the established No-D limits. The existing records of incidence of DCS from this region suggest that previously they must have dived longer or deeper or both during times of abundant resources.

Adult

Response properties of hypogastric afferent fibers supplying the uterus in the cat.

The present study was undertaken to examine the sensory function of uterine afferent fibers in cats at unknown stages of the estrous cycle. Single unit activity was recorded from strands of the hypogastric nerve of the anesthetized cat. Once a unit was found, the conduction velocity was determined and the mechanical receptive field localized on the uterus. The response properties of the unit to mechanical stimuli applied to the receptive field and to chemical stimuli applied by intra-arterial injection of algesic chemicals (bradykinin, KCl and capsaicin) into the uterine artery were studied. Single unit activity from a total of 52 units was examined in this study. Based on the conduction velocities, about 2/3 of these fibers were found to be unmyelinated C fibers and the remaining 1/3 were thinly myelinated A delta fibers. The receptive fields of most of these fibers were located at different parts of the uterine horn and body while a few were at the uterine cervix. Mechanical thresholds, as determined by von Frey filaments applied to the external surface of the uterus, varied more than 150-fold among mechanically sensitive units, ranging from extremely low to high thresholds. In addition, most of these afferents were activated by intra-arterially injected algesic chemicals, often by more than one chemical. The data in the present study suggest that a large portion of the cat uterus is innervated by the hypogastric nerve and that these afferents originate from sensory receptors that have potentially a wide range of functions. Their potential functions as low threshold mechanoreceptors and nociceptors are discussed.

Afferent Pathways

Renal response to head-out water immersion in Korean women divers.

Head-out water immersion (HOI) induces a profound diuresis and natriuresis, which may endanger the body fluid balance of breath-hold divers during prolonged diving work. To investigate if adaptation is acquired by professional breath-hold divers, we have evaluated renal responses to 3-h HOI in 5 Korean women divers (Amas) and 11 nondiving housewives (controls). In both control and diver groups, the average urine flow during 3-h immersion was four times greater and Na+ excretion was 70%-80% greater than the pre-immersion value [urine flow: 3.7 (SD 1.0) ml.min-1 vs 0.9 (SD 0.4), P < 0.001, in controls; 4.3 (SD 0.9) vs 1.1 (SD 0.4), P < 0.001, in divers; Na+ excretion: 270 (SD 176) mumol.min-1 vs 161 (SD 84), P < 0.025, in controls; 303 (SD 31) vs 164 (SD 62), P < 0.005, in divers]. In all cases, the values for a given period were not significantly different between the two groups. The plasma concentrations of Na+ and osmolality, and renal clearance of creatinine did not change significantly. However, the osmolal clearance increased [from 2.0 (SD 0.8) ml.min-1 to 2.8 (SD 0.7), P < 0.05, in the controls; from 2.2 (SD 0.4) to 2.6 (SD 0.4), P < 0.05, in the divers] and free water clearance changed from negative to positive values [from -1.1 (SD 0.5) ml.min-1 to 1.2 (SD 0.3), P < 0.005, in the controls; from -1.2 (SD 0.4) to 1.6 (SD 1.1), P < 0.01, in the divers] during immersion, again the pattern of change being similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of protein kinase inhibitors on in vitro protein phosphorylation and cellular differentiation of Streptomyces griseus.

In vitro phosphorylation reactions using extracts of Streptomyces griseus cells and gamma-[32P]ATP revealed the presence of multiple phosphorylated proteins. Most of the phosphorylations were distinctly inhibited by staurosporine and K-252a which are known to be eukaryotic protein kinase inhibitors. The in vitro experiments also showed that phosphorylation was greatly enhanced by manganese and inhibition of phosphorylation by staurosporine and K-252a was partially circumvented by 10 mM manganese. A calcium-activated protein kinase(s) was little affected by these inhibitors. Herbimycin and radicicol, known to be tyrosine kinase inhibitors, completely inhibited the phosphorylation of one protein. Consistent with their in vitro effects the protein kinase inhibitors inhibited aerial mycelium formation and pigment production by S. griseus. All these data suggest that S. griseus possesses several protein kinases of eukaryotic type which are essential for morphogenesis and secondary metabolism. In vitro phosphorylation of some proteins in a staurosporine-producing Streptomyces sp. was also inhibited by staurosporine, K-252a and herbimycin, which suggests the presence of a mechanism for self-protection in this microorganism.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Arterial blood gas tensions during breath-hold diving in the Korean ama.

Korean female unassisted divers (cachido ama) breath-hold dive > 100 times to depths of 3-7 m during a work day. We sought to determine the extent of arterial hypoxemia during normal working dives and reasonable time limits for breath-hold diving by measuring radial artery blood gas tensions and pH in five cachido ama who dove to a fixed depth of 4-5 m and then continued to breath hold for various times after their return to the surface. Eighty-two blood samples were withdrawn from indwelling radial artery catheters during 37 ocean dives. We measured compression hyperoxia [arterial PO2 = 141 +/- 24 (SD) Torr] and hypercapnia (arterial PCO2 = 46.6 +/- 2.4 Torr) at depth. Mean arterial PO2 near the end of breath-hold dives lasting 32-95 s (62 +/- 14 s) was decreased (62.6 +/- 13.5 Torr). Mean arterial PCO2 reached 49.9 +/- 5.4 Torr. Complete return of these values to their baseline did not occur until 15-20 s after breathing was resumed. In dives of usual working duration (< 30 s), blood gas tensions remained within normal ranges. Detailed analysis of hemoglobin components and intrinsic oxygenation properties revealed no evidence for adaptive changes that could increase the tolerance of the ama to hypoxic or hypothermic conditions associated with repetitive diving.

2,3-Diphosphoglycerate