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Biomedical subjects

J L Hall

Publications and source records attributed to J L Hall.

At least 73 records · Page 4Linked to original sources
PubMed1995

The predictive value of serum progesterone and 17-OH progesterone levels on in vitro fertilization outcome.

PURPOSE: In order to identify parameters which predict prognosis for success with in vitro fertilization, 17-hydroxyprogesterone and progesterone levels were evaluated in 254 patients undergoing 296 in vitro fertilization cycles. Selected response and outcome data were recorded. RESULTS: Patients with intermediate values of serum progesterone (0.7-0.8 ng/ml) at the time of human chorionic gonadotropin administration achieved significantly higher pregnancy rates than patients with lower (< 0.7 ng/ml) or higher (> 0.8 ng/ml) levels. The clinical pregnancy rates were 46%, 31%, and 27% respectively (P = 0.02). There was no change in 17-hydroxyprogesterone concentration which predicted a higher pregnancy rate. CONCLUSION: Excellent clinical pregnancy rates were noted in cycles with a progesterone level of 0.7-0.8 ng/ml, as well as good results in cycles above 0.8 ng/ml. There is therefore no reason to administer human chorionic gonadotropin at a smaller follicle size to prevent a rise in serum progesterone.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Functional and metabolic evidence for two different vanilloid (VN1 and VN2) receptors in perfused rat hindlimb.

Vanilloid spice principles, including capsaicin, stimulate vasoconstriction in the rat hindlimb perfused at constant flow and, depending on dose, either stimulate or inhibit oxygen consumption by this vascular bed. We now present metabolic and functional evidence for two different vanilloid (VN1 and VN2) receptor types. These receptors can be distinguished on the basis of their differing agonist affinity for capsaicin, their different calcium and oxygen dependencies for inducing vasoconstriction, and whether they stimulate, or inhibit, oxygen consumption. The higher affinity vanilloid receptor, VN1 can be distinguished on the basis of initiating vasoconstriction at low doses of capsaicin and simultaneously stimulating oxygen consumption. Its apparent biological function is dependent on the presence of oxygen and external calcium. In contrast, the lower affinity receptor, VN2 induces vasoconstriction associated with inhibition of oxygen consumption. Its vasoconstriction action can occur independently of either external calcium ions, or the presence of oxygen in the perfusate.

Animals↗
PubMed1995

Mechanical and metabolic functions in pig hearts after 4 days of chronic coronary stenosis.

OBJECTIVES: This study sought to evaluate the functional and metabolic consequences of imposing a chronic external coronary stenosis around the left anterior descending coronary artery for 4 days in an intact pig model. BACKGROUND: A clinical condition termed hibernating myocardium has been described wherein as a result of chronic sustained or intermittent coronary hypoperfusion, heart muscle minimizes energy demands by decreasing mechanical function and thus avoids cell death. The use of chronic animal models to stimulate this disorder may assist in establishing causative associations among determinants to explain this phenomenon. METHODS: A hydraulic cuff occluder was placed around the left anterior descending coronary artery in eight pigs. Coronary flow velocity was reduced by a mean (+/- SE) of 49 +/- 5% of prestenotic values, as estimated by a Doppler velocity probe. After 4 days the pigs were prepared with extracorporeal coronary circulation and evaluated at flow conditions dictated by the cuff occluder. Substrate utilizations were described using equilibrium labeling with [U-14C]palmitate and [5-3H]glucose. Results were compared with a combined group of 21 acute and chronic (4 day) sham animals. RESULTS: Four days of partial coronary stenosis significantly decreased regional systolic shortening by 54%. Myocardial oxygen consumption was maintained at aerobic levels, and rest coronary flows were normal. Fatty acid oxidation was decreased by 43% below composite sham values, and exogenous glucose utilization was increased severalfold. Alterations in myocardial metabolism were accompanied by a decline in tissue content of adenosine triphosphate. CONCLUSIONS: These data suggest that chronic coronary stenosis in the absence of macroscarring imparts an impairment in mechanical function, whereas coronary flow and myocardial oxygen consumption are preserved at rest. The increases in glycolytic flux of exogenous glucose are similar to observations on glucose uptake assessed by fluorine-18 2-deoxy-2-fluoro-D-glucose in patients with advanced coronary artery disease. We speculate that intermittent episodes of ischemia and reperfusion are the cause of this phenomenon.

Analysis of Variance↗
PubMed1995

Adrenergic desensitization in left ventricle from streptozotocin diabetic swine.

Patients with diabetes mellitus that exhibit cardiac pump failure display compromised stroke volume, ejection fraction, and slower rates of rise and fall of left ventricular (LV) dP/dt in the absence of ischemic injury. We hypothesized that diabetic cardiomyopathy may involve decrements in adrenergic sensitivity, with specific molecular alterations in the beta-adrenergic receptor (beta AR)- G protein- adenylyl cyclase (AC) signal transduction system. We assessed the effects of 3 months of streptozotocin-induced diabetes (125 mg/kg i.v.; DIAB, n = 10) on myocardial signal transduction in mini-pigs. DIAB were hyperglycemic compared to controls (CON, n = 10; 20.92 +/- 2.64 v 5.24 +/- 0.35 mM glucose), and had lower fasting insulin levels (6.46 +/- 0.97 v 13.68 +/- 3.91 microU/ml). Transmural LV free wall homogenates from DIAB exhibited similar beta AR density as CON, but decreased cAMP production (pmol cAMP/mg prot.min) using these pharmacological stimulators: 10 microM Isoproterenol plus 100 microM GTP (74 +/- 5 v 97 +/- 11); 100 microM Gpp(NH)p (116 +/- 7 v 161 +/- 17); 10 mM fluoride ion (266 +/- 16 v 324 +/- 25). No differences between DIAB and CON were observed when stimulated by 100 microM forskolin (440 +/- 20 v 429 +/- 33), suggesting no alterations in the catalytic subunit of AC. In DIAB, quantitative immunoblotting indicated slightly depressed levels of Gs (552 +/- 44 v 630 +/- 59 pmol/g ww; NS), but a significant redistribution of alpha s from the sarcolemma to the cytosol (32.7 +/- 0.82% v 25.9 +/- 1.7%). Significantly elevated levels of cardiac Gi were seen in DIAB homogenates compared to CON ventricles (2326 +/- 145 v 1522 +/- 181 pmol/g ww), with no alpha i subunit redistribution. We conclude that despite maintained beta AR density, receptor-dependent and G protein-dependent stimulation of AC is depressed so that streptozotocin-induced diabetic LV is affected by increased cardiac Gi, redistribution of Gs alpha to the cytosol, and an increase in the Gi/Gs ratio. These results help explain depressed catecholamine responsiveness and cardiac performance exhibited by diabetic patients.

Adenylyl Cyclases↗
PubMed1995

A Chlamydomonas genomic library in yeast artificial chromosomes.

We have constructed and characterized a Chlamydomonas reinhardtii total genomic library in yeast artificial chromosomes (YACs). The library contains 7500 clones with inserts ranging in size from 100-200 kb. The representation of the library was assessed by screening one-third of it with a probe derived from the dispersed repeat, Gulliver, which occurs approximately 13 times in the genome. At least 10 of these Gulliver loci were isolated within 15 independent YACs. Two of these YACs encompass the Gulliver element designated G, which was reported to map to the uni linkage group (ULG). The end clones of these two YACs have been genetically mapped by RFLP analysis in an interspecific cross and thereby shown to be closely linked to the APM locus on the ULG. A third uni-specific YAC has also been isolated and its ends have been mapped by RFLP analysis. Genetic and RFLP analysis of these and other YACs indicates that the frequency of chimeric YACs in the library is very low. The library was constructed in a second generation vector that enables plasmid rescue of YAC end clones as well as copy number amplification of artificial chromosomes. We provide evidence that amplification of intact YACs requires a rad1:rad52 yeast strain.

Animals↗
PubMed1995

Lineage tracing demonstrates that blastomeres of early cleavage-stage human pre-embryos contribute to both trophectoderm and inner cell mass.

We injected a fluorescent lineage tracer (Texas Red-lysine-dextran) into individual blastomeres of donated human diploid 2- to 8-cell pre-embryos and cultured them to blastocysts. Once pre-embryos reached the expanded blastocyst stage, they were fixed and examined in a scanning confocal microscope to identify the location of fluorescent tracer. In successfully injected pre-embryos that developed to expanded blastocysts, we found that randomly injected blastomeres formed both trophectoderm (TE) and inner cell mass (ICM). More labelled progeny were found in TE than in ICM. Our results show that individual early blastomeres are not yet committed to form either TE or ICM but instead can form both rudiments.

Blastomeres↗
PubMed1995

Vascular and endocrine control of muscle metabolism.

Important differences exist between perfused and incubated (or perifused) skeletal muscle preparations with regard to their metabolism and control. A growing body of evidence suggests that the differences may be due to the role played by the vascular system. In the constant-flow perfused rat hindlimb preparation, a group of vasoconstrictors has been identified that enhance muscle metabolism and aerobic contractility. Another group of vasoconstrictors decrease muscle metabolism and aerobic contractility even though perfusate flow remains constant. All effects of both groups of vasoconstrictors are opposed by vasodilators. Because none of the vasoconstrictor effects is evident when isolated muscles are incubated or perifused, involvement of an active vascular system is indicated. Although some hormones may act directly on muscle by purely endocrine effects, a vascular component of their actions is now emerging. Mechanisms to account for vascular control of perfused skeletal muscle metabolism may involve 1) functional vascular shunts where the proportion of flow processed by these is regulated by site-specific vasomodulators, 2) a direct response to a change in the rate of supply of nutrients and removal of products, and 3) a signal substance released by vascular tissue in association with vasoconstriction that interacts with surrounding skeletal muscle cells. Impaired control at the level of the vascular system may have implications for long-term access of nutrients and hormones and therefore the control of skeletal muscle metabolism and contractile performance.

Animals↗
PubMed1995

Exercise training attenuates the reduction in myocardial GLUT-4 in diabetic rats.

The purpose of this study was to determine the interactive effects of 10-12 wk of streptozotocin-induced diabetes (65 mg/kg) and moderate-intensity exercise training on total myocardial GLUT-4 and GLUT-1 proteins. Sprague-Dawley rats (n = 52) were randomly divided into sedentary control (SC), exercise-trained control (ETC), sedentary diabetic (SD), and exercise-trained control (ETD) groups. Diabetes (SD), and exercise-trained diabetic (ETD) groups. Diabetes resulted in a 70% reduction in myocardial GLUT-4 (28.3+/- 3.1 and 94.6 +/- 3.4% for SD and SC, respectively; P < 0.0001) and an 18.5% decrease in GLUT-1 (62.5 +/- 4.7 and 76.8 +/- 4.5% for SD and SC, respectively; P = 0.06). Exercise training increased citrate synthase activity in the medial and long heads of the triceps brachii in both groups (P < 0.001). Fasting blood glucose improved with training in diabetic animals (348 +/- 27 and 569 +/- 28 mg/dl for ETD and SD, respectively; P < 0.05). The diabetes-induced reduction in GLUT-4 was attenuated with exercise training (46.8 +/- 9.3% for ETD; P < 0.02 compared with SD). In contrast, training resulted in a further 25% decrease compared with SD in GLUT-1 in ETD (46.8 +/- 9.3%; P < 0.03 compared with SD). Exercise training had no effect on either GLUT-4 (87.2 +/- 4.0%) or GLUT-1 (75.4 +/- 5.1%) in ETC. GLUT-4 inversely correlated (r = -0.81; P < or = 0.001) with fasting blood glucose. In conclusion, diabetes resulted in a 70% reduction in myocardial GLUT-4 and an 18% decrease in GLUT-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Myocardial interstitial purine metabolites and lactate with increased work in swine.

OBJECTIVE: Dobutamine stimulates the beta-receptors in the heart and increases myocardial blood flow and oxygen consumption 2-3-fold, similar to effects seen with exercise. The purpose of this study was to assess temporal changes in myocardial interstitial purine metabolites, adenosine monophosphate (AMP) and lactate during and following 30 min of dobutamine infusion. METHODS: Dobutamine (15 micrograms/kg/min) was infused via the jugular vein into 9 anesthetized, open-chest, domestic swine. Interstitial fluid was sampled with microdialysis probes placed in the midmyocardium. The effluent from the probes, referred to as the dialysate, was used to estimate myocardial interstitial purine metabolites, AMP, and lactate levels before, during, and following a dobutamine-induced increased work state. RESULTS: Dobutamine infusion resulted in a 77% increase in heart rate, a 258% increase in left ventricular dP/dt, a 208% increase in myocardial oxygen consumption, and a 155% increase in rate x pressure product. Myocardial blood flow was increased in the subepicardium, midmyocardium, and subendocardium by 207, 268, and 268%, respectively, compared to the control period. Neither coronary venous nor dialysate lactate concentrations changed throughout the protocol. Dialysate adenosine and AMP levels were both significantly elevated (P < 0.05) during the dobutamine period and fell back to control values during the recovery period. CONCLUSIONS: The dobutamine-induced increases in myocardial oxygen consumption, rate x pressure product, and blood flow, without an increase in coronary venous or interstitial lactate suggest that energy balance is maintained during dobutamine infusion. Thus an increase in myocardial work, in the absence of demand-induced ischemia, resulted in accumulation of adenosine and AMP in the interstitium.

Adenosine↗
PubMed1995

Prognostic value of day 3 estradiol on in vitro fertilization outcome.

OBJECTIVE: To evaluate the prognostic value of day 3 E2 levels, independent of day 3 FSH levels, on responses to ovulation induction and subsequent pregnancy rates (PRs) in IVF-ET patients. DESIGN: Prospective, observational. SETTING: University-based tertiary care and private reproductive endocrine-infertility units. PATIENTS AND INTERVENTIONS: A total of 225 patients underwent 292 IVF cycles with luteal phase GnRH agonist suppression and hMG stimulation. MAIN OUTCOME MEASURES: We evaluated response and outcome data including age, day 3 FSH and E2 levels from a menstrual cycle before IVF, ampules of hMG used, maximum E2 level, cancellation rates, and clinical PR. RESULTS: Despite similar age, number of ampules of hMG, and peak E2 levels, patients with an elevated E2 level (E2 > or = 80 pg/mL) (conversion factor to SI unit, 3.671) on day 3 of a cycle before IVF-ET achieved a lower PR per initiated cycle (14.8% versus 37.0%) and had a higher cancellation rate (18.5% versus 0.4%) compared with those with E2 levels < 80 pg/mL. Even when patients with elevated FSH levels (FSH > or = 15 mIU/mL) (conversion factor to SI unit, 1.00) were excluded (leaving 279 cycles), those with an elevated day 3 E2 still had a lower PR per initiated cycle (14.8% versus 38.9%) and maintained a higher cancellation rate (18.5% versus 0.4%). When the day 3 E2 was > or = 100 pg/mL there was a 33.3% cancellation rate and no pregnancies were achieved. CONCLUSION: Patients who presented with an elevated day 3 E2 (> or = 80 pg/mL) in a cycle before IVF-ET had a higher cancellation rate and achieved a lower PR independent of FSH level. A day 3 E2 level, in addition to a day 3 FSH level, appears very helpful in prospectively counseling patients regarding cancellation risk and ultimate IVF-ET success.

Adult↗
PubMed1994

Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine.

We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Utility of in vitro fertilization at diagnostic laparoscopy.

OBJECTIVE: To compare stimulation and outcome variables for IVF in stimulated cycles when ova are retrieved during diagnostic infertility laparoscopy versus transvaginal ultrasound (US) directed retrieval and to investigate the presence of unexpected failed fertilization in the diagnostic laparoscopy group, which allows an opportunity to diagnosis an etiology of infertility based on gamete interaction. DESIGN: Consecutive patients who needed infertility diagnostic laparoscopy and agreed to combination with IVF were compared with concurrent patients undergoing transvaginal US IVF. Male factor screening parameters (semen analysis, sperm penetrating assay) and resultant fertilization were analyzed for these patients. SETTING: The George Washington University Hospital, a tertiary referral center offering assisted reproductive technologies. Patients for diagnostic laparoscopy combined with IVF were enrolled in the Program of Oocyte Retrieval at Diagnostic Laparoscopy (PORDL). PARTICIPANTS: One hundred twenty-four women enrolled for diagnostic laparoscopy combined with IVF; 237 women were concurrently enrolled for transvaginal US IVF. RESULTS: Response variables (number of follicles, days of monitoring, ampules of hMG, maximum E2) between the two groups were similar. Outcome variables (ova retrieved, ova fertilized, ova cleaved, clinical pregnancy rate per embryo transferred) were similar despite a significantly higher number of embryos transferred for the transvaginal US group. The clinical pregnancy rate per cycle was similar, 26% versus 28% for the women in the transvaginal US versus those women in the PORDL group, as was the clinical pregnancy rate per ET, 31% versus 34%, respectively. The number of fertilized ova for each group was not significantly different: 5.5 +/- 0.3 for the transvaginal group versus 4.8 +/- 0.4 for the PORDL group. Patients in the PORDL group with a known male factor (group B) had a lower fertilization rate than those with no male factor (group A). Within the group A with no detectable male factor prospectively, 17.2% had unexpectedly poor fertilization (group A1), whereas the rest of the group A patients had higher fertilization rates as was expected (group A2). The clinical pregnancy rate per ET for group A1 was 0% compared with 43.4% for the group A2 patients. CONCLUSIONS: In vitro fertilization can be successfully performed during diagnostic laparoscopy yielding comparable results to transvaginal ultrasound IVF while gaining diagnostic information concerning sperm-ova interaction (i.e., fertilization).

Adult↗
PubMed1994

The Chlamydomonas FLA10 gene encodes a novel kinesin-homologous protein.

Many genes on the uni linkage group of Chlamydomonas affect the basal body/flagellar apparatus. Among these are five FLA genes, whose mutations cause temperature-sensitive defects in flagellar assembly. We present the molecular analysis of a gene which maps to fla10 and functionally rescues the fla10 phenotype. Nucleotide sequencing revealed that the gene encodes a kinesin-homologous protein, KHP1. The 87-kD predicted KHP1 protein, like kinesin heavy chain, has an amino-terminal motor domain, a central alpha-helical stalk, and a basic, globular carboxy-terminal tail. Comparison to other kinesin superfamily members indicated striking similarity (64% identity in motor domains) to a mouse gene, KIF3, expressed primarily in cerebellum. In synchronized cultures, the KHP1 mRNA accumulated after cell division, as did flagellar dynein mRNAs. KHP1 mRNA levels also increased following deflagellation. Polyclonal antibodies detected KHP1 protein in Western blots of purified flagella and axonemes. The protein was partially released from axonemes with ATP treatment, but not with AMP-PNP. Western blot analysis of axonemes from various motility mutants suggested that KHP1 is not a component of radial spokes, dynein arms, or the central pair complex. The quantity of KHP1 protein in axonemes of the mutant fla10-1 was markedly reduced, although no reduction was observed in two other uni linkage group mutants, fla9 and fla11. Furthermore, fla10-1 was rescued by transformation with KHP1 genomic DNA. These results indicate that KHP1 is the gene product of FLA10 and suggest a novel role for this kinesin-related protein in flagellar assembly and maintenance.

Algal Proteins↗
PubMed1994

Nonsurgical closure of esophago-respiratory fistulas: role for the somatostatin analogue octreotide acetate?

Esophago-respiratory fistulas (ERF) do not close spontaneously and are uniformly fatal. A somatostatin analogue (octreotide acetate) was used in three consecutive patients to promote the closure of ERF. In 2 patients with esophageal cancer, treatment with octreotide acetate was associated with fistula closure in 30 and 46 days, respectively. In a third patient with virally-induced ERF, treatment was associated with improvement of the inflammation of the fistula before the patient's death from pulmonary aspiration after 40 days of treatment. These preliminary observations suggest that octreotide acetate treatment of ERF should receive further investigative scrutiny.

Aged↗
PubMed1994

Exercise training does not compensate for age-related decrease in myocardial GLUT-4 content.

We assessed the effects of age and endurance exercise training (treadmill running at 75% maximal running capacity, 1 h/day, 5 days/wk for 10 wk) on the total concentration of insulin-regulatable glucose transporters (GLUT-4) and GLUT-4 mRNA levels in the myocardium of male Fischer 344 rats aged 7, 15, and 25 mo. Myocardial GLUT-4 concentration was quantified with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting and detected with a polyclonal antibody to the GLUT-4 transporter. Myocardial GLUT-4 mRNA levels were quantified with slot-blot analysis and a cDNA probe for GLUT-4. Myocardial GLUT-4 concentration in the 25-mo group decreased 27 and 20% compared with the 7- and 15-mo group, respectively (P < 0.0001 and P < 0.003). GLUT-4 mRNA also decreased significantly in the 25-mo group compared with the 7-mo group (20% in the trained and 11% in the untrained group, P < 0.05). Endurance training did not significantly affect myocardial GLUT-4 concentrations in any age group despite a significant increase in GLUT-4 mRNA in the 7- and 25-mo trained groups. In conclusion, myocardial GLUT-4 protein levels in the rat are significantly decreased with age but are unaffected by 10 wk of treadmill running.

Aging↗
PubMed1993

Biosynthesis and degradation of meprins, kidney brush border proteinases.

Meprins, which are cell surface metalloendopeptidases, consist of two types of subunits, alpha and beta. Genetic factors determine which subunits and oligomeric forms of the enzyme exist in kidney in different strains of mice. In order to further explore factors that determine the concentration and activity of meprins, the rates of biosynthesis and degradation of the meprin subunits were determined in an organ culture system using ICR and C3H/He mouse kidneys. In biosynthesis experiments, the rate of incorporation of radiolabeled amino acids into immunoprecipitable forms of the alpha and beta subunits was determined. The rate of loss of radiolabel from the subunits was measured in pulse-chase experiments to determine the half-lives of the subunits. The rate of synthesis of the alpha subunit was twofold greater than that of the beta subunit: 861 +/- 32 vs 361 +/- 23 dpm/micrograms subunit protein/min for alpha vs beta. The rate of synthesis for total kidney protein in both strains was approximately 700 dpm/micrograms/min. The half-life for alpha was 8.9 +/- 0.24 h compared to 12.1 +/- 0.7 h for beta; the half-life for total protein in kidney was approximately 35 h. Thus, the half-lives of alpha and beta were similar and shorter than the half-lives of the average protein in kidney cells. The higher rate of synthesis of alpha is probably responsible for the greater abundance of this protein compared to beta in microvillus membranes.

Animals↗
PubMed1993

Genetic linkage analysis of chromosome 19 markers in malignant hyperthermia.

Previous studies have reported that malignant hyperthermia susceptibility is caused in some families by inherited variation in a gene located on the short arm of chromosome 19 near to, or identical with, the ryanodine receptor gene (RYR1); this is expressed in skeletal muscle as a calcium release channel of the sarcoplasm reticulum. In other families, a gene in this location is excluded, but the locations of the genes involved have not yet been defined. We have analysed DNA samples from members of three large British families in whom in vitro muscle contracture tests for malignant hyperthermia susceptibility have been carried out in accordance with the procedure recommended by the European Malignant Hyperthermia Group. The results presented here strongly suggest that the gene for malignant hyperthermia susceptibility in one or more of these three British families is located in the same region of chromosome 19q, although further work is required to decide whether or not the RYR1 gene itself is causative in these families. As genetic heterogeneity could not be excluded, we cannot yet recommend the use of DNA markers to replace in vitro contracture tests in the diagnosis of malignant hyperthermia susceptibility.

Chromosome Mapping↗