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Biomedical subjects

J B Graham

Publications and source records attributed to J B Graham.

At least 55 records · Page 3Linked to original sources
PubMed1989

O2 tension, swimming-velocity, and thermal effects on the metabolic rate of the Pacific albacore Thunnus alalunga.

The oxygen consumption rates (VO2) of 9 albacore tuna, Thunnus alalunga (8.5-12 kg) were measured at sea in a swimming respirometer to determine the effects of relative swimming velocity, ambient O2 tension, and water temperature. Significant positive relationships were obtained between tail-beat frequency and relative speed and between relative speed and VO2. The albacore metabolic rate was not appreciably affected by exposure to water temperatures ranging from 13.5 degrees to 16.9 degrees C. Brief exposure to hyperoxia (200-400 mmHg), which was done to reduce the initial stress upon fish in the respirometer, did not affect VO2. Hypoxia (50-99 mmHg), however, did tend to reduce VO2 and affect swimming velocity.

Animals↗
PubMed1988

Prostatic aspiration biopsy: an assessment of accuracy based on long-term observations.

We present the results of transrectal thin needle aspiration biopsy of the prostate in 133 patients. Test specificity was 94 per cent and sensitivity also appeared to be high initially. However, with repeated rectal examinations and biopsies during an 11-year period a number of additional false negatives became apparent, which resulted in an apparent test sensitivity of 82 per cent, lower than most previously published reports. Our data suggest that aspiration biopsy has specificity and sensitivity similar to core biopsy, it is important to re-test patients who have a palpable abnormality and an initially benign biopsy, and aspiration biopsy simplicity allows for a low threshold of suspicion of subtle abnormalities and for repeating biopsies after negative findings.

Biopsy, Needle↗
PubMed1988

The Malmö polymorphism of coagulation factor IX, an immunologic polymorphism due to dimorphism of residue 148 that is in linkage disequilibrium with two other F.IX polymorphisms.

A mouse monoclonal antibody (MAB 9.9) to coagulation factor IX (F.IX) detects a polymorphism in the plasma of normal people. Its epitope has been narrowed down to less than 6 amino acids in the activation peptide of the X-linked F.IX protein. The activation peptide contains a dimorphism--Thr:Ala--at position 148 of the protein. Using synthetic oligonucleotides, we have demonstrated that (1) the F.IX which reacts with 9.9 has Thr at position 148 and (2) that which does not has Ala. Positive reactors (148thr) are designated Malmö A, and negative reactors (148ala) are designated Malmö B. The plasma levels of AA women are indistinguishable from those of A men, and both B men and BB women are null against MAB 9.9. The plasma level of Malmö A in AB women is approximately half that of AA women, and "lyonization" is clearly operating in the heterozygotes. The dimorphism is in strong linkage disequilibrium with two other intragenic RFLPs, TaqI and XmnI. Furthermore, intragenic crossing-over--including double crossing-over--appears to have occurred between the three sites. Seven of the eight possible haplotypes have been identified, five in men and two others in women. The immunoassay that identifies approximately 50% of the AB women in the pool of Malmö A females with 95% confidence identifies men unambiguously as A or B. The assay would be very useful for population-genetic studies of the Malmö epitope if the studies were limited to men.

Antibodies, Monoclonal↗
PubMed1987

Population genetics of coagulant factor IX: frequencies of two DNA polymorphisms in five ethnic groups.

Two frequently used restriction-enzyme polymorphisms (RFLPs) of coagulant F.IX, TaqI and XmnI, have been examined in five ethnic groups: white Americans, black Americans, East Indians, Chinese, and Malays. There is a distinct "cline" in the frequencies of both polymorphisms, from white Americans to Malays. The rarer type 2 alleles of both polymorphisms, in which middle recognition sites are present--and which in our sample reach their highest frequencies in white Americans--are marginally higher in four groups of Europeans previously reported by others. The frequencies of the rarer alleles are significantly higher in Europeans than in black Americans and East Indians, and these alleles are essentially absent in Chinese and Malays. The frequency of heterozygosity diminishes in the same order, being zero in Malays for both polymorphisms. The polymorphisms are in strong linkage disequilibrium, and in all groups the type 1 allele for TaqI is disproportionately accompanied by the type 1 allele for XmnI. The paucity of type 2 alleles and the low rate of heterozygosity in four non-European groups suggest that the polymorphisms will be of little diagnostic value south of Gibraltar and east of Suez. This prediction is confirmed by the observed haplotype frequencies in the black American and the Oriental groups.

Alleles↗
PubMed1987

Pericardial and vascular pressures and blood flow in the albacore tuna, Thunnus alalunga.

Pericardial, ventricular, and dorsal aortic pressures, and blood flow were measured in tabled, anesthetized albacore tuna, Thunnus alalunga (7.8-10.7 kg) captured at sea off Monterey, California (USA) during August 1985. Mean pericardial pressure was -10.0/-2.6 cm H2O (Systolic/Diastolic, [S/D]) and mean pericardial pulse pressure was 7.5. Heart rate averaged 87 beats per minute. Mean ventricular pressure was 97.0/12.9 cm H2O [S/D] and mean dorsal aortic pressure was 64. High ventricular and dorsal aortic pressures of albacore reflect the perfusion requirement of its metabolically active tissues and compensate for the energy losses resulting from blood flow through the gills to arterial heat exchanger to capillaries and again back to the venous heat exchanger. As in elasmobranchs, the remarkably high pericardial pulse pressure, large pericardial volume, and negative pericardial pressure in the albacore suggest that its pericardium is more rigid than that of most teleosts and thus facilitates cardiac filling. Published cardiac output values for most non-tunas, when corrected for body size differences, are less than the mean weight specific cardiac output of albacore (29.4 ml/kg per min, range 12.9-51.9).

Animals↗
PubMed1986

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype.

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non-O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.

ABO Blood-Group System↗
PubMed1986

Carrier detection in hemophilia A: a cooperative international study. II. The efficacy of a universal discriminant.

Factor VIII (F.VIII) and von Willebrand factor (VWF):Ag data collected by eight laboratories on a total of 336 obligatory carriers of hemophilia A and 137 normal women were used to answer several questions concerning the construction of linear discriminants for carrier detection. It was found: that a "universal" linear discriminant can be constructed which is suitable for use in all laboratories and is nearly as effective as laboratory-specific discriminants; that inclusion of age and ABO blood type data improved the efficacy of these discriminants; that substitution of alternative assays for F.VIII and VWF:Ag did not generally improve the efficacy of the discriminants over that obtained using the bioassay for F.VIII:C and Laurell's immunoassay for VWF:Ag; that linear discriminants were far more effective than discriminants based on the F.VIII:C/VWF:Ag ratio. A step-wise procedure is given which any laboratory may follow in using the universal discriminant for carrier detection.

ABO Blood-Group System↗
PubMed1985

Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX.

We have independently isolated and characterized cDNA and genomic clones for the human coagulation factor IX. Sequence analysis in both cases indicates that threonine is encoded by the triplet ACT as the third residue of the activation peptide. This is in agreement with some earlier reports but in disagreement with others that show the alanine triplet GCT at this position. The discrepancy can thus be accounted for by natural variation of a single nucleotide in the normal population. Amino acid sequence analyses of activated factor IX from plasma samples of four individuals yielded two cases of alanine and two cases of threonine at the third position of the activation peptide. In factor IX from pooled plasma and in factor IX from a heterozygous individual, however, both alanine and threonine were found. Taken together, the findings show that a prevalent nondeleterious dimorphism exists in the activation peptide of human coagulation factor IX.

Alleles↗
PubMed1985

Function of the pericardium and pericardioperitoneal canal in elasmobranch fishes.

Previous studies of cardiac function in elasmobranch fishes have not included the influence of the pericardioperitoneal canal on pericardial pressure and volume and thus on cardiac function. Accordingly, we studied the function of the pericardium and pericardioperitoneal canal in sharks and rays. We found negative pericardial pressure that rose to a plateau of approximately 0 mmHg when fluid was infused into the pericardium with the canal undisturbed. However, this pericardial pressure elevation caused severe cardiac tamponade. After the canal was occluded, the pressure plateau was substituted with an exponential rise. We injected radioisotopes into the pericardial cavity and obtained scintigrams several hours later. The scans and counts of body fluids and tissues indicated absorption, disputing the suggestion that the primary function of the canal may be inadequate absorption of pericardial fluid. We conclude that the pericardioperitoneal canal maintains negative pericardial pressure, which is a prerequisite in elasmobranch fishes and may serve to regulate pericardial pressure level to optimize cardiac function in relation to changes in cardiac size.

Absorption↗
PubMed1985

PGM1 null allele detected in a Caucasian mother-son pair.

The presence of a PGM1 null allele in a mother and her son was deduced from their inconsistent phenotypes. Quantitation studies were done to confirm the half-normal enzyme activity. Phenotype analysis of 29 additional genetic markers gave no indication of non-parentage, making non-maternity a very unlikely explanation for the discrepancy.

Alleles↗
PubMed1985

Application of molecular genetics to prenatal diagnosis and carrier detection in the hemophilias: some limitations.

Prenatal diagnosis and carrier detection in the hemophilias have received much attention in recent years. The error rate in prenatal diagnosis by fetoscopy is less than 1%; fetoscopy is not possible, however, until the second trimester of pregnancy. Carrier detection based on bioassays of plasma has an irreducible error rate (approximately 5%?), because of the "lyonization" phenomenon in heterozygous women, and the final results are always probabilistic. New DNA methods promise to alleviate these difficulties. Prenatal diagnosis can be accomplished in the first trimester. "Lyonization" is bypassed in carrier detection, and the results may sometimes be essentially nonprobabilistic. But the DNA methods have certain limitations of their own which are not widely appreciated. Aside from cost and the necessity to adopt a new technology, there are inherent genetic problems: mothers must be heterozygous for both a disease gene and a marker gene, final results are probabilistic if the marker gene lies outside the disease gene, and multiple marker genes are often in linkage disequilibrium. We have concluded that a clinical unit planning to use the DNA methods must also maintain the conventional methods at a high level of performance.

Crossing Over, Genetic↗
PubMed1985

Factor VIII and factor IX in a twin population. Evidence for a major effect of ABO locus on factor VIII level.

In order to establish the relative importance of genetic factors on the variation in plasma concentration of coagulation factors VIII and IX, these parameters were determined in 74 monozygotic and 84 like-sexed dizygotic twin pairs. The twins belonged to two age groups: 33-39 years and 57-62 years. Factor VIII was determined as factor VIII coagulant antigen (VIIICAg) and as factor VIII-related antigen (VIIIRAg). Factor IX was determined as factor IX antigen (IXAg). A higher value for each coagulation factor was found in the older-age group compared to the younger group, whereas no difference was found between the sexes. A significant correlation was found between values for VIIIRAg and VIIICAg (r = .56). For VIIICAg, it could be demonstrated that the age effect was secondary to the age effect on VIIIRAg. The concentration of VIIICAg and VIIIRAg varied among ABO blood types, being lowest in type O individuals, higher in A2 individuals, and highest in A1 and B individuals. The effect of the ABO locus on VIIICAg was secondary to an effect on VIIIRAg. Analysis of variance revealed a significant genetic influence on the variance of VIIICAg and VIIIRAg with a heritability estimate of .57 for VIIICAg and .66 for VIIIRAg. This is in agreement with a previous hypothesis of an effect of several autosomal genes on factor VIII concentration. Thirty percent of the genetic variance of VIIIRAg was due to the effect of ABO blood type. The ABO locus is therefore a major locus for the determination of factor VIII concentration. No significant genetic effect on the variation in plasma concentration of IXAg could be detected.

ABO Blood-Group System↗
PubMed1984

Coagulation factor XIII: a useful polymorphic genetic marker.

The plasmas of two groups of subjects were examined for blood coagulation Factor XIII-A (FXIII-A, F13A) by electrophoresis in agarose using a Tris-EDTA-borate buffer to separate the common variants, F13A*1, F13A*2, and F13A*3. Dimeric subunits were visualized in UV light as monodansyl cadaverine bound to casein at the position of the transglutaminase activity representing F13A. One test group consisted of 307 members of three large Caucasian families. The other consisted of 148 consecutive patients whose plasmas had been sent to the clinical laboratory for determination of prothrombin time. Segregation analysis and father-to-son transmission confirmed that F13A is inherited as an autosomal co-dominant trait. The allelic frequencies in the random sample were F13A*1 = 0.82 and F13A*2 = 0.18. This sample included both blacks and whites, and the gene frequencies were not significantly different in the two races. The gene frequencies among the unrelated spouses of the three white families were A*1 = 0.75, A*2 = 0.24, A*3 = 0.01. Genetic equilibrium was present in both groups. The degree of polymorphism, the availability of blood, the ease of assessment, the absence of selective pressure, and the uniformity of gene frequencies in two major American ethnic groups make F13A a very useful marker for linkage studies and paternity testing. F13A has been provisionally assigned to chromosome 6. Linkage analysis of our family data did not provide evidence of linkage to two chromosome 6 markers, properdin factor B (BF) and glyoxalase 1 (GLO). The highest lod score (Z) was between F13A and the Kidd (Jk) blood group (theta = 0.68 at = 0.24).

Alleles↗