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Biomedical subjects

J Griffith

Publications and source records attributed to J Griffith.

At least 127 records · Page 7Linked to original sources
PubMed1992

Visualization of diagnostic heteroduplex DNAs from cystic fibrosis deletion heterozygotes provides an estimate of the kinking of DNA by bulged bases.

Previous studies (Hsieh, C.-H., and Griffith, J. D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4833-4837) of DNAs containing extra or bulged bases on one of the two strands of a duplex showed that they exhibit slower electrophoretic mobility than non-bulged DNAs, indicating that bulges create stiff kinks in the DNA. Here we paired a 97-base single-stranded DNA from the intact cystic fibrosis (CF) gene with a complementary 94-base strand containing a central 3-base deletion (delta F508), common to many CF patients. This produced a 94-base pair DNA with a central 3-base bulge. Visualization of these DNAs by electron microscopy showed that twice as many bulge-containing DNAs had a central kink as compared with the non-bulged controls. Examination of the distribution of kinking angles showed that the bulged population contained 5-7-fold more molecules with a central kink of 80 +/- 10 degrees than did the control molecules. When the 3-base bulge was replaced by a 3-base gap, the resulting duplex DNA showed central kinks with a somewhat lower frequency but greater range of kinking angles.

Base Sequence↗
PubMed1992

Early gastric cancer: 46 cases treated in one surgical department.

Forty six consecutive patients with early gastric cancer were treated between 1970 and 1990. The proportion of cases of early gastric cancer increased significantly (p < 0.01) from 1% of all cases in the first five year period to 15% in the last five year period, because of greater awareness of the condition and more widespread use of endoscopy. There were 33 men and 13 women, of median age 69 years (range 38-86). Most patients (91%) presented with symptoms indistinguishable from those of peptic ulceration. The median duration of symptoms was four months (range 0.1-36 months). All 46 patients were treated surgically. Three patients (6.5%) died after operation and a further 10 (22%) suffered postoperative complications. None of the surviving patients has been lost to follow up and 25 have been followed up for a minimum period of five years. Five year survival by life table analysis was 98%. These findings suggest that in Britain in the 1990s, as in Japan, it may be possible to diagnose an increasing proportion of patients with gastric cancer at a relatively early pathological stage, when most patients can be cured by radical surgical resection with lymphadenectomy.

Adult↗
PubMed1992

Anatomic and functional assessment of stenosis severity with intravascular ultrasound imaging in vitro.

An in vitro study was performed to evaluate the accuracy of intravascular ultrasound imaging compared with roentgenography for determining the cross-sectional area of a lumen; and to determine if the functional significance of an irregular stenosis is predicted more accurately by intravascular ultrasound than roentgenography. Varying degrees of stenosis were made in 17 rubber tubings by adjusting a plastic constrictor. The cross-sectional areas at the normal and the stenotic segments were determined by intravascular ultrasound, roentgenography, and then measured directly from an acrylamide gel cast of the lumen. To evaluate the functional significance of a stenosis, the pressure drop across the stenosis was measured using a fluid pumping circuit. The actual pressure drop was then compared with the predicted pressure drop derived from hydrodynamic equations using cross-sectional areas obtained by intravascular ultrasound or roentgenography. There was an excellent correlation between the cross-sectional areas at the tightest stenosis measured by intravascular ultrasound compared with the area from the acrylamide cast (7.2 +/- 2.6 v 6.6 +/- 2.4 mm 2, mean +/- SD, r = .93). Measurements of cross-sectional area from the roentgenograms (10.9 +/- 3.9 mm 2) also provided a relatively good correlation with those from the acrylamide casts (r = .84); however, the roentgenograms consistently overestimated the cross-sectional area of the stenosis. The mean values of the actual pressure drop and the predicted pressure drop by intravascular ultrasound and roentgenograms were 15.7 +/- 13.5, 11.3 +/- 11.9, and 4.3 +/- 4.5 mmHg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1992

Rapid regression of enterochromaffinlike cell gastric carcinoids in pernicious anemia after antrectomy.

In rats, hypergastrinemia due to achlorhydria produced by antisecretory drugs or resection of the gastric fundus leads to enterochromaffinlike (ECL) cell hyperplasia and gastric carcinoids. In humans, achlorhydria due to pernicious anemia may also lead to ECL cell hyperplasia and multicentric gastric carcinoids in as many as 5% of cases. To examine the apparent gastrin dependence of gastric ECL carcinoids, three patients were studied (2 men aged 59 and 73 years; 1 woman aged 45 years) who had pernicious anemia, serum gastrin concentrations of greater than 1000 ng/L (greater than 1000 pg/mL), and multicentric gastric carcinoids. Antrectomy resulted in normalization of serum gastrin levels within 8 hours and disappearance of carcinoids in 6-16 weeks. In each of the three patients, a focus of microcarcinoid was found at 12-18 months. Further follow-up in each of the three patients 21-30 months after antrectomy again showed no carcinoids or ECL cell hyperplasia. It is concluded that multicentric ECL gastric carcinoids in patients with pernicious anemia and achlorhydria appear to be gastrin dependent and disappear after normalization of serum gastrin by antrectomy. Antrectomy rather than total gastrectomy may be the most appropriate treatment for this condition.

Aged↗
PubMed1992

Gallium-67 scintiscan in the diagnosis of primary splenic non-Hodgkin's lymphoma after the treatment of Hodgkin's disease.

A rare primary non-Hodgkin's lymphoma (diffuse large cell) of the spleen developed in a 72-yr-old man who had successful radiotherapy to the right inguinal region for Hodgkin's disease 23 yr ago. Radiologic findings, particularly the 67Ga scintigraphy finding, were very useful in leading to the correct diagnosis of malignant splenic lymphoma, in this case, preoperatively.

Aged↗
PubMed1991

Chromosome-specific recombinant DNA libraries from the fungus Aspergillus nidulans.

Development of physical genomic maps is facilitated by identification of overlapping recombinant DNA clones containing long chromosomal DNA inserts. To simplify the analysis required to determine which clones in a genomic library overlap one another, we partitioned Aspergillus nidulans cosmid libraries into chromosome-specific subcollections. The eight A. nidulans chromosomes were resolved by pulsed field gel electrophoresis and hybridized to filter replicas of cosmid libraries. The subcollections obtained appeared to be representative of the chromosomes based on the correspondence between subcollection size and chromosome length. A sufficient number of clones was obtained in each chromosome-specific subcollection to predict the overlap and assembly of individual clones into a limited number of contiguous regions. This approach should be applicable to many organisms whose genomes can be resolved by pulsed field gel electrophoresis.

Aspergillus nidulans↗
PubMed1991

NaeI endonuclease binding to pBR322 DNA induces looping.

Previous work has demonstrated the existence of both resistant and cleavable NaeI sites. Cleavable sites introduced on exogenous DNA can act in trans to increase the catalysis of NaeI endonuclease cleavage at resistant sites without affecting the apparent binding affinity of the enzyme for the resistant site [Conrad, M., & Topal, M. D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9707-9711]. This activation suggests allosteric regulation of NaeI cleavage by distant cis- and trans-acting sites in DNAs containing both resistant and cleavable sites. Plasmid pBR322 contains four NaeI sites, at least one of which is resistant to cleavage. Electron microscopy is used here to demonstrate that NaeI endonuclease simultaneously binds to multiple recognition sites in pBR322 DNA to form loops with NaeI protein bound at the loop's base. The maximum number of loops formed with a common base suggests four binding sites per enzyme molecule. Looping was inhibited by addition of enzyme-saturating amounts of double-stranded oligonucleotide containing an NaeI site, whereas another double-strand oligonucleotide without the NaeI site had no effect. The number of loops seen was not above background when double-stranded M13 DNA, which contains only a single NaeI recognition site, was used as substrate.

DNA Restriction Enzymes↗
PubMed1991

Effects of bulge composition and flanking sequence on the kinking of DNA by bulged bases.

We recently showed that bulged bases kink duplex DNA, with the degree of kinking increasing in roughly equal increments as the number of bases in the bulge increases from one to four [Hsieh, C.-H., & Griffith, J.D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4833-4837]. Here we have examined the kinking of DNA by single A, C, G, or T bulges with different neighboring base pairs. Synthetic 30 base pair (bp) duplex DNAs containing 2 single-base bulges spaced by 10 bp were ligated head to tail, and their electrophoretic behavior in highly cross-linked gels was examined. All bulge-containing DNAs showed marked electrophoretic retardations as compared to non-bulge-containing DNA. Regardless of the sequence of the flanking base pairs, purine bulges produced greater retardations than pyrimidine bulges. Furthermore, C and T bulges produced the same retardations as did G and A bulges. Bulged DNA containing different flanking base pairs showed marked differences in electrophoretic mobility. For C-bulged DNA, the greatest retardations were observed with G.C neighbors, the least with T.A neighbors, and an intermediate amount with a mixture of neighboring base pairs. For A-bulged DNA, the retardations were greatest with G.C neighbors, less with T.A neighbors, even less with a mixture of neighboring base pairs, and finally least with C.G neighbors. Thus flanking base pairs affect C-bulged DNA and A-bulged DNA differently, and G.C and C.G flanking base pairs were seen to have very different effects. These results imply an important role of base stacking in determining how neighboring base pairs influence the kinking of DNA by a single-base bulge.

Base Sequence↗
PubMed1991

Phosphine-mediated Heinz body formation and hemoglobin oxidation in human erythrocytes.

In this work the in vitro reactions of phosphine with intact red blood cells and membrane-free hemoglobin extracts are reported. We demonstrate that phosphine or phosphine derivatives induce dense aggregates of denatured hemoglobin known as 'Heinz bodies' in intact red blood cells. The reaction products include irreversible hemichrome formation. We further demonstrate an oxygen requirement for these effects. PH3 appears to act as a novel type of O2 radical chain initiator or propagator with heme proteins.

Erythrocytes↗
PubMed1991

Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens.

BACKGROUND: Intravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas. METHODS AND RESULTS: A 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec. The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media. The presence of dissection between the media and the atheroma was well visualized. These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations. The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques. Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo. Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2. The mean residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area. At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2 mm2, which was a mean of 35 +/- 23% of the available area bounded by the media. CONCLUSIONS: Intravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification. Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty.

Angiography↗
PubMed1990

Three-stranded paranemic joints: architecture, topological constraints and movement.

The RecA and SSB proteins will catalyze the joining of two DNA molecules containing homologous sequences but lacking homologous ends in a reaction termed paranemic joining. The absence of homologous ends can be achieved by (1) pairing two circular DNAs or (2) using linear DNA(s) with ends lacking homology to the pairing partner. Here we have used electron microscopy (EM) to examine such pairings. Circular M13 single-stranded (ss) DNA enveloped by RecA protein into a presynaptic filament was paired with linear M13mp7 double-stranded (ds) DNA containing non-M13 sequences at its ends. Joint complexes were frequently seen in which the dsDNA was joined with the presynaptic filament over several kilobase (10(3) bases) lengths of the dsDNA. In this region, the presynaptic filament appeared disorganized as contrasted to the customary helical structure of the filament containing only a single strand of DNA. The same ultrastructure, but with greater detail, was observed when the samples were prepared for EM without fixation using a new method of fast-freezing and freeze-drying. EM immunogold staining demonstrated the presence of SSB protein in the disorganized region containing all three strands, but not in the regular helically arranged region. Psoralen photo-crosslinking of the DNA in the joint complexes revealed that the three DNA strands were in close proximity only over a single short (200 to 300 base-pairs) region. The joining of nicked circular M13 dsDNA and presynaptic filaments containing circular M13 ssDNA resulted in the intertwining of the dsDNA about the circular presynaptic filament. The joints produced in this case were short, as was the single region of psoralen photo-crosslinking of the three DNA strands. A model of how these long three-stranded joints form is presented involving the movement of a short "true" paranemic joint along the presynaptic filament.

Bacteriophages↗
PubMed1990

Preparation for human study of pesticide applicators: sister chromatid exchanges and chromosome aberrations in cultured human lymphocytes exposed to selected fumigants.

In preparation for a human study of worker exposure to grain fumigants and pesticides, we decided to screen commonly used fumigants for genotoxic effects in vitro. This research strategy was employed to test the possibility that structurally simple chemicals might have similar genotoxic properties in vivo and in vitro. As a first step, we designed our in vitro protocol to mimic to the extent possible, a single in vivo exposure of lymphocytes to fumigants. Go lymphocytes were treated with different doses of carbon tetrachloride, carbon disulfide, methyl bromide, chloropicrin, and melathion with and without addition of rat liver homogenate for 1/2 hour, washed free of toxicant, and stimulated with PHA. After culture, the prepared slides were studied for chromosome aberrations and SCEs. Malathion, methyl bromide, and chloropicrin significantly induced SCEs without S-9. Carbon disulfide alone required S-9 for significant SCE induction. Chromosome aberrations were significantly increased by malathion and methyl bromide. Carbon tetrachloride failed to induce SCEs or chromosome aberrations with or without S-9. We concluded from these preliminary studies and other comparable work that the fumigants studied here may be less likely to express genotoxicity in terms of SCEs or chromosome aberrations than ethylene oxide or phosphine given a single short-term in vivo exposure. The final design of our human study was altered to focus on seasonal worker exposure rather than on a single exposure event.

Adult↗
PubMed1990

Assessment of normal and atherosclerotic arterial wall thickness with an intravascular ultrasound imaging catheter.

A prototype intravascular ultrasound imaging catheter with a 20 MHz transducer was used to obtain 59 cross-sectional images in 14 segments of human atherosclerotic arteries. Three distinct components of the arterial wall were visualized on the ultrasound images: a highly reflective intima, an echolucent media, and a moderately reflective adventitia. Images were obtained at 1 mm increments in vitro and were compared with histologic sections at the same levels. Measurements of the arterial layers showed a close correlation between ultrasound images and histologic sections for the thickness of the intimal plaque (r = 0.91), the media (r = 0.83), and the total wall thickness (r = 0.85). The ultrasound images overestimated the mean intimal and total wall thickness by 0.3 mm and 0.7 mm compared to measurements in histologic sections (p less than 0.001). Intravascular imaging with high-frequency ultrasound is an accurate method for measuring microanatomic arterial dimensions and the extent of atheromatous involvement of the arterial wall. This method could represent an important adjunct to traditional angiographic techniques for assessing the severity of atherosclerosis.

Arteries↗