Rapid emergence of life shown by discovery of 3,700-million-year-old microbial structures.

Biological activity is a major factor in Earth's chemical cycles, including facilitating CO2 sequestration and providing climate feedbacks. Thus a key question in Earth's evolution is when did life arise and impact hydrosphere-atmosphere-lithosphere chemical cycles? Until now, evidence for the oldest life on Earth focused on debated stable isotopic signatures of 3,800-3,700 million year (Myr)-old metamorphosed sedimentary rocks and minerals from the Isua supracrustal belt (ISB), southwest Greenland. Here we report evidence for ancient life from a newly exposed outcrop of 3,700-Myr-old metacarbonate rocks in the ISB that contain 1-4-cm-high stromatolites-macroscopically layered structures produced by microbial communities. The ISB stromatolites grew in a shallow marine environment, as indicated by seawater-like rare-earth element plus yttrium trace element signatures of the metacarbonates, and by interlayered detrital sedimentary rocks with cross-lamination and storm-wave generated breccias. The ISB stromatolites predate by 220 Myr the previous most convincing and generally accepted multidisciplinary evidence for oldest life remains in the 3,480-Myr-old Dresser Formation of the Pilbara Craton, Australia. The presence of the ISB stromatolites demonstrates the establishment of shallow marine carbonate production with biotic CO2 sequestration by 3,700 million years ago (Ma), near the start of Earth's sedimentary record. A sophistication of life by 3,700 Ma is in accord with genetic molecular clock studies placing life's origin in the Hadean eon (>4,000 Ma).

Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor.

Considerable evidence has associated the expression of matrix metalloproteinases (MMPs) with the degradation of cartilage and bone in chronic conditions such as arthritis. Direct evaluation of MMPs' role in vivo has awaited the development of MMP inhibitors with appropriate pharmacological properties. We have identified butanediamide, N4-hydroxy-2-(2-methylpropyl)-N1-[2-[[2-(morpholinyl)ethyl]-,[S- (R*,S*)] (GI168) as a potent MMP inhibitor with sufficient solubility and stability to permit evaluation in an experimental model of chronic destructive arthritis (adjuvant-induced arthritis) in rats. In this model, pronounced acute and chronic synovial inflammation, distal tibia and metatarsal marrow hyperplasia associated with osteoclasia, severe bone and cartilage destruction, and ectopic new bone growth are well developed by 3 wk after adjuvant injection. Rats were injected with Freund's adjuvant on day 0. GI168 was was administered systemically from days 8 to 21 by osmotic minipumps implanted subcutaneously. GI168 at 6, 12, and 25 mg/kg per d reduced ankle swelling in a dose-related fashion. Radiological and histological ankle joint evaluation on day 22 revealed a profound dose related inhibition of bone and cartilage destruction in treated rats relative to rats receiving vehicle alone. A significant reduction in edema, pannus formation, periosteal new bone growth and the numbers of adherent marrow osteoclasts was also noted. However, no significant decrease in polymorphonuclear and mononuclear leukocyte infiltration of synovium and marrow hematopoietic cellularity was seen. This unique profile of antiarthritic activity indicates that GI168 is osteo- and chondro-protective, and it supports a direct role for MMP in cartilage and bone damage and pannus formation in adjuvant-induced arthritis.

Morphogenesis in dictyostelium: an orbital hypothesis.

Free-living amoebae of Dictyostelium discoideum aggregate when deprived food, guided by the intercellular transmission of signals of adenosine 3',5'-monophosphate. A succession of multicellular forms is then constructed, each with a circular cross section in every plane normal to its central axis. Amoebae are in constant circular and helical motion around the circumference of these structures. A theory is proposed wherein the sustained progagation of waves of cyclic adenosine 3',5'-monophosphate secretion in cellular loops determines their circumference and thereby organizes morphogenesis in this organism.

Increasing mammography utilization: a controlled study.

BACKGROUND: Despite the effectiveness of breast cancer screening for women older than 50 years of age, only about one third of these women in the United States receive annual mammography. PURPOSE: This study was designed to determine if a community-wide intervention could increase use of mammography screening for breast cancer. Secondary end points were determination of changes in women's knowledge and attitudes toward mammography and physicians' self-reported screening practices. METHODS: We conducted a controlled study from January 1987 through January 1990 in two eastern North Carolina communities--New Hanover County (the experimental community) and Pitt County (the control community). Before development and implementation of the intervention program in New Hanover County and after the program had been in operation for 1 year, 500 women of ages 50-74 years and all primary-care physicians in each community were interviewed by telephone. In these interviews, we determined the use of mammography for breast cancer screening and the knowledge and attitudes about it. We also established the number of screening mammograms performed in 1987 and 1989 in each county and reviewed medical records to determine the percentage of women the physicians had referred for mammograms. RESULTS: The percentage of women who reported receiving a mammogram in the previous year increased from 35% to 55% in the experimental community and from 30% to 40% in the control community (difference of differences, 10%; P = .03 after adjustment for race, education, age, and having a regular doctor; 95% confidence interval, 1%-18%). Increases were greater in New Hanover County regardless of age, race, income, and education. However, the increase was less for Black women than for White women, both overall and in most demographic subgroups. The total number of mammograms performed increased 89% in the experimental community and 45% in the control community. Women's knowledge about mammography changed little, but the intention to get a mammogram increased 30% in New Hanover County, compared with a 17% increase in Pitt County--a statistically significant difference (P < .01). Physician reports and medical record reviews in the two communities showed similar increases in the number of mammograms ordered. CONCLUSIONS: A community-wide effort to increase use of breast cancer screening was successful, but more work must be done to reach the National Cancer Institute's goal of annual mammograms for 80% of women of ages 50-74.

Earth's oldest mantle fabrics indicate Eoarchaean subduction.

The extension of subduction processes into the Eoarchaean era (4.0-3.6 Ga) is controversial. The oldest reported terrestrial olivine, from two dunite lenses within the ∼3,720 Ma Isua supracrustal belt in Greenland, record a shape-preferred orientation of olivine crystals defining a weak foliation and a well-defined lattice-preferred orientation (LPO). [001] parallel to the maximum finite elongation direction and (010) perpendicular to the foliation plane define a B-type LPO. In the modern Earth such fabrics are associated with deformation of mantle rocks in the hanging wall of subduction systems; an interpretation supported by experiments. Here we show that the presence of B-type fabrics in the studied Isua dunites is consistent with a mantle origin and a supra-subduction mantle wedge setting, the latter supported by compositional data from nearby mafic rocks. Our results provide independent microstructural data consistent with the operation of Eoarchaean subduction and indicate that microstructural analyses of ancient ultramafic rocks provide a valuable record of Archaean geodynamics.

Studies of enzyme polymorphism in the Kamuela population of Drosophila mercatorum. III. Effects of variation at the alpha GPD locus and subflight stress on the energy charge and glycolytic intermediate concentrations.

We have employed a "level crossing" strategy to study the primary effects of an enzyme polymorphism in Drosophila mercatorum. This strategy consists of following genetic differences across intervening phenotypes to possible fitness effects. In this paper, we report the steady state concentrations of the glycolytic intermediates and the adenylates (intervening phenotypes) in two genotypes (alpha GPD-F, alpha GPD-S) at two stress levels (rest, subflight). We did not detect a genotype or a genotype by stress interaction effect on glycolytic intermediate or adenylate concentrations despite the ability of the experimental design to detect a 20 to 50% difference from the mean of a control. The flux of glycolysis is adequate to maintain the energy charge in both strains under the stress levels considered. If there is a fitness difference between these alpha GPD variants, it is unlikely to be a result of modifications of glycolysis. Subflight stress, however, resulted in an increase in metabolic flux. The observed pattern of intermediate concentration differences is consistent with the modulation of glycolysis by the ratio of the ATP and AMP concentrations acting on phosphofructokinase activity.

Studies of Enzyme Polymorphisms in the Kamuela Population of D. MERCATORUM. I. Estimation of the Level of Polymorphism.

A Kamuela, Hawaii, population of Drosophila mercatorum was surveyed for enzyme variability. The mean heterozygosity and the proportion of polymorphic loci were estimated as 0.1255 and 0.37, respectively. Neither deviates more than one standard error from their respective means for 43 Drosophila species (Nevo 1978). Heterozygosity was distributed across enzyme categories in much the same manner as observed in other species (Gillespie and Kojima 1968; Johnson 1974), and enzymes associated with glycolysis were about as variable as other enzymes of central metabolism.--The levels of heterozygosity and polymorphism in this population do not seem to have been affected by a low-level capacity for parthenogenesis. The observed parthenogenetic reproduction is not strongly associated with particular allelic variants among viable parthenogenetic adults; however, the capacity to establish a self-sustaining parthenogenetic clone is strongly associated with the phenotype with the most frequent allele at every locus studied. We interpret these results to mean that isozyme variants do not strongly influence viability under total homozygosity (the genetic condition imposed by parthenogenesis), but they do have an impact upon the reproductive biology of parthenogenetic adults.

Impact of therapy for differentiated carcinoma of the thyroid: an analysis of 706 cases.

A retrospective analysis of clinical and pathological data was conducted on 706 patients (514 females and 192 males) treated for differentiated thyroid carcinoma at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston from 1951 to 1975 and followed to 1981. The histological diagnoses were mixed papillary/follicular carcinoma (66.7%), papillary carcinoma (14.6%), follicular carcinoma (15.3%), or Hurthle cell carcinoma (3.4%). Patients diagnosed before the age of 40 yr lived significantly longer than those diagnosed over the age of 40 yr, and females lived longer than males. According to survival analyses and disease-free intervals, the order of increasing aggressiveness of the tumors was papillary, mixed, follicular, and Hurthle cell. Total thyroidectomy was associated with longer disease-free intervals and fewer recurrences. The 136 patients who received ablative 131I after surgery had fewer recurrences than a matched group who did not, but the disease-free interval and survival rate showed no significant difference. Further classification showed that patients with follicular and mixed tumors, and those who underwent total thyroidectomy benefited from 131I. There were 78 deaths attributed to thyroid cancer in the whole group. Approximately two thirds occurred in the first 10 yr after diagnosis. In conclusion, total thyroidectomy is recommended, when feasible, for differentiated thyroid cancer, followed by ablative 131I therapy, at least for follicular and mixed varieties.

2-(Substituted phenyl)oxazolo[4,5-b]pyridines and 2-(substituted phenyl)oxazolo[5,4-b]pyridines as nonacidic antiinflammatory agents.

Some 2-(substituted phenyl)oxazolo[4,5-b]pyridines and 2-(substituted phenyl)oxazolo[5,4-b]pyridines have good antiinflammatory and analgesic activity. A few possess activity comparable to phenylbutazone or indomethacin without producing the irritation in the gastrointestinal tract that acidic antiinflammatory compounds cause.

Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.

In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.

Aggressive behavior in Huntington's disease: treatment with propranolol.

Episodic aggressive behavior that responded poorly to neuroleptics was reduced by a carefully titrated dose of propranolol in three patients with advanced Huntington's disease. The optimal doses were 180, 30, and 30 mg/day, respectively.

Comparative microangiographic studies of glycerol- and mercuric chloride-induced acute renal failure in rats.

Microcirculatory abnormalities may be important in the genesis and/or maintenance of acute renal failure. This work describes the functional, microangiographic, and histopathologic alterations in two experimental models of acute renal failure. Glycerol and mercuric chloride (HgCl2) administration to dehydrated rats produced acute renal failure characterized by a similar degree of renal dysfunction at 24 hours and almost complete functional recovery at one week. Both toxins were associated with early (1/2-1 hour) microangiographically determined perfusion alterations, but in the rats given glycerol, a return to near normal appearance was noted at 2 to 6 hours. Subsequent studies did show mild to moderate residual changes at one week. In contrast, HgCl2 treatment was associated with progressive microcirculatory abnormalities that correlated in part with residual histopathologic alterations. These studies emphasize the discrepancy between functional, circulatory, and pathologic abnormalities in experimental acute renal failure and may improve our understanding of this complex disorder.

Pulmonary microangiography. A comparison of in vitro versus in vivo perfusion techniques in dogs.

Because of a need to correlate pulmonary microvascular changes with physiologic data during lung injury, in vitro and in vivo pulmonary capillary microangiography was performed on normal dogs and those subjected to oleic acid injury and glass bead microembolization. During these studies, no significant differences were found between microangiograms obtained after in vitro and in vivo perfusion techniques. This work therefore suggests that in vitro microangiography yields reliable morphologic information more conveniently than more expensive and difficult in vivo techniques. In vitro pulmonary capillary microangiography can provide reliable structural information which can be correlated with physiologic data.

Microvascular changes in canine renal allograft rejection: a correlative microangiographic and histologic study.

The progressive microvascular changes occurring during unmodified renal allograft rejection were studied in 22 dogs utilizing post-mortem barium sulfate perfusion microangiography. Sixteen dogs (7 autografts, 8 ischemia controls and 1 hydronephrotic animal) made up a control group. The microradiographic findings were correlated with intravenous urography, coagulation profiles and histopathologic studies. Vascular obstruction and obliteration occur from the outer cortex inward and involve sequentially, capillaries, efferent arterioles, glomeruli, afferent arterioles and interlobular arteries. A-V communications develop late and are due to a loss in vascular integrity. Medullary vascular obliteration occurs subsequent to cortical changes. The microangiographic changes mirror the hstologically evident cellular infiltrate, vascular damage and eventual hemorrhagic necrosis. The appearance of fibrin split products in the plasma late in rejection and the dramatic vascular occlusive changes seen microangiographically suggest that localized intravascular coagulation occurs during rejection.

Needle localization biopsy of occult lesions of the breast. Experience in 199 cases.

From January 1980 through June 1986, 199 percutaneous needle localizations for clinically occult breast lesions were performed at North Carolina Memorial Hospital. A retrospective analysis of the medical records, mammograms, operative notes, and pathology reports was undertaken to evaluate the success of this procedure. In our series, biopsy was prompted by abnormal calcifications in 27.1% of lesions, occult masses in 37.2%, and by a combination of occult masses and microcalcification in 35.7%. Overall, we had a yield of positive biopsies for cancer of 16.3%, with the yield improving from 12.3% in the earlier years of our study, to 18.7% in the latter years. Of the cancer cases detected, 89.7% were stage I. The localization procedure was successful in 95.9% of the cases. Analysis of our eight failures, along with a review of the literature, shows the major reasons for failure to be incomplete removal of areas with multiple calcifications, dislodgement of the needle, and problems resulting from lack of communication between the radiologist and surgeon. We conclude that the failure rate is low, the yield good, and needle localization a worthwhile procedure for localizing nonpalpable occult lesions.

Post-ligation dilatation of the fallopian tube.

RATIONALE AND OBJECTIVES: Dilatation of fallopian tube remnants after ligation has been described but never systematically studied in post-ligation hysterosalpingograms (HSGs). This study describes the frequency and appearance of proximal tubal remnant dilatation as seen on HSGs in women with a history of bilateral tubal ligation (BTL). METHODS: A retrospective review of medical records and a subjective and objective evaluation of dilatation seen on HSGs included 68 consecutive women seen for pre-reanastomosis HSG. RESULTS: Among the 68 women, 44 (67%) had objectively measured dilatation on one or both tubes. Dilatation was present in both short and long tubal remnants. There were no measurable differences between women with and without presence of dilatation. Neither length nor dilatation of tubal remnant was associated with pregnancy outcome. CONCLUSIONS: Dilatation of the tubal remnant after bilateral tubal ligation is a common finding on HSG and can be accurately identified from the HSG by radiologists. Dilatation is not strictly related to length, and in our small sample with follow-up, was not associated with pregnancy outcome.

Lymphatic visualization during renal transplant rejection.

Intrarenal microlymphatic filling was observed during a microangiographic and histologic study of unmodified canine allograft rejection. The extent of lymphatic visualization was correlated with the pathophysiologic state of the allograft. An example of renal lymphatic visualization following arterial perfusion of a human specimen is also presented. During early rejection, as microvascular and histologic alteration became more severe, there was prominent visualization of lymphatics. However, in late rejection, as cortical necrosis developed, lymphatic filling was less evident. Lymphatic visualization following arterial perfusion during rejection depends on progressive loss of microvascular integrity, contrast extravasation and subsequent filling of lymphatics which are acting as an alternate route of drainage for the excess interstitial edema present due to immune injury.

Experimental renal papillary necrosis in rats: microangiographic and tubular micropuncture injection studies.

Proposed causes of renal papillary necrosis (RPN) include tubular toxicity due to hyperconcentration of toxins in the renal medulla and vasoconstriction of medullary vessels with ischemic necrosis. The authors studied these mechanisms in bromoethylamine hydrobromide-induced RPN in rats by microvascular and tubular micropuncture injection studies. During early stages of RPN, microvascular studies revealed reduced perfusion of vasa recta, and tubular injection studies showed unobstructed tubules and collecting ducts. In the late stage, medullary vascular obliteration and intratubular debris with tubular obstruction were seen. This evidence suggests that RPN in this model is initiated by vasoconstriction rather than direct tubular toxicity.

Pyelovenous and pyelolymphatic backflow during retrograde pyelography in renal vein thrombosis.

Pyelovenous and pyelolymphatic backflow have been observed during retrograde pyelography in three patients with renal vein thrombosis. The radiographic patterns of backflow following experimental unilateral renal vein occlusion in rabbits were analyzed and correlated with the clinical findings. Capsular, perihilar, periureteric, and retroperitoneal collateral vein networks and lymphatic channels were demonstrated on the venous occluded side. The appearance shown in the experimental study correlate well with the clinical observations.

The effects of diltiazem and captopril on glycerol-induced acute renal failure in the rat. Functional, pathologic, and microangiographic studies.

To evaluate the effects of pharmacologic vasodilatation on glycerol-induced acute renal failure, we studied untreated animals and those given Captopril and Diltiazem at periods ranging from 30 minutes to four weeks after the onset of acute renal failure. At each time frame, comparative coded assessments of renal function, histology, and microangiography were performed. Diltiazem, a calcium channel blocker, significantly reduced the severity of the renal failure, decreased the extent of tubular cell necrosis, and was associated with a more rapid histologic and functional recovery. Captopril, an angiotensin converting enzyme inhibitor, did not influence renal function or pathology throughout the four-week observation period. Microangiography revealed marked differences among the experimental groups. Most notably, there was better visualization of the microvasculature in Diltiazem-treated kidneys at one and two weeks. However, at four weeks, all groups showed similar, severe microangiographic abnormalities. Diltiazem offers significant protection against glycerol-induced acute renal failure in rats. Its mechanism of action in this context remains unknown. Renal function and pathology do not correlate well with microangiographic perfusion patterns in this model of acute renal failure.