Observations of Buried Lake Drainage on the Antarctic Ice Sheet.

Between 1992 and 2017, the Antarctic Ice Sheet (AIS) lost ice equivalent to 7.6 ± 3.9 mm of sea level rise. AIS mass loss is mitigated by ice shelves that provide a buttress by regulating ice flow from tributary glaciers. However, ice-shelf stability is threatened by meltwater ponding, which may initiate, or reactivate preexisting, fractures, currently poorly understood processes. Here, through ground penetrating radar (GPR) analysis over a buried lake in the grounding zone of an East Antarctic ice shelf, we present the first field observations of a lake drainage event in Antarctica via vertical fractures. Concurrent with the lake drainage event, we observe a decrease in surface elevation and an increase in Sentinel-1 backscatter. Finally, we suggest that fractures that are initiated or reactivated by lake drainage events in a grounding zone will propagate with ice flow onto the ice shelf itself, where they may have implications for its stability.

Oncogenes result in genomic alterations that activate a transcriptionally silent, dominantly selectable reporter gene (neo).

Although oncogenes and tumor suppressor genes have been implicated in carcinogenesis and tumor progression, their relationship to the development of genomic instability has not been elucidated. To examine this role, we transfected oncogenes (polyomavirus middle [Py] and large T [MT and LT]) and adenovirus serotype 5 E1A) into two NIH 3T3-derived cell lines, EN/NIH 2-4 and EN/NIH 2-20. Both cell lines contain two stable integrants of a variant of the retrovirus vector pZipNeoSV(x)1 that has been modified by deletion of the enhancer elements from the long terminal repeats. DNA rearrangements activating the silent neomycin phosphotransferase gene (neo) present in these integrants were identified by selection of cells in the antibiotic G418. Whereas control-transfected EN/NIH cell lines do not yield G418-resistant subclones (GRSs), a fraction of oncogene-transfected EN/NIH 2-4 (8 of 19 Py MT, 5 of 17 Py LT, and 11 of 19 E1A) and 2-20 (7 of 15 Py MT) cell lines gave rise to GRSs at differing frequencies (0.33 x 10(-6) to 46 x 10(-6) for line 2-4 versus 0.11 x 10(-6) to 1.3 x 10(-6) for line 2-20) independent of cell generation time. In contrast, a distinctly smaller fraction of mutant Py MT-transfected EN/NIH cell lines (1 of 10 MT23, 1 of 10 MT1015, and 0 of 10 MT59b) resulted in GRSs. Southern analysis of DNA from selected oncogene-transfected GRSs demonstrated genomic rearrangements of neo-containing cellular DNA that varied in type (amplification and/or novel fragments) and frequency depending on the specific oncogene and EN/NIH cell line used in transfection. Furthermore, only one of the two neo-containing genomic loci present in both EN/NIH cell lines appeared to be involved in these genomic events. In addition to effects related to the genomic locus, these observations support a role for oncogenes in the development of genetic changes associated with tumor progression.

Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line.

Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers' size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability.

Distinct effects of CD30 and Fas signaling in cutaneous anaplastic lymphomas: a possible mechanism for disease progression.

Lymphomatoid papulosis is part of a spectrum of CD30+ cutaneous lymphoproliferative disorders characterized by spontaneous tumor regression. The mechanism(s) of regression is unknown. In a recent study, a selective increase in CD30 ligand expression in regressing lesions of lymphomatoid papulosis and cutaneous CD30+ anaplastic large cell lymphoma was shown, suggesting that activation of the CD30 signaling pathway may be responsible for tumor regression, whereas no difference in Fas/Fas ligand expression was found between regressing and nonregressing lesions. Therefore we tested the effects of CD30 and Fas activation on three CD30+ cutaneous lymphoma cell lines (Mac-1, Mac-2 A, JK) derived from nonregressing tumors of two patients who had progressed from lymphomatoid papulosis to systemic anaplastic large cell lymphoma. To evaluate the effects of CD30 signaling, the cell lines were incubated with a CD30 agonistic antibody, HeFi-1. Proliferative responses, mitogen-activated protein kinase, and nuclear factor kappa B activities were determined with and without CD30 activation. Mac-1 and Mac-2 A showed increased proliferative responses to incubation with CD30 activating antibody, HeFi-1. Inhibition of the mitogen-activated protein kinase activity caused growth inhibition of the Mac-1, Mac-2 A, and JK cell lines. Activation of the Fas pathway induced apoptosis in all three cell lines. Taken together, these findings suggest that resistance to CD30-mediated growth inhibition provides a possible mechanism for escape of cutaneous anaplastic large cell lymphoma from tumor regression. Mitogen-activated protein kinase inhibitors are potential therapeutic agents for the treatment of advanced cutaneous anaplastic large cell lymphoma. J Invest Dermatol 115:1034-1040, 2000

DNAzol: a reagent for the rapid isolation of genomic DNA.

In this report, we present DNAzol, a patent-pending DNA isolation reagent containing guanidine thiocyanate and a detergent mixture. It is a complete, nontoxic and ready-to-use reagent for the isolation of genomic DNA from various biological sources. In the DNAzol protocol, a biological sample is homogenized (or lysed) in DNAzol, and the DNA is precipitated with ethanol, washed and dissolved in 8 mM NaOH. Following pH adjustment, the DNA can be used immediately for analysis or stored at 4 degrees C. The entire isolation can be completed in 20-30 min, and a wide range of DNA molecules can be isolated including genomic DNA and DNA fragments down to 0.1 kb in length. If necessary, samples can be stored in DNAzol at room temperature for extended periods of time. The isolated DNA is ready for PCR, Southern blotting and other molecular biology applications without any additional purification.

Reciprocal changes in serum 3, 3', 5'-tri-iodothyronine concentration and the peripheral thyroxine inner ring monodeiodination during food restriction in the young pig.

Utilizing the difference in pH optima between two distinct enzyme systems responsible for the thyroxine (T4) inner and outer ring monodeiodination, and a specific radioimmunoassay for iodothyronines, the net T4 conversion to 3, 3', 5'-tri-iodothyronine (rT3) and 3, 5', 3'-tri-iodothyronine (T3) in growing pigs kept under various food restrictions was determined in vitro. It has been found that fasting lowers deiodination of T4 to T3 by liver and kidney homogenates. The conversion of T4 to rT3 was reduced in the liver but not in the kidney, unless the animals were completely fasted. During food restriction serum T4 and T3 decreased whereas rT3 increased, which indicated that the serum rT3 level is not a good reflection of T4 to rT3 converting activity in the liver or kidney. The data suggest that a rise in rT3 reflects a lowered degradation rate of the hormone or an increased secretion by the thyroid gland rather than changes in rT3 neogenesis in the periphery.

Identification of G protein alpha subunit mutations in human growth hormone (GH)- and GH/prolactin-secreting pituitary tumors by single-strand conformation polymorphism (SSCP) analysis.

We have applied the polymerase chain reaction (PCR) and single-strand conformation polymorphism analysis (SSCP) to detect activating mutations in the Gs alpha subunit gene, amplifying genomic DNA extracted from growth hormone (GH)- and GH/prolactin (PRL)-secreting human pituitary tumors. Of 15 tumors tested six contained mutations in the analyzed regions of the Gs alpha. SSCP analysis revealed band shift in exon 8 in four GH- and in one GH/PRL-secreting tumors, and in exon 9 in one GH/PRL-secreting tumor. Direct sequencing of PCR reaction products identified the mutations as R201-H, R201-S and R201-C in exon 8 and Q227-L in exon 9. These results show the efficacy of PCR/SSCP analysis in the detection of G protein mutations and extend the generalization that these sites are hot spots in tumor-inducing mutations.

G proteins in normal rat pituitaries and in prolactin-secreting rat pituitary tumors.

It is still undetermined which GTP-binding (G) protein is involved in the regulation of prolactin (PRL) release and through which effector. This study shows that, when compared to normal pituitary tissue, the levels of alpha o protein were very low in dopamine (DA)-resistant, PRL-secreting pituitary tumors 7315a and MtTW15, while alpha o mRNA was present in the two tumors. In the MtTW15 tumor alpha i1, alpha i2 and alpha i3 levels were decreased while those of alpha s42 and alpha s47 were increased, and in the 7315a tumor alpha i2, alpha i3 and beta levels were decreased and those of alpha s47 increased. In an estrone-induced, DA-sensitive prolactinoma the levels of alpha i3 were greatly reduced. DA was unable to inhibit basal PRL release by 7315a and MtTW15 and basal cAMP accumulation by adenomatous and MtTW15 cells. Vasoactive intestinal peptide (VIP) increased both cAMP accumulation and PRL release by all cell preparations which could be suppressed by DA with adenomatous and 7315a but not with MtTW15 cells. These and previously published results provide circumstantial evidence that alpha o, alpha i1 and alpha i3 are all involved in the transduction of the DA inhibitory message while alpha s47 transduces cAMP activating messages and alpha s42 is responsible for the constitutive activation of L-type Ca2+ channels, adenylate cyclase and baseline PRL release.

MMQ cells: a model for evaluating the role of G proteins in the modulation of prolactin release.

It is well known that dopamine (DA) inhibits while vasoactive intestinal peptide (VIP) and angiotensin II (ANG II) stimulate prolactin (PRL) release from normal anterior pituitary lactotrophs; however, elucidation of the intracellular mechanisms involved in these effects has been hindered by the cellular heterogeneity of the anterior pituitary. MMQ cells, isolated from the PRL-secreting rat pituitary tumor 7315a is an interesting model since they only secrete PRL. In order to determine whether and which GTP-binding (G) proteins are involved in the modulation of cyclic 3',5'-adenosine monophosphate (cAMP) accumulation and phospholipids turnover and eventually PRL release, we have performed studies with MMQ cells. For this purpose, the levels of various G proteins (alpha o, alpha s, alpha i, alpha q and beta) and their mRNAs, measured by Western and Northern blots respectively, were correlated with intracellular cAMP accumulation in response to DA, VIP or DA plus VIP, and with inositol phosphates (IPx) formation in response to ANG II, DA or DA plus ANG II. This study shows that, when compared to normal pituitary tissue, the levels of alpha o, alpha o2 and alpha i3 were significantly decreased in MMQ cells; those of alpha o1, alpha i (alpha i1 + alpha i2), alpha s42 and alpha q were very low or undetectable while those of alpha s47 and beta were normal. DA was unable to inhibit basal PRL release and cAMP accumulation. VIP increased both cAMP accumulation and PRL release, while cAMP accumulation elicited by VIP could be suppressed by DA. BAY K 8644-induced PRL release also could be suppressed by DA.(ABSTRACT TRUNCATED AT 250 WORDS)

POEMS syndrome with myocardial infarction: observations concerning pathogenesis and review of the literature.

A 27-year-old white man with no significant risk factors for coronary artery disease presented with a 9-month history of progressive impotence, gynecomastia, lower extremity paresthesias, and extensive myocardial infarction and subsequently developed ulcerative proctitis. A diagnosis of POEMS syndrome was made based on the clinical presentation; additional physical findings of papilledema, clubbing, and hyperpigmentation; and laboratory findings of an immunoglobulin G M component of the lambda subtype, elevated cerebrospinal fluid protein, and typical sclerotic bone lesions. Abnormal in vitro binding of the patient's serum immunoglobulin to testicular tissue was also seen. Cardiac catheterization showed evidence of diffuse coronary artery narrowing and left ventricular wall motion abnormalities. Diffuse coronary involvement and ulcerative proctitis have not been previously described in POEMS syndrome. It is hypothesized that an abnormal immunoglobin (or fragment) is responsible for both findings. Furthermore, the detection of antitesticular autoantibodies suggests the possibility of an interaction between the antibody and Leydig cells, leading to an alteration in the synthesis and release of sex steroids and thereby explaining the gonadal failure seen in this syndrome. Long-term glucocorticoid therapy for the past 5 years has resulted in marked subjective and objective improvement.

Hodgkin's lymphoma of T-cell type: clonal association with a CD30+ cutaneous lymphoma.

The derivation of Reed-Sternberg cells in Hodgkin's lymphoma has been a subject of great interest. In most cases, Reed-Sternberg cells seem to be derived from germinal center B cells. In few sporadic cases, a T-cell origin has been shown. This article supports the concept of a T-cell derivation for rare cases of Hodgkin's lymphoma and provides evidence of a novel mechanism of pathogenesis from chronic inflammation in the skin.

Dying with cancer: patients' function, symptoms, and care preferences as death approaches.

OBJECTIVE: To characterize the dying experience of patients with cancer over the last 6 months of life. STUDY DESIGN: A retrospective analysis of the last 6 months of life among patients with colon cancer and non-small cell lung cancer enrolled in a prospective cohort study from June 1989 to June 1991 and from January 1992 to January 1994. SETTING: Five geographically diverse tertiary care academic medical centers participating in the Study to Understand Patient Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) Project. PARTICIPANTS: All patients enrolled in SUPPORT who had either colon cancer, metastatic to the liver or stage III or stage IV non-small cell lung cancer and died within 1 year of their index hospitalization. This report examines 316 of 520 patients with metastatic colon cancer and 747 of 939 patients with lung cancer enrolled in SUPPORT. METHODS: Data were collected by interview and chart abstraction at several time points in the SUPPORT Project. To describe progression to death, we constructed four observational windows backward in time beginning with patients' date of death and ending with their date of entry into the SUPPORT Project or 6 months before their death, whichever came first: (1) 3 days before death, (2) 3 days to 1 month before death, (3) 1 month to 3 months before death, and (4) 3 months to 6 months before death. For each outcome, patients contributed information to all windows during which they had data collected. We describe the frequency distributions of each outcome over time and report tests for trend. OUTCOME MEASURES: We examined several outcomes over time, including: percentage of days spent in a hospital; prognosis as measured by model-based prognostic estimates of 6-month survival; severity of illness as measured by the acute physiology score; functional status as measured by dependencies in activities of daily living (ADLs); severe physical and emotional symptoms, including pain, depression, and anxiety; patients' preferences for care; and the financial impact on patients' families. RESULTS: The death rate within 1 year of study entry was high among patients with metastatic colon cancer and advanced non-small cell lung cancer enrolled in SUPPORT (61% and 80%, respectively). As patients with cancer progress toward death, their estimated 6-month prognosis decreases significantly and the severity of their disease worsens. Patients' functional status also declines significantly as they approach death, such that most patients have four or more impairments within the 3 days before death. Patients with cancer experience significantly more pain and confusion as death approaches. Severe pain is common; more than one-quarter of patients with cancer experience serious pain 3 to 6 months before death and more than 40% were in serious pain during their last 3 days of life. However, dying patients are only modestly depressed and anxious during their last 3 days of life. As death approaches, patients favor comfort measures over life-extension, and about two-thirds want to forego resuscitation within 3 days of death. Families of patients dying with cancer incurred significant financial burdens during the last 6 months of life, and much of this burden was already experienced by 3 to 6 months before death. CONCLUSIONS: The last 6 months of life for patients with cancer is characterized by functional decline and poorly controlled severe pain and confusion. Although patients increasingly prefer comfort care as they near death, many die in severe pain. These findings highlight important opportunities to improve the quality of care at the end of life for patients dying with cancer.

The moving fluid field in ophthalmic surgery.

A microscope mounted dripper and a cottonold wick for removal of excess fluid provide a moving fluid field for anterior segment microsurgery. The advantages of the moving fluid field include protection of the corneal epithelium, a field cleaned of debris and blood, and optimum visualization of the anterior segment.

Intermittent touch syndrome.

Intermittent touch of a pseudophakos to the corneal endothelium is heralded by three signs: ciliary flush, (local) corneal dystrophy, and cystoid macular edema. This syndrome is often missed, and should be ruled out whenever any one of these three signs is detected. Once diagnosed, elimination of the touch should be accomplished promptly. If discovered early, the syndrome may be reversed.

Static perimetry in chloroquine retinopathy. Perifoveal patterns of visual field depression.

Results of threshold static perimetry in nine cases of toxic retinopathy produced by chloroquine phosphate and hydroxychloroquine sulfate are reported. Pericentral visual field defects in an advanced case correlated well with ophthalmoscopically visible defects in the pigment epithelium. In a less advanced case, perifoveal defects in the visual field of one eye were found to be demonstrable in the absence of any fundus abnormalities by either ophthalmoscopy or fluorescein angiography. In both cases, visual field defects were deepest on the superior or vertical meridian, just above the point of fixation. Since defects were found to be deepest along the superior vertical meridian, threshold static perimetry that includes this location should be the most sensitive method of detecting the early stages of visual field damage in chloroquine retinopathy.

Mirror fixation.

A mirror is the ideal fixation device for an ophthalmoscopic examination: it is the essense of simplicity, and there is nothing the patient would rather watch than himself.

Clinical experience with the Fieldmaster perimeter.

Perimetry performed on a Fieldmaster Model 200 on a consecutive series of 167 patients in a clinical practice setting demonstrated that Fieldmaster testing elicited 95% of defects found on Goldmann kinetic perimetry with very few false-positive or false-negative results; relatively unskilled personnel were able to conduct Fieldmaster testing well; and as our personnel and patients became familiar with the test, the rate of incomplete examinations declined to less than 2%.

Results in patients with high and low power intraocular lenses.

Seventy patients who received lens implants of unusually high or low power were studied retrospectively. There were 36 myopes and 34 hyperopes. All were followed a minimum of two years. Although both groups of patients presented technical problems at surgery, the visual acuity and general results were good.

Five year study of astigmatic stability after cataract surgery with intraocular lens implantation: comparison of wound sizes.

PURPOSE: To assess the long-term stability of cataract wounds of various lengths. SETTING: Private practice. METHODS: This retrospective study comprised 5 groups of consecutive cataract surgery cases and 1 control group with similar mean ages and wound lengths of 10.0, 6.0, 4.0, 2.0, and 0 (control) mm. Except for the 4.0 mm cases, follow-up was 5 years, with few patients lost during that time. Cases within each group had the same wound position, configuration, and suturing. Refractive data, controlled by keratometry, were collected and analyzed preoperatively and 1 day, 1 and 6 weeks, 3 and 6 months, and 1, 2, 3, 4, and 5 years postoperatively. No sutures were cut. RESULTS: With long-term follow-up, there was a progressive against-the-rule shift in astigmatism. Smaller wounds showed less immediate induced astigmatism. However, except for the unsutured 2.0 mm iridectomy wounds and the control group, all shifted similarly. Data were not available for the 4.0 mm wounds beyond 1 year. CONCLUSION: Wounds were not necessarily "stable" at 6 months. Larger wounds continued to shift years after surgery. Smaller wounds have significant postoperative advantages, but absolute long-term refractive stability may not be one.

Astigmatism after cataract surgery: nylon versus Mersilene. Five-year data.

This is a follow-up of a previous study that evaluated astigmatism after cataract surgery. In that study with a six-month follow-up, there was no statistically significant difference in astigmatism between eyes with nylon sutures and those with polyester fiber (Mersilene) sutures. This article reports the five-year data on this series of eyes.