Dynamic pore-pressure fluctuations in rapidly shearing granular materials.

Results from two types of experiments show that intergranular pore pressures fluctuated dynamically during rapid, steady shear deformation of water-saturated granular materials. During some fluctuations, the pore water locally supported all normal and shear stresses, while grain-contact stresses transiently fell to zero. Fluctuations also propagated outward from the shear zone; this process modifies grain-contact stresses in adjacent areas and potentially instigates shear-zone growth.

Rate of protein synthesis: regulation during first division cycle of sea urchin eggs.

Protein synthesis in fertilized sea urchin eggs, or in 12,000g supernatants derived from them, increased linearly during the period preceding prophase of the first mitotic cycle, dropped during metaphase and anaphase, and increased again after telophase. Similar results were observed for whole cells incubated in the presence of colchicine. These changes in the rate of protein synthesis during the mitotic cycle may be regulated at the translational level.

Physical effects of vehicular disturbances on arid landscapes.

Field experiments indicate that the use of off-road vehicles on arid land increases the amount and frequency of water runoff and erosion by decreasing soil porosity, infiltration capacity, effectiveness of surface stabilizers, and hydraulic resistance to overland flow. These effects are long-lived and may result even when the use of these vehicles is slight.

Acute sensitivity of landslide rates to initial soil porosity.

Some landslides move imperceptibly downslope, whereas others accelerate catastrophically. Experimental landslides triggered by rising pore water pressure moved at sharply contrasting rates due to small differences in initial porosity. Wet sandy soil with porosity of about 0.5 contracted during slope failure, partially liquefied, and accelerated within 1 second to speeds over 1 meter per second. The same soil with porosity of about 0.4 dilated during failure and slipped episodically at rates averaging 0.002 meter per second. Repeated slip episodes were induced by gradually rising pore water pressure and were arrested by pore dilation and attendant pore pressure decline.

An adenosine 3':5' monophosphate dependent protein kinase from sea urchin spermatozoa.

A cyclic AMP dependent protein kinase (EC 2.7.1.37) from sea urchin sperm as purified to near homogeneity and characterized. A 68-fold purification of the enzyme was obtained. This preparation had a specific activity of 389 000 units/mg protein with protamine as the substrate. On the basis of the purification required, it may be calculated that the protein kinase constitutes as much as 1.5% of the soluble protein in sperm. There appeared to be a single form of the enzyme in sea urchin sperm, based on the behavior of the enzyme during DEAE-cellulose and Sephadex G-200 column chromatography. Magnesium ion was required for enzyme activity. The rate of phosphorylation of protamine was stimulated 2.5-fold by an optimal concentration of 0.9 M NaCl. The Km for ATP (minus cyclic AMP) was 0.119 +/- 0.013 (S.D.) and 0.055 mM +/- 0.009 (S.D.) in the presence of cyclic AMP. The specificity of the enzyme toward protein acceptors, in decreasing order of phosphorylation, was found to be histone f1 protamine, histone f2b, histone f3 and histone f2a; casein and phosvitin were not phosphorylated. The holoenzyme was found to have an apparent molecular weight of 230 000 by Sephadex G-200 chromatography. In the presence of 5 - 10(-6) M cyclic AMP, the holoenzyme was dissociated on Sephadex G-200 to a regulatory subunit of molecular weight 165 000 and a catalytic subunit of Mr 73 000. The dissociation could also be demonstrated by disc gel electrophoresis in the presence and absence of cyclic AMP.

Clustered point mutation analysis of the rat prolactin promoter.

To identify DNA regions important for basal and hormone-stimulated transcription of the rat PRL gene, a series of clustered point mutations were prepared within the immediate 5' flanking region. DNA fragments representing the wild-type and 19 different linker-scanner mutations of the PRL gene were each linked to a luciferase marker gene, and the DNA constructs were transferred into GH3 pituitary tumor cells by electroporation. Luciferase activity was determined 24 h after transfection in extracts from control cells or cells treated with 0.5 mM chlorophenylthio-cAMP, 100 nM TRH, or 100 nM phorbol myristate acetate. The individual clustered point mutations covered a region from just up-stream of the TATA box (position -30) to a position 193 basepairs up-stream from the start of transcription. Five regions in which mutations produced substantial decreases in both basal and cAMP-, TRH-, or phorbol ester-stimulated expression of the marker gene were detected. Three of these regions (positions -41 to -58, -113 to -124, and -149 to -156) correspond to previously identified binding sites for the pituitary-specific, homeobox protein, Pit-1/GHF-1. The fourth and fifth regions do not correspond to Pit-1/GHF-1-binding sites and presumably represent sites for an unidentified factor. Within these regions, sequences with some similarity to a consensus cAMP response element and an AP-2-binding site have been detected. These data confirm the importance of Pit-1/GHF-1 as a key factor in PRL gene transcription. In addition, the results suggest that additional transcription factors are probably required for efficient expression of the PRL gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of low frequency low energy pulsing electromagnetic field (PEMF) on X-ray-irradiated mice.

C3H/Km flora-defined mice were used to investigate the effect of exposure to pulsing electromagnetic field (PEMF) after total body x-ray irradiation. Prolonged exposure to PEMF had no effect on normal nonirradiated mice. When mice irradiated with different doses of x-ray (8.5 Gy, 6.8 Gy, and 6.3 Gy) were exposed to PEMF 24 h a day, we observed a more rapid decline in white blood cells (WBC) in the peripheral blood of mice exposed to PEMF at all the x-ray dosages used. No effect of exposure to PEMF was observed on the survival of the mice irradiated with 6.3 Gy and 8.5 Gy; in mice irradiated with 6.8 Gy, 2 out of 12 survived when exposed to PEMF as compared to 10 out of 12 control mice that were irradiated only. At day 4 after irradiation autoradiographic studies performed on bone marrow and spleen of 8.5-Gy-irradiated mice showed no difference between controls and mice exposed to PEMF, whereas on 6.8-Gy mice the bone marrow labeling index was lower in mice exposed to PEMF. In mice irradiated to 6.3 Gy we observed that the recovery of WBC in the peripheral blood was slowed in mice exposed to PEMF and their body weight was significantly lower than in control mice that were irradiated only. The spleen and bone marrow of the mice irradiated to 6.3 Gy and sacrificed at days 4, 14, 20, and 25 after irradiation were analyzed by autoradiography to evaluate the labeling index. Half of the spleens from mice sacrificed at day 25 after irradiation were used to evaluate the RNA content. Autoradiography showed that in the spleen and bone marrow of control mice, there were more cells labeled with [3H]thymidine at days 4 and 14 and less at days 20 and 25 after irradiation in comparison with mice irradiated and exposed to PEMF. The Northern blot analysis of histone H3 and p53 protein RNAs extracted from the spleens at day 25 after irradiation showed a slight increase in cycling cells among spleens of mice exposed to PEMF. We suggest that the exposure to PEMF immediately after x-ray irradiation results in increased damage.

ALS and heavy metals: a pilot case-control study.

We conducted a case-control study of suspected risk factors for ALS among referral patients seen at the Mayo Clinic. Responses to questions about demographic factors, diet, medical history, travel, infectious disease, and other variables were similar in ALS patients and controls. In all but a few items, the responses of the cases and controls did not differ significantly. A significant level of shared exposure to an exogenous agent or environmental insult among cases was noted mainly for heavy metals.

Lack of progression of neurologic deficit in survivors of paralytic polio: a 5-year prospective population-based study.

We completed a prospective, population-based cohort study of polio survivors in Olmsted County, Minnesota, between 1986 and 1993. We identified 50 individuals who had had paralytic polio between 1935 and 1960, as representative of all 300 cases of paralytic polio in the county. We completed detailed quantitative clinical and electrophysiologic studies at entry and after 5 years. These studies demonstrated stable neuromuscular function within the cohort, although 60% of the individuals were symptomatic. In two-thirds of the symptomatic patients, the causes of their symptoms were unrelated to earlier polio. For the 20% of patients who had unexplained muscle pain, perception of weakness, and fatigue, a mechanical disorder most likely underlies their symptoms.

Late effects of paralytic poliomyelitis in Olmsted County, Minnesota.

We identified a cohort of 300 individuals who had paralytic polio between 1935 and 1955. All lived in Olmsted County, Minnesota. From the 247 survivors, we selected 50 subjects for detailed historical, functional, psychological, clinical, and electrophysiologic evaluation. Sixty-four percent of these 50 survivors complained of new symptoms of muscle pain, fatigue, and weakness after a period of prolonged stability. This led to changes in lifestyle or activity in only 18%. The likelihood of expressing new complaints was not related to present age or interval since polio, and electrophysiologic testing did not distinguish between those with or without new problems. The development of new difficulties in a limb was most strongly predicted by significant paralysis of that limb at the time of the acute illness. Patients with leg weakness were twice as likely to complain of new problems compared to those with arm weakness. Elevated creatine kinase levels were present only in those with new complaints.

Effects of alterations in pulmonary function and sleep variables on survival in patients with amyotrophic lateral sclerosis.

Breathing abnormalities and nocturnal hypoventilation occur in patients with amyotrophic lateral sclerosis (ALS). A prospective study was undertaken to determine the relationship of pulmonary function test abnormalities with quality of sleep and survival in 21 patients with ALS. Results of spirometry including determination of maximal respiratory pressures and arterial blood gases were compared with several formal polysomnographic variables and then also with 18-month survival. The patients had mild to moderate pulmonary function deficits, but the quality of sleep was best related to age (mean age, 58.5 years). The results of pulmonary function tests and arterial blood gas measurements did not correlate well with the presence of nocturnal breathing events or survival time, but the maximal inspiratory pressure was 86% sensitive for predicting the presence of a nocturnal oxygen saturation nadir of 80% or less and 100% sensitive for predicting 18-month survival. Although obstructive breathing events occurred, the primary explanation for the decline in nocturnal oxygen saturation was hypoventilation. We conclude that routine pulmonary function tests may be useful for screening for reductions in nocturnal oxygen saturation and also may have prognostic value. Further studies may determine whether treatment of nocturnal hypoventilation will have an effect on survival in patients with ALS who have breathing impairment.

Relative morbidity of abdominal hysterectomy and myomectomy for management of uterine leiomyomas.

OBJECTIVE: To compare the morbidity of total abdominal hysterectomy and abdominal myomectomy in the surgical management of uterine leiomyomas. METHODS: Hospital records were reviewed for all women who underwent hysterectomy (n = 89) or myomectomy (n = 103) between May 1, 1988, and May 1, 1993, for the preoperative diagnosis of leiomyoma. RESULTS: There were significant differences between the two groups for average age (hysterectomy 39.2 years, myomectomy 34.4 years; mean difference 4.8, 95% confidence interval [CI] of difference 3.7-5.9), uterine size (hysterectomy 15.2, myomectomy 11.5 weeks; mean difference 3.8, 95% CI of difference 2.0-5.4) and use of a GnRH agonist (hysterectomy 23.6%, myomectomy 55.3%; relative risk [RR] 0.4, 95% CI 0.3-0.6). Myomectomy was associated with decreased estimated blood loss (hysterectomy 796 mL, myomectomy 464 mL; mean difference 331, 95% CI 121-542) and febrile morbidity (risk of temperature 38C or 48 or more hours postoperatively: for hysterectomy 49.4%, for myomectomy 32%; RR 1.5, 95% CI 1.1-2.2). Using multivariate linear regression, estimated blood loss was similar between the groups after controlling for uterine size. There was no difference in blood transfusion rates. There were two ureteral, one bladder, one bowel, and one femoral nerve injury in the hysterectomy group, and there were no intraoperative visceral injuries in the myomectomy group. CONCLUSION: Myomectomy compares favorably to hysterectomy in the surgical management of leiomyomas, with a possible decreased risk for visceral injury and infection.

Myomectomy fever: testing the dogma.

OBJECTIVE: To test the hypothesis that elevated temperature is more common after abdominal myomectomy than after hysterectomy. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): One hundred one women who underwent abdominal myomectomy and 160 women who underwent total abdominal hysterectomy for benign disease from 1988-1993. INTERVENTION(S): Abdominal myomectomy. MAIN OUTCOME MEASURE(S): Temperature of > or = 38.5 degrees C within 48 hours after operation. RESULT(S): Although univariate analysis showed that the incidence of elevated temperature was slightly greater among patients who underwent myomectomy (33% versus 26%, relative risk 1.29, 95% confidence interval 0.88-1.90), multivariate logistic regression analysis showed a 3.29 relative risk of elevated temperature (95% confidence interval 1.56-6.96) with myomectomy after controlling for age, parity, estimated blood loss, and treatment by the general gynecology service. CONCLUSION(S): After controlling for confounders, myomectomy was found to be an independent predictor for fever in the first 48 hours after operation.

Metabolism of pregnenolone by human breast cancer. Evidence for 17 alpha-hydroxylase and 17,20-lyase.

The metabolism of 7-(3)H-pregnenolone was studied in vitro using 16 human breast carcinomas. All mammary tumors transformed pregnenolone to progesterone. All estrogen receptor poor tumors and 4 out of 8 estrogen receptor rich tumors converted pregnenolone to 17-hydroxypregnenolone. Five estrogen receptor poor tumors showed the presence of 17,20-lyase as evidenced by formation of dehydroepiandrosterone and androstenedione. In two estrogen receptor poor tumors, conversions of pregnenolone to progesterone, 17-hydroxy pregnenolone, dehydroepiandrosterone, androstenedione and finally to estradiol was documented, providing a hypothetical pathway for steroid metabolism in human breast cancer. The conversion of pregnenolone to 17-hydroxypregnenolone was significantly less in receptor rich tumors and was totally absent in 4 receptor rich tumors with estrogen receptors of over 45 fmol/mg protein.

Aromatization of androgens by human breast cancer.

The metabolism of dehydroepiandrosterone and testosterone by human mammary tumor was investigated. Estrogen synthesis from dehydroepiandrosterone was observed in 9 of 10 estrogen-receptor-negative tumors and only in 2 of 8 receptor-positive tumors (p less than 0.025). Conversion of testosterone to estrogens was observed in 7 of 8 receptor-negative and 2 of 7 receptor-positive tumors. Tumors which are capable of transforming dehydroepiandrosterone to estrogens were also able to aromatize testosterone suggesting that the presence of the aromatase enzyme is inherent to certain tumor cells. No estrogen formation was detected by the mitochondrial-microsomal fraction of normal breast cells while fractions from both fat cell and tumor cell showed estrogen synthesis. Estrogen formation by tumor cell fraction ranged from 5 to 190 times that observed for fat cells. The physiological significance of these results in the neoplastic tissue and its relationship to hormone dependence are discussed.

Estradiol 17 beta-dehydrogenase and estradiol binding in human mammary tumors.

The metabolism of estradiol was studied in 31 human breast carcinoma in vitro. All 16 estrogen-receptor-poor tumors transformed estradiol to estrone with percent conversions ranging from 11.4 to 95 except for one poorly differentiated tumor where 0.5% conversion to estrone was observed. On the contrary, only 3 out of 15 estrogen-receptor-rich tumors showed higher than 10% conversion of estradiol to estrone (p = 0.001). There is indication that the enzymatic activity in receptor-poor tumors steadily decreases in premenopausal patients as they approach menopausal age, whereas, the activity steadily increases in post-menopausal patients as the duration of menopause lengthens.

Development and qualification of a novel virus removal filter for cell culture applications.

Commercial bioreactors employing mammalian cell cultures to express biological or pharmaceutical products can become contaminated with adventitious viruses. The high expense of such a contamination can be reduced by passing all gases and fluids feeding the bioreactor through virus inactivation or removal steps, which act as viral barriers around the bioreactor. A novel virus barrier filter has been developed for removing viruses from serum-free cell culture media. This filter removes the 20 nm minute virus of mice by >3 log reduction value (LRV), the 28 nm bacteriophage PhiX174 by >4.5 LRV, the mycoplasma Acholeplasma laidlawii by > or =8.8 LRV, and the bacteria Brevundimonas diminuta by > or =9.2 LRV. Robust removal occurs primarily by size exclusion as demonstrated over a wide range of feedstocks and operating conditions. The filtered media are indistinguishable from unfiltered media in growth of cells to high densities, maintenance of cell viability, and productivity in expressing protein product. Insulin and transferrin show high passage through the filter. The virus barrier filter can be autoclaved. The relatively high membrane permeability enables the use of a moderate filtration area.

Septic shock: a clinical perspective.

Septic shock may occur in otherwise normal individuals but is frequently a fatal sequel to infection in the elderly, the diabetic, or the debilitated patient. Mortality rates range from 40 to 95 per cent depending both on host factors and on the speed of initiation of appropriate therapy. The complexities of shock pathophysiology and biochemistry are elusive, but certain hemodynamic derangements are clearly described and create obvious therapeutic imperatives. Correction of the supply-dependent phase of oxygen consumption is the cornerstone of supportive therapy. Survival is primarily dependent on the rapid delivery of the appropriate antibiotics, surgical drainage and debridement of any infected tissues or abscesses, and aggressive volume resuscitation at the very time early sepsis is diagnosed. Septic shock is a medical emergency.

Establishing an administrative core curriculum for critical care physicians.

Summary recommendations for a core curriculum in intensive care unit administration and management are presented for inclusion in critical care medicine fellowship training programs. Attention is focused on program content and teaching formats that may be adapted to various educational priorities.