Upon heat stress processing of ribosomal RNA precursors into mature rRNAs is compromised after cleavage at primary P site in Arabidopsis thaliana.

Transcription and processing of 45S rRNAs in the nucleolus are keystones of ribosome biogenesis. While these processes are severely impacted by stress conditions in multiple species, primarily upon heat exposure, we lack information about the molecular mechanisms allowing sessile organisms without a temperature-control system, like plants, to cope with such circumstances. We show that heat stress disturbs nucleolar structure, inhibits pre-rRNA processing and provokes imbalanced ribosome profiles in Arabidopsis thaliana plants. Notably, the accuracy of transcription initiation and cleavage at the primary P site in the 5'ETS (5' External Transcribed Spacer) are not affected but the levels of primary 45S and 35S transcripts are, respectively, increased and reduced. In contrast, precursors of 18S, 5.8S and 25S RNAs are rapidly undetectable upon heat stress. Remarkably, nucleolar structure, pre-rRNAs from major ITS1 processing pathway and ribosome profiles are restored after returning to optimal conditions, shedding light on the extreme plasticity of nucleolar functions in plant cells. Further genetic and molecular analysis to identify molecular clues implicated in these nucleolar responses indicate that cleavage rate at P site and nucleolin protein expression can act as a checkpoint control towards a productive pre-rRNA processing pathway.

Implementing a hospital based injury surveillance system: a case study in Nigeria.

A pilot study of violent injury surveillance was implemented in two hospitals in Kano, Nigeria, in two phases: a formative evaluation including training and arranging the collection of hospital information, followed by a 6 month prospective data collection. Road traffic injuries constituted about 80 per cent of the cases, gunshot injuries were the commonest in victims of interpersonal violence (IPV). The causes and context of IPV, the relationship of victims and perpetrators, and the place, related activities and anatomical site of injuries from IPV are summarized.

Direct evidence of a role for mast cells in the pathogenesis of antigen-induced bronchoconstriction.

We measured bronchoalveolar lavage (BAL) fluid histamine levels in allergic asthmatics and nonallergic normal subjects after local airway antigen and cold 22 degrees C normal saline challenges. Immediately after instillation of antigen through a bronchoscope wedged into a subsegmental airway, all 17 allergic asthmatics but none of the nine normal subjects had visible airway constriction. The asthmatics had a concomitant mean increase in BAL histamine of 23% (P = 0.005), whereas the normals had no change in BAL histamine. Among the allergic asthmatics, the change in BAL histamine content in response to antigen directly correlated with the control (baseline) BAL histamine content (r = 0.66, P = 0.003). Moreover, asthmatics with large antigen-induced changes in BAL histamine had greater airway methacholine sensitivity than did asthmatics without measurable increases in BAL histamine (8 +/- 2 vs. 41 +/- 31 breath units). Neither asthmatics nor normal subjects had airway constriction or changes in BAL histamine levels in response to nonspecific challenge with cold saline. Our data suggest that when allergic asthmatics are exposed to relevant antigens they have in vivo lung mast cell degranulation which results in airway constriction and contributes to nonspecific airway hyperresponsiveness.

Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with methacholine bronchial hyperresponsiveness.

Using a sensitive single isotope enzymatic assay we measured bronchoalveolar lavage (BAL) fluid histamine in asymptomatic normal (nonallergic), allergic rhinitic, and allergic asthmatic subjects. Normal subjects were found to have little or no detectable amounts of histamine in BAL fluid (11 +/- 11 pg/ml), and few BAL fluid mast cells. In comparison, the allergic rhinitics and allergic asthmatics had much higher amounts of BAL fluid histamine (113 +/- 53 and 188 +/- 42 pg/ml, respectively), and a significantly greater number of BAL fluid mast cells. Furthermore, despite having equivalent baseline pulmonary function values, allergic asthmatics with BAL fluid histamine levels greater than 100 pg/ml required only 7 +/- 2 breath units of methacholine to induce a 20% drop in forced expiratory volume in 1 s (FEV1) (PD20FEV1) while asthmatics with BAL fluid histamine levels less than 100 pg/ml required 49 +/- 19 breath units (P less than 0.05). These data suggest that allergic asthmatics have ongoing lung mast cell degranulation that might contribute to the etiology of airway hyperresponsiveness.

Diet and chronic atrophic gastritis: a case-control study.

A hospital-based case-control study of gastric cancer precursor lesions was conducted in a high-risk black population in southern Louisiana. Ninety-three subjects with biopsy-proved advanced chronic atrophic gastritis were compared to two control series: a gastroscopy clinic series and a general hospital-admission series. Dietary case-control differences indicated a protective effect associated with fruit and vegetable intake and with dietary vitamin C and a risk elevation associated with milk consumption. The protective effect associated with consumption of fruits, vegetables, and vitamin C is consistent with findings for gastric cancer and with the etiologic hypothesis of intragastric nitrosation. A twofold increased risk was associated with cigarette smoking. Gastric juice pH, NO3-, and NO2- were determined for subjects undergoing gastroscopy, and comparisons were made between this high-risk U.S. group and a Colombian population with a much greater magnitude of risk; the latter had higher NO3- and NO2- levels. An increase in pH was associated with increasing severity of gastric lesions. Levels of pH and NO2- concentration were significantly correlated (P less than .0005); however, in Louisiana the large difference in NO2- concentration associated with pH elevation is not associated with histopathologic severity. Divergent trends with severity of lesions for NO3- concentration were seen in the two populations.

Proliferative and antigenic modifications in human epithelial cells in chronic atrophic gastritis.

For the study of both proliferative and antigenic changes in epithelial cells in a disease predisposing to gastric cancer, endoscopic biopsy specimens were analyzed following removal from individuals with chronic atrophic gastritis (CAG); comparisons were made with specimens from normal gastric mucosa. All subjects were from Nariño, Colombia, the population of which has a high age-adjusted incidence of gastric cancer (150/100,000 population) occurring mainly in gastric antrum. After pulse incubation of biopsy specimens with tritiated thymidine ([3H]dThd), microautoradiographic distributions of [3H]dThd-labeled cells in the epithelial lining of gastric pits were correlated with expression of serologically defined gamma-fetal antigen (FA) as a second marker. Measurements were done both in gastric corpus and in antrum for entire gastric pits and over multiple gastric pit compartments. Total numbers of cells per gastric pit column did not differ between the normal and the CAG specimens either in corpus or in antrum; however, both in corpus and in antrum mean numbers of [3H]dThd-labeled cells per gastric pit column and labeling index were almost twice as large for the CAG population (P less than .006). Labeling index differences also were significant over most gastric pit compartments (P less than .02). In antrum gamma-FA-positive lesions had an expanded proliferative compartment with labeling indices significantly greater than those of antigen-negative lesions (P less than .02). This correlation did not extend to biopsy specimens obtained from corpus of stomach where the frequency of carcinoma is low. Findings indicate a hyperproliferative state in CAG compared to the proliferative state in normal gastric mucosa and, in gastric antrum, a further correlation with expression of gamma-FA in hyperproliferating cells. The two markers can be used to aid definition of the gastric mucosa in a disease associated with the development of gastric cancer and in prophylactic dietary intervention programs.

Esophageal cancer in Uruguay: a case-control study.

Esophageal cancer has constituted a major public health problem in Uruguay, with age-adjusted death rates of 14.5 X 10(5) for males and of 3.8 X 10(5) for females. A case-control study was undertaken to ascertain the possible association of the local custom of drinking infusions of Ilex paraguariensis ("maté") with cancer of the esophagus, after controlling for well-known risk factors, such as alcohol and tobacco consumption. Two hundred twenty-six patients with esophageal cancer and 469 controls (control:case = 2.1) were interviewed at the time of admission or consultation at the Oncology Institute of Montevideo from 1979 through 1984. Males showed elevated risks of esophageal cancer associated with heavy tobacco [relative risk (RR) = 10.8] and alcohol (RR = 10.3) exposures. Among females, the independent effects of tobacco and alcohol were nonsignificant. Maté consumption had an independent effect in both males and females, with odds ratios of 6.5 and 34.6, respectively, for heavy users. Moreover, a well-defined dose response was evident in both sexes.

Urinary excretion of nitrate, N-nitrosoproline, 3-methyladenine, and 7-methylguanine in a Colombian population at high risk for stomach cancer.

Urinary excretion levels of nitrate and N-nitrosoproline were determined in 160 individuals in a Colombian population at high risk for gastric cancer. In 156 of these subjects urinary levels of 3-methyladenine and 7-methylguanine were determined. Gastric biopsy specimens were obtained from 118 individuals and were histologically characterized according to pathological criteria into the following groups: normal, superficial gastritis, chronic atrophic gastritis, chronic atrophic gastritis with intestinal metaplasia, and dysplastic. The histological changes were correlated with the four variables listed above. There were no significant differences in the excretion of nitrate, N-nitrosoproline, 3-methyladenine, or 7-methylguanine in subjects with different pathological changes. A statistically significant correlation was present between nitrate and N-nitrosoproline excretion in the total population group (r = 0.297, P = 0.0001). A highly significant correlation (r = 0.56, P = 0.0002) was noted for urinary nitrate and N-nitrosoproline excretion in individuals with intestinal metaplasia and dysplasia. An increase in the urinary excretion of 3-methyladenine and 7-methylguanine was associated with tobacco smoking in the total population group.

Gastric precancerous process in a high risk population: cross-sectional studies.

The gastric precancerous process is evaluated in 1788 participants in a gastroscopy survey in the population of Nariño, Colombia, which has one of the highest gastric cancer incidence rates on record. A detailed histological classification is used, and a hierarchical distribution of lesions is described with the main stages being gland neck hyperplasia, atrophy (gland loss), intestinal metaplasia and dysplasia. Acute inflammation was not found to be a specific stage in the sequence but rather a common finding in all stages of the precancerous spectrum. Indices of disease progression for the different steps are calculated and found to increase with gastric pH and nitrate and nitrite content of the gastric juice. The effects of high pH and nitrite content are intimately correlated. Relative risks of specific lesions, namely, hyperplasia, atrophy, metaplasia, and dysplasia, increase linearly with higher pH, nitrate, and nitrite values in the gastric juice. The severity of atrophy correlates with the prevalence of metaplasia, suggesting a sequential relationship between the described stages, a finding supported by all parameters examined. The model of progression described may serve as a basis for comparisons with populations at different levels of gastric cancer risk but it fails to provide information concerning the time required for each change, which should be provided by follow-up (cohort) studies.

Gastric precancerous process in a high risk population: cohort follow-up.

In an attempt to characterize the natural history of the gastric precancerous process, 1422 residents of a high risk area of Nariño, Columbia, have been followed from 3-16 years (average 5.1) with repeated gastric biopsies, for a total of 7290 person-years. The original cohort consisted of 1788 individuals yielding a successful completion rate of 79.5%. Comparison of initial and subsequent biopsies revealed a very complex dynamic flow of both progressive and regressive events, suggesting sporadic environmental forces of modulation. One-time measurement of gastric juice, pH, and nitrite failed to predict future events in the gastric mucosa. The net loss of individuals whose gastric mucosa initially showed normal histology or superficial gastritis was 3.3%/year, representing a net gain of 1.7% for chronic atrophic gastritis, 0.9% for intestinal metaplasia, and 0.7% for dysplasia. The incidence rate of gastric cancer in this population was 0.16/100 person-years. The net rates of progression were higher and those of regression lower in older compared to younger individuals. The general pattern detected is that of a slow forward movement in the previously described hierarchical organization of precursor lesions. The presence of progressive as well as regressive changes and the slow pace of change offer special opportunities to inhibit progression through intervention strategies targeting previously identified etiological factors. The difficulties and opportunities offered by the long term follow-up studies as well as the congruency of the findings with current etiological hypotheses are discussed.

Basal oxygen uptake: a new technique for an old test.

To assess the metabolic effects of T4 and T3, we measured serum total T4 (TT4), free T4 (FT4), total T3 (TT3), TSH, and basal oxygen uptake (VO2) in eight normal subjects in the basal state and after treatment with L-T3 (T3) and sodium ipodate for 2 weeks. T3 treatment resulted in a rise of serum TT3 from a baseline of 137 +/- 16 (+/- SE) to a peak of 239 +/- 15 ng/dl. Serum TT4 declined from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, FT4 from 1.59 +/- 0.13 to 1.03 +/- 0.05 ng/dl, and TSH from 1.74 +/- 0.24 to 0.56 +/- 0.16 microU/ml. Basal VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg X min. Ipodate, on the other hand, led to a lower serum TT3 concentration (102 +/- 21 ng/dl), higher serum TT4 and FT4 (9.59 +/- 0.5 micrograms/dl and 1.91 +/- 0.13 ng/dl, respectively), and elevated TSH (3.64 +/- 0.14 microU/ml). Basal VO2 was reduced to 2.44 +/- 0.06 ml/kg X min. Linear regression analysis revealed an excellent positive correlation between serum TT3 and basal VO2 (n = 25; r = 0.747; P less than 0.001) and a significant negative correlation between serum TT3 and TSH (n = 26; r = -0.526; P less than 0.01). Serum TT4 and FT4 correlated negatively with VO2 and positively with serum TSH. The higher T4 level during ipodate treatment was associated with lower VO2 and higher TSH, and vice versa when T4 was suppressed while receiving T3. When ipodate was given concomitantly with T3 to five subjects, only the effects of T3, characterized by increased VO2 and decreased TSH, were evident. These data indicate that both basal VO2 and serum TSH are sensitive indices of thyroid hormone activities. The latter gives only the directional change (hyper- or hypothyroidism), while the former more accurately quantitates the magnitude of the derangement. Moreover, it appears that in man, T3, and not T4, is the primary hormone that regulates thermogenesis and TSH secretion.

Prospective study of Lewis antigen alterations in the gastric precancerous process.

A prospective study with two gastric biopsies taken several years apart was carried out in 117 subjects with intestinal metaplasia who are of the Lewis(a-b+) phenotype. They are residents of a rural Andean region in Colombia displaying very high rates of gastric cancer. The anomalous expression of Lewis(a) antigens in the metaplastic epithelium carried a significantly increased risk of colonic metaplasia and dysplasia. Such risk was much higher when the simultaneous expression of sulfomucins and Lewis(a) antigen was observed.

The effect of alcohol on the risk of lung cancer in Uruguay.

A hospital-based case-control study of the association between alcohol drinking and lung cancer was carried out in Uruguay between January 1988 and December 1990. The sample included 327 men with lung cancer and 350 male controls. Personal interviews were conducted in the Institute of Oncology by trained personnel using a structured questionnaire. The results showed a significant positive association between beer intake and the risk of lung cancer. The odds ratio for beer drinkers in the highest quartile was 3.4 (95% confidence limits, 1.3-6.6) after adjustment for tobacco. The association between beer and lung cancer was consistent for all the cell types, analyzed separately. A moderate effect for total alcohol consumption was also observed, with a relative risk of 2.2 for those subjects in the highest quartile.

The pathophysiology of acute high-altitude illness.

Complex physiologic responses occur as nonacclimatized lowland dwellers ascend above 10,000 feet, with a resulting partial pressure of arterial oxygen of less than 60 mm Hg. There are marked hemodynamic changes and shifts in body fluids that may result in organ dysfunction. The suspected pathogenesis of these acute hypobaric hypoxic-induced illnesses is discussed. Cerebral dysfunction may present as acute mountain sickness or high-altitude cerebral edema. Usually asymptomatic high-altitude retinal hemorrhage and noncardiogenic high-altitude pulmonary edema also are described. All of these illnesses apparently represent a spectrum of pathologic states initiated by an exaggerated vascular response to hypoxia. With the exception of retinopathy, high-altitude illness can be prevented by slow ascent. Early recognition of cerebral or pulmonary edema and immediate descent will prevent serious consequences of nonacclimatized persons who are acutely exposed to hypobaric environments.

Diagnostic fiberoptic bronchoscopy: Techniques and results of biopsy in 600 patients.

Six hundred patients underwent diagnostic flexible fiberoptic bronchoscopy (FFB). The two diseases most frequently encountered were bronchogenic carcinoma in 330 patients (55 percent) and bacterial infection in 94 (16 percent). A positive cytology on biopsy material was obtained in 279 of 330 patients (85 percent) with primary lung cancer. Fluoroscopy was a valuable aid in diagnosing bronchogenic carcinoma, since 42 percent of the tumors were not visible endoscopically and required fluoroscopic control for placement of the biopsy instrument. Of the 55 patients with hemoptysis and negative chest x-ray films, nine (15 percent) had fiberoptically visible endobronchial carcinomas! In addition, two patients with carcinoma of the larynx and one with carcinoma of the nasopharynx were discovered. Transbronchial biopsy (TBB) in 68 patinets with diffuse and localized disease achieved an overall 69 percent diagnostic success, including a correct diagnosis in each of four patients with Pneumocystis carinii pneumonia. Brush biopsy provided additional valuable laboratory data in bacterial, mycobacterial and cytomegalovirsu infectious but had a poor yield in Pneumocystis infection. Complications as a result of forceps biopsy were minimal, except for brisk bleeding in six patients.

Pulmonary hemorrhage in fiberoptic transbronchial biopsy.

Transbronchial forceps biopsy via the flexible fiberoptic bronchoscope is described as a "safe," high-yielding procedure, but the potential danger of serious hemorrhage is of concern to chest physicians. In a collected series of 438 patients, the incidence of mild to "explosive" hemorrhage was 9 percent in "routine" cases, 29 percent (eight) in 31 immunosuppressed patients, and 45 percent (five) in 11 uremic patients. One death resulted from massive hemorrhage. A new "wedge" method of transbronchial forceps biopsy is now being utilized in our bronchoscopic unit. The tip of the flexible fiberoptic bronchoscope is lodged into the appropriate segmental bronchus to tamponade any bleeding and, thus, prevent blood from flooding the airway. Careful screening of patients and competence in procedural techniques are necessary. Otherwise, transbronchial forceps biopsy should be performed through a rigid open-tube bronchoscopicronchoscope or performed through a rigid open-tube bronchoscope or lung tissue should be obtained via thoracotomy.

Serial exercise testing in pulmonary embolism.

A patient underwent exercise testing during evaluation for unexplained dyspnea. Evidence of ventilation-perfusion mismatch was noted and subsequent testing revealed multiple pulmonary emboli. Ventilation perfusion parameters by serial exercise testing progressively improved during the course of the patient's illness but did not totally normalize. A discussion of the utility of exercise testing in the evaluation of the patient with unexplained dyspnea is provided and the potential value of serial exercise testing in the management of patients with pulmonary emboli is discussed.

An effect of paraquat on the lungs of rabbits. Its implications in smoking contaminated marihuana.

Thirty-six rabbits received the herbicide, paraquat (1,1'-dimethyl-4,4'-dipyridylium dichloride), by selective intrabronchial instillation in doses ranging from 0.1 gm to 1 pg. Sixteen additional rabbits were given paraquat dichloride (25 mg/kg of body weight) intraperitoneally, subcutaneously, intravenously, or orally. The lung of the rabbit proved to be highly sensitive to paraquat administered by intrabronchial deposition, moderately sensitive to intravenously administered paraquat, and resistant to the chemical when given intraperitoneally or subcutaneously. One picogram of paraquat dichloride delivered by bronchial catheter produced a 1.0-mm pulmonary lesion consisting of focal hemorrhage, congestion of capillaries, intra-alveolar macrophages, and moderate thickening of the alveolar septa. This finding suggests that pulmonary damage could potentially result from smoking marihuana that has been sprayed with paraquat.

The response to atropine sulfate given by aerosol and intramuscular routes to patients undergoing fiberoptic bronchoscopy.

Two groups of 11 patients each were studied in their responses to intramuscular (IM) or aerosolized atropine sulfate, given in preparation for fiberoptic bronchoscopy. The patients in group 1 received 1.0 mg of atropine IM, and those in group 2 were given a prepared solution of atropine in saline (5 mg/ml) at a dosage of 0.1 mg/kg by nebulization (IPPB). Statistical analysis of the FVC, FEV1, FEF25-75%, and FEFmax showed excellent protective bronchodilatory effects of both IM and aerosolized atropine. In fact, the beneficial result was more prolonged when the drug was administered by inhalation. One possible factor to consider, however, is that atropine given by the aerosol route did not inhibit the vasovagal response in three of the 11 patients. Another factor to take into account is that atropine by IM injection is quicker to administer, more convenient, and requires less instrumentation than atropine given by aerosol.

Plasma levels of lidocaine following nebulized aerosol administration.

The venous (plasma) levels of lidocaine were measured in five subjects following nebulization of a 280-mg dose via intermittent positive pressure breathing (IPPB) and nebulization of a 400-mg dose via ultrasound. Even though a lower dose of lidocaine was given by IPPB, this system of delivery produced higher plasma concentrations of the drug than ultrasound and also was more effective in eliminating the gag reflex. In the entire study, plasma concentrations of lidocaine did not exceed 1.1 mug/ml, which is far below toxic levels. Aerosolized lidocaine, administered by IPPB, is a safe and effective topical anesthetic agent which may be useful for instrumentation of the upper airway.